Thunyaseth Format Check Edited

MATHEMATICAL MODEL FOR HEMODYNAMIC AND
INTRACRANIAL WINDKESSEL MECHANISM
by
THUNYASETH SETHAPUT
Submitted in partial fulfillment of the requirements

For the degree of Doctor of Philosophy
Dissertation Advisor: Dr. Kenneth A. Loparo
Department of Electrical Engineering & Computer Science
CASE WESTERN RESERVE UNIVERSITY
May 2013
CASE WESTERN RESERVE UNIVERSITY
SCHOOL OF GRADUATE STUDIES
We hereby approve the thesis/dissertation of
John JamesSethaput
Thunyaseth Doe
______________________________________________________
Doctorof
Doctor of Philosophy
Philosophy
candidate for the ________________________________degree *.
Kenneth A. Committee
Loparo Chair
(signed)_______________________________________________
(chair of the committee)
Committee Member
Vira Chankong
________________________________________________
Committee Member
Mark Buchner
________________________________________________
Committee Member
Evren Gurkan-Cavusoglu
________________________________________________
Committee Member
________________________________________________
Committee Member
________________________________________________
07Date of Defense
December 2012
(date) _______________________
*We also certify that written approval has been obtained for any
proprietary material contained therein.
Table of Contents
Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

List of Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
List of Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi
Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvi
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xviii
1 Introduction 1
1.1 Motivation and Literature Survey . . . . . . . . . . . . . . . . . . . . 1
1.2 Contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3 Outline of the Dissertation . . . . . . . . . . . . . . . . . . . . . . . . 8
2 Review of Physiology 11
2.1 The Cardiovascular System . . . . . . . . . . . . . . . . . . . . . . . 11
2.1.1 Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.1.2 Vascular System . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.2 Intracranial Space . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.2.1 Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.2.2 CSF and Ventricular System . . . . . . . . . . . . . . . . . . . 23
2.2.3 Cerebral Blood Flow . . . . . . . . . . . . . . . . . . . . . . . 25
2.3 Pathological Conditions . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.3.1 Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.3.2 Traumatic Brain Injury . . . . . . . . . . . . . . . . . . . . . . 29
2.3.3 Hydrocephalus . . . . . . . . . . . . . . . . . . . . . . . . . . 32
3 Associated Intracranial System 38

3.1 Windkessel Mechanism and Pulsatility . . . . . . . . . . . . . . . . . 39
3.2 Monro-Kellie Doctrine . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3.3 Intracranial Compliance . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.4 Interhemispheric Pressure Gradients . . . . . . . . . . . . . . . . . . 57
3.5 Effect of Neurosurgical Disorders on Cerebral Blood Flow . . . . . . 64
iii
4 Review of Windkessel Model and the Model of Intracranial System 72
4.1 Review of Windkessel Model . . . . . . . . . . . . . . . . . . . . . . . 72
4.2 Review of the Model of Intracranial System . . . . . . . . . . . . . . 76
5 Mathematical Model 90
5.1 Continuity Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5.2 The Equation for the Acceleration of the Elastic Blood Vessel . . . . 92
5.3 Hagen-Poiseuille’s Law . . . . . . . . . . . . . . . . . . . . . . . . . . 93
5.4 The Relationship of Flow and Pressure in Orifice . . . . . . . . . . . 94
5.5 Blood Flow through Cranium . . . . . . . . . . . . . . . . . . . . . . 95
5.6 Pressure-Volume Relationship . . . . . . . . . . . . . . . . . . . . . . 97
5.7 Interhemispheric Pressure Gradients . . . . . . . . . . . . . . . . . . . 98
5.8 Interhemispheric Asymmetry of Cerebral Blood Flow . . . . . . . . . 99
5.9 The Case of Neurosurgical Disorder . . . . . . . . . . . . . . . . . . . 100
5.10 The Case of Treatment by using a Medical Balloon . . . . . . . . . . 101
6 Simulation Results 103

6.1 Normal Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.1.1 Lower Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
6.1.2 Upper Body and Intracranial Space . . . . . . . . . . . . . . . 104
6.2 Case of Neurosurgical Disorder . . . . . . . . . . . . . . . . . . . . . 112
6.2.1 Small mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.2.2 Large mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . 115
6.3 Case of Treatment by using a Medical Balloon . . . . . . . . . . . . . 120
6.3.1 Small mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . 120
6.3.2 Large mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . 124
6.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
7 Summary and Conclusions 134

7.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
7.2 Recommendations for Future Development . . . . . . . . . . . . . . . 136
A Parameters for the Model of Hemodynamics and Intracranial Sys-

tem 137
iv
List of Tables
2.1 Characteristics of various types of blood vessels in humans [10]. . . . 14
3.1 Summary of types of lesion according to CT scan and ICP pattern [144]. 62
3.2 Effect of extradural expanding lesion on cerebral blood flow [163]. . . 68
3.3 Regional and total brain cerebral blood flow in rats subjected to fluid-
percussion brain injury [197]. . . . . . . . . . . . . . . . . . . . . . . 69
4.1 Summary of the equivalent between pulsation of CSF and oscillations

of electricity in an AC electrical circuit [46] . . . . . . . . . . . . . . . 83
6.1 Comparison table of ICP, cerebral blood flow (Qbrain) and flow to
hands (Qhand) during normal condition, with small mass lesion and
after inversion treatment . . . . . . . . . . . . . . . . . . . . . . . . . 123
6.2 Comparison table of ICP, cerebral blood flow (Qbrain) and flow to
hands (Qhand) during normal condition, with large mass lesion, and
A.1 Parameters for the Model of Hemodynamics and Intracranial System 137
v
List of Figures
1.1 Current and projected numbers of patients with hydrocephalus, aged

18 to 35, treated in the United States. Dark bars indicate projec-
tions of numbers of patients based on the actual numbers treated at
Intermountain Healthcare; lighter bars indicate future projections for
young adults with hydrocephalus. Data source from Intermountain
Healthcare [154]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2.1 Pulsatile blood flow in the root of the aorta recorded using an electro-
magnetic flowmeter [69]. . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.2 Blood pressure in different segments of the vascular system [78]. . . . 14
2.3 Movement of blood into and out of the arteries during the cardiac cycle.
The lengths of the arrows denote relative quantities flowing into and
out of the arteries and remaining in the arteries [193]. . . . . . . . . 16
2.4 Changes in the pulse pressure contour as the pulse wave travels toward
the smaller vessels [69]. . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.5 The major arteries that carry blood from the left ventricle of the heart
to the tissues of the body [148]. . . . . . . . . . . . . . . . . . . . . . 20
2.6 (a) The surface of the cerebral cortex and the divisions of the brain
shown in sagittal section [193], (b) Investing membranes of the brain,
showing their relation to the skull and to brain tissue [10]. . . . . . . 22
2.7 (a) The pathway CSF flow from the choroid plexus in the lateral ven-
tricles to arachnoid villi penetrating into sagittal sinus [69]. (b) Ven-
tricular system of the brain [173] . . . . . . . . . . . . . . . . . . . . 24
2.8 The internal carotid artery and vertebro-basilar system. Note the cere-
bral arterial circle (circle of Willis; marked by a dashed black line) [152]. 26
2.9 Axial noncontrast CT demonstrates an epidural hematoma [199]. . . 30
2.10 (a) Axial view of a subdural hematoma [110]. (b) Computed tomogra-
phy indicated a large right-sided acute on chronic subdural hematoma
(maximum depth, 1.9 cm) occupying the frontal, parietal and temporal
convexities, and a possible small subarachnoid hemorrhage [196]. . . . 32
vi
2.11 T1 weighted axial and sagittal magnetic resonance images of the brain
in patients with ((b) and (d)) and without ((a) and (c)) hydrocephalus.
The ventricles are markedly enlarged compared to normal. The cere-
bral aqueduct (arrow) is patent and there is no evidence of obstruction
within the ventricular system. This is a case of communicating hydro-
cephalus [28]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.12 Cerebral blood flow in (a) healthy individuals and in (b) communicat-
ing hydrocephalus. (a) The arterial windkessel mechanism, the wide
intracranial vessels with small vascular resistance and the venous out-
flow resistance that keep the cerebral veins distended maintain the
high normal blood flow. The venous outflow resistance is caused by
a small positive intracranial pressure and is increased during systole.
The venous outflow resistance is a mandatory prerequisite for the “wa-
terfall phenomenon”, i.e. the pressure drop occurring from the cortical
veins to the venous sinus. (b) In communicating hydrocephalus, the in-
creased transmantle pulsatile stress (i.e. difference in pressure between
ventricle and subarachnoid space) and the ventricular dilation com-
presses the cerebral veins and capillaries in their entire length. This
significantly increases the vascular resistance and decreases the blood
flow. The reduced venous outflow resistance facilitates collapse of the
compressed capacitance vessels, which further decreases cerebral blood
flow [66]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.13 (a) Preoperative MRI of a 7-year-old boy with monoventricular hy-
drocephalus due to shunt overdrainage: marked dilatation of the left
lateral ventricle (b) MRI performed 10 days after the endoscopic fen-
estration of the septum pellucidum: marked decrease of size of the left
lateral ventricle and reappearance of the subarachnoid spaces [55]. . . 36
3.1 The concept of Windkessel mechanism. The air reservoir (chamber)

is the actual Windkessel, and the large arteries act as the Windkessel.
The combination of compliance, together with aortic valves and pe-
ripheral resistance, results in a rather constant peripheral flow [189] . 39
3.2 Pressure-dependent arterial compliance [103] . . . . . . . . . . . . . . 40
vii
3.3 Central pressure contours and aging. The observed central pressure
contours (upper tracings) are the sum (lower tracings) of the incident
or forward-traveling wave (broken lines) and the reflected or backward-
traveling wave (dotted lines). In younger subjects (right panel), the
reflected wave (arrow) returns to the aortic root during diastole. As
vessels get stiffer during the aging process (left panel), pulse wave veloc-
ity increases and the reflected wave returns during late systole (arrow),
where it summates with the forward systolic wave to augment central
systolic pressure and increase ventricular afterload [77]. (Adapted from
Asmar R. Arterial Stiffness. 1999. [4]) . . . . . . . . . . . . . . . . . 42
3.4 Diagram showing the phase relationships of intracranial volume change
measured by using flow-sensitive MRI in (a) normal individuals and (b)
patients with hydrocephalus. The curve of the volume changes in the
artery is constructed as the inverse to the sum of the changes in the
veins and intracranial CSF. In normal individuals, the expansion in the
precapillary vessels is assumed to be somewhat larger than the corre-
sponding compression on the venous side in order to correspond with
the small brain expansion. In patients with hydrocephalus, the arterial
is small as reflected in the small volume changes in the veins and in the
intracranial CSF. As a result of the small arterial pulsations in SAS
the pulse wave penetrates into compliant less distended intracerebral
vessels resulting in a decreased intrinsic redistribution and large brain
expansion [61]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.5 Normal intracranial hydrodynamics. The relative thickness of the ar-
rows in the artery (red) indicates the magnitude of pressure. The
relative thickness of the arrows in the venous system (blue) and sub-
arachnoid space indicates the magnitude of flow [162]. (Modified from
Greitz [66]) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.6 Illustration of the ICP-volume curve and its relationship to the in-
tracranial pulsatility parameters. Under normal physiological condi-
tions with high intracranial compliance, the ICP wave amplitude is cor-
respondingly small. As intracranial compliance decreases (steep part of
the pressure-volume curve), the brain behaves increasingly like a linear
elastance and so variations in intracranial volume correlate increasingly
well with changes in mean ICP, the steepness of the pressure-volume
curve also accounts for large-amplitude ICP waveforms [48]. . . . . . 48
3.7 (a) The CSF volume-pressure curve (b) The same data plotted on
semilogarithmic axis can be approximated by a straight line which its
slope is equal to the pressure-volume index (PVI) [113]. . . . . . . . . 49
viii
3.8 Schematic depiction of the pressure-volume compensation index (RAP)
theory [83]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
3.9 Timetrends of intracranial pressure (ICP), arterial blood pressure (ABP),
cerebral perfusion pressure (CPP), mean cerebral blood flow velocity
(FVm), pulsatility index (PI) and cerebrovascular resistance (CVR) in
patient with head-injury [44]. . . . . . . . . . . . . . . . . . . . . . . 53
3.10 (a) Arterial and venous flow in the superior sigital sinus (SSS) territory
in a healthy patient. (b) In NPH patient, arterial and venous flows are
almost identical shape with minimal delay. The mean volumetric blood
flow through SSS in NPH patients is 27% lower than in the healthy
individuals. (c) After shunting (removal of 30 mL of CSF), the arterial
flow has earlier, higher, and thinner peak. The venous flow peaks later,
is lower, and wider. Modified from Bateman [11]. . . . . . . . . . . . 55
3.11 Mean values of epidural pressure on the right (PR ) and left (PL ) sides
in various groups of animals. Oil embolization always performed on
the right side. All pressures are positive. The animals in which epidu-
ral pressure increase was more pronounced on the right (embolized)
side were inscribed above the x-axis. The animals which epidural pres-
sure increase was more pronounced on the left (non-embolized) side
were inscribed below x-axis. Interhemispheric pressure gradients were
more pronounced when epidural pressure increased more on the non-
embolized (left) side. [20] . . . . . . . . . . . . . . . . . . . . . . . . . 59
3.12 Injection of Pantopaque into right middle cerebral artery of cat [167] 60
3.13 Alternating inflation of two balloons over left and right hemisphere of
baboon [167] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.14 Difference between ipsilateral and contralateral ICP recording from pa-
tients with (a) subdural hematoma and (b) contusions or intracerebral
hematoma [27] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.15 Interhemispheric ICP gradients and infarct volumes for all animals.
Hourly interhemispheric ICP gradients (mmHg) are plotted over time.
Percent ipsilateral hemispheric infarct volume is noted for each animal
[39]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.16 Effect of acute expansion of the extradural balloon on carotid blood
flow (BF), jugular vein pressure (Jug), intracranial pressure (ICP),
sagittal sinus pressure (Sag), lumbar subarachnoid pressure (Lum)
and systemic arterial pressure (SAP). Arrow indicate beginning and
end of injection. Time between triangles one minute. In this and all
subsequent illustrations pressures are indicated in mmHg and flow in
ml/min. [93]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
ix
3.17 Mean right and left cerebral hemisphere blood flow levels, with increas-
ing mean intraventricular pressure [79]. . . . . . . . . . . . . . . . . . 67
3.18 Changes in regional cerebral blood flow (rCBF) in the visual (A), pari-
etal (B), sensorimotor (C), and frontal cortices (D) of the injured and
the contralateral sides. rCBF decreased remarkably in the injured side
following insult for 4 hours. After 24 hours, rCBF recovered except in
the visual cortex. rCBF also decreased slightly in the non-injured side.
Modified from Ozawa et al. [135]. . . . . . . . . . . . . . . . . . . . . 70
3.19 Graph showing ipsilateral and contralateral regional cerebral blood
flow (CBF) values in measured areas in patients with intracranial
hematomas. Regional CBF in parietal and temporal lobes was sig-
nificantly lower on the side ipsilateral to the hematoma. Error bars
indicate standard error of the mean. FR = frontal lobes; PA = pari-
etal lobes; TE = temporal lobes; OCC = occipital lobes; BASG =
basal ganglia; CBL = cerebellum; BS = brain stem [19]. . . . . . . . 71
4.1 (a) Two-element Windkessel model, (b) Three-element Windkessel model

and (c) Four-element Windkessel model presented in hydraulic and
electrical circuits [189]. . . . . . . . . . . . . . . . . . . . . . . . . . . 73
4.2 The measured aortic input impedance and impedance predicted by
two-element,three-element and four-element Windkessel [189]. . . . . 75
4.3 Top: schematics of 3- and 4-element Windkessel (WK) models pre-
sented in electrical form. Rc and Rp , characteristic and peripheral
resistance; C, total arterial compliance; L, inertance. Middle: aortic
flow measured in dog. Bottom: measured and model derived aortic
pressure [161]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4.4 Lumped-parameter seven compartmental model of the cerebrovascular
system. [ ] represents pressure in mmHg, ( ) represents flow in ml/min.,
and <> represents volume in ml [80]. . . . . . . . . . . . . . . . . . . 77
4.5 Hydrodynamic equivalent of the model, comprising pathways of CBF
and the CSF circulation.A rigid skull is represented by the outer box,
with a compensatory reserve Ci associated with the compliant dural
sac within the lumbar channel [35]. . . . . . . . . . . . . . . . . . . . 79
4.6 Electrical circuit equivalent to the hydrodynamic model [35]. . . . . . 79
x
4.7 Electric analog (A) and corresponding mechanical analog (B) of in-
tracranial dynamics according to present model. Cerebral blood flow
(CBF, q) enters skull at pressure approximately equal to systemic ar-
terial pressure (Pa ). Arterial-arteriolar cerebrovascular bed consists
of a regulated capacity (Ca), which stores a certain amount of blood
volume, and a regulated resistance (Ra ), which accounts for pressure
drop to capillary pressure (Pc ). At capillary level, cerebrospinal fluid
(CSF) is produced through a CSF formation resistance (Rf ). CBF
then passes through venous cerebrovascular bed, mimicked as series
arrangement of proximal venous resistance (Rpv ) and resistance of col-
lapsing lateral lacunae and bridge veins (Rdv ). Model assumes that,
because of collapse of last section, cerebral venous pressure (Pv ) is al-
ways approximately equal to intracranial pressure (Pic ). Finally, CSF
is reabsorbed at venous sinus pressure (Pvs ) through CSF outflow resis-
tance (Ro ). Intracranial pressure is determined by amount of volume
stored in nonlinear intracranial compliance (Cic ). This volume results
from a balance between CSF inflow (qf ), CSF outflow (qo ), blood vol-
ume changes in arterial capacity, and mock CSF injection rate (Ii ).
Modified from Ursino and Lodi [171]. . . . . . . . . . . . . . . . . . . 80
4.8 The 16 compartment whole-body model. A filled arrow indicates a one-
way flow and a hollow arrow indicates a pressure dependent resistance.
Compartment labels are enclosed in parentheses with the spatially-
averaged mean pressures in square brackets. The thick line indicates
the cranial wall [89]. . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.9 (a) A model of CSF pulsation with a single degree of freedom.The CSF
pulsation, which is the mass of CSF (mCSF ) displaced by the maximum
expansion of the vessel is represented by sphere. The instantaneous
displacement of the CSF pulsation is represented by xCSF (t). The
external force of the vascular pulsation is assumed to be sinusoidal,
and given by F0 sin ωt. The other forces acting on the pulsating CSF
include a resistance force RẋCSF (t) and an elastic force kE xCSF (t),
representing the elasticity of the walls of the space. The net force
acting on the CSF pulsation is the inertial force mCSF ẍCSF (t). (b)
Equivalent RLC electrical circuit for CSF pulsation. Modified from
Egnor et al. [46]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
xi
4.10 (a) The intracranial Windkessel effect, which is the dissipation of ar-
terial pulsations into the CSF, can be modeled by representing the in-
tracranial blood and CSF as two separate masses connected by springs
representing the elastic elements of vasculature and craniospinal con-
tents. (b) The electical analog to a mechanical absorber is a wave
trap, which is main RLC circuit representing the capillary blood and
a smaller parallel RLC circuit representing the CSF. Modified from
Egnor et al. [46]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
4.11 The intracranial filter circuit and the windkessel mechanism. Intracra-
nial blood vessels and CSF spaces are arranged as parallel pathways
branching from a series flow. Normal intracranial blood flow and CSF
dynamics can be represented by a series-parallel array of blood vessels
and CSF spaces. Modified from Egnor et al. [47]. . . . . . . . . . . . 85
4.12 (a) Schematic of CSF pathways, the vascular system and brain parenchyma.
(b) The discretized model of CSF flow induced by choroid expansion
a(t). Modified from Linninger et al. [101]. . . . . . . . . . . . . . . . 86
4.13 The Linninger et al.’s multi-compartment model with one arterial pres-
sure in the carotid Pinit as input signal and the venous pressure in the
jugular vein is Pout . Modified from Linninger et al. [102]. . . . . . . . 88
5.1 The initial pulse cardiac output, generated by heart, is the combination
of three sets of sinusoidal wave with random heart rate. . . . . . . . . 91
5.2 (a) Cross-sectional area of blood vessel (b) Elastic blood vessel (c) Free
body diagram of blood with pressure and elastic forces exerting on . . 92
5.3 Hagen-Poiseuille’s law represent the blood flow resistance caused by
the length of artery in term of the pressure drop between inflow and
outflow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
5.4 The relationship of flow and pressure in orifice represented the periph-
eral resistance of blood flow due to the change of lumen size. . . . . . 94
5.5 (a) There are three forces exerting arterial and venous blood. (b) Blood
flow through artery, capillaries and vein in the enclosed cranium space.
(c) There are only two forces exerting on capillary blood. . . . . . . . 96
5.6 Combination of blood vessel’s stiffness (kart and kvein ) and stiffness of
elastic intracranial contents (kCSF ) in series result in less equivalent
stiffness (keq ) or more intracranial compliance of the CSF system . . . 97
5.7 (a) Intracranial space is divided into left and right hemispheres with
midline displacement to describe the transmission of pressure and vol-
ume between left and right cerebral hemispheres. (b) Free body dia-
gram of midline displacement. . . . . . . . . . . . . . . . . . . . . . . 98
5.8 Blood flow to hand and cranium after passing ascending aorta . . . . 101
xii
5.9 Three different balloon cycle including augmentation, reduction and in-
version used to increase cerebral blood flow. Modified from laboratory
research data at Cleveland clinic . . . . . . . . . . . . . . . . . . . . . 102
6.1 Arterial blood flow through major arteries to lower limbs. Cardiac
output (dark-blue), generated by heart, flow into ascending aorta and
flow out at aortic arch (green). Then, blood flow into descending aorta
to common iliac artery (orange), pass through external iliac artery
(blue) and femoral artery (purple). . . . . . . . . . . . . . . . . . . . 105
6.2 Pressure and velocity pulse waveforms in the aorta and arterial branches
of a dog. Note that the pressure maximum becomes amplified while
the velocity maximum decreases as the blood moves downstream [26] 106
6.3 Ascending aortic blood pressure and flow waveforms. . . . . . . . . . 107
6.4 Common iliac arterial blood pressure and flow waveforms. . . . . . . 107
6.5 Blood, after passing ascending aorta, flows into intracranial artery
(dark blue) and capillaries (green) then flows into intracranial vein
(red). Blood exits the intracranial space via intracranial vein repre-
sented by blue waveform. . . . . . . . . . . . . . . . . . . . . . . . . . 108
6.6 Arterial (dark blue), capillary (green), and venous (red) blood pressure
in the intracranial space. . . . . . . . . . . . . . . . . . . . . . . . . . 109
6.7 Plot of vertebral artery pulsatile change in cerebral blood volume (CBV)
and ventricular fluid pressure (VFP) during five cardiac cycles in dog.
Note also the synchronization of the extreme values of the change in
CBV and CSF pulse [6]. . . . . . . . . . . . . . . . . . . . . . . . . . 109
6.8 The phase relationship of predicted blood flow and pressure waveform
in the intracranial space show that intracranial pressure (ICP), cere-
bral blood volume (CBV), intracranial arterial blood pressure (ABP)
and arterial blood outflow (dark blue) are in-phase which delay from
arterial blood inflow (black). ICP and ABP are in mmHg. CBV is in
ml. Arterial blood inflow and outflow are in ml/sec. This figure is in
agreement with Avezaat et al.’s MRI data [6](Figure 6.7). . . . . . . . 110
6.9 The expansion of intracranial arteries (∆xart) result in venous contrac-
tion (∆xvein ) and intracranial volume reduction (Vol.) synchronously.
Also, the delay of capillary expansion (∆xcap ) after arterial expansion.
This simulation results agree with Monro-Kellie doctrine and the dia-
gram of phase relationship of blood and CSF from Greitz [61]’s MRI
data (Figure 3.4). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
xiii
6.10 Upper: the timing relationship between arterial blood pressure (ABP)
at femoral artery and ICP signal are observed in canine’s experimen-
tation conducted by Cleveland clinic researchers. Lower: the small
delay of ABP and ICP signal are predicted from the mathematical
model based on human physiology which are in agreement with ca-
nine’s monitoring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
6.11 After small mass lesion placing in right cerebral hemisphere, left hemi-
sphere (dark blue) has higher ICP than right hemisphere (green). Dash
black waveform represents ICP in normal condition (without mass le-
sion). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.12 After small mass lesion placing in right cerebral hemisphere, positive
displacement of midline refers to midline shift to right hemisphere
which has lower ICP. . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
6.13 After small mass lesion placing in right cerebral hemisphere, cerebral
blood flow to the right hemisphere (thick green) becomes greatly lower.
Also, the high pulsatility with shorter delay of right cerebral blood
outflow (thin green) after systolic peak of arterial inflow is observed.
However, no significant change of blood inflow (thick dark blue) and
outflow waveform (thin dark blue) over left hemisphere is observed. . 115
6.14 After small mass lesion placing in right cerebral hemisphere, systolic
expansion of artery in lesion hemisphere (green) becomes significantly
lower compared to non-lesion side (dark blue). . . . . . . . . . . . . . 116
6.15 After large mass lesion placing in right cerebral hemisphere, left hemi-
sphere (dark blue) has lower ICP than right hemisphere (green). The
dampened ICP waveform over lesion hemisphere is also observed. . . 117
6.16 After large mass lesion placing in right cerebral hemisphere, negative
displacement of midline represent the displacement of midline forward
to left hemisphere which has lower ICP. . . . . . . . . . . . . . . . . . 117
6.17 After large mass lesion placing in right cerebral hemisphere, cerebral
blood flow to both hemisphere becomes lower. Especially, on the lesion
side, blood flow to the right hemisphere (thick green) ceases after 5
seconds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
6.18 After large mass lesion placing in right cerebral hemisphere, arterial
expansion of artery in lesion hemisphere (green) is severely restricted
and becomes lower than the expansion of artery in contralateral hemi-
sphere (dark blue). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
6.19 After large mass lesion placing in right cerebral hemisphere, capillary
in both hemisphere becomes more restriction compared to normal con-
dition (dash black). Especially, the marked restriction of capillary in
lesion hemisphere (green) is observed. . . . . . . . . . . . . . . . . . . 119
xiv
6.20 Inversion (blue) should do synchronously with cardiac output (thick
red) to obtain most cerebral blood flow improvement. ICP response in
left (dark blue) and right (green) cerebral hemisphere along inversion
cycle are also plotted. . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
6.21 Intracranial pressure in left (dark blue) and right (green) hemisphere
with small mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . . 121
6.23 Cerebral blood flow to the left (thick dark blue) and right (thick green)
hemisphere with small mass lesion . . . . . . . . . . . . . . . . . . . 122
hemisphere after inversion treatment . . . . . . . . . . . . . . . . . . 122
6.25 Expansion of left cerebral artery (dark blue) and right (green) cerebral
artery with small mass lesion . . . . . . . . . . . . . . . . . . . . . . 122
6.26 Expansion of left cerebral artery (dark blue) and right (green) cerebral
artery after inversion treatment . . . . . . . . . . . . . . . . . . . . . 122
6.27 Inversion (blue) should do nearly synchronously with cardiac output
(thick red) to obtain most cerebral blood flow improvement. ICP re-
sponse in left (dark blue) and right (green) cerebral hemisphere along
inversion cycle are also plotted. . . . . . . . . . . . . . . . . . . . . . 124
with large mass lesion . . . . . . . . . . . . . . . . . . . . . . . . . . 125
hemisphere with large mass lesion . . . . . . . . . . . . . . . . . . . 126
hemisphere after inversion treatment . . . . . . . . . . . . . . . . . . 126
6.32 Developmental cycle of hydrocephalus . . . . . . . . . . . . . . . . . . 130
xv
ACKNOWLEDGEMENTS
Before I can fulfill the requirements for Ph.D in the School of Engineering at Case
Western Reserve University, I have experienced a long critical passage of my life. I
left a hot and humid city of Bangkok for a cold and snowy city of Cleveland by myself.
I turned from familiar field of mechanical engineering to no background knowledge of
systems engineering. I have faced various kinds of challenges and hindrances to test
my patience as well as my self-discipline. As years go by, these obstacles strengthen
and enhance my subsistence. I have not only gained tremendous knowledge from
the Faculty, but also many experience that provide me the understanding of life.
However, without their constant help and encouragement from the following persons,
my academic pursuits cannot be possible.
First of all, I am profoundly grateful to Professor Kenneth A. Loparo, my research
advisor who introduced biomedical system and modeling to me. He has persuasively
provided the guidelines for my research methodology, critical thinking and problem
solving. Without his invaluable guidance, my potentiality as researcher will not be
kindled. He is really my role model of academic career. I am impressive with his
academic devotion. His researching concept will be imprinted on my mind and my
academic life.
My heartily gratitude goes to Professor Vira Chankong, my academic and research
co-advisor for his continuous academic and personal supports since I first came to the
University. He gave me more opportunities for my study here in addition to introduce
me to Professor Loparo and my challenging research topic. I always remember his
care and warmth as same as my family members.
I would like to extend my thanks to Dr. Mark Luciano, Dr. Stephen Dombrowski
and Cleveland Clinic researcher who provided experimental data. They shared use-
ful experiences of intracranial system and gave valuable comments and reflections.
This research was supported in part by the National Institute of Health, grant R01
xvi
NS060916.
My sincere thanks also give to Professor Mark Buchner and Professor Evren
Gurkan-Cavusoglu, my thesis defense examination committee. Their comments are
very useful for me to improve my dissertation.
My friends in Cleveland are “the friends indeed”, though I cannot mention all
names. I certainly say a big thanks to Assistant Professor Adirak Kanchanaharuthai,
Dr. Arsit Boonyaprapasorn and Wanchat Theeranaew. They are the part and parcel
along the way of my success stories. They have rendered helps and advises when-
ever I needed. They supported by reminding me of Dharma- the tool to cure my
mind. I always remember their kindness and friendship. My stay in Cleveland will
be memorable forever.
Last but not least, I am greatly indebted to my beloved parents and my brother
for their unconditionally spiritual supports since I was born. My ways of living and
thinking have been taught by my family, which is an essential part of my success. I
believe this success is the one that my parents are waiting for and proud of. Now it
is apparent that our dream comes true. Thank you for believing in me.
Finally, after I stand every hardship to overcome the barrier of success, I have
been essentially developed to be a potential human resource in order to contribute to
my motherland.
xvii
Mathematical model for hemodynamic and intracranial Windkessel mechanism
Abstract
by
THUNYASETH SETHAPUT
The understanding of intracranial system so that one can explain its related patho-
logical condition such as hydrocephalus and traumatic brain injury (TBI) is still sub-
tle. Especially, the cause of hydrocephalus which is known as the common birth
defect is not well defined. Traditionally, hydrocephalus was described as imbalance
between production and absorption process of cerebrospinal fluid (CSF). However,
many recent observations show that the bulk flow theory can no longer explain the
cause of hydrocephalus. Hence, the new concept of hydrocephalus has been deviated
from the bulk flow theory and comes to focus on the pulsatile dynamic of intracranial
system and abnormalities of intracranial Windkessel mechanism. Windkessel mecha-
nism is normally observed in major arterial system as well as intracranial space which
is the absorbing function of artery provided by its elastic properties and peripheral
resistance. The effectiveness of Windkessel mechanism can convert the pulsatile na-
ture of blood flow generated by cardiac cycle into nearly pulseless outflow to capillary
bed. Thus, the simulation via mathematical model based on Windkessel mechanism,
which is one of the most useful tool to clarify the pulsatile dynamic within intracranial
cavity is proposed. The mathematical model is constructed based on the mechanical
and fluid mechanics principles to predict the hemodynamics throughout major arte-
rial system and intracranial space. For intracranial system, the dynamical interaction
xviii
among major intracranial contents and intracranial pressure (ICP) is simulated. Also,
the constraints of Monro-Kellie doctrine is also another requirement to include in this
model. To verify the model, the predicted results is compared to clinical data such
as MRI data which have a good agreement.
Typically, the intracranial disorders are associated with elevated intracranial pres-
sure (ICP) and decreased cerebral blood flow. As the central nervous system (CNS)
and brain require the sufficient cerebral blood supply to function normally, a marked
reduction of cerebral blood flow known as stroke can result in the brain ischemia and
further lead to a failure of brain’s neurological functions. For the patient with trau-
matic brain injury (TBI), an appearance of unilateral mass lesion such as hematoma
is commonly observed. This mass effect can occupy the finite volume of intracranial
space which reduces its volume compensatory capacity and brings about interhemi-
spheric asymmetry of ICP and cerebral blood flow. The effect of an appearance
of unilateral mass lesion on interhemisperic asymmetry of ICP and cerebral blood
flow is also investigated. The significant difference of waveform and timing between
two hemispheres is observed. This observation can be used as the indicator to predict
and classify the patients with normal or abnormal intracranial Windkessel mechanism
which is the useful information for real-time patient monitoring.
As mentioned, the reduction of cerebral blood flow is typically observed in the
patients with neurosurgical disorders, the medical balloon insertion is introduced as
the alternative treatment. To recover the cerebral blood flow, the cadence balloon
with inversion cycle provides the most significant improvement in the simulation
results which support the possibility of using cadence medical balloon as the treatment
options for the patient with decreased cerebral blood flow.
According to the simulation results, the failure of intracranial Windkessel mecha-
nism might be the key factor which provide the appropriate explanation to define the
cause of hydrocephalus especially communicating hydrocephalus. The developmental
cycle of hydrocephalus is also hypothesized. This hypothesis might explore the un-
derstanding and direct the effective treatment procedure for the patient who suffers
xix
from disorder related to intracranial system.
xx
Chapter 1
Introduction
1.1 Motivation and Literature Survey

Each year, a significant number of patients who suffer from the disorders associated
with intracranial system was reported. In the United States, traumatic brain injury
(TBI) is a contributing factor to one thirds (30.5%) of all injury-related deaths [50].
The Centers for Disease Control and Prevention has estimated that an approximately
1.7 million Americans sustain a TBI-related emergency department visits (about 1.365
million), hospitalizations (about 275,000 cases), and deaths (about 52,000 cases) an-
nually [50].
Another well known neurosurgical disorders which label as one of the most com-
mon birth defects is hydrocephalus. According to the World Health Organization
(WHO) hydrocephalus statistics show that one birth in every 2,000 are affected by
hydrocephalus. However, hydrocephalus can occur at any age, but is most commonly
occur in infants or the elderly. In the United States, approximately 69,000 hospital
discharges with the diagnosis of hydrocephalus have been reported annually [136]. In
2003, there were 38,200 to 39,900 admissions for pediatric hydrocephalus which ac-
counted for 0.6% of all pediatric hospital admissions in the United States [155]. The
American Hydrocephalus Association has estimated that an approximately 375,000
older Americans suffer from normal pressure hydrocephalus (NPH). In addition, the
1
pediatric center for Intermountain Healthcare, a health care system in the Intermoun-
tain West (Utah, Montana,Idaho, Wyoming, and Nevada), estimated that the number
of American people living in the United States and were treated for hydrocephalus
ranged between 120,000 and 150,000 each year while one sixth of this group of pa-
tients were young adults between 18 and 35 years of age [154]. Hence, the number of
young adults who have hydrocephalus, aged 18 to 35 needed treatment in the United
States was predicted to exceed 40,000 annually within the next two decades [154]
as shown in Figure 1.1. Nowadays, the causes of hydrocephalus are still not clearly
understood. Hence, the lack of appropriate diagnosis and treatment often undergo.
Figure 1.1: Current and projected numbers of patients with hydrocephalus, aged 18
to 35, treated in the United States. Dark bars indicate projections of numbers of
patients based on the actual numbers treated at Intermountain Healthcare; lighter
bars indicate future projections for young adults with hydrocephalus. Data source
from Intermountain Healthcare [154].
Hydrocephalus were clinically studied for almost a century but the cause and
understanding of this disorder were still hassle. Conventionally, hydrocephalus was
originally explained as the cerebrospinal fluid (CSF) bulk flow theory based on the
animal experimentation by Dandy in 1914 [40]. The bulk flow theory considers the
cause of hydrocephalus as an imbalance between CSF formation by choroid plexus
2
and absorption process at arachnoid granulation [66]. The definition of hydrocephalus
as disorder of CSF circulation is able to provide the good explanation of obstructive
hydrocephalus which is caused by an intraventicular obstruction of CSF. However,
the modern clinical observation of CSF absorption accepts that the majority of CSF
absorbs at the capillaries of the central nervous system and not at arachnoid granu-
lation [61, 66]. Thus, communicating hydrocephalus cannot be simply explained by
the CSF bulk flow theory alone.
According to clinical MRI data and experiments, new attention of hydrocephalus
was focused on the pulsation of intracranial dynamics to explain the phenomena. Gre-
itz et al. [61, 63, 65, 66] explained that communicating hydrocephalus was caused by
abnormality of intracranial pulsations which was associated with intracranial Wind-
kessel mechanism. Windkessel mechanism was the pulsation absorbing function of
elastic arterial wall that could be observed in aorta and large arteries on entire body
as well as intracranial cavity. The effective Windkessel mechanism was able to convert
the pulsatile nature of arterial inflow into a continuous and almost pulseless outflow
to capillary. Most important parameters describing intracranial Windkessel mech-
anism was its elasticity of intracranial contents referred to intracranial compliance.
Decreased intracranial compliance leds to the breakdown of the intracranial Wind-
kessel mechanism which caused dramatic changes in intracranial system including
properties and pulsatile dynamics of flow and pressure. This might be one of the key
concepts to explain the causes of communicating hydrocephalus.
The major function of cerebral blood flow is to supply oxygen and other nutrients
to the central nervous system (CNS) and remove carbon dioxide and other metabolic
end products from the CNS which required a steady blood supply to maintain well
neurological function of CNS. However, the malfunction and destruction of any con-
tents within closed cranium commonly observed in the patients with neurosurgical
disorders leads to the reduction of cerebral blood flow. Decreased cerebral blood
flow normally known as cerebrovascular accident or “stroke” may result in secondary
cerebral ischemia and then a failure of brains neurological function due to insufficient
3
oxygen supply. In the patients with TBI, an appearance of mass lesion due to the
abnormal collection of internal bleeding blood (hemorrhage) brings about the com-
pression of cerebrovascular bed and variation of intracranial dynamics. Moreover,
the marked enlargement of cerebral ventricles with an excess accumulation of CSF
observed in hydrocephalic patients might compress cerebral blood vessel between the
rigid cranium and the ventricular dilation. Hence, a space-occupying effect produced
by mass lesion or enlarged ventricles will exert the force on the surrounding brain
parenchyma, resulting in collapsing of cerebrovascular system. In order to respond to
the intracranial space occupation, reduced cerebral blood flow, elevated intracranial
pressure (ICP) and brain herniation may occur after injury.
Generally, cranium is considered as a single rigid compartment with uniform dis-
tribution of intracranial pressure (ICP) over entire intracranial space [39]. However,
significant differences in ICP between left and right hemispheres (interhemispheric
ICP gradients) were reported in many animal experimentations and clinical obser-
vations. In head-injured patients, a formation of hematoma from bleeding blood in
the injured hemisphere (unilateral mass lesion) exerted an irregular force to occupy
the space within a finite volume of the cranium which distorted the intracranial dy-
namics. Typically, a large expansion of unilateral mass lesion also brought about an
appearance of midline shift over its center line on CT scan image. Furthermore, the
reduction of global cerebral blood flow was typically found in clinical case reports of
the patients with TBI and hydrocephalus. In the studies of regional cerebral blood
flow, the interhemispheric asymmetry of cerebral blood flow was also observed in
the patients who suffered from unilateral mass effect. However, the understanding
of the interhemispheric asymmetry of ICP and cerebral blood flow which depended
on various physiological factors and a wide variation of anatomical lesions were still
unclear.
For the patients with TBI or hydrocephalus secondary to tumor or mass effect, the
practical treatment is to remove the cause of intracranial space occupation. Also, the
treatment focuses on handling elevated ICP and maintaining adequate cerebral blood
4
flow to normal level to prevent the secondary injury and repair the damaged neurons.
Shunting is commonly used to relieve the patients who suffer from hydrocephalus with
high success rate when the cause of hydrocephalus is revealed. Removal of excess in-
tracranial CSF and transport it into the bloodstream or other body cavities that
compress intracranial vessel by shunt placement can recover intracranial compliance
and consequently restore normal cerebral blood flow and hemodynamics conditions
[62, 64, 68]. However, there are many complications associated with shunting proce-
dures including shunt dependency, infection, over-drainage of CSF and development
of the slit ventricle syndrome (SVS) [180]. Moreover, no significant improvement of
CBF after shunting was observed in many case reports [72, 88, 109, 116, 127]. Since
the cause of communicating hydrocephalus is inexplicit, shunting is only a symp-
tomatic treatment of hydrocephalus [66]. For more effective diagnosis and treatment
of communicating hydrocephalus, the complex dynamical system related to intracra-
nial Windkessel mechanism should be reconsidered.
A very useful tool to understand the intracranial system and its Windkessel mech-
anism is mathematical model. Early mathematical models for intracranial system
focused on the bulk flow theory and multi-compartmental lumped model. However,
as mentioned above, the new concept to define the cause of hydrocephalus focused on
the pulsatile nature of intracranial contents. Hence, the pulsatility model of intracra-
nial system should be introduced to facilitate the understanding of the interaction
between intracranial contents during cardiac cycle. Based on the equivalent electrical
circuit, Egnor et al. [46, 47] recently proposed the model of intracranial pulsation
as a simple spring mass system. They also concluded that communicating hydro-
cephalus was resulted from the abnormalities of intracranial Windkessel mechanism.
However, the effect of compliance and blood volume alterations on intracranial dy-
namics was not included which was the limitation of this electrical circuit model.
To understand intracranial dynamics based on Windkessel mechanism, the variation
of arterial and intracranial compliance and cerebral blood volume might be the sig-
nificant factor. Thus, mechanical model based on fluid dynamics principles which
5
describes the effect of vascular expansion and compression on intracranial pulsation
should be constructed. Also, the dynamical interaction to compensate the volumet-
ric change of intracranial contents within a rigid container of cranium according to
Monro-Kellie doctrine is another important constraint to be satisfied.
The purposes of this dissertation are as follows:
• to elaborate hemodynamics through human major arterial system and intracra-

nial space based on Windkessel mechanism using mathematical model
• to investigate the interaction among intracranial pressure (ICP) and main in-
tracranial contents based on Monro-Kellie doctrine
• to compare intracranial dynamics response for different intracranial conditions
• to identify the interhemispheric asymmetry of ICP and cerebral blood flow due
to an appearance of unilateral mass lesion
• to assess the possibility of medical balloon insertion with cadence action in

intracranial cavity on cerebral blood flow improvement
• to provide the hypothesis of the cause of hydrocephalus related to intracranial

Windkessel mechanism
1.2 Contributions
The major contributions of this dissertation can be summarized as follows:
• Based on Windkessel mechanism, hemodynamics through major arterial system

and intracranial cavity is scrutinized by using mathematical model. It shows
that the development of mathematical model governing by fluid mechanics and
mechanical principles is the effective tool to study the behavior of blood flow
through arterial and intracranial system.
6
• Intracranial dynamic response of intracranial pressure (ICP) and major intracra-
nial contents in waveform and timing aspect are proposed. As well as, in term of
timing and waveform, the relationship of ICP signal and blood flow at femoral
artery is compared in normal condition. The interactional relationship within
intracranial space provides the dynamical understanding of intracranial system
in healthy patients which the fundamental information for further studies re-
lated to pathological condition.
• The effect of unilateral mass lesion on intracranial dynamic especially interhemi-

spheric asymmetry of ICP and cerebral blood flow is observed. In addition, the
relationship between the size of mass lesion and interhemispheric asymmetry
of ICP and cerebral blood flow is investigated. This observation can assist the
health care providers to predict the patient outcome and directly focus on the
proper target for treatment.
• The abnormalities of intracranial Windkessel mechanism due to space occupying

mass lesion is analyzed. Many simulation results can be used as the indicators
to predict the failure of intracranial Windkessel mechanism which is valuable
information for real-time patient monitoring.
• To improve cerebral blood flow, the alternative treatment using a medical bal-
loon insertion with cadence action is applied which enhances the possibility to
use the balloon in the patient with decreased cerebral blood flow.
• The cause of hydrocephalus especially communicating hydrocephalus is hypoth-

esized. The breakdown of intracranial Windkessel mechanism might be the fac-
tor associated with the causation of hydrocephalus. Also, this hypothesis might
provide the effective direction for the treatment of hydrocephalic patients.
7
1.3 Outline of the Dissertation
This dissertation is organized as follows:
• Chapter 1: Introduction
In this chapter, the motivation of this dissertation is presented which includes
the disorder related to intracranial system and its understanding. The concept
of mathematical model to understand the intracranial system dynamically is
also introduced. Furthermore, the major purposes and contributions are sum-
marized.
• Chapter 2: Review of Physiology

An overview of the physiological background associated with hemodynamics and
intracranial system is introduced which consists of major contents of cardiovas-
cular system and intracranial space. This information provides the physiological
parameters used as reference for constructing mathematical model. Common
pathological conditions related to intracranial system and treatment procedure
are also briefly reviewed.
• Chapter 3: Associated Intracranial System

In order to describe the hemodynamics of major arteries and intracranial space,
a concept of Windkessel mechanism is introduced. Moreover, main principles
and constraints involved in the dynamic of intracranial system are presented. In
clinical and experimental observation, the change in intracranial dynamics and
Windkessel mechanism with common techniques for assessment its abnormality
are reviewed. This chapter also includes the effects of pathological conditions on
interhemispheric asymmetry of intracranial pressure (ICP) and cerebral blood
flow. This behavior of hemodynamics and intracranial system with its abnor-
mality is essential for modeling the dynamics simulation.
• Chapter 4: Review of Windkessel Model and the Model of Intracra-

nial System
8
In this chapter, some early mathematical models related to intracranial system
are reviewed which are divided into two sections. First, Windkessel model is
the mathematical model to describe the hemodynamics through arterial system
represented by the electrical element in the simple RLC circuit. Second, the
model of intracranial system is reviewed which is categorized into two major
types of modeling to describe the behavior of intracranial system: (1) complex
compartmental model and (2) pulsatility model.
• Chapter 5: Mathematical Model

Based on Windkessel mechanism, the mathematical model of hemodynamics
through major arterial system and intracranial space is developed. The prin-
ciples of mechanical and fluid mechanics is applied in this pulsatility model to
explain the hemodynamics and the interaction among intracranial contents and
intracranial pressure. In this chapter, the effects of intracranial space occupa-
tion on interhemispheric asymmetry of intracranial pressure and cerebral blood
flow and the improvement of cerebral blood flow by using medical balloon are
also investigated.
• Chapter 6: Simulation Results

The simulation mainly focuses on three cases including (1) normal condition,
(2) neurosurgical condition, and (3) treatment by using a medical balloon. For
normal condition, the hemodynamics downward through major arterial system
to femoral artery and upward to intracranial space are presented. For neuro-
surgical condition, the simulation results show the effects of an appearance of
unilateral mass lesion on intracranial dynamics, as well as the interhemispheric
asymmetry of intracranial pressure and cerebral blood flow. Also, the effects of
mass lesion size on the dynamics of intracranial system are demonstrated. In
case of treatment, the results show that an insertion of medical balloon with
intermittent action is related to the improvement of cerebral blood flow. Addi-
tionally, the results predicted by mathematical model are compared to clinical
9
and experimental observations which are in good agreement. According to sim-
ulation results, the unknown cause of hydrocephalus especially communicating
hydrocephalus is hypothesized which related to the failure of intracranial Wind-
kessel mechanism. This hypothesis might be essential for future prevention and
treatment of patient with hydrocephalus.
• Chapter 7: Summary and Conclusions

The results of this dissertation are summarized, and further research direction
are suggested.
• Appendix: Parameters for the Model of Hemodynamics and Intracra-

nial System
Table of the parameters which used for constructing the mathematical model is
presented.
10
Chapter 2
Review of Physiology
In order to understand and see a clear picture of the intracranial system and its
relevant, a brief background of human physiology is necessary. This section provides
a basic knowledge of cardiovascular system and intracranial space including brain and
intracranial fluid. Moreover, the pathological conditions associated with intracranial
system and their practical treatment methods are reviewed
2.1 The Cardiovascular System

In human cardiovascular system, heart and an extensive network of blood vessels
are the main components to circulate blood throughout the body for distribution of
oxygen via respiration system and nutrient transportation via digestive system which
regulates body temperature, and distributes hormones and other agents that regulate
cell function [10]. The closed loop of circulatory system is divided into the pulmonary
circulation and the systematic circulation. The role of pulmonary circulation is to
carry the de-oxygenated blood from the heart, to the lungs where gas exchange can
occur, and return the oxygenated blood to the heart. The function of systematic
circulation, which contain about 84 percent of the entire blood volume of the body
[69], is to supply blood to all the peripheral organs and tissues of the body. The heart
and circulation are controlled, to provide the necessary cardiac output and arterial
11
pressure [69], by multiple regulatory systems that function in general to maintain
adequate capillary blood flow when possible in all organs, but particularly in the
heart and brain [10].
2.1.1 Heart
The heart, consists primarily of a special type of muscle called cardiac muscle, is the
major source of squeezing power to provide blood flow through the entire bodys cir-
culatory system. The pumping action of the heart is pulsatile rather than continuous
[78]. The heart intermittently pumps the volume of oxygenated blood throughout
the body in the time interval of a minute called “cardiac output” (Figure 2.1). The
cardiac output of a healthy adult, at rest, is approximately 5 liters (L) of blood per
minute [148]. The cardiac cycle, the cardiac events that occur from the beginning
of one heartbeat to beginning of the next [69], consists of a period of ventricular
relaxation during the heart chambers refill with blood called “diastole” followed by
contraction of the heart ventricles called “systole” which pumps blood into circulatory
system. The frequency or discharge rate of the recurring cardiac cycle is described
by the heart rate, the number of beats the heart contracts per minute. Heart rate
in normal adults is about 72 beats/min, each cardiac cycle lasts approximately 0.8
s, with 0.3 s in systole and 0.5 s in diastole [193]. The stroke volume is the volume
of blood ejected from each heart’s ventricle per stroke during systole which can be
calculated by substracting end-diastolic volume by end-systolic volume. The stroke
volume in a healthy man at rest is approximately 70 ml, end-diastole volume is 135
ml, and end-systolic volume is 65 ml [193]. Thus, the cardiac output (L/min) can be
calculated by multiplying the heart rate (beats/min) and the stroke volume (L/beat).
2.1.2 Vascular System

Blood vessels are a tubular closed-loop network that carry blood from the heart to
the tissue and back to the heart. Blood leaving the heart passes through vessels
12
Figure 2.1: Pulsatile blood flow in the root of the aorta recorded using an electro-
magnetic flowmeter [69].
of progressively smaller diameters, referred to as arteries, arterioles, and capillaries.

Then, blood returning to the heart from the capillaries pass through vessels of pro-
gressively larger diameters, called venules and veins. The structural characteristics of
the blood vessels change with successive branching [193] which reflect their function.
The characteristics of various types of blood vessels are listed in Table 2.1. Because
of the different total cross-sectional area of blood vessels, the blood flow velocity is
very high in aorta and progressively slow in arteries. Then, flow velocity is markedly
slow while passing through capillaries due to their larger total diameter, and become
higher again when flow through veins.
The force that blood applies to the wall of a blood vessel in known as blood
pressure. Blood pressure varies throughout the cardiovascular system, being the
highest in the aorta and large arteries (120 to 80 mmHg), lower in the capillaries (35
mmHg near the arteriolar ends to as low as 10 mmHg near the venous ends [69]),
and the lowest in vein as shown in Figure 2.2. Since the pumping action of heart
is pulsatile, the peak arterial pressure level reached during ventricular contraction to
eject blood from the heart refers to systolic pressure. The minimum arterial pressure
level, occurs during ventricular diastole before next ventricular ejection begins, refers
to diastolic pressure. In a young adult human, the systolic arterial pressure in the
aorta and in the large arteries is about 120 mmHg and diastolic pressure is about
13
Table 2.1: Characteristics of various types of blood vessels in humans [10].
80 mmHg [78]. The arterial pressure conventionally written as systolic pressure over
diastolic pressure [10], for example, 120/80 mmHg. The difference between systolic
pressure and diastolic pressure is called the pulse pressure [193], about 120 - 80 = 40
mmHg.
Figure 2.2: Blood pressure in different segments of the vascular system [78].
14
Arteries
The major function of the systemetic and pulmonary arterial systems is to transport
blood to various capillary beds. Under high blood pressure condition, the thick mus-
cular walls of the aorta and other large arteries, contain a relatively large amount of
elastic tissue; however,the walls of the arterioles,the last small branches of the arte-
rial system, contain less elastic tissue but much more smooth muscle [10]. Due to
elastic properties of arterial wall of the aorta and the other large diameter arteries,
they act as pressure reservoir for maintaining blood flow through the tissues dur-
ing diastole [193] because the volume of blood pumped into can be stored in them
with each cardiac cycle. Also, they act as a hydraulic filter because they converts
pulsatile flow generated by heart to the continuous steady state flow through capil-
laries. The contraction of ventricles ejected blood into arteries and then arterial walls
are stretched to accommodate the extra blood volume, and arterial blood pressure
rises during systole. When the ventricular contraction ends, the stretched arterial
walls recoil passively and blood continues to be driven into the arteries and flow out
to capillaries during diastole as shown in Figure 2.3. As blood leaves the arteries,
the arterial volume and pressure slowly fall, but the next ventricular contraction
occurs while there is still adequate blood on the arteries [193]. The term used to
describe the distensibility of artery or how easily an artery can be stretched is com-
pliance. An artery with high compliance can be stretched very easily. Compliance
(Compliance = ∆V olume/∆P ressure) can be defined as the total quantity of blood
that can be stored in a given portion of the circulation for each unit of pressure rise
[69]. Hence, arterial blood volume and arterial compliance are two main physical fac-
tors that determine arterial pressure. Stroke volume, speed of ejection of the stroke
volume during systole, and arterial compliance are the most important physiological
factors that affect the magnitude of arterial pulse pressure [193].
In hemodynamics studies, the transmission of pulse pressure while traveling from
heart to aorta through the progressively smaller blood vessel can be expressed in term
15
Figure 2.3: Movement of blood into and out of the arteries during the cardiac cycle.
The lengths of the arrows denote relative quantities flowing into and out of the arteries
and remaining in the arteries [193].
of blood inertia that prevents sudden blood movement all the way to the periphery
[69] as shown in Figure 2.4. Thus, the transmission of pulse pressure is slow in the
large blood vessel with high compliance; however, the transmission become faster in
the smaller blood vessel with lower compliance. Also, the progressively less pulsatility
of prssure pulse, described in term of damping of the pressure pulse, when blood flow
toward the smaller vessels almost directly depend on their resistance and compliance
[69]. Greater resistance or compliance result in greater degree of damping of the
pressure pulse.
Because an immediate change in arterial blood pressure causes drastic change in
blood flow; however, most blood vessels have an intrinsic capacity to compensate for
change of arterial pressure to regulate blood flow to normal level by changing in vascu-
lar resistance through its radius. This intrinsic regulatory mechanisms that maintain
blood flow and circulation against changes in systemic arterial pressure called “au-
16
Figure 2.4: Changes in the pulse pressure contour as the pulse wave travels toward
the smaller vessels [69].
toregulation”. The autoregulation reacts to a variation of systemic arterial pressure

by automatically expansion of arteries when blood pressure fall and contraction when
pressure rise.
Capillaries
Thin-walled vessels of capillaries form branching networks, known as capillary beds,
among the cell of body tissues. Approximately 5 percent of the total circulating
blood is flowing through the capillaries [193]. The extensive porous walls branching of
capillaries provide very small diffusion distances to body cells which allow nutrients
and metabolic end product (waste product), such as carbon dioxide and urea, to
exchange between cells of the body and blood. Low blood pressure in the capillaries
17
enhances the rate of exchange between blood and tissues. Also, the large total cross-
sectional area of capillaries result in the slowest flow velocity while passing through
capillaries to provide the time availability for substances to exchange between the
blood and interstitial fluid [193]. In the lungs and in highly metabolic tissues, such as
the liver, kidneys, skeletal muscle, and cardiac muscle, capillaries form more numerous
and more extensive networks than in other tissue types [148].
Viens
The veins are the last set of vessels through which blood flows on its way back to the
heart. A major function of the veins is to act as low-resistance conduits for blood flow
from tissue to the heart [193]. The wall of veins are thinner and much more compliant
than arteries, therefore maintaining peripheral venous pressure and facilitating venous
return to the heart are the additional functions of veins. Veins also serve as blood
reservoir for the circulatory system [69] because they can accommodate large volume
of blood (approximately two-thirds of the total blood volume [78]) with relative small
increase in internal pressure. The contraction of the veins, called venous pump [69],
decrease the diameter and compliance of the vessels and raise the venous pressure to
propel more blood out of the vein into the right heart. Not only pressure difference
between the peripheral veins and the heart, and the mechanism of venous contraction
assist the veins in returning blood to the heart, but one-way valves inside the veins
also prevents backflow and allows blood to flow in one direction only toward the heart
[78]. In nearly rigid intracranial space, venous blood is able to compensate for the
arterial pulsations because intracranial pulsation from nearby artery may compress
veins.
18
Major Arteries of the Systemic Circulation
In systemic circulation (Figure 2.5), the blood flow from the heart through the first
set of systemic blood vessel called aorta which usually considered in three parts: the
ascending aorta, the aortic arch and the descending aorta [148]. Blood, after passing
through the ascending aorta and then the aortic arch, flow to two major parts of
the body which are the head and upper limbs, and the abdomen and lower limbs by
following pathways:
Arteries of Head, Neck and Upper Limbs
The brachiocephalic artery is the first short artery branch of the aortic arch. The
brachiocephalic artery divides into the right common carotid artery, which transports
blood to the right side of head and neck, and right subclavian artery, which transports
blood to the right upper limb [148]. However, to supply blood to the left side of head,
neck, and the upper limb, the left common carotid and subclavian artery branch
directly off the aortic arch with no brachiocephalic artery. In each side of neck,
the common carotid arteries branch into several branches of external carotid arteries
which supply blood to the structure of the neck, face, nose, and mouth [148], and
internal carotid arteries which is the major arteries that supply to the brain via the
carotid canals. Blood supply to each side of the upper limb through the subclavian
artery, followed by axillary artery, brachial artery, ulnar artery and radial artery which
supply blood to the forearm and hand.
Arteries of Abdomen and Lower Limbs
The first artery from the aortic arch that transport blood through the chest and
abdomen to lower limbs called descending aorta. The descending aorta, the longest
part of the aorta [148], is divided into two portions: a thoracic aorta which located
between thorax and thoracic diaphragm, and an abdominal aorta which located in
the abdominal cavity. The abdominal aorta, then, branched into two common iliac
19
Figure 2.5: The major arteries that carry blood from the left ventricle of the heart
to the tissues of the body [148].
20
arteries. Also, each common iliac artery (left and right) divides into an internal iliac
artery to supply blood for pelvic area, external iliac artery to supply blood for the
lower limb. The external iliac artery further connect to the femoral artery in th human
thigh, and the extension of femoral artery called popliteal artery. The popliteal artery
bifurcates into anterior and posterior tibial artery for transporting blood to the feet.
2.2 Intracranial Space

The intracranial space or cranial cavity is the space formed inside the skull. The
volume of intracranial space is approximately 1,600-1,700 ml [69] in average adults.
The normal contents of the intracranial space are brain, spinal cord, cerebrospinal
fluid (CSF) and cerebral blood.
2.2.1 Brain
The brain is part of the central nervous system (CNS) which receives sensory informa-
tion in the form of action potentials from various nerves and the spinal cord, integrates
it, and generates the appropriate response, so that it is well protected against phys-
ical injury and disease [78]. The brain, weighs about 1400 g [10], is housed by the
skull, a rigid bony closure that protects it from injury. As shown in Figure 2.6(a),
the brain can be subdivided into four major subdivisions: cerebrum, diencephalon,
brainstem, and cerebellum [193]. The composition of cerebrum and diencephalon
called the forebrain. The brainstem can be divided into three regions: the midbrain,
rostral to the pons and continuous with the diencephalon; the pons, rostral to the
medulla oblongata; and the medulla oblongata, rostral to and continuous with the
spinal cord [152]. The brainstem connects the spinal cord to the remainder of the
brain and contains several nuclei involved in vital body functions such as the control
of heart rate and breathing [148].
The additional protection of brain and spinal cord is provided by a watery liquid
called cerebrospinal fluid (CSF) and membranous covering called meninges. As pre-
21
(a) (b)
Figure 2.6: (a) The surface of the cerebral cortex and the divisions of the brain shown
in sagittal section [193], (b) Investing membranes of the brain, showing their relation
to the skull and to brain tissue [10].
sented in Figure 2.6(b), Meninges consists of three layers of connective tissue: dura
mater, arachnoid mater, and pia mater next to the nervous tissue. The dura mater,
the most superficial and thickest of the meninges, around the brain is tightly attached
to the periosteum of the skull [148]. The space between the arachnoid and the pia
mater, known as subarachnoid space (SAS), is filled with CSF and contains cerebral
blood vessels. The brain is supported within the arachnoid by the cerebral blood ves-
sels and nerve roots and the multiple fine fiberous arachnoid trabeculae [10]. These
trabeculae arise from the arachnoid, span the subarachnoid space,and then connect
with the pia, help to keep the brain suspended within the meninges [152].
The brain also contains four interconnected CSF-filled cavities called the cerebral
ventricles which are the main components in CSF circulating process. The cerebral
ventricles consist of two large lateral ventricles located in each cerebral hemisphere,
the third ventricle which is a smaller midline cavity located within the center of the
diencephalon between the two halves of the thalamus, and the fourth ventricle located
at the base of the cerebellum [148].
22
2.2.2 CSF and Ventricular System
Cerebrospinal fluid (CSF) is clear and colorless fluid. However, it may be colored
in pathological conditions; for example, several hours after subarachnoid hemorrhage
results in the yellow color of CSF [152]. The CSF is similar to the interstitial fluid
that bathes all cells, but it does not exchange substances as freely with blood [78].
In normal adults, the volume of CSF is about 90-140 ml which contains within the
cerebral ventricles about 23 ml and and the remaining is in the subarachnoid space
of brain and spinal cord [152]. Because of the specific gravity of the brain and the
CSF are approximately equal (only about 4 percent different), the brain simply floats
in the CSF [69]. Due to the buoyancy or floating of the brain in the CSF, the brain
has a net weight of only 50 g compared to 1400 g of the weight of brain in air [10].
Also, this buoyant effect of the CSF can reduce the traction exerted on the nerves
and blood vessels connected with the CNS [152].
The major function of the CSF is to protect brain from physical traumas of ev-
eryday living by cushioning the brain within rigid skull. Without this protection of
CSF and meninges, the brain can be easily damaged even by minor head injury [10].
In the normal healthy person, the normal pressure in the cerebrospinal fluid sys-
tem, may refer to intracranial pressure (ICP), is about 10 mmHg [69]. An enlargement
of size or volume of any intracranial contents can cause an increase in ICP [152]. High
ICP result from many pathological conditions of the brain such as brain tumor, hem-
orrhage inside the cranium, and also hydrocephalus which sometimes elevates the
ICP about four times over its normal pressure [69]. Because of the cranium is the
rigid chamber which does not allow any physical swelling toward outside, so the el-
evated ICP is the unique problem compared with similar situations elsewhere in the
body [193]. The increased ICP exerts a collapsing force on intracranial vasculature.
The smaller radius of blood vessel greatly increases the resistance of blood flow to
the brain, and also reduce the cerebral blood flow below the level needed to satisfy
metabolic requirements [193]. An increased ICP may cause the following symptoms:
23
headache, nausea, vomiting, loss of consciousness, and an increase in systemic blood
pressure [152]. In practice, the only way to restore brain blood flow at a normal mean
arterial pressure is to remove the tumor or accumulated fluid [193].
Formation, Flow, and Absorption of Cerebrospinal Fluid
The rate of CSF production, relatively constant regardless of systemic blood pressure
or intraventricular pressure [28], is approximately 500 ml/day for normal adults which
is three to four times as much as the total volume of fluid in the entire cerebrospinal
fluid system [69]. Thus the CSF turns over about 3.7 times a day [10]. In experiments
on animals, approximately 50-70% of CSF is produced and secreted by the epithelial
in the wall of the four ventricles called “choroid plexus” and the remainder of CSF is
formed around blood vessels and along ventricular walls [10]. Choroid plexus produces
the bulk flow of CSF and the pulsatile flow of CSF is provided by active secretion
from cardiac pulsation. During systole, the expansion of choroid plexus with arterial
blood generate a pressure pulse to the CSF. Hence, the choroid plexus play a role as
a pump to stimulate the CSF circulation in ventricular system.
(a) (b)
Figure 2.7: (a) The pathway CSF flow from the choroid plexus in the lateral ventricles
to arachnoid villi penetrating into sagittal sinus [69]. (b) Ventricular system of the
brain [173]
As illustrated in Figure 2.7, the normal circulation of CSF flows from the two
lateral ventricles (left and right) to the third ventricle through the two cavities of
24
foramen of Monro where it mixes with more CSF [152]. Then, CSF flows from
the third ventricle into the fourth ventricle via cerebral aqueduct or aqueduct of
Silvius which is the narrowest CSF pathway in the ventricle system. The flow of
CSF from the fourth ventricle is transmitted to the subarachnoid space (SAS) that
surround the brain and the spinal cord by using the pathway of foramina of Magendie
and lateral foramina of Luschka. Some CSF flow around the tentorium upwards for
absorption process at the superior sagittal sinus. Some CSF flow downward into
the basal cisterns and spinal subarachnoid space. For downward flow, the pressure-
volume compensatory mechanism may take place to compensate the expansion of
lumber space by elasticity of spinal theca which act to dampen the cerebral arterial
pulse [38, 66]. Thus, the elasticity of spinal theca is one of the most important element
of the intracranial Windkessel mechanism which allow the pulsatile energy of CSF
flow from the intracranial space to absorb in the spinal subarachnoid space.
The conventional bulk flow theory of CSF believe that the major absorption into
venous system of CSF penetrate the sagittal sinus’s wall via arachnoid granulation
or arachnoid villi. This drainage, follows the hydrostatic pressure gradient principle
between CSF and venous sinuses pressure, transport when subarachnoid ICP is higher
than sigittal sinus pressure and stop otherwise. However, the modern concept of CSF
absorption accept that the majority of CSF absorb at the capillaries of the central
nervous system based on the Starling principle [61, 66].
2.2.3 Cerebral Blood Flow

The metabolic demands of the brain must be met with the blood supply to this organ
with normal cerebral blood flow is about 50 mL/100 g of brain tissue/min [152].
With average weight of brain about 1,400 - 1,500 g, the average cerebral blood flow
for the whole brain is about 700 to 750 ml/min [152] or about 15 percent of total
cardiac output at rest [69]. Most of the blood supply to brain (about 350 ml/min
[152]) via two internal carotid (left and right) arteries which branch from each side of
common carotid arteries. Some of the blood to the brain is supplied by two vertebral
25
arteries which branch arising from each side of subclavian arteries [148]. Then, the
two vertebral arteries combine at the caudal of the pons to form a single basilar artery
[152]. The combination of two internal carotid arteries and vertebro-basilar system
(two vertebral arteries and a basilar artery) form a circle of blood vessel to supply
blood to the brain called the cerebral arterial circle [148] or the circle of Willis as
shown in Figure 2.8.
Figure 2.8: The internal carotid artery and vertebro-basilar system. Note the cerebral
arterial circle (circle of Willis; marked by a dashed black line) [152].
A unique characteristic of the cerebral circulation is that it all envelopes within

a rigid cranium. According to Monro-Kellie doctrine, the volume of cerebral blood,
CSF, and brain in the rigid cranium is relatively constant at any time; changes in
either of these fluid volumes must be coincident with a reciprocal change in the
other. Hence, cerebral blood supply can be interrupted by many risk factors such
as an excessive accumulation of CSF within the brain referred to hydrocephalus or
26
a bleeding of cerebral blood vessel resulting from head injury referred to intracranial
hemorrhage. A brief cessation of cerebral blood flow to central nervous system as little
as 10 minutes may cause loss of consciousness and serious neurological disorders. A
blood supply to the brain below the level of 25 ml/100 g of brain tissue/min can
lead to ischemic penumbra [152], a condition of inadequate blood to meet brain’s
metabolic demand, and further result in the irreversible brain tissue damage and loss
brain function due to insufficient oxygen supply. Also, a blood flow to brain below 8
ml/100 g of brain tissue/min leads to an almost complete loss of functional neurons
[152].
2.3 Pathological Conditions

As mentioned, the major function of cerebral blood flow is to supply oxygen and
other nutrients to the central nervous system (CNS) and remove carbon dioxide and
other metabolic end products from the CNS which required a steady blood supply
(about 15% of the cardiac output at rest) to function normally. The malfunction and
destruction of any contents within closed cranium affect their dynamics and lead to
cerebral blood supply decrease which is normally known as cerebrovascular accident
or “stroke”.
2.3.1 Stroke
Due to reduced cerebral blood flow, the delivery of oxygen and other nutrients to
the brain is reduced and the carry of carbon dioxide and other waste products away
become slower which greatly increase in the local concentration of carbon dioxide
[69]. The condition of insufficient oxygenated blood supply to the brain is called
brain ischemia. In addition, prolonged brain ischemia can lead to a failure of brain’s
neurological functions and localized neuronal tissue death called brain infarction or
cerebral infarction [152]. Cerebral strokes can be classified into two major causes:
1) ischemic stroke, resulted from blockage of arteries supplying brain tissue, and 2)
27
hemorrhagic stroke, resulted from rupture of cerebral arteries that bleeding into the
brain.
Ischemic Stroke
Ischemic stroke or occlusion stroke accounts for about 85% of all cases of stroke [58].
Ischemic strokes are generally caused by an obstruction of blood flow within the artery
that supply blood to the brain resulting from the accumulation of fatty deposits such
as cholesterol called atherosclerotic plaques. For example, the person who suffers from
a blockage of the middle cerebral artery on the left hemisphere becomes almost totally
demented because the lost of function in speech comprehension area and also unable
to speak words because the loss of word formation function [69]. The blockage in
ischemic stroke can result from two major subtypes of obstruction which are cerebral
thrombosis and cerebral embolism. Cerebral thrombosis is a blood clot develops
within a part of artery that supplies blood to the brain such as blockage of the
carotid artery, called carotid atherosclerosis. About 23% of ischemic stroke originates
from carotid atherosclerosis [58]. Cerebral embolism is a blood clot that forms or
has detached from a larger clot elsewhere in the circulatory system (often a vein
[78]) travels toward the brain until reach too narrow blood vessel to pass and finally
lodge in and block the cerebral blood vessel [148]. Only small size of plaque can
lead to dangerous clots, because the major arteries of the Circle of Willis have lumen
diameters of <4 mm [58]. Risk factors for ischemic stroke include factor that raise
degree of atherosclerosis such as high blood pressure (hypertension), diabetes, poor
diet, physical inactivity, and obesity.
Hemorrhagic Stroke
Hemorrhagic stroke or bleeding stroke is caused by the bleeding of the blood within
cranial space from the ruptured blood vessel. Hemorrhage can cause an intracranial
mass lesion which is a mass effect from the accumulation of bleeding blood. Most
common type of intracranial mass lesion is hematoma. This abnormal collection of ex-
28
travascular blood (hematoma) inside the skull can compress the local brain tissue and
increase intracranial pressure. Hemorrhagic stroke can be roughly categorized into
two types which are intracerebral hemorrhage (ICH) and subarachnoid hemorrhage
(SAH). Intracerebral hemorrhage (ICH) is the bleeding of blood within the brain tis-
sue. ICH accounts for about 10-15% of all cases of stroke with approximately 77-78%
of all ICH resulting from small intracranial blood vessel are ruptured by chronic hy-
pertension (hypertensive hemorrhage) or cerebral amyloid angiopathy [153]. Up to
70% of patients with primary ICH is founded the expansion of hematoma over the
initial few hours [43]. While, subarachnoid hemorrhage (SAH) is the bleeding of blood
in the subarachnoid space which is CSF-filled space between the arachnoid and the
pia. About 90% of SAH often occured in the Circle of Willis by a cerebral aneurysm
(abnormal ballooning outward of the arterial wall) [129]. A formation of cerebral
aneurysm results from a weakened portion of blood vessel which allow extravascular
blood to fill in and create a bulge of blood. Then, extravascular blood in aneurysm
can leak into the surrounding subarachnoid space.
Risk factors for ischemic stroke include the factors that raise degree of atherosclero-
sis such as high blood pressure (hypertension), diabetes, poor diet, physical inactivity,
and obesity. Major risk factor for hemorrhagic stroke is also hypertension. However,
two additional common causes of stroke ,especially hemorrhagic stroke, are traumatic
brain injury (TBI) and hydrocephalus.
2.3.2 Traumatic Brain Injury

Traumatic brain injury (TBI) is a damaged injury to the brain resulting from exter-
nal mechanical force. The major causes of TBI are: motor vehicle accidents, falls,
violence, and sports injuries [110]. TBI can cause the internal bleeding (hemorrhage)
from an injured blood vessel. The collection of bleeding blood brings about a forma-
tion of hematoma to occupy the space within the skull which has a finite volume. In
order to response to the space-occupying intracranial lesion, elevated intracranial pres-
sure (intracranial hypertension), brain herniation (displacement of brain), stroke, and
29
serious neurological deficits may occur after injury. Not include subarachnoid hem-
orrhage, there are two dangerous forms of hematoma, located adjacent to the brain
parenchyma, caused by TBI including epidural hematoma and subdural hematoma.
Epidural Hematoma
An epidural or extradural hematoma (Figure 2.9) is a collection of blood results from

the loosening of the periosteal dura layer from the inner table of skull by the dissection
of damaged artery [70]. The most common cause of an epidural hematoma is a skull
fracture that results in bleeding of a major dural vessel, most notably the middle
meningeal artery and about 15% of cases may result from a venous sinus bleeding
[71]. These lesions tend to be smaller and more confined than subdural hematomas
because the firm attachment of the dura layer to the inner table of the rigid skull is
confined and may exert a closure effect to limit the size of the hematoma [129].
Figure 2.9: Axial noncontrast CT demonstrates an epidural hematoma [199].
30
Subdural Hematoma
A subdural hematoma is a collection of blood commonly caused by a rupture of

the cortical bridging veins which flow within the subdural space through the sub-
arachnoid space and drain toward superior sagittal sinus or other dural venous sinus
[129]. Naturally, there is no occurring space between two layers of connective tis-
sue of meninges which are dura mater and arachnoid mater [70]. However, this
dura-arachniod space called subdural space will become a potential space and radi-
ologically evident whereas there is fluid, hemorrhage or purulent material between
the dura and arachnoid mater [129]. As shown in Figure 2.10, subdural hematoma
appears long and thin compared to an epidural hematoma, along the entire surface
of the brain [71]. Because of the relatively unconfined nature of the subdural space,
subdural hematomas can be enlarged easily which brings about higher mortality rate
compared to epidural hematomas [129]. Furthermore, a large expansion of these
hematomas will exert mass effect on the surrounding brain parenchyma, resulting in
compression of sulci and ventricle, or the presence of midline shift and herniation
when severe [129]. As shown in Figure 2.10(b), an appearance of midline shift on CT
scan occurs when an irregular force within the skull, resulting from the interruption of
intracranial contents such as space-occupying lesion from brain tumor or hematoma,
exert into brain to shift over its center line. The degree of midline shift depends on
the size of mass lesion [3].
Because of essentially finite intracranial volume with 3 major intracranial con-
tents (brain, CSF and blood) referred to Monro-Kellie doctrine, an expansion of any
intracranial contents bring about compression of other contents. Moreover, volume
compensatory capacity will be exhausted and result in elevated ICP. Large expansion
of hematoma after brain injury may raise ICP over 30 mmHg which increase risk of
transtentorial or brainstem herniation [192]. In patient with brain injury, reduced
cerebral blood flow is commonly observed which may result in secondary cerebral
ischemia. Thus, the treatment of TBI focus on handling elevated ICP and maintain-
31
(a) (b)
Figure 2.10: (a) Axial view of a subdural hematoma [110]. (b) Computed tomography
indicated a large right-sided acute on chronic subdural hematoma (maximum depth,
1.9 cm) occupying the frontal, parietal and temporal convexities, and a possible small
subarachnoid hemorrhage [196].
ing adequate cerebral blood flow to normal level to prevent the secondary injury and
repair the damaged neurons. To minimize this complication and increase chance of
recovery, the prompt surgical treatment after a severe traumatic injury is required
[192].
2.3.3 Hydrocephalus
Hydrocephalus is a clinical condition of the excessive accumulation of CSF within
or around the brain. Currently, there is no obvious cause of hydrocephalus [142].
The traditional theory of hydrocephalus is generally understood as an imbalance be-
tween CSF formation and absorption and a disorder of CSF bulk flow circulation [66].
However, the new attention of hydrocephalus has focused on the pulsatile nature of
the fluid flow and pressure within the intracranial cavity [46, 47, 66, 101, 106]. Due
to blockage of CSF circulation with continuous production of CSF, hydrocephalus
result in marked enlargement of cerebral ventricles (Figure 2.11) with an excess ac-
cumulation of CSF and then increase in ICP and CSF pulse pressure. Moreover, the
32
brain parenchyma and cerebral blood vessel might be compressed between the rigid
cranium and the ventricular dilation lead to a progressive loss of brain neural func-
tion and reduction of cerebral blood flow. Hydrocephalus is common birth defects
(one birth in every 2,000 results in hydrocephalus according to the World Health
Organization studies) for unknown reasons [181] which may develop before birth or
during the first few months [152]. In infant with stretchable skull bone, the cerebral
ventricular dilation may lead to abnormal enlargement of head and damage the de-
veloping brain. Traditionally, hydrocephalus can be classified as communicating and
non-communicating based on its mechanism.
Communicating hydrocephalus (non-obstructive) results from the accumulating
in ventricles and cease of CSF-flow into the subarachniod space. Traditional theory
believe that communicating hydrocephalus is caused by the functional impairment
of arachnoid granulations or arachnoid villi where absorption of CSF into the ve-
nous sinuses occurs. However, new understanding of communicating hydrocephalus
is caused by decreased intracranial compliance and restriction of arterial expansion
as shown in Figure 2.12 [66]. Communicating hydrocephalus have a variety of causes
such as tumors or infection involving in the CNS [70] which may cause adhesions to
form in the subarachnoid space resulting in decreased intracranial compliance [66].
Also, communicating hydrocephalus can be caused by subarachnoid hemorrhage [129]
which in 15-20 % of patients with SAH acutely develop communicating hydrocephalus
[153]. One of the most common communicating hydrocephalus in the elderly is normal
pressure hydrocephalus (NPH). NPH defined by gradual enlargement of the ventricles
with excess CSF and slightly increase in ICP but still within the normal range. MRI
data showed that patients with NPH have significantly lower vascular compliance
than that of healthy individuals [11]. This reduction of vascular compliance decrease
the amount of CSF flow downward to spinal cavity through the foramen magnum
during systole [162]. NPH can be classified into two types: idiopathic and secondary.
Idiopathic NPH (unknown cause of the disorder) is a condition of the elderly [134].
Secondary NPH is commonly caused by subarachnoid or intraventricular hemorrhage,
33
Figure 2.11: T1 weighted axial and sagittal magnetic resonance images of the brain in
patients with ((b) and (d)) and without ((a) and (c)) hydrocephalus. The ventricles
are markedly enlarged compared to normal. The cerebral aqueduct (arrow) is patent
and there is no evidence of obstruction within the ventricular system. This is a case
of communicating hydrocephalus [28].
34
Figure 2.12: Cerebral blood flow in (a) healthy individuals and in (b) communicating
hydrocephalus. (a) The arterial windkessel mechanism, the wide intracranial ves-
sels with small vascular resistance and the venous outflow resistance that keep the
cerebral veins distended maintain the high normal blood flow. The venous outflow
resistance is caused by a small positive intracranial pressure and is increased during
systole. The venous outflow resistance is a mandatory prerequisite for the “waterfall
phenomenon”, i.e. the pressure drop occurring from the cortical veins to the venous
sinus. (b) In communicating hydrocephalus, the increased transmantle pulsatile stress
(i.e. difference in pressure between ventricle and subarachnoid space) and the ven-
tricular dilation compresses the cerebral veins and capillaries in their entire length.
This significantly increases the vascular resistance and decreases the blood flow. The
reduced venous outflow resistance facilitates collapse of the compressed capacitance
vessels, which further decreases cerebral blood flow [66].
meningitis or head trauma [134].

Non-communicating hydrocephalus (obstructive), condition of the fluid accumu-
lation within the ventricular system, result from the blockage of CSF-flow by ob-
struction of cerebral aqueduct or interventricular foramina (foramina of Luschka and
Magendie) into subarachniod space either due to congenital malformations, external
compression of CSF-flow pathways or intraventricular mass lesions (intraventricular
hemorrhage) that disrupt the ventricular anatomy. Blockage of both interventricu-
lar foramina, for example by a congenital growth of colliod cyst (colloid tumor), will
result in both lateral ventricle dilation [70]. However, unilateral obstruction of one in-
terventricular foramina may results in enlargement of ipsilateral ventricle [70] called
unilateral or monoventricular hydrocephalus as presented in Figure 2.13. For the
acute phase of obstructive hydrocephalus, increased ICP are the most common clini-
35
Figure 2.13: (a) Preoperative MRI of a 7-year-old boy with monoventricular hydro-
cephalus due to shunt overdrainage: marked dilatation of the left lateral ventricle
(b) MRI performed 10 days after the endoscopic fenestration of the septum pellu-
cidum: marked decrease of size of the left lateral ventricle and reappearance of the
subarachnoid spaces [55].
cal symptom [66]. For chronic obstructive hydrocephalus, the ventricular enlargement
compress the brain parenchyma and cerebral veins which lead to decreased intracra-
nial compliance and consequently a breakdown of intracranial Windkessel mechanism
[66]. Thus, the hydrodynamics and clinical conditions of chronic obstructive hydro-
cephalus and communicating hydrocephalus are identical [66].
Hydrocephalus is commonly relieved by surgical interventions called shunt. Shunt
is surgically implanted device used to bypass the obstruction and drain excess in-
tracranial CSF and transport it into the bloodstream or other body cavities capa-
ble of absorbing the fluid [28] such as the peritoneal cavity [38]. Removal of CSF
that compress intracranial vessel by shunt placement can recover intracranial com-
pliance and consequently normal cerebral blood flow and hemodynamics conditions
[62, 64, 68] by dilating cerebral veins or by reconnecting the free CSF communica-
tion between cranial subachnoid space and compliant spinal cavity [66]. This logical
explanation support the view that communicating hydrocephalus is the disorder of
intracranial pulsation [66]. Shunt also can be applied for other related diseases treat-
36
ment. However, there are many complications associated with shunting procedures
including shunt dependency, infection, over-drainage of CSF and development of the
slit ventricle syndrome (SVS) [180]. In addition, shunt placement in patients with
subarachnoid hemorrhage from head injury can reduce CSF volume but increase the
risk of brain herniation [192]. As commonly appearance of narrowed ventricles in
patients with head injury, shunt become less effective due to accessibility limitation
[192]. There is no question that reliable shunt system can cure hydrocephalus problem
especially obstructive hydrocephalus; however, shunt placement significantly changes
the pulsatility and dynamics of intracranial contents [180].
37
Chapter 3
Associated Intracranial System
Cardiac pumping action provides the pulsatile nature of arterial blood flow. However,
capillary beds require continuous bulk flow for nutrient and waste product exchanging
process. Therefore, the buffering function of aorta and large arteries is essential for
smoothing out the pulsatility called “Windkessel mechanism” (Section 3.1) which
provided by an expansion of elastic artery to accommodate the change of blood volume
called arterial compliance. Windkessel mechanism is commonly observed in major
arteries entire the body including intracranial space. However, unique characteristic
of the intracranial space has fixed volume within rigid cranium. Also, the volume
of four major intracranial contents (brain, arterial blood, venous blood and CSF)
interact within this enclosed cranial cavity based on Monro-Kellie doctrine (Section
3.2). Hence, Windkessel mechanism of intracranial system provided by its arterial
compliance and additional elastic properties of intra- and extracranial contents called
intracranial compliance (Section 3.3). In healthy individuals, intracranial pressure
(ICP) is distributed uniformly over entire intracranial space with bilaterally balance
of cerebral blood flow (CBF). In contrast, the interhemispheric ICP gradients (Section
3.4) and asymmetry of CBF between two hemispheres (Section 3.5) are observed under
pathological conditions.
38
3.1 Windkessel Mechanism and Pulsatility
Windkessel is the German word for air-chamber was first introduced as mathematical
model by Otto Frank (German physiologist) to describe the hemodynamics in elastic
arterial system [53]. As the Windkessel present in an old-fashioned fire engines (Fig-
ure 3.1), water is pumped intermittently into an air-and water-filled chamber. Then,
an air compressibility converts the pulsatile inflow of water into steady outflow at
the hose nozzle while leaving the chamber. Likewise the cardiovascular system, blood
pulsation created by the heart’s pumping action flows through the expansion and
contraction of the elastic major arteries which act as buffering chambers. Blood then
flows from the major arteries into smaller diameter vessels with intrinsic obstructive
force then with continuous and pulseless outflow. Two main parameters describing
Windkessel mechanism of arterial system are its elasticity of artery referred to “ar-
terial compliance” and obstruction of blood flow from large artery to smaller artery
referred to “peripheral resistance”.
Pump Chamber Nozzle
Heart Elastic Artery Peripheral Resistance
Figure 3.1: The concept of Windkessel mechanism. The air reservoir (chamber) is the
actual Windkessel, and the large arteries act as the Windkessel. The combination of
compliance, together with aortic valves and peripheral resistance, results in a rather
constant peripheral flow [189]
39
The arterial compliance plays an important role in absorbing and releasing energy
during systolic and diastolic period. During systole, heart discharge the entire stroke
volume of blood in form of kinetic energy into the arterial system. Approximately
50% of blood volume from cardiac contraction is dissipated forward to peripheral cir-
culation, while remainder is stored as potential energy in the arterial vessel [16]. The
storage of the remainder blood volume is provided by the role of peripheral resistance
and elastic expansion of arterial wall by increasing arterial blood pressure. During
diastole when arterial pressure falls, this elastic artery passively recoils and forces the
storage volume into peripheral circulation by reconverting the stored potential energy
during systole into kinetic energy [16]. Thus, this effective Windkessel function which
act as hydraulic filter can convert pulsatile blood flow into nearly continuous periph-
eral flow by buffering function of elastic artery. In capillaries, this elastic properties
of artery can also protect the damaging force from pulsatile flow in absorbing process
between capillaries and cells.
Figure 3.2: Pressure-dependent arterial compliance [103]
The arterial compliance is defined as the change in volume stored per change in
internal pressure (Compliance = ∆V olume/∆P ressure) which is not constant but
depends on the blood pressure with nonlinear relationship [77] as shown in Figure
3.2. Arteries with high compliance can accommodate large amount of blood with only
40
small increase in systolic pressure, therefore pulse pressure is in small range which
reflects low aortic wall tension and heart work load [77]. Conversely, aging is usually
much involved in loss of arterial elasticity which lead to reduced arterial compliance
and increased pulse wave velocity [41]. In youth with high arterial elasticity, the
forward-traveling wave (incident wave) transmission which generate and travel away
from heart during systole is slow, thus during diastole its reflected wave returns
from peripheral sites to the heart distally. In elderly with low arterial elasticity, the
forward-traveling wave transmission is fast, thus its reflected wave returns to heart
much earlier which allows the reflected wave to merge with the forward systolic wave
[130]. As shown in Figure 3.3, in the elderly, the combination of the reflected wave
which shifts from early diastole to late diastole and the forward systolic wave result in
increased systolic pressure augmentation and decreased diastolic pressure, hence also
increased central pulse pressure [41]. Consequently, high systolic blood pressure will
increase the velocity of systolic blood flow by harder work of the heart’s left ventricle to
eject blood to aorta [16] because noncompliant aorta cannot accommodate the cardiac
stroke volume [77]. Thus, the normal cushioning function of Windkessel mechanism
not only maintains the blood supply continuous throughout the body during diastole,
when the heart is refilling and preparing for the next systolic contraction, but also
reduces the cardiac afterload.
Blood vessel tissue is mainly composed of smooth muscle, the highly elastic bundle
of protein called elastin and very stiff protein in connective tissue called collagen
[190]. As mentioned, the elastic properties of arteries, usually determined by smooth
muscle and elastin [190] is diminished when the arterial stiffness increases due to
the course of aging [16]. The stiffness of artery increase with aging results from
the gradual loss of its elastic fibers with gradual replacement by collagen fibers [7].
Furthermore, there are other variables influence arterial elastic properties including
gender [25, 96, 98, 104] and pathophysiologic conditions. Most of pathophysiologic
conditions affect large arterial elastic properties [41] especially the aorta [16] and
its first branches [172]. Under pathophysiologic conditions such as hypertension [17,
41
Figure 3.3: Central pressure contours and aging. The observed central pressure con-
tours (upper tracings) are the sum (lower tracings) of the incident or forward-traveling
wave (broken lines) and the reflected or backward-traveling wave (dotted lines). In
younger subjects (right panel), the reflected wave (arrow) returns to the aortic root
during diastole. As vessels get stiffer during the aging process (left panel), pulse wave
velocity increases and the reflected wave returns during late systole (arrow), where
it summates with the forward systolic wave to augment central systolic pressure and
increase ventricular afterload [77]. (Adapted from Asmar R. Arterial Stiffness. 1999.
[4])
76], hypercholesterolemia [99, 100] and atherosclerosis [42, 97], Windkessel buffering
function is demolished which result from the large arterial wall stiffening due to
the change in vascular structure including wall thickness and lumen diameter [190].
Arterial wall stiffening will reduce arterial compliance, increase pulse wave velocity
and importantly widen pulse pressure. The widening of pulse pressure may induce
additional decay of the arterial wall, then accelerate the loss of elastin [190].
For intracranial system, the cerebral blood flow through intracranial cavity has a
unique characteristics which are different from any other part of the body because
they are enclosed within rigid container for the purpose of brain protection. To main-
tain the normal cerebral blood flow and to ensure pulseless flow through cerebral
capillaries, the effective intracranial pulsation absorber is required. During systole,
42
pulsatile arterial blood flow into the cranial cavity. The pulsatile energy from systolic
arterial flow is transmitted and dissipated in the surrounding intracranial contents
including CSF, elastic intracranial veins and subarachnoid space (SAS) which act as
intracranial pulsation absorber. For example, since vanous blood and CSF connected
to lower pressure region outside the cranium, the systolic expansion of cerebral ar-
teries expulses the venous blood into the dural venous sinuses by compressing the
venous outlets of the bridging vein [66]. Moreover, due to the spinal region (refers
to spinal thecal sac) has higher compliance than the intracranial SAS during systole
(and vice versa during diastole) [133], the pulsatile displacement of CSF downwards
and upwards between cranium and spinal SAS through the foramen magnum [66, 84]
to maintain the constant amount of volume within rigid cranium according to Monro-
Kellie doctrine is the example of volume compensation mechanism to response to the
systolic expansion of cerebral arteries. In addition, appropriate resistance of arteriole
and capillary also must be provided to smooth out pulsatile arterial flow to non-
pulsatile cerebral capillary flow for the effective nutrient exchanging process. The
combination of intracranial Windkessel mechanism is essential for the maintenance of
normal cerebral blood flow and a constant cerebral perfusion pressure [84]. The in-
terruption of intracranial contents, for example, from the external force such as brain
injury or intracranial disorder such as hydrocephalus can breakdown the intracranial
Windkessel mechanism due to decreased intracranial compliance. The breakdown of
the intracranial Windkessel mechanism results in increased intracranial CSF pulse
pressure, restriction of arterial expansion, causing increased arterial resistance and
reduced cerebral blood flow [46, 47, 61]. The restriction of arterial expansion will
transmit outflow with high pulsatility to capillary which this pulse energy is ab-
sorbed in the capillary instead of the artery [66]. Then, this systolic pressure pulse
transmits from capillary to brain tissue and increases brain tissue pressure which de-
creases cerebral perfusion [66]. Also, the decreased intracranial compliance affects the
autoregulatory mechanism of artery to maintain the normal level of cerebral blood
flow [62].
43
3.2 Monro-Kellie Doctrine
The central nervous system is composed of incompressible intracranial contents which
covered within a rigid container of skull. Variation in any of its intracranial content’s
volume, the volume of the other contents will be compensated. To describe this
complex compensatory situation, the principle of homeostatic intracerebral volume
mechanism [82] was originally introduced in 1783 by Alexander Monro, a Scottish
professor of anatomy. Monro [125] considered the cranium as a rigid structure of
bone and only two intracranial contents (nearly incompressible brain and the vol-
ume of incompressible blood) interplay within this closed cranial cavity. Since the
brain is nearly incompressible, the volume of blood circulating in the cranium is con-
stant at all times which is a continuous outflow from the cranium of venous blood
is compensated by a continuous inflow of arterial blood [124]. George Kellie [81],
a former Monro’s pupil, supported Monro’s original hypothesis by his experiments
and published in 1824. Based on animal experimentations, Kellie verified Monro’s
hypothesis by considering three intracranial contents, i.e arterial blood, venous blood
and brain tissue. He also stated that the removal of any circulating fluid from the cra-
nium was not required simultaneous equivalent replacement; or the additional of any
circulating fluid into the cranium was not required simultaneous equivalent displace-
ment. In this literature, many Kellie’s observations agree with John Abercrombies’s
literature which published before Kellie’s, and thus the term Monro-Abercrombie doc-
trine was found in Kelle’s literature [105]. In Abercrombie’s monograph [1] in 1828,
Abercrombie strongly supported Monro’s and Kellie’s hypothesis based on his animal
observations [105] and then their doctrine became widely accepted [185]. Although
CSF was discovered before Monro’s publication [185] and CSF intraventricular flow
through foramen was described and bound his name referred to foramen of Monro
[105]. Monro obviously ignored the existence of CSF as a normal intracranial con-
tent [105]. The role of CSF in the cranium was first ignited by Francois Magendie
in 1825. Magendie [108] proposed the flow of CSF from the fourth ventricle to the
44
subarachnoid space via the pathway of foramen which bears his name (foramen of
Magendie). The revised version of the Monro-Kellie doctrine by accounting the vol-
ume of CSF into this equation of conservation of volume within rigid cranium was
introduced by George Burrows in 1846. Burrows [24] observed replacement of blood
lost due to systemic hemorrhage by CSF volume [185]. According to his experiments,
the reciprocal relationship between volume of CSF and cerebral blood can be inferred.
Finally, Monro-Kellie doctrine became known as the total volume within rigid cra-
nium; the summation of the volume of brain tissue, arterial blood, venous blood and
CSF, remain constant. A change in either content had to be compensated by the
remainders.
Figure 3.4: Diagram showing the phase relationships of intracranial volume change
measured by using flow-sensitive MRI in (a) normal individuals and (b) patients with
hydrocephalus. The curve of the volume changes in the artery is constructed as
the inverse to the sum of the changes in the veins and intracranial CSF. In normal
individuals, the expansion in the precapillary vessels is assumed to be somewhat larger
than the corresponding compression on the venous side in order to correspond with
the small brain expansion. In patients with hydrocephalus, the arterial is small as
reflected in the small volume changes in the veins and in the intracranial CSF. As a
result of the small arterial pulsations in SAS the pulse wave penetrates into compliant
less distended intracerebral vessels resulting in a decreased intrinsic redistribution and
large brain expansion [61].
The development of magnetic resonance imaging (MRI) technique in the past

decade brings about the explanation of intracranial dynamics and volume compen-
45
satory mechanism within cranial cavity to describe the relationship between pulsatile
flow of blood and CSF during cardiac cycle. Greitz et al. [61, 63, 65, 66] stud-
ied pulsatile motion of intracranial contents by using MRI technique. According
to Monro-Kellie doctrine, the intracranial dynamics are related to the demand for
volume by four intracranial contents, i.e. the arterial blood, brain volume, venous
blood and CSF [65]. During systole, the expansion of carotid and basilar arteries in
the closed cranial cavity [63] plays an important role in the dynamics and variation
of intracranial volume which represented in Figure 3.4. The change of the arterial
volume is inversely proportional to the summation of change in venous and intracra-
nial CSF volume which mean the expulsion of the CSF and compression of veins are
almost identical [61]. As shown in Figure 3.5, this systolic arterial expansion simul-
taneously dissipates the pulsatile energy to entire subarachnoid space which causes
a compression of intracranial vein and expulsion of the extraventricular CSF upward
to the intracranial subarachnoid space and downward to compliant spinal subarach-
noid space (thacal sac) through the foramen magnum. During mid-systole, the less
pulsatile and delay of arterial pulse wave outflow due to energy absorbing function
of Windkessel mechanism is transmitted to the brain capillaries lead to small dila-
tion of capillary and then cause brain parenchymal expansion [61]. Brian expansion,
typically very small in the healthy individuals (about 2% of the arterial expansion
[66]), leads to the compression of the brain ventricles (mainly on the lateral ventricles)
which occurs simultaneously with an inflow of CSF towards the ventricular system to
drive out the intraventricular flow of CSF [65]. During diastole, the higher pressure
in spinal cavity result in flowback of CSF from spinal cavity into the cranial cavity.
Thus, CSF repeatedly flow upward and downward between cranial and spinal cavity
during the entire cardiac cycle.
Nowadays, Monro-Kellie doctrine is essential for many clinical applications i.e. to
explain the failure of volume compensatory mechanisms due to space occupying lesion
such as hematoma in patient with traumatic brain injury (TBI) which often develop
intracranial hypertension [82]. Also, CSF volume depletion caused by CSF leakage or
46
Figure 3.5: Normal intracranial hydrodynamics. The relative thickness of the arrows
in the artery (red) indicates the magnitude of pressure. The relative thickness of the
arrows in the venous system (blue) and subarachnoid space indicates the magnitude
of flow [162]. (Modified from Greitz [66])
CSF over-drainage during shunt placement which require volume compensation can
be explained by Monro-Kellie doctrine [124].
3.3 Intracranial Compliance

To smooth out arterial pulsatile flow into a continuous and steady flow through pe-
ripheral tissue within the cranium, the effective intracranial Windkessel mechanism
which depends on a storage capacity of both vascular compliance and compliance of
CSF space are required. These combination of volume compensatory mechanism act
as pulsation absorber in intracranial system called intracranial compliance. Thus,
overall intracranial compliance depends on the compliance of four main intracranial
contents [178]: brain tissue (typically is small in healthy individual [61]), arteries,
veins (very high compliant venous wall [69, 78]) and spinal thacal sac (located in
lumber space which buffer CSF pulsatile flow from cranial cavity during systolic ex-
pansion of intracranial arteries [66]). In addition, the elastic property of other intra-
and extracranial contents (i.e. ependyma, dura mater, intracranial and spinal sub-
arachnoid space) is another factor that affects intracranial compliance. Intracranial
compliance is defined by the change in CSF volume per unit change in intracranial
pressure (C = dV/dPICP ).
47
Figure 3.6: Illustration of the ICP-volume curve and its relationship to the intracra-
nial pulsatility parameters. Under normal physiological conditions with high intracra-
nial compliance, the ICP wave amplitude is correspondingly small. As intracranial
compliance decreases (steep part of the pressure-volume curve), the brain behaves
increasingly like a linear elastance and so variations in intracranial volume correlate
increasingly well with changes in mean ICP, the steepness of the pressure-volume
curve also accounts for large-amplitude ICP waveforms [48].
Based on the experimental observation, Marmarou et al. [112, 113] invasively mea-
sured intracranial compliance by injecting known fluid volumes via a balloon insertion
into the CSF space to analyze the ICP response to changes in CSF volume. They
found that the intracranial compliance decreased as mean ICP increased exponen-
tially along a pressure-volume curve as presented in Figure 3.6. The pressure-volume
curve describes the relationship of ICP pulse pressure and volume by the amplitude
of ICP pulse pressure increase with exponentially rise of mean ICP. Also, the ex-
ponential pressure-volume curve can be used to explain the effectiveness of volume
compensatory mechanism in the cranium. At normal ICP levels, the large increase in
intracranial volume causes a small increase in mean ICP and only small change in ICP
pulse pressure which indicates good intracranial compensatory reserve. Conversely,
48
while the mean ICP is elevated, the intracranial volume compensatory capacity be-
comes exhausted progressively. Only small increase in volume results in the larger in
the amplitude of ICP pulse.
(a) (b)
Figure 3.7: (a) The CSF volume-pressure curve (b) The same data plotted on semilog-
arithmic axis can be approximated by a straight line which its slope is equal to the
pressure-volume index (PVI) [113].
As shown in Figure 3.7, the exponential pressure-volume curve can be simplified

to linear approximation slope by plotting the logarithm of the pressure against the
volume change which is defined as pressure-volume index (PVI). The PVI is defined
as the amount of fluid volume (∆V ) necessary to raise pressure by a factor of 10 and
can be calculated from the relationship [112, 113]:
∆V
PV I =
log10 PP0
where P0 and P are initial and peak pressure level respectively.

The PVI can be used for calculation from the standard clinical method to deter-
mine intracranial compliance known as “bolus injection” by injecting the amount of
fluid volume in the spinal subarachnoid space required to achieve a tenfold increase
in ICP and record the pressure rise. Also, the PVI can be used to access the CSF
dynamic and identify the neurosurgical patients with exhausted intracranial volume
49
compensatory capacity such as traumatic brain injury (TBI) [114] and hydrocephalus
[145, 150] by comparing to the reference. For normal adult, a mean PVI of 25.9 ml, a
mean ICP of 13.2 mmHg and a mean intracranial compliance of 0.85 ml/mmHg were
used as clinical references [151].
The measurement of intracranial compliance plays an important role in clinical
diagnosis or treatment the pathological conditions related to intracranial compliance
changes such as hydrocephalus and TBI. However, direct measurement of intracranial
compliance is technically difficult [178] and not practically performed because the
pressure-volume response test might increase the risk of patients who already load
with intracranial space occupation [164]. Typically, most investigators have used
the intracranial pulsatility as an indicator of the change in intracranial compliance.
Three primary measuring techniques have been used for assessment of intracranial
pulsatility: continuous ICP monitoring, transcranial Doppler ultrasound (TCD), and
magnetic resonance imaging (MRI) [178].
ICP monitoring is invasive measurement of pressure pulsatility to assess the dy-
namics and pulse amplitude of intracranial pressure either in the time domain or
the frequency domain. As described above in the exponential pressure-volume rela-
tionship, intracranial compliance is reduced with increased mean ICP which result
in larger amplitude of CSF pulse pressure along the curve. Hence, the amplitude of
CSF pulse pressure in the time domain (i.e. diastole-to-systole ICP difference over
one cardiac cycle) can be clinically used as an indicator of intracranial compliance
[5, 6]. However, some observation in the patient with pathological conditions such
as SAH [48] and hydrocephalus [52], Eide et al. [48] observed that the relationship
between mean ICP and amplitude of CSF pulse pressure along the curve has good
correlation only 60% of observations. Also, Foltz et al. [52] observed an increase in
amplitude of CSF pulse pressure with reduced mean ICP in some patients. These
observations may imply that the correlation of mean and its amplitude pulse is more
complicated to explain by the predicted pressure-volume curve [48] because reduced
intracranial compliance may not necessarily lead to higher mean ICP or ICP pulse
50
Figure 3.8: Schematic depiction of the pressure-volume compensation index (RAP)
theory [83].
pressure [178]. For analyzing pressure pulsatility in the frequency domain, the ICP
waveform consists of three overlapping components in the time domain which can be
separated in the frequency domain by using the fast Fourier transform [34]. Czosnyka
et al. studied the amplitude of fundamental frequency component (AMP) [37] which
is the harmonic component of ICP pulse waveform that has a frequency equal to the
heart rate [34]. Thus, AMP is the amplitude of the fundamental harmonic frequency
component of the ICP pulse waveform derived from the Fourier decomposition with
a reasonably time period window [83]. Interestingly, AMP has a good correlation
to mean ICP and the degree of this correlation over short periods of time can be
expressed as an index of pressure-volume compensatory reserve (RAP) [34, 37]. RAP
51
index can be calculated as a linear correlation coefficient between AMP and mean
ICP from a reasonably time period (usually 6-10 s) and data points (usually 40 data
points) [34]. As shown in Figure 3.8, the pressure-volume curve (Figure 3.8 (A)) can
be mainly divided into 3 regions. In region I, RAP coefficient (Figure 3.8 (C)) close to
0 indicates less correlation between the changes in AMP and the mean ICP (Figure
3.8 (B)). This linear relationship between volume and pressure in region I implies
a good compensatory reserve at low ICP where change in volume is independent of
mean ICP [34]. In region II, exponentially rise in ICP with increase in volume along
pressure-volume curve indicates decrease of intracranial compliance and exhaustion
of capacity to compensate for change in intracerebral volume [38]. AMP directly in-
crease with mean ICP, consequently RAP usually rises to +1 to response to a poor
compensatory reserve in region II [83]. In region III, passively compression of cerebral
arterioles [34] and then decrease in transmission of arterial pulse pressure to intracra-
nial space result from impairment of active cerebrovascular regulatory mechanisms
which can be developed to the brain ischemia [83]. Critically rise in ICP toward
the right in pressure-volume curve bring about decrease in AMP and below 0 in
RAP level. RAP index is useful for diagnostic purposes in patients with intracranial
pathology; for example, to distinguish chance of recovery for head injured patients
[32] and to diagnosis hydrocephalus in children [147]. Because ICP monitoring is
invasive technique, it can simultaneously monitor and compare the pulse pressure
wave in different intracranial regions which is the advantage of invasive technique
over non-invasive measuring techniques [178].
Transcranial Doppler ultrasound (TCD) is non-invasive technique to measure
blood flow velocity through major intracranial arteries which commonly performed on
the middle cerebral artery (MCA). The output of a TCD measurement is a flow veloc-
ity waveform in the time domain for typically many cardiac cycle of monitoring period
[178]. This flow velocity waveform obtained from TCD provides an important cerebral
hemodynamics information called pulsatility index (PI) which describes the velocity
pulsatility of intracranial artery [44]. Based on Gosling’s method [59], PI is commonly
52
expressed as (peak systolic flow velocity - peak diastolic flow velocity)/mean velocity.
Because PI (flow velocity) depends on many intracranial hemodynamics factors, a
good correlation between PI and various intracranial parameters including arterial
pressure pulsatitily, ICP [15, 73, 128, 141], cerebrovascular resistance (CVR) [36, 56],
cerebral perfusion pressure (CPP) [33, 126, 170] as shown in Figure 3.9 can be used
for clinical assessment. However, measuring only blood flow velocity, not volumetric
flow due to unknown of vascular diameter is the common technical limitation of TCD
investigations [15]. Frequently, decreased intracranial compliance is associated with
increase in PI because PI is a ratio absolute pulsatility and mean velocity [178]. Since
PI depends on both pulsatility and mean flow velocity, increase in PI may result from
decreased cerebral mean velocity due to lower blood flow rather than an increase in
absolute pulsatility [178]. Thus, PI cannot interpret entire intracranial physiological
condition individually, other information is required to support this complex function
of various interdependent dynamics for clinical diagnostic accuracy [44].
Figure 3.9: Timetrends of intracranial pressure (ICP), arterial blood pressure (ABP),
cerebral perfusion pressure (CPP), mean cerebral blood flow velocity (FVm), pul-
satility index (PI) and cerebrovascular resistance (CVR) in patient with head-injury
[44].
Magnetic resonance imaging (MRI) is also non-invasive flow-based method for

measurement of intracranial blood flow (within large intracranial arteries or veins)
53
and CSF flow (within CSF circulatory pathways) collected over many cardiac cycles
[178]. The output of MRI measurement, one cardiac cycle waveform which represents
an average resultant over many cardiac cycles’ dataset, can be both two-dimensional
(flow velocity waveform) and three-dimensional image (volumetric flow) which is MRI-
specific advantage over TCD technique [178]. As described in the previous section,
the volumetric relationship between intracranial blood and CSF pulsatile flow during
cardiac cycle can be investigated by MRI method which provide an essential infor-
mation for assessment of intracranial compliance. The intracranial compliance can
be estimated by using either direct or indirect approach [164].
For direct approach, the intracranial compliance is directly calculated from the
ratio of the change in the intracranial volume and pressure during the cardiac cycle
according to the definition of compliance. The intracranial volume change (net tran-
scranial volumetric flow rate) is the differences between volume of fluid (blood and
CSF) inflow to and outflow of the cranium during the cardiac cycle [2, 164]. The
intracranial volume change include the total volumetric arterial inflow rate, the total
volumetric venous outflow rate, and the CSF of outflow rate through the foramen
magnum with the constraint of volume conservation based on Monro-Kellie doctrine
[2, 164]. The volumetric flow rates are obtained from integration of the velocity
waveform within blood vessel and CSF lumen with respect to time [164]. The to-
tal volumetric arterial inflow rate (total cerebral blood flow) is the summation of the
volumetric flow through four major arteries supplying blood to the brain including bi-
lateral internal carotid arteries and vertebral arteries [2]. The total volumetric venous
outflow rate is the summation of the outflow through the jugular veins and secondary
veins including epidural, vertebral and deep cervical veins [2]. The intracranial pres-
sure gradient waveforms are approximately derived from a time derivative of the CSF
flow velocity waveform based on the Navier-Stokes relationship between pressure gra-
dient and temporal-spatial derivatives of the fluid velocity for incompressible fluid in
a rigid tube [2, 164] which the measuring method for pulsatile pressure gradients by
using MRI was proposed by Urchuk and Plewes [169].
54
(a) (b) (c)
Figure 3.10: (a) Arterial and venous flow in the superior sigital sinus (SSS) territory in
a healthy patient. (b) In NPH patient, arterial and venous flows are almost identical
shape with minimal delay. The mean volumetric blood flow through SSS in NPH
patients is 27% lower than in the healthy individuals. (c) After shunting (removal of
30 mL of CSF), the arterial flow has earlier, higher, and thinner peak. The venous
flow peaks later, is lower, and wider. Modified from Bateman [11].
For indirect approach, since the intracranial compliance has influence on the tim-
ing or phase-lag of flow and pressure waveforms entering the cranium which have a
unique morphology, it is the useful indicator to analyze the intracranial compliance
and its abnormality [178]. The phage-lag method [164] focuses on the phase shift
or relative timing between arterial flow or pressure waveform (typically used as ref-
erence waveform because intracranial pulsation is generated by arterial blood flow
[178]) and other intracranial waveforms such as CSF flow [8, 9, 46, 177], ICP and
venous outflow [11, 13]. For example, Baledent et al. [9] found the smaller phase
55
shift between the systolic peak of arterial inflow and cervical CSF flow in hydro-
cephalic patients compared to healthy individuals. In addition, Bateman [11] showed
the shorter delay between arterial inflow and venous outflow systolic peaks in NPH
patients, while venous peak became lower and longer delay after surgical shunting
as shown in Figure 3.10. In the studies of intracranial compliance by using either
MRI-based or model-based investigators, there are other aspects also can be used as
the estimator of intracranial compliance such as shape of ICP waveform, CSF flow
rate, and amplitude of intracranial waveform. The transformation of peaks and dips
characteristic pattern [178] along systolic and diastolic cardiac cycle of ICP wave-
form have been observed in the patients with hydrocephalus [74] and/or elevated ICP
[165, 179] by smoothing out their characteristic features. Based on MRI data of CSF
flow through cerebral aqueduct (connect between the third ventricle and the fourth
ventricle), many investigators have been reported a significant increase in CSF pul-
stile flow rate through cerebral aqueduct under hydrocephalic conditions [14, 61, 176].
In the studies of change in pulsatility of vascular flow in NPH patients [11, 12, 14],
the decrease in arterial flow pulsation and change in venous pulse wave have been
observed in NPH patients (Figure 3.10). Based on model approach, the amplitude of
the ICP pulse wave increase with pathological conditions such as hydrocephalus have
been proposed [138, 139, 140].
In summary, intracranial compliance is associated with the intracranial volume
compensatory mechanism which is illustrated by an exponential pressure-volume
curve (Figure 3.6). In patients with neurological conditions such as hydrocephalus
or TBI, the development of intracranial space occupation within the closed cranium
based on Monro-Kellie doctrine may exhaust its compensatory mechanism which is
the indication of reduced intracranial compliance. Moreover, the exhaustion of vol-
ume compensatory mechanism can cause the change in intracranial pulsatility (i.e.
amplitude, waveform, velocity, flow rate, timing, etc.) in various aspects including
ICP, blood and CSF flow dynamics which can be observed by using many different
measuring techniques such as ICP monitoring, transcranial doppler ultrasound (TCD)
56
and magnetic resonance imaging (MRI). Hence, the assessment of intracranial compli-
ance by measuring the intracranial pulsatility brings about the valuable information
of intracranial compliance’s role for clinical diagnosis and decision making.
3.4 Interhemispheric Pressure Gradients

Based on Monro-Kellie doctrine, cranium is generally considered as a single rigid
compartment with uniform distribution of intracranial pressure (ICP) over entire in-
tracranial space [39]. However, there are many experimental studies in animal and
clinical reports in head-injured patients associated with differences in ICP between
intracranial tissues [137] and between left and right cerebral hemispheres. For exper-
imental observation, researchers used various techniques to induce elevated ICP and
monitor the interhemispheric ICP gradients such as intracranial balloon expansion,
fluid injections and stroke.
In 1885, von Bergmann’s experimental studies [174] demonstrated the first exis-
tence of intercompartmental pressure difference and concluded that the brain does
not transmit pressure equally in all directions. In 1902, Cushing [31] described an
unequal transmission of intracranial pressure throughout the intracranial space and
regional differences in cerebrovascular response resulted from “local compression” ex-
perimentally produced by mercury-filled rubber bag expansion in subdural space.
Langfitt et al. [92, 94] demonstrated unequally transmission of pressure between
left and right cerebral hemispheres by injecting saline into monkey’s extradural space.
Also, the authors found that a failure of pressure communication from the supraten-
torial to the infratentorial space occur as cerebral tissue obstruct the tentorial in-
cisura [94]. Furthermore, the transmission of increased intracranial pressure within
the supratentorial space were experimentally designed by inserting a balloon with
saline into the frontal lobe and injecting Pantopaque into the extradural space via
a catheter. This experimental observations had shown the higher ICP in the fluid-
injected side but lower and slightly lag of contralateral ICP followed the injected side
57
in most case. The brain herniation was also observed in animal with markedly ele-
vated ICP. The authors summarized that the failure transmission of increased ICP
due to mass lesion resulted from the distensibility limitation of the brain and the in-
tracranial tissues. However, without subarachnoid space obstruction, subarachnoidal
pressure was transmitted freely over the cerebral hemisphere [92].
Brock et al. [20] reported ICP gradients associated with cerebral embolism by
injecting an oil emulsion through the right lingual artery catheter to create unilateral
oil embolism of the cerebral blood vessel or vascular occlusion in a series of 20 cats.
All animals died eventually following the oil injection and categorized into 3 groups
depended on the survival time. The result (Figure 3.11) showed that the higher
epidural pressure of non-embolized hemisphere and larger interhemispheric pressured
differences between two cerebral hemispheres existed in 12 cats following oil injection.
This might be due to large vascular blockage of embolized side. Higher epidural
pressure would be either on the embolized or non-embolized side, the authors stated,
“... may be related to the degree of vascular occlusion achieved or to the distribution
pattern of oil emboli” [20].
Reulen and Kreysch [143] performed cold lesion experiment and recorded brain
tissue pressure in 15 cats by using wick probe. A cold injury induced the highest
pressure in the adjacent to the lesion and followed by remote from the lesion, cisternal
fluid pressure and on the non-lesion side respectively. Also, the pressure gradients
from each recorded position became larger when the hypercapnia was observed.
By using wick-type pressure transducers, Tulleken et al. [167] recorded regional
cerebral tissue pressure under 4 different experimental conditions in 31 animals (14
cats, 7 macaques and 10 baboons). The injection of Pantopaque in the middle cerebral
artery and in the common carotid artery, represented a localized rapidly intracerebral
volume or infarction by vascular occlusion, resulted in marked degree of interhemi-
spheric ICP gradients (Figure 3.12). In addition, the rapid inflation of a subdural
or epidural balloon, represented a rapidly growing extracerebral volume, resulted in
moderate degree of interhemispheric ICP gradients (Figure 3.13).
58
Figure 3.11: Mean values of epidural pressure on the right (PR ) and left (PL ) sides in
various groups of animals. Oil embolization always performed on the right side. All
pressures are positive. The animals in which epidural pressure increase was more pro-
nounced on the right (embolized) side were inscribed above the x-axis. The animals
which epidural pressure increase was more pronounced on the left (non-embolized)
side were inscribed below x-axis. Interhemispheric pressure gradients were more pro-
nounced when epidural pressure increased more on the non-embolized (left) side. [20]
Significant interhemispheric ICP gradient ranging from 5 to 14 mmHg was ob-

served from Miller et al. ’s experimental model [121]. After subdural balloon in-
flation and intracerebral silicone injection in cats and rhesus monkeys, the authors
observed that “the pressure being greatest in the ipsilateral hemisphere and lowest in
the contralateral hemisphere” [121].
Wolfla et al. [195] measured the regional intraparenchymal pressure in 5 locations
including the right (RF) and left (LF) frontal lobes, the right (RT) and left (LT)
temporal lobes, the midbrain (MB) and the cerebellum (CB). A balloon catheter was
inserted into the right frontal epidural space (RF) and expanded by saline injection
to create a frontal epidural space mass lesion in 10 domestic pigs. The experimental
results showed “the pressure differentials between intracranial regions increased as
the size of the mass increased” [195]. Also, a consistent relationship between the
59
Figure 3.12: Injection of Pantopaque into right middle cerebral artery of cat [167]
intracranial regions was RF >LF >RT=LT >MB >CB. In this study, the authors
also stated that “...if a gradient forms, the highest tissue pressures would occur closest
to a mass lesion” [195]. Moreover, the authors conducted similar experiment to
previous report in the following year. In this study [194], an extradural temporal
mass lesion was created by balloon expansion in the right temporal lope (RT). The
pressure relationship after the balloon expansion was RT >LF=LT >RF >MB >CB.
The authors concluded that the presence of pressure gradients depended on, not only
lesion size, but also the mass location [194].
In clinical case report, Weaver et al. [184] reported 4 of 20 patients with most
clearly interhemispheric ICP gradients by using bilateral subarachnoidal pressure
catheters due to mass lesions including temporal tip contusion, internal capsule hem-
orrhage, frontoparietal subdural hematoma and temporal tip hematoma. The authors
also stated that “more than 50% of the 20 patients evaluated demonstrated significant
differential ICP’s at sometime during their period of continuous monitoring” [184].
Chambers et al. [27] monitored ICP bilaterally in 10 severe head-injured patients
(5 contusions, 2 intracerebral hematoma (ICH), and 3 subdural hematoma (SDH)). In
60
Figure 3.13: Alternating inflation of two balloons over left and right hemisphere of
baboon [167]
patients with subdural hematoma (SDH) as presented in Figure 3.14(a), the reading
showed the positive interhemispheric ICP gradients (ipsilateral-contralateral) which
mean ipsilateral side has higher ICP than contralateral side. However, the recording in
patients with contusions and ICH (Figure 3.14(b)) showed both positive and negative
interhemispheric ICP gradients. Hence, this observation might imply that the higher
ICP side would either on the ipsilatheral or contralateral side might depend on the
severity of head injury and appearance of mass lesion.
Sahuquillo et al. [144] have observed the interhemispheric supratentorial ICP gra-
dients in 50 head-injured patients. According to CT scanning criteria, each patient
was categorized into one of three groups depend on the size of mass lesion and mid-
line shift. In addition, the recorded supratentorial ICP pattern was classified into 4
patterns: Pattern I a difference of mean ICP (<3 mmHg) and global ICP amplitude
(<2 mmHg) were very small so the intracranial compartment can be considered as a
unicameral space, Pattern II, III and IV the ICP recording was showed clearly inter-
hemispheric pressure gradients with larger difference of mean ICP (>3 mmHg) and
global ICP amplitude (>2 mmHg). The summary of types of lesions according to CT
scan and ICP pattern table (Table 3.1) showed that the head-injured patients with
mass lesion size larger than 25 ml (Focal A) and with midline shift greater than 3 mm
61
(a) (b)
Figure 3.14: Difference between ipsilateral and contralateral ICP recording from pa-
tients with (a) subdural hematoma and (b) contusions or intracerebral hematoma
[27]
(Focal B) had more chance to observe the interhemispheric ICP gradients than the
patient with small mass lesion (<25 ml). In this study, the authors suggested that
the interhemispheric ICP gradient be probably due to the partial blockage of cistern
or the complete obstruction of the subarachnoid spaces.
Table 3.1: Summary of types of lesion according to CT scan and ICP pattern [144].
D’Ambrosio et al. [39] studied interhemispheric ICP gradients in 7 adult male ba-
boons with stroke. Each baboon was subjected to left focal cerebral ischemia/reperfusion
62
(I/R) injury by temporary ligation of the left internal carotid and bilateral anterior
cerebral arteries. In this study, animals with large infarct volume (>20%), the ipsi-
lateral ICP was higher than the contralateral ICP with a mean pressure gradient of
13.8 ± 4.3 mmHg. However, the contralateral ICP was higher than the ipsilateral
ICP with a mean ICP gradient of 2.6 ± 1.1 mmHg for animals with ≤ 15% infarction
volume as shown in Figure 3.15. The authors also stated that “This dichotomization
of pressure gradients based on infarct size is likely due to multiple factors including
the compliance of the intracranial tissues and the rate at which edema accumulates
in cerebral ischemia” [39].
Figure 3.15: Interhemispheric ICP gradients and infarct volumes for all animals.
Hourly interhemispheric ICP gradients (mmHg) are plotted over time. Percent ipsi-
lateral hemispheric infarct volume is noted for each animal [39].
In many clinical cases recorded in patients with unilateral mass lesions, the signif-
icant difference between ipsilateral and contralateral ICP with the higher ICP in the
lesion side were observed [54, 123, 182]. However, the existence of interhermispheric
ICP gradients and inquality distribution of ICP in the intracranial space are still con-
troversial clinical issue. For example, in the study of 15 head-injured patients with
mass lesions, Yano et al. [198] observed contradictory results with no significant inter-
hemispheric ICP gradients throughout the supratentorial space. They concluded that
“... the intracranial space, especially the supratentorial space, in one compartment
in which pressure distribution is generally uniform” [198].
63
Various factors are involved in the confliction in interhemispheric ICP gradients
observations. Basic anatomic difference between non-primate and primate model
bring about conflicting experimental findings [39]. Intracranial anatomic structure
of non-primate model are different from primate model, so the obtained results can
not be compared directly. In addition, different location of monitor placement, mea-
surement method and equipment can provide different experimental results. Many
researchers suggest that ICP monitoring should be placed in both hemispheres to
control ICP of patients with neurosurgical disorders. Possibly, the contralateral side
may has higher ICP than the injured hemisphere. Furthermore, in the study of the
relationship between interhemispheric ICP gradients, clinical signs and CT scans from
6 patients with severe head trauma, Mindermann and Gratzl [122] summarized that “
clinical signs and CT scans do not seem to predict reliably a lateralized ICP” [122]. In
order to understand the unclear interhemispheric ICP gradients various physiological
factors including CSF dynamical flow, cerebrovascular reactivity, elastic and plastic
properties of brain tissue should be focused as well [184].
3.5 Effect of Neurosurgical Disorders on Cerebral

Blood Flow
Neurosurgical disorders such as hydrocephalus and TBI which may be secondary to
intracranial hypertension can cause numerous effects on intracranial space including
brain distortion, herniation of intracranial contents, blockage of CSF flow, and espe-
cially reduced cerebral blood flow. Reduced cerebral blood flow (CBF) further results
in irreversible brain ischemia (CBF <18 ml/100 g/minute) and dysfunction of nervous
system. There are two main factors related to reduced CBF. First, acute intracranial
hypertention can cause the reduction of CBF. When ICP is increasing, CBF becomes
progressively reduced because of decreased cerebral perfusion pressure. Then, CBF
will stop eventually when ICP equals to the systolic arterial blood pressure [90]. Sec-
ond, a space-occupying lesion also can increase ICP and produce the compression and
64
distortion of brain tissue. These effects are associated with the size of mass lesion
and the rate of mass lesion expansion [91]. When the mass lesion expand beyond
the intracranial volume compensatory capacity, the ICP will increase and then CBF
will reduce due to the compression of cerebrovascular bed. The exhaustion of volume
compensatory mechanism might be resulted from the blockage of CSF flow pathway
which provide pressure communication to the posterior fossa and spinal canal [94].
The blockage of CSF flow pathway, caused by brain-stem compression produced by
mass expansion, can build up ICP and herniation of cerebral tissue [94]. The studies
of decreased global CBF and regional CBF were reported in the observation of animal
testings and clinical case reports of the patients with traumatic brain injury (TBI)
and hydrocephalus.
Langfitt et al. [93] observed 28 rhesus monkeys with marked intracranial hyper-
tension created by expansion of balloon in the right parieto-occipital subdural space.
ICP, carotid arterial blood flow, sagittal sinus, jugular vein lumbar subarachnoid and
systemic arterial pressure were recorded as shown in Figure 3.16. The authors found
that the acute expansion of the extradural balloon resulted in increased ICP and re-
duced carotid arterial blood flow due to the reduction of the cerebrovascular bed di-
ameter proximal to the sinus. Also, during the period of occlusion of common carotid
artery, produced by balloon injection, the contralateral common carotid artery was
ligated. Same group of researchers [149] conducted similar monkey’s experiment and
morphologically demonstrated the compression of both the sagittal sinus and proxi-
mal vessels due to increased ICP. Major cerebral vessel and small arteries and veins
in sulci were collapsed due to expansion of balloon or brain swelling. However, the
other small vessels were unaffected. The authors also discussed about cerebrovascular
collapse produced by brain swelling and intracranial hypertension. The thickness and
diameter of vessel as well as the intravascular and extravascular blood pressure were
the important factors for inducing or preventing cerebrovascular collapse.
The study of cerebrovascular compression, the displacement and distortion of brain
tissue in monkeys and cats, created by acute expansion of an extracerebral balloon,
65
Figure 3.16: Effect of acute expansion of the extradural balloon on carotid blood flow
(BF), jugular vein pressure (Jug), intracranial pressure (ICP), sagittal sinus pressure
(Sag), lumbar subarachnoid pressure (Lum) and systemic arterial pressure (SAP).
Arrow indicate beginning and end of injection. Time between triangles one minute.
In this and all subsequent illustrations pressures are indicated in mmHg and flow in
ml/min. [93].
were observed by Weinstein et al. [186]. They found that rapid expansion of an
extracerebral balloon lead to brain ischemia which caused by ceasing of cerebral blood
flow for both adjacent and remote to the balloon. Also, the degree of displacement
and distortion of various intracranial contents such as tentorium, inferior colliculus,
occipital lope, corpus callosum, cerebellum, cerebellar tonsils and hypothalamus were
related to the location, the function of volume and the rate of fluid-injection of the
balloon. However,“ the pathological effects of diffuse intracranial hypertension were
much less profound than those produced by rapidly expanding mass” [186] due to
space availability for volume accommodation and the elasticity of brain tissue and
intracranial contents.
Johnston and Rowan [79] measured CBF and several intracranial site including
ventricle, subdura, and cisterna magna in each cerebral hemisphere separately. El-
66
Figure 3.17: Mean right and left cerebral hemisphere blood flow levels, with increasing
mean intraventricular pressure [79].
evated ICP was produced by expansion of balloon which placed in supratentorial

subdura of the right cerebral hemisphere. They found that as ICP was progressively
increased, the CBF for both hemispheres became lower as presented in Figure 3.17.
Especially, the blood flow in the lesion hemisphere was consistently lower than that
in the contralateral side. In this study, an intercompartmental pressure gradient be-
tween supratentorial and infratentorial pressure caused by balloon expansion was also
monitored.
By gradually expanding extradural balloon in the parieto-occipital zone of the
right cerebral hemisphere in baboons, Symon et al. [163] studied the effect of supra-
tentorial space-occupying lesions on intracranial pressure, CBF, pressure perfusion
and the displacement and distortion of intracranial tissue. During gradually expand-
ing balloon, resulted in an increased ICP, the supratentorial pressure of the inflated-
balloon hemisphere is higher than the contralateral side, the interhemispheric supra-
tentorial pressure gradients become larger and reducing of total CBF. Also, cerebral
blood flow of lesion side is less than the contralateral side as shown in the comparison
67
table of blood flow (Table 3.2). The authors explained the evidence of experimental
observations resulted from the failure of autoregulatory capacity.
Table 3.2: Effect of extradural expanding lesion on cerebral blood flow [163].
In experimental brain injury induced by fluid-percussion model in animal, the

reduction of global CBF was widely observed [45, 131, 168]. In the measurement of
regional CBF after experimental TBI by inducing unilateral fluid-percussion brain
injury in rat, Yamakami and McIntosh [197] found that 15 minutes after injury,
significantly decreased global and regional CBF in all brain region as presented in
Table 3.3. At 0.5 to 2 hour after injury, the most reduction of regional CBF was
found in the injured site. CBF gradually recovered to near normal (pre-injury) level
at 4 hour after injury. In addition, similar experiment and results were performed by
Ozawa et al. [135] as illustrated in Figure 3.18.
Moreover, the marked reduction of global CBF below normal levels typically found
in patients with severe TBI [18, 19, 30, 49, 111, 132]. For regional CBF, the signifi-
cantly lower CBF within [117] and adjacent [19, 117, 132] to the mass lesion than that
global CBF virtually observed in the TBI case report. These findings also agreed with
animal models [22, 120]. In measurements of CBF in 35 severe head-injured patients,
Bouma et al. [19] found that the patients with acute intracranial hematomas had the
68
Table 3.3: Regional and total brain cerebral blood flow in rats subjected to fluid-
percussion brain injury [197].
lower CBF on the ipsilateral hemisphere than the contralateral side. The most severe
reduction was found in the the parietal and temporal region where the hematomas
commonly observed as presented in Figure 3.19. The changes of regional CBF under
various pathophysiological conditions caused by subarachnoid hemorrahage (SAH) in
patients with ruptures intracranial aneurysms were studied by Ishii [75]. The author
found that most patients with severe diffuse vasospasm (a constriction of a vascular
lumen), or with large intracerebral hematoma, or with ventricular dilation (hydro-
cephalus) showed marked reduction of global and regional CBF. Further reduction of
regional CBF in hematoma and vasospasm region when accompanied by venticular
dilation was also observed. The author concluded that the degree of reduction in
CBF correlated well with the clinical severity of neurological deficits and the relief
of hematoma and ventricular dilation might improve CBF and consequently clinical
outcomes [75].
In clinical case report of CBF in patients with normal pressure hydrocephalus
(NPH) by using various measurement techniques, most researchers found significantly
reduced global CBF in patients with NPH compared to normal individuals [21, 60, 67,
68, 72, 86, 88, 116, 118, 175]. Also, the reduction of regional CBF was reported with
the most profound reduction in frontal region [60, 85, 107, 119, 134]. For cerebral
69
Figure 3.18: Changes in regional cerebral blood flow (rCBF) in the visual (A), parietal
(B), sensorimotor (C), and frontal cortices (D) of the injured and the contralateral
sides. rCBF decreased remarkably in the injured side following insult for 4 hours.
After 24 hours, rCBF recovered except in the visual cortex. rCBF also decreased
slightly in the non-injured side. Modified from Ozawa et al. [135].
blood flow improvement after surgical intervention, shunting can increase in CBF
in many studies [21, 67, 68, 85, 86, 118, 119, 175]. However, in the study of 43
patients with communicating hydrocephalus secondary to subarachnoid hemorrhage
(SAH), Hayashi et al. [72] found that shunting cannot improve CBF in the patients
with mean CBF less than 25 ml/100 g/min. Moreover, no significant improvement
of CBF after shunting was observed in some case reports [88, 109, 116, 127]. Because
NPH was related to ventricular dilation, the relationship between decreased CBF and
ventricular size was controversial issue [134]. Some observations found the correlation
between reduction in CBF and size of ventricular dilation [67, 68, 72, 175]. However,
no correlation was found in some reports [109, 116, 127]
To maintain well neurological function, various factors related to cerebral vascula-
70
Figure 3.19: Graph showing ipsilateral and contralateral regional cerebral blood flow
(CBF) values in measured areas in patients with intracranial hematomas. Regional
CBF in parietal and temporal lobes was significantly lower on the side ipsilateral to
the hematoma. Error bars indicate standard error of the mean. FR = frontal lobes;
PA = parietal lobes; TE = temporal lobes; OCC = occipital lobes; BASG = basal
ganglia; CBL = cerebellum; BS = brain stem [19].
ture and blood flow such as ICP, cerebral perfusion pressure (CPP), arterial distensi-
bility and autoregulation should be controlled in normal level otherwise cerebral blood
flow would be reduced and further intracranial contents would be distorted. Cere-
brovascular collapse (vasospasm) was one of the most common effect to morbidity and
mortality of the patients with TBI secondary to an expansion of mass lesion. This
collapse occured when the intracranial tension beyond its limitation which caused the
reduction of cerebral blood flow and further resulted in cerebral ischemia and infarc-
tion. A wide variation of anatomical lesions such as type, size and location of lesion
is the factor that effect cerebral vasculature and blood flow [19, 111]. The studies of
regional cerebral blood flow found that the cerebral blood flow of the injured side and
adjacent to the lesion was typically lower than the contralateral hemisphere. Hence,
these findings enhance that these vulnerable regions should be particularly considered
in the treatment of head-injured patients.
71
Chapter 4
Review of Windkessel Model and

the Model of Intracranial System
In this chapter, the model of intracranial system based on Windkessel mechanism

will be reviewed which is divided into two sections. First, to describe the blood flow
and pressure through the major arterial system and electrical element provided by
Windkessel model will be reviewed. Second, the intracranial system model focusing
on the study of intracranial behavior based on two major types of model i.e. complex
compartment and pulsatility models.
4.1 Review of Windkessel Model

A lumped parameter or one-dimensional model called Windkessel model was well-
known tool to explain the hemodynamics through arterial system by using electrical
element. The characteristic function of artery can be represented by the electrical
element in the simple RLC circuit. For example, the ability to store the electric
energy of capacitor (C) represents the ability to store the volume of blood by arterial
elasticity or compliance. Also, the ability to reduce the electric energy of resistor (R)
represents the resistance of blood flow due to the change in vascular lumen or the
length of artery.
Windkessel model was first introduced as mathematical model by Otto Frank [53]
72
in 1899. Frank formulated the hemodynamics of the arterial system consisting of an
arterial compliance and peripheral resistance called two-element Windkessel model
which represented by electric capacitor (C) and resistor (R) respectively as presented
in Figure 4.1(a). In the Frank’s Windkessel model, the entire artery was modeled as an
elastic chamber with constant arterial compliance [157] where the arterial compliance
was the ratio of the total arterial volume change over the arterial pressure change.
(a)
(b)
(c)
Figure 4.1: (a) Two-element Windkessel model, (b) Three-element Windkessel model
and (c) Four-element Windkessel model presented in hydraulic and electrical circuits
[189].
The developments in computing capabilities and measurement of aortic flow shown

that two-element Windkessel model was unable to produce realistic systemic input
impedance and aortic pressure waveform when aortic flow was used as input [156, 157].
This result led to the clearly difference between the calculation of input impedance and
the measured one in high frequency range as shown in Figure 4.2 [189]. This issue
came up with the addition of aortic characteristic impedance to the two-element
Windkessel model. Westerhof et al. [188, 191] modified the Frank’s Windkessel
model by adding the characteristic impedance (Zc ) connected in series with two-
element Windkessel known as the three-element Windkessel model as presented in
Figure 4.1(b). The characteristic impedance was typically replaced by resistor for the
73
modeling of large artery such as aorta. A relationship between the lumped model and
wave travel was represented as characteristic impedance equals to wave speed times
blood density divided by cross-sectional area [189].
In 2003, Wang et al. [183] proposed the arterial model in time domain by fit-
ting two-element Windkessel model to determine peripheral resistance and arterial
compliance. They compared the calculated aortic pressure and flow obtained from
Windkessel model with the measured data derived from anesthetized dogs. When
the calculated pressure was subtracted from the measured pressure, they found that
the difference (excess pressure) was proportional to aortic flow. Thus, the differences
in shape between aortic pressure and flow waveform can be predicted realistically
by the addition of resistance to two-element Windkessel model. This observation
ensured that it was necessary to add the characteristic impedance of aorta as the
third element to describe pressure and flow though the entire cardiac cycle, in time
domain [189]. In the studies of the three-element Windkessel model, Fogliardi et al.
[51] compared the constant compliance and pressure-dependent compliance. Even in
the presence of better data fit obtained from pressure-dependent compliance, they
concluded that “the nonlinear three-element Windkessel cannot be preferred over the
traditional linear version of this model” [51]. The three-element Windkessel model
was most widely accepted for systemic circulation modeling because it was able to
mimic pressure and flow waveform and fitted well with experimental results [159].
However, the realistic pressure and flow waveform predicted by three-element
Windkessel model would be provided when the modeled parameter of capacitor (C)
and characteristic impedance (Zc ) differed from the actual physiological properties
of artery where C and Zc obtained from the standard estimation method tended
to be overestimated and underestimated respectively for the time domain fit [159].
Moreover, as shown in Figure 4.2, the error of aortic input impedance predicted by
three-element Windkessel model in low frequency range led to the additional of in-
ertance (L) in parallel with the characteristic impedance (Zc ) as a fourth element
[189]. Burattini and Gnudi [23] suggested this fourth element was an inertance which
74
Figure 4.2: The measured aortic input impedance and impedance predicted by two-
element,three-element and four-element Windkessel [189].
equaled to the addition of all inertances (total arterial inertance) in the whole arterial
system as presented Figure in 4.1(c). The additional of inertance (L) was able to re-
duce the errors in the low frequency range and allowed the characteristic impedance
(Zc ) to handle with medium and high frequency range [159]. The sample simulation
results of three- and four-element Windkessel model were shown in Figure 4.3.
Nowadays, the application of Windkessel model was still used in various aspects
to explain physiological phenomena. For example, Wesseling et al. [187] computed
the aortic flow from the pressure by using nonlinear three-element Winkessel model.
Stergiopulos et al. [156, 157, 159] used Windkessel model for estimation of total
arterial compliance which played an important role in the determination of systolic
and diastolic aortic pressure [158, 160]. Furthermore, Windkessel model was used in
the studies of heart assist device [57], heart valve [29, 146] and ventricular afterload
[87, 95]. However, Windkessel model was unable to be used in the studies of wave
travel and the reflections of wave which was the limitation of the lumped model [189].
75
Figure 4.3: Top: schematics of 3- and 4-element Windkessel (WK) models presented
in electrical form. Rc and Rp , characteristic and peripheral resistance; C, total arterial
compliance; L, inertance. Middle: aortic flow measured in dog. Bottom: measured
and model derived aortic pressure [161].
4.2 Review of the Model of Intracranial System

The model of intracranial system can be categorized into two major types of model.
First, complex compartment model is the lumped parameter model which is based on
the steady state approach to study the behavior of intracranial system represented by
electrical elements. Second, pulsatility model is the dynamical model to describe the
interaction of intracranial contents during cardiac cycle which focus on the effect of
pulsatile nature of blood flow on the variation of intracranial dynamics and properties.
Karni et al. [80] considered the Monro-Kellie doctrine as rigid compartment and
subdivided into seven compartments as shown in Figure 4.4, then solved for quasi-
steady state flow. The resistance flow due to a particular vessel type was lumped at
76
the outflow of its compartment. Also, the change in volume of each compartment was
represented as an overall compartment property. The compliance was the increasing
in volume of one compartments which was equal to the volume displaced from the
neighboring compartments.
Figure 4.4: Lumped-parameter seven compartmental model of the cerebrovascular

system. [ ] represents pressure in mmHg, ( ) represents flow in ml/min., and <>
represents volume in ml [80].
The governing equations for this lumped-parameter compartmental model of cere-

brovascular fluid system was the continuity equations for the balance of mass
dP
C + ZP = Q (4.1)
dt
where P was the pressure column vector, Z was the symmetric fluidity (inverse of
resistivity) matrix, C was the symmetric compliance matrix and Q was the flux
column vector
For the steady-state, the equation (4.1) of constant pressure was reduced to
ZP ∗ = Q∗
77
where P ∗ and Q∗ indicated the average, time-independent P and Q respectively.
For the non steady-state, Z was determined from the steady state. The equation
(4.1) was rearranged into
dP (t)
C = Q(t) − ZP (t)
dt
where C and Z were constant

For the quasi steady state, the compliance term was considered to be negligible,
C dP
dt
= 0. Then, equation (4.1) became
ZP (t) = Q(t)
However, this model did not relate events to their spatial localization which was
the limitation of a compartmental approach.
Czosnyka et al. [35] studied the time-dependent interactions between pressure,
flow, and volume of cerebral blood and CSF through the hydrodynamic equivalent of
the model which contained two major flow pathways as presented in Figure 4.5.
As shown in Figure 4.6, the equivalent electrical circuit corresponded directly
to the hydrodynamic structure (Figure 4.5) and was described by set of non-linear
differential equations:
dPi 1 ABP − Pa Pi − Pss Pv − Pss

= ( − − )
dt Ci Ra RCSF Rb
dPv dPi 1 Pa − Pv Pv − Pss
= + ( − )
dt dt Cv CV R Rb
dPa dPi 1 ABP − Pa Pa − Pv
= + ( − − If )
dt dt Ca Ra CV R
This model simulated changes in arterial blood inflow and storage, arterial and cap-
illary blood flow controlled by cerebral autoregulation, venous blood storage and
venous outflow modulated by changes in ICP and CSF storage and reabsorption.
Both autoregulating and non-autoregulating system were simulated and compared.
78
Figure 4.5: Hydrodynamic equivalent of the model, comprising pathways of CBF and
the CSF circulation.A rigid skull is represented by the outer box, with a compensatory
reserve Ci associated with the compliant dural sac within the lumbar channel [35].
Figure 4.6: Electrical circuit equivalent to the hydrodynamic model [35].
Ursino and Lodi [171] constructed lumped-compartmental model to describe the

hemodynamics of the arterial-arteriole cerebrovascular bed, CSF production and re-
absorption processes, the nonlinear pressure-volume relationship of the craniospinal
compartment, and a Starling resistor mechanism for cerebral veins as shown in Fig-
ure 4.7. The interaction between ICP,cerebral blood volume and autoregulation were
simulated where resistance and compliance were actively adjusted by the action of
cerebrovascular control mechanism. Also, three different related phenomena were
analyzed: the generation of plateau waves, the effect of acute arterial hypertension
79
on ICP, and the role of cerebral hemodynamics during pressure-volume index (PVI)
tests. This model was able to reproduce various clinical results, such as the pattern
of ICP pulsatile change, the origin of pathological self-sustained ICP wave and the
different ICP responses to fluid injection into or fluid removal from the craniospinal
space. The authors suggested that PVI testing used to extract information not only
1
on intracranial compliance (Cic = kE Pic
, where kE was elastance coefficient of the
craniospinal system) and CSF circulation, but also on the status of mechanisms con-
trolling cerebral blood flow. ICP pulsatility was affected by large intracranial arteries
and venous circulation. However, this model was unable to be used to study ICP
pulsating wave synchronous with cardiac beat.
Figure 4.7: Electric analog (A) and corresponding mechanical analog (B) of intracra-
nial dynamics according to present model. Cerebral blood flow (CBF, q) enters skull
at pressure approximately equal to systemic arterial pressure (Pa ). Arterial-arteriolar
cerebrovascular bed consists of a regulated capacity (Ca), which stores a certain
amount of blood volume, and a regulated resistance (Ra ), which accounts for pres-
sure drop to capillary pressure (Pc ). At capillary level, cerebrospinal fluid (CSF) is
produced through a CSF formation resistance (Rf ). CBF then passes through venous
cerebrovascular bed, mimicked as series arrangement of proximal venous resistance
(Rpv ) and resistance of collapsing lateral lacunae and bridge veins (Rdv ). Model as-
sumes that, because of collapse of last section, cerebral venous pressure (Pv ) is always
approximately equal to intracranial pressure (Pic ). Finally, CSF is reabsorbed at ve-
nous sinus pressure (Pvs ) through CSF outflow resistance (Ro ). Intracranial pressure
is determined by amount of volume stored in nonlinear intracranial compliance (Cic ).
This volume results from a balance between CSF inflow (qf ), CSF outflow (qo ), blood
volume changes in arterial capacity, and mock CSF injection rate (Ii). Modified from
Ursino and Lodi [171].
80
Lakin et al. [89] introduced 16-compartment whole-body model for intracranial
pressure as illustrated in Figure 4.8. This model developed the Monro-Kellie doc-
trine by adding a spinal-subarachnoid CSF compartment bridged intracranial and
extracranial physiology allowing the buffering effects of intracranial pressure fluctu-
ations by the spinal theca. The physical constituents in subunits were blood, CSF,
and tissue and interstitial fluid. The body first was divided into intracranial and ex-
tracranial compartments. The extracranial compartment was subdivided into a lower
region (below the pelvis) and a central region (between the pelvis and clavicles). The
vascular system in each compartment was divided into artery, capillary, and vein.
In order to maintain the production of CSF by autoregulation, the choroid plexus
was placed in a separate compartment. Each compartment in the model was defined
by a lumped, i.e. time-dependent function. Volume interactions took place at the
interfaces between compartment through input and output bulk flow or through bulk
membrane deformations across adjacent compartment. This model also included the
interaction between the external environment through flows representing the inges-
tion and elimination of fluid via the central body, as well as the transfer of fluid
between capillaries and tissue by filtration defined by the Starling-Landis equation,
and lymphatic system.
However, previous complex compartment model did not cooperate the pulsatile
nature of arterial flow. This arterial pulsatile flow related to interaction of intracranial
contents that significantly described Windkessel mechanism within rigid cranium.
In 2001, Egnor et al. [46] applied mathematical model to describe oscillation of
blood and CSF, represented by phasors on the complex plane, and analyze of pul-
satile motion within the cranium which was the first CSF pulsatile dynamics model as
shown in Figure 4.9(a). The authors performed the simulation of intracranial pulsa-
tions in case of normal intracranial dynamic (resonance) and diminished intracranial
compliance (elevated ICP) where their mathematics governing the oscillations of the
CSF space was
81
Figure 4.8: The 16 compartment whole-body model. A filled arrow indicates a one-
way flow and a hollow arrow indicates a pressure dependent resistance. Compartment
labels are enclosed in parentheses with the spatially-averaged mean pressures in square
brackets. The thick line indicates the cranial wall [89].
F0 sin ωt = mCSF ẍCSF (t) + RẋCSF (t) + kE xCSF (t)
The oscillations was able to be simulated through a series RLC electrical circuit
as presented in Figure 4.9(b), based on the analogy between mechanical and electrical
oscillation summarized in the Table 4.1.
Also, the pulsatile cerebral blood flow and the Windkessel effect had been simu-
lated through two degree of freedom mass spring system as presented in Figure 4.10(a)
and equivalent RLC circuit as presented in Figure 4.10(b). This motion of blood and
82
(a) (b)
Figure 4.9: (a) A model of CSF pulsation with a single degree of freedom.The CSF
pulsation, which is the mass of CSF (mCSF ) displaced by the maximum expansion
of the vessel is represented by sphere. The instantaneous displacement of the CSF
pulsation is represented by xCSF (t). The external force of the vascular pulsation is
assumed to be sinusoidal, and given by F0 sin ωt. The other forces acting on the
pulsating CSF include a resistance force RẋCSF (t) and an elastic force kE xCSF (t),
representing the elasticity of the walls of the space. The net force acting on the CSF
pulsation is the inertial force mCSF ẍCSF (t). (b) Equivalent RLC electrical circuit for
CSF pulsation. Modified from Egnor et al. [46].
Table 4.1: Summary of the equivalent between pulsation of CSF and oscillations of
electricity in an AC electrical circuit [46]
CSF were governed by
mblood ẍblood (t) + (kblood + kCSF )xCSF (t) + kCSF xCSF (t) = Fheart sin ωt
mblood ẍblood (t) + kCSF (xCSF (t) − xblood (t)) = 0
This model was able to be concluded that Windkessel mechanism would be effec-
tive if CSF space was oscillating in or near resonance which depended on the specific
value of inertia, elasticity and heart rate. However, Tenti et al. [166] countered Egnor
et al.’s conclusion that “the synchrony of arterial and CSF pulsations is not due to
83
(a) (b)
Figure 4.10: (a) The intracranial Windkessel effect, which is the dissipation of arterial
pulsations into the CSF, can be modeled by representing the intracranial blood and
CSF as two separate masses connected by springs representing the elastic elements
of vasculature and craniospinal contents. (b) The electical analog to a mechanical
absorber is a wave trap, which is main RLC circuit representing the capillary blood
and a smaller parallel RLC circuit representing the CSF. Modified from Egnor et al.
[46].
resonance” [166].
In 2002, Egnor et al. [47] extended their previous model of pulsation by focusing
on communicating hydrocephalus. This model was still based on the equivalent pul-
satile motion of blood and CSF in an electrical circuit as shown in Figure 4.11. The
model simulated dynamic of normal intracranial pulsatile and the salient features
of communicating hydrocephalus such as ventricular dilation, intracranial pressure
waves, narrowing of the CSF-vanous pressure gradient, diminished cerebral blood
flow, elevated resistive index and malabsorption of CSF. From this pulsation model’s
result, “malabsorption of CSF is the result, not the cause, of communicating hydro-
cephalus” [47] which differed from traditional theories. The author also concluded
that “communicating hydrocephalus is a disorder of intracranial pulsations” [47].
However, due to a simple sinusoidal waveform was used as initial forcing func-
tion instead of cardiac output function in Egnor et al.’s model [46, 47], the realistic
response in term of waveform and timing was distorted.
Linninger et al. [101] proposed the fluid-structure interaction model to predict
pulsatile flow and pressures of CSF through the brain’s ventricles based on the first
principles of fluid mechanics with linear elasticity. The goal of this model was to
84
Figure 4.11: The intracranial filter circuit and the windkessel mechanism. Intracranial
blood vessels and CSF spaces are arranged as parallel pathways branching from a
series flow. Normal intracranial blood flow and CSF dynamics can be represented by
a series-parallel array of blood vessels and CSF spaces. Modified from Egnor et al.
[47].
simulate ICP and CSF velocity during normal and hydrocephalus condition for com-
parison with clinical and MRI data. The first principles model for pulsatile CSF
flow related three dynamically interacting system: the cerebral vascular system, the
CSF-filled ventricular and subarachnoid space, and the brain parenchyma.
As presented in Figure 4.12(a), arterial blood flowed into the expandable choroid
plexus caused it to expand and acted like a pump to drive the pulsatile CSF cir-
culation. CSF transmitted the lateral ventricles (V1 and V2) to the third ventricle
(V3) via the foramen of Monro (FM), the fourth ventricle (V4) via the aqueduct of
Sylvius (AS), reached the subarachnoid space (SAS) via foramen of Luschke (FL),
and then CSF was reabsorbed into the sagittal sinus. However, no absorption of CSF
by parenchyma was assumed.
The governing equation of discretized model of CSF flow (Figure 4.12(b)) was
85
(a) (b)
Figure 4.12: (a) Schematic of CSF pathways, the vascular system and brain
parenchyma. (b) The discretized model of CSF flow induced by choroid expansion
a(t). Modified from Linninger et al. [101].
cyclic motion of choroid plexus followed the cardiac cycle by forcing function
π 1 π
a(t) = α(1.3 + sin(ωt − ) − cos(2ωt − ))
2 2 2
The equation for the acceleration of the elastic tissue
(ρw Ai δ)ÿi(t) + kd ẏi (t) + ke yi (t) − Ai [Pi (t) − P0 (t)] = 0, i ∈ {V 1 − V 4, SAS}
where k was linear spring elasticity

The continuity of CSF flow in the ventricles
∂{Ai[hi + a(t) + yi(t)]}

= qf,i − qi , i ∈ {V 1 − V 4}
∂t
The elastic foramina was governed by the axial momentum equation
∂vi ∂vi ∂Pi (t) 8µ

ρ[ + vi ]+ = −Fi = − 2 vi , i ∈ {F M, AS, F L}
∂t ∂z ∂z ri
For subarachnoid space (SAS), the continuity equation was
∂{Ai[hi + yi (t)]}
= qj−1 − qe,j , j ∈ {SAS}
∂t
86
and diffusive reabsorbtion of CSF qe,j = κ[pj (t) − p0 (t)] where κ was reabsoption
constant.
Also, 2-D computational fluid dynamic (CFD) simulations and a set of simple
hydraulic experiment to explain the expansion of lateral ventricles were included in
this paper. The model clarified the role of ICP rise during the formation of com-
munication hydrocephalus. “The rise is not a cause of hydrocephalus, but an effect
of increased fluid due to lowered absorption of CSF” [101]. This model had been
modified in Masoumi et al.’s model [115] by considering CSF pulsatile formation as
the principal driver of CSF motion instead of the choroid plexus expansion.
In 2009, Linninger et al. [102] constructed the multi-compartment mathematical
model to simulate the intracranial dynamics for normal and pathological conditions,
i.e. communicating hydrocephalus. MRI-data and the predicted results were com-
pared. As presented in Figure 4.13, this model was designed for predicting the force
interaction of three main elements; 1) blood flow through cerebral vasculature which
was divided into arteries (Ar), arterioles (Al), capillaries (Cp), veinules (V l), veins
(V ) and venous sinus (vSinus), 2) the CSF system was included the lateral (Lv), third
(3V ) and fourth (4V ) ventricles, cerebral subarachnoid space (SAS) and the spinal
canal, 3) the left and right brain parenchyma were treated as a bi-phatic medium
composed of extracellular fluid and a solid cell matrix.
Flow through each compartment of cerebral vasculature and CSF system were
governed by three principle equations:
The continuity equation
∂A
l = fin − fout
∂t
where l was the length of compartment, A was a cross-sectional area, fin and fout
were the volumetric flow rate in and out of compartment, respectively.
The axial momentum equation governed by Hagen-Poiseuille law
Pin − P = ∆P = afin
87
Figure 4.13: The Linninger et al.’s multi-compartment model with one arterial pres-
sure in the carotid Pinit as input signal and the venous pressure in the jugular vein is
Pout . Modified from Linninger et al. [102].
where a was flow resistance (a = 8πµl/A2 ), µ was fluid viscosity and Pin and P were
the upstream and current compartment pressure, respectively.
Compartment expansion or compression
A − A0
Plumen − Pbrain = E( )
A0
where Plumen -Pbrain was the pressure difference between the vessel lumen and the bi-
phasic brain compartment, E was vessel’s elastance and A − A0 was the change in a
vessels cross-sectional area.
This model also strictly satisfied the Monro-Kellie doctrine for each brain hemi-
sphere where total volume of all parenchyma, blood and CSF compartment remained
constant. The predicted results from this model were in well agreement with various
aspect of clinical data such as pulsatility index and pressure-volume index (PVI).
88
However, the inertia term had been neglected for convenience and avoiding wave re-
flection problem. The authors suggested that the inertia term should be included,
especially for large arteries.
89
Chapter 5
Mathematical Model
The goal of this mathematical model is to study hemodynamics of major arteries

and intracranial system based on Windkessel mechanism by simulating the human
cardiovascular system which is the blood flow from heart through the network of
elastic blood vessel. In this mathematical model, ascending aorta is considered as
the first blood vessel that pulsatile blood flow through. Then assume that 30% of
blood supply to upper limbs and 70% to lower limbs. For hemodynamics of lower
limbs, blood after passing ascending aorta then flow through three set of arteries to
femoral artery including descending aorta, common iliac artery, external iliac artery
successively before reaching femoral artery. For upper limbs and cerebral blood flow,
blood after passing ascending aorta then flow to left and right side of upper body
including left and right hands via subclavian artery, and left and right hemispheres
via common carotid artery and internal carotid artery.
Intermittently pumping action of heart generates pulsatile blood flow throughout
the body in the time interval called cardiac output. As shown in Figure 5.1, cardiac
output (Qin ) is simulated by the combination of three sets of sinusoidal wave which
acted as the input of the model:
Qin = 350(sin(ωt))11 + 150(sin(ωt + 0.11))11 + 20(sin(ωt + 0.45))5
where ω is the heart rate which is randomly created between range of ω = 2.3π − 2.4π
90
radian/second.
Initial Cardiac Output

350
Cardiac Output (ml/sec.)
300
250
200
150
100
50
0
1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7
Time (sec.)
Figure 5.1: The initial pulse cardiac output, generated by heart, is the combination
of three sets of sinusoidal wave with random heart rate.
To compare the dynamic response for different intracranial conditions, three cases
of simulation are considered: (1) normal condition, (2) the case of neurosurgical
disorder and (3) the case of treatment by using a medical balloon. The basis for
Windkessel mechanism of major arteries and intracranial system will be described by
the following equations:
5.1 Continuity Equation

During systole, cardiac contraction discharges entire stroke volume of blood into the
arterial system. About 50% of blood flow forward to the peripheral circulation while
the remainder is stored within the arterial system [16] which provided by elastic
expansion of arterial wall (section 5.2) and peripheral resistance (section 5.3 and
5.4). During diastole, this elastic artery passively recoils and forces the storage volume
into peripheral circulation [16]. To analyze the flowing fluid within vessel, the basic
concept of Windkessel mechanism is described by the principle of conservation of
mass called the continuity equation. The rate of volumetric flow into blood vessel
91
Qin is equal to the rate of stored flow Qstored plus the rate of flow out of blood vessel
Qout , which is given by
Qin = Qstored + Qout

dVvessel dxvessel
Qin − Qout = Qstored = = Avessel
dt dt
Qin − Qout = π(x0,vessel + ∆xvessel )2 ∆ẋvessel (5.1)
where x0,vessel is initial radius of blood vessel and ∆xvessel is radius displacement of
blood vessel.
5.2 The Equation for the Acceleration of the Elas-

tic Blood Vessel
∆xvessel kvessel − kvessel ∆xvessel
x0,vessel Pblood mblood mblood
Pblood Avessel
lvessel
(a) (b) (c)
Figure 5.2: (a) Cross-sectional area of blood vessel (b) Elastic blood vessel (c) Free
body diagram of blood with pressure and elastic forces exerting on
To describe the buffering function of Windkessel mechanism which accommodates

the extra blood during systole and drive blood out during diastole, the pulsatile blood
flow through the expansion and contraction of elastic vascular wall are represented
by two type of forces act on the pulsatile blood. As illustrated in Figure 5.2, pressure
force exerted by the blood (Fblood = Pblood Avessel = Pblood π(x0,vessel +∆xvessel )2 ) and the
elastic force representing elasticity of the blood vessel based on Hooke’s law (Fspring =
92
kvessel ∆xvessel ) are equal to total force exerted on blood which is the force of inertia
mblood ablood = ρblood Vvessel ∆ẍvessel .
The motion of arterial pulsation is represented by the equation
Fblood + Fspring = mblood ablood

Pblood Avessel − kvessel ∆xvessel = ρblood Vvessel ablood
Pblood π(x0,vessel + ∆xvessel )2 − kvessel ∆xvessel = ρblood Vvessel ∆ẍvessel (5.2)
where Vvessel = π(x0,vessel + ∆xvessel )2 lvessel , Pblood is blood pressure, kvessel is blood
vessel’s stiffness, ρblood is the density of blood and lvessel is blood vessel’s length
Another significant parameter describing Windkessel mechanism for filtering pul-
satile inflow into non-pulsatile outflow is the peripheral resistance which can be rep-
resented by two different equations:
5.3 Hagen-Poiseuille’s Law
∆xvessel
x0,vessel
Qin Qout
Pin Pout
lvessel
Figure 5.3: Hagen-Poiseuille’s law represent the blood flow resistance caused by the
length of artery in term of the pressure drop between inflow and outflow.
Hagen-Poiseuille’s law describe the pressure drop between inflow and outflow in
a long narrow tube with assumption of laminar and incompressible flow as shown in
93
Figure 5.3. This fluid dynamics’s law represents the blood flow resistance due to the
length of artery which is given by
4
(Pblood − Pout )πrvessel
Qout =
8µblood lvessel
8µblood lvessel Qout
Pblood = Pout + (5.3)
π(x0,vessel + ∆xvessel )4
combining equation (5.1) and (5.3)
8µblood lvessel (Qin − π(x0,vessel + ∆xvessel )2 ∆ẋvessel )

π(x0,vessel + ∆xvessel )4
where µblood is dynamic viscosity of blood, Qout is volumetric flow rate of blood
outflow, and Pout is pressure in blood vessel’s outlet.
The continuity equation (equation 5.1) combine with the equation for the acceler-
ation of elastic blood vessel (equation 5.2) and Hagen-Poiseuille’s law (equation 5.3)
are applied for all extracranial arteries and intracranial capillaries and veins.
5.4 The Relationship of Flow and Pressure in Ori-

fice
∆xvessel
Qin x0,vessel xout Qout
Pblood Pout
Figure 5.4: The relationship of flow and pressure in orifice represented the peripheral
resistance of blood flow due to the change of lumen size.
94
As shown in Figure 5.4, the mechanical device called “orifice” represented the
peripheral resistance of blood flow. Orifice is used for measuring the fluid flow rate
through the differences in pressure from the upstream side to the downstream of a
partially obstructed pipe which based on the Bernoulli’s principle to describe the
relationship between the pressure and velocity of fluid. This equation describes blood
flow from large artery to smaller with resistance due to the change of vascular lumen
diameter which is represented by
p
Qout = α Pblood − Pout (5.5)
q q
2 2 v πx2out
where α = q Aout = 2 ,
ρblood A
1−( A out )2 ρblood u
πx2
u
vessel
out
u
t1−
π(x0,vessel +∆xvessel)2
where xout is radius of blood vessel’s outlet

combining equation (5.1) and (5.5)
(Qin − π(x0,vessel + ∆xvessel )2 ∆ẋvessel )2

α2
The continuity equation (equation 5.1), the equation for the acceleration of elas-
tic blood vessel (equation 5.2), and the relationship of flow and pressure in orifice
(equation 5.5) are applied for intracranial arteries.
5.5 Blood Flow through Cranium

For intracranial system, the cerebral blood flow from artery to capillaries and vein
through intracranial cavity is presented in Figure 5.5. For the brain protection,
intracranial system has a unique characteristic which is different from any other part
of the body, i.e. enclosed within a fixed volume of rigid cranium based on Monro-
Kellie doctrine. Moreover, the pressure inside the cranium called intracranial pressure
(PICP ) which exerts against the displacement of arterial and venous wall is additional
force in intracranial system (Figure 5.5(a)). Hence, equation (5.2) has been modified
into
95
(Part − PICP )π(x0,art + ∆xart)2 − keq,art ∆xart = ρblood Vart ∆ẍart (5.7)
kart kCSF
where keq,art = kart +kCSF
for arterial blood
(Pcap )π(x0,cap + ∆xcap)2 − kcap ∆xcap = ρblood Vcap ∆ẍcap (5.8)
for capillary blood
(Pvein − PICP )π(x0,vein + ∆xvein )2 − keq,vein ∆xvein = ρblood Vvein ∆ẍvein (5.9)
kvein kCSF
where keq,vein = kvein +kCSF
for venous blood
where Part ,Pcap ,Pvein and PICP are arterial, capillaries, venous blood pressure and
intracranial pressure, respectively.
PICP
−PICP Aart − keq ∆xart − kcap∆xcap

∆xart
∆xvein
Qin x0,art xout x0,vein
mblood mblood
Part Pvein
PartAart Pcap Acap
(a) (b) (c)
Figure 5.5: (a) There are three forces exerting arterial and venous blood. (b) Blood
flow through artery, capillaries and vein in the enclosed cranium space. (c) There are
only two forces exerting on capillary blood.
To maintain continuous cerebral blood flow and to ensure pulseless flow through
cerebral capillaries, the additional pulsation absorber is required which provided by
96
kCSF
keq
kart
Figure 5.6: Combination of blood vessel’s stiffness (kart and kvein ) and stiffness of
elastic intracranial contents (kCSF ) in series result in less equivalent stiffness (keq ) or
more intracranial compliance of the CSF system
the elastic properties of other intra- and extracranial contents (i.e. brain tissue,
intracranial subarachnoid space, and spinal thecal sac). As shown in Figure 5.6
the combination of blood vessel’s stiffness (kart and kvein ) and stiffness of elastic
intracranial contents (kCSF ) in series result in less equivalent stiffness (keq ) which
provide more intracranial compliance to the CSF system.
5.6 Pressure-Volume Relationship

Monro-Kellie doctrine states that the total volume (Vtotal ) of cranium is constant.
Any increase in the volume of intracranial content (e.g. arterial blood Vart , venous
blood Vvein , brain or CSF) will bring about the decrease in the volume of another.
However, only interaction of three intracranial contents (arterial blood, venous blood
and CSF) are considered in this model because brain expansion is typically very
small in the healthy individuals (about 2% of the arterial expansion [66]). During
the systolic expansion of cerebral arteries, ICP (PICP ) rises with the expulsion of ex-
traventricular CSF downward through foramen magnum to contractible spinal theca
located in lumber space. This mechanism allows the pulsatile energy from intracranial
space to absorb in spinal region because spinal subarachnoid space has higher com-
pliance during systole (and vice versa during diastole) [133]. During diastole, elastic
arteries passively recoil with ICP falls and CSF flow back into intracranial space. In
97
this model, this pressure-volume compensatory mechanism between intracranial and
spinal region is imitated by the displacement behavior of piston in cylinder filled with
compressible fluid. Thus, the absolute ICP and residual volume (Vtotal − Vart − Vvein )
in intracranial space are inversely proportioned along exponential curve which repre-
sented by
PV = constant
PICP (Vtotal − Vart − Vvein ) = constantICP (5.10)
5.7 Interhemispheric Pressure Gradients

Left Hemisphere Right Hemisphere
vein
vein
PICP,L PICP,R
artery
artery
(a)
−PICP,L Amid −PICP,R Amid − kmid ∆xmid
(b)
Figure 5.7: (a) Intracranial space is divided into left and right hemispheres with
midline displacement to describe the transmission of pressure and volume between
left and right cerebral hemispheres. (b) Free body diagram of midline displacement.
98
Generally, cranium is considered as a single rigid compartment with uniform distri-
bution of ICP over entire intracranial space [39]. However, differences in ICP between
two hemispheres (interhemispheric ICP gradients) were observed in many experimen-
tal studies in animal and clinical case reports in patients with head injury. In this
mathematical model, the intracranial space is divided into left and right hemispheres
as presented in Figure 5.7. A movable separator is constructed to represent the center
line or midline in order to describe the transmission of pressure and volume between
left and right cerebral hemispheres.
The equation for midline displacement is given by
(PICP,L − PICP,R )Amid − kmid ∆xmid = mmid ∆ẍmid (5.11)
Thus, the pressure-volume relationship within the rigid cranium and between left
and right cerebral hemisphere become
PICP,L ((VL + Amid ∆xmid ) − Vart,L − Vvein,L ) = PICP,R ((VR − Amid ∆xmid ) − Vart,R − Vvein,R )
= constant (5.12)
where PICP,L and PICP,R are left and right hemisphere intracranial pressure, Amid
is the cross-sectional area of midline, kmid is midline tissue’s stiffness, mmid is the
mass of midline, ∆xmid is the displacement of midline, VL and VR are left and right
hemispheric volume, Vart,L and Vart,R are left and right arterial blood volume, and
Vvein,L and Vvein,R are left and right venous blood volume.
5.8 Interhemispheric Asymmetry of Cerebral Blood

Flow
A steady cerebral blood supply is required to provide a normal function of central
nervous system. However, most of severe intracranial disorders are associated with
decreased global and regional cerebral blood flow. One major cause of cerebral blood
flow reduction is the compression of cerebrovascular bed. The smaller vascular diam-
eter markedly increase the resistance of blood flow which reduce cerebral blood flow
99
below the level needed to meet the metabolic demands of the brain [193]. Hence, the
idea of flow through parallel pipes with different diameters (Figure 5.8) is applied to
describe blood flow to hand and cranium. Also, the interhemispheric asymmetry of
cerebral blood flow is studied with two following conditions:
(1) The principle of continuity, total blood flow to each side of upper body equal
to summation of blood flow to each side of hand (QL,hand and QR,hand ) and cranium
(QL,cranium and QR,cranium ). Also, total blood flow of left side (QL,total) and right side
(QR,total) are equal.
QL,hand + QL,cranium = QL,total = QR,total = QR,hand + QR,cranium
(2) Blood flow depend on the cross-sectional area of artery
QL,hand AL,hand VL,hand QR,hand AR,hand VR,hand

= , = (5.13)
QL,cranium AL,cranium VL,cranium QR,cranium AR,cranium VR,cranium
and assume that blood flow velocity (V ) to hand and cranium are approximately
equal, then equation (5.13) can be modified to
QL,hand AL,hand QR,hand AR,hand

= , = (5.14)
QL,cranium AL,cranium QR,cranium AR,cranium
5.9 The Case of Neurosurgical Disorder

Space-occupying lesion is typically observed in patients with TBI. TBI can cause the
internal bleeding (hemorrhage) from an injured blood vessel. This abnormal accu-
mulation of bleeding blood brings a mass effect called mass lesion. Most common
type of intracranial mass lesion is hematoma. A formation of hematoma will occupy
the space within the skull which essentially has a finite volume. In this mathemat-
ical model, the interhemispheric asymmetry of ICP and cerebral blood flow will be
observed. Unilateral mass lesion is created by placing the volume of mass lesion
100
QL,cranium QR,cranium
QL,hand QR,hand
QL,total QR,total
Ascending Aorta
Figure 5.8: Blood flow to hand and cranium after passing ascending aorta
(Vlesion ) in the right cerebral hemisphere. Also, the intracranial dynamic response to
space-occupying mass lesion will be observed.
Then equation (5.12) become
PICP,L ((VL + Amid ∆xmid ) − Vart,L − Vvein,L ) =

PICP,R ((VR − Amid ∆xmid ) − Vart,R − Vvein,R − Vlesion ) = constant (5.15)
5.10 The Case of Treatment by using a Medical

Balloon
Practically, the only way to restore cerebral blood flow is to remove the tumor or
accumulated fluid by shunting [193]. Shunting is commonly used to relieve the pa-
tients who suffer from hydrocephalus or disorders related to reduced cerebral blood
flow. However, there are many complications associated with shunting procedures
including shunt dependency, infection, over-drainage of CSF and development of the
slit ventricle syndrome (SVS) [180]. Moreover, no significant improvement of CBF
after shunting was observed in some case reports [72, 88, 109, 116, 127]. Thus, a med-
101
ical balloon is introduced as an alternative treatment device. The medical balloon
is a medical device with a wide range of clinical applications such as cardiological,
neurological and vascular application. In animal-testing laboratory research at Cleve-
land clinic, the medical balloon is inserted into animal’s right cerebral hemisphere.
Then, the balloon is pressurized intermittently, by air compressor, along the cycle of
intracranial pressure (ICP). As shown in Figure 5.9, there are three different balloon
cycle (1) augmentation, (2) reduction and (3) inversion used to increase cerebral blood
flow. Likewise, in this mathematical model, medical balloon is placed in the right
cerebral hemisphere and applied three different balloon cycle for treatment purpose
which is to maximize cerebral blood flow.
CARDIAC CYCLE (msec)
0 100 200 300 400 500

PRESSURE (mmHg)
200 Peak ICP

Amplitude
150
AUGMENTATION
0
REDUCTION
-150
INVERSION
-200
Figure 5.9: Three different balloon cycle including augmentation, reduction and in-
version used to increase cerebral blood flow. Modified from laboratory research data
at Cleveland clinic
102
Chapter 6
Simulation Results
The methematical model is implemented in Simulink to study the hemodynamics

throughout human major arteries and intracranial system which based on Windkessel
mechanism. For intracranial system, the simulations focus on intracranial pressure
(ICP) and the interaction of main intracranial contents based on Monro-Kellie doc-
trine. To compare the dynamic response for different intracranial conditions, the
simulation results can be categorized into three cases: (1) normal condition, (2) the
case of neurosurgical disorder and (3) the case of treatment by using a medical bal-
loon.
6.1 Normal Condition

In case of normal condition, the simulations focus on the blood flow throughout major
arterial system of human based on Windkessel mechanism which include blood supply
to lower and upper limbs. The heart intermittently pumps blood out along the cardiac
cycle as pulsatile nature of blood flow called cardiac output. The first set of elastic
artery that blood passing through is ascending aorta to aortic arch. After that, some
of blood flow upward to supply upper limbs and intracranial system which is assume
to be about 30% of total blood volume. The remainders (about 70%) flow downward
to supply abdominal cavity and lower limbs. In term of timing and waveform, the
103
relationship of blood flow or pressure signal between lower body especially at femoral
artery and intracranial system can be compared in this simulation.
6.1.1 Lower Body

Cardiac output, first generated by heart, is used as initial input of the system. Pul-
satile blood flow through major arteries to lower limbs with different diameter and
elastic property. In this model, four sets of major artery are considered including (1)
ascending aorta to aortic arch, (2) aortic arch to common iliac artery via the longest
part of the aorta called descending aorta, (3) common iliac artery to external iliac
artery, and (4) external iliac artery to femoral artery. As shown in Figure 6.1, the
phase lag and less pulsatility of predicted blood outflow waveform after passing each
set of major artery. The predicted result is caused by the effectiveness of Windkessel
mechanism which provided by the expansion of artery and flow resistance due to
the length of artery. This also show that buffering function of large arteries acts as
hydraulic filter of the cardiovascular system which converts pulsatile flow generated
by heart to the continuous steady state flow through capillary bed for exchanging
process.
As illustrated in Figure 6.2, pressure and velocity pulse waveforms in the aorta and
arterial branches of a dog from Caro et al. [26] have characteristic pulsatile waveforms
in different parts of arterial system. Also, the delay of pulse pressure waveform after
arterial blood flow waveform presented in arterial system are agree with the predicted
results, for example, at ascending aorta and at common iliac artery as shown in Figure
6.3 and Figure 6.4 respectively.
6.1.2 Upper Body and Intracranial Space

Most of the blood supply into intracranial space via left and right internal carotid
arteries which branches from each side of common carotid arteries. For normal condi-
tion, cerebral blood flow to left and right hemispheres are bilaterally equal and without
104
Arterial Blood Flow to Lower Body
350
Cardiac Output
Qout@Aortic Arch
Qout@Common illiac Artery
Blood Flow (ml/sec.)

Qout@External illiac Artery
300 Qout@Femoral Artery
250
200
150
100
50
0
3.4 3.5 3.6 3.7 3.8 3.9 4 4.1 4.2 4.3 4.4
Time (sec.)
Figure 6.1: Arterial blood flow through major arteries to lower limbs. Cardiac output
(dark-blue), generated by heart, flow into ascending aorta and flow out at aortic arch
(green). Then, blood flow into descending aorta to common iliac artery (orange),
pass through external iliac artery (blue) and femoral artery (purple).
interhemispheric ICP gradients. Hence, no midline displacement is found. As shown

in Figure 6.5, the effectiveness of intracranial Windkessel mechanism converts the
pulsatile arterial inflow to less pulsatile arterial outflow with significant phase shift.
The intracranial Windkessel mechanism is provided by overall intracranial compliance
(combination of vascular compliance and elastic property of intra- and extracranial
contents) and peripheral resistance due to partial obstruction from change of vascular
lumen diameter. However, intracranial capillary and venous outflow perform almost
identical waveform to arterial outflow.
In Figure 6.6, blood pressure in intracranial artery is highest with widest arterial
pulse pressure and becomes lower in capillary and vein respectively. The different
width of pulse pressure in each pulsatile cycle is caused by the different heart rate
which randomly created by cardiac action. This result also leads to random variation
of intracranial contents’ dynamic and ICP waveform during cardiac cycle.
The phase relationship of predicted blood flow and pressure waveform in the in-
tracranial space are in agreement with Avezaat et al.’s MRI data from dog [6] which
presented in Figure 6.7). As illustrated in Figure 6.8, the peak of intracranial pres-
105
Figure 6.2: Pressure and velocity pulse waveforms in the aorta and arterial branches
of a dog. Note that the pressure maximum becomes amplified while the velocity
maximum decreases as the blood moves downstream [26]
.
106
Ascending Aortic Blood Pressure and Flow
Flow(ml/s) Pressure(mmHg)
130
125
120
115
110
105
100
95
90
85
80
3.3 3.4 3.5 3.6 3.7 3.8 3.9 4 4.1 4.2 4.3
350
300
250
200
150
100
50
0
3.3 3.4 3.5 3.6 3.7 3.8 3.9 4 4.1 4.2 4.3
Time (sec.)
Figure 6.3: Ascending aortic blood pressure and flow waveforms.
70
Common Iliac Arterial Blood Pressure and Flow
Flow(ml/s)
60
50
40
30
20
10
3.4 3.5 3.6 3.7 3.8 3.9 4 4.1 4.2 4.3

105
100
Pressure
95
90
85
80
75
70
65
60
3.4 3.5 3.6 3.7 3.8 3.9 4 4.1 4.2 4.3
Time (sec.)
Figure 6.4: Common iliac arterial blood pressure and flow waveforms.
107
35
Intracranial Blood Flow
Qin@Common Carotid
Qout@Common Carotid
Qout@Capillaries
Blood Flow(ml/sec.)
30 Qout@Vein
25
20
15
10
0
2.6 2.7 2.8 2.9 3 3.1 3.2 3.3 3.4 3.5 3.6
Time (sec.)
Figure 6.5: Blood, after passing ascending aorta, flows into intracranial artery (dark
blue) and capillaries (green) then flows into intracranial vein (red). Blood exits the
intracranial space via intracranial vein represented by blue waveform.
sure (ICP), cerebral blood volume (CBV), arterial blood pressure (ABP), and arterial
blood outflow are synchronized which delay after arterial blood inflow to cranium.
In Figure 6.9, the intracranial dynamics related to the demand of intracranial
contents according to Monro-Kellie doctrine are simulated. The systolic expansion
of intracranial arteries leads to synchronously compression of intracranial vein and
reduction of intracranial volume. Also, the delay of arterial outflow after expansion
of arterial inflow due to Windkessel mechanism leads to delay of capillary dilation
(brain parenchymal expansion). The phase relationship of predicted pulsatile blood
flow has a good correlation with the diagram of phase relationship of blood and CSF
velocity waveform observed by Greitz [61] by using flow-sensitive MRI technique as
presented in Figure 3.4.
Femoral artery is commonly selected as site of transducer insertion for arterial
blood pressure (ABP) monitoring. As shown in Figure 6.10 (upper), the timing rela-
tionship between ABP at femoral artery and ICP signal in canine’s experimentation
conducted by Cleveland clinic researchers are observed. The small delay of ABP at
femoral artery and ICP signal found in this animal observation is in agreement with
the predicted result from this mathematical model based on human physiology as
shown in Figure 6.10 (lower). This correlation may result from the different distance
108
90
Intracranial Blood Pressure
Blood Pressure (mmHg)

80
70
60
50
40
P@Common Carotid
P@Capillaries
P@Vein
30
20
10
0
1 2 3 4 5 6 7
Time (sec.)
Figure 6.6: Arterial (dark blue), capillary (green), and venous (red) blood pressure
in the intracranial space.
Figure 6.7: Plot of vertebral artery pulsatile change in cerebral blood volume (CBV)
and ventricular fluid pressure (VFP) during five cardiac cycles in dog. Note also the
synchronization of the extreme values of the change in CBV and CSF pulse [6].
109
14
ICP
13
12
11
10
3 3.5 4 4.5 5 5.5 6
95
CBV
90
85
80
75
3 3.5 4 4.5 5 5.5 6
ABP100
80
60
40
3 3.5 4 4.5 5 5.5 6
40
Flow
30
20
10
0
3 3.5 4 4.5 5 5.5 6
Time (sec.)
Figure 6.8: The phase relationship of predicted blood flow and pressure waveform in
the intracranial space show that intracranial pressure (ICP), cerebral blood volume
(CBV), intracranial arterial blood pressure (ABP) and arterial blood outflow (dark
blue) are in-phase which delay from arterial blood inflow (black). ICP and ABP are
in mmHg. CBV is in ml. Arterial blood inflow and outflow are in ml/sec. This figure
is in agreement with Avezaat et al.’s MRI data [6](Figure 6.7).
∆xart
1.6
1.5
1.4
1.3
1.2
3.2 3.4 3.6 3.8 4 4.2 4.4 4.6 4.8 5
0.06
∆xcap
0.05
0.04
0.03
0.02
3.2 3.4 3.6 3.8 4 4.2 4.4 4.6 4.8 5
0.02
∆xvein
0.01
−0.01
3.2 3.4 3.6 3.8 4 4.2 4.4 4.6 4.8 5
80
75
Vol.
70
65
60
55
3.2 3.4 3.6 3.8 4 4.2 4.4 4.6 4.8 5
Time (sec.)
Figure 6.9: The expansion of intracranial arteries (∆xart) result in venous contraction
(∆xvein ) and intracranial volume reduction (Vol.) synchronously. Also, the delay of
capillary expansion (∆xcap) after arterial expansion. This simulation results agree
with Monro-Kellie doctrine and the diagram of phase relationship of blood and CSF
from Greitz [61]’s MRI data (Figure 3.4).
110
Lab Data (Canine)
16
15
14
13
ICP
12
11
10
7
200 300 400 500 600 700 800 900 1000
ABP(Femoral) 120
110
100
90
80
70
60
50
200 300 400 500 600 700 800 900 1000
Time (200ticks:sec.)
Simulation (Human)
14
13.5
13
ICP
12.5
12
11.5
11
10.5
10
1 2 3 4 5 6
ABP(Femoral)
105
100
95
90
85
80
75
70
1 2 3 4 5 6
Time (sec.)
Figure 6.10: Upper: the timing relationship between arterial blood pressure (ABP)
at femoral artery and ICP signal are observed in canine’s experimentation conducted
by Cleveland clinic researchers. Lower: the small delay of ABP and ICP signal are
predicted from the mathematical model based on human physiology which are in
agreement with canine’s monitoring.
between heart to intracranial space and heart to femoral artery.
111
6.2 Case of Neurosurgical Disorder
Because cranium is the rigid chambers, an interruption of intracranial space such as
an enlargement in volume of intracranial contents brings about the variation of in-
tracranial dynamics. In patients with TBI, a bleeding of cerebral blood vessel referred
to intracranial hemorrhage is commonly observed. Intracranial hemorrhage is an ab-
normal collection of bleeding blood in cranial vault which can cause a mass effect
called intracranial mass lesion. An expansion of intracranial mass lesion normally
leads to elevated ICP which exerts a collapsing force on intracranial vasculature and
brain tissue. Most common type of intracranial mass lesion is hematoma. A for-
mation of hematoma can occupy a finite volume of intracranial space. Intracranial
hypertension, reduced cerebral blood flow and brain herniation is common outcome
in order to response to the space-occupying intracranial mass lesion. Moreover, an
appearance of midline shift on CT scan is typically found in the patients with severe
unilateral mass lesion as presented in Figure 2.10(b). Virtually, ICP and cerebral
blood flow is bilateral hemisphere balance in healthy individuals. In many clinical
reports in patients and animal experimentations with unilateral mass lesion, the dif-
ference of ICP between left and right hemisphere (interhemispheric ICP gradients)
are observed. For cerebral blood flow, reduced global cerebral blood flow is usually
observed in patients who suffer from hydrocephalus and TBI. Moreover, the signifi-
cantly lower of cerebral blood flow in injured hemisphere than contralateral side are
reported in the studies of regional cerebral blood flow.
In this mathematical model, studies of the dynamic response related to the size
of mass lesion are simulated in two cases: (1) small mass lesion (about 5% of total
volume of one hemisphere) and (2) large mass lesion (about 30% of total volume of
one hemisphere).
112
6.2.1 Small mass lesion
In case of small mass lesion, volume of small mass (about 5% of total volume of
one hemisphere) is placed in the right hemisphere. Interestingly, ICP of lesion side
is lower than the non-injured side (left hemisphere) after placing small mass. As
shown in Figure 6.11, ICP in normal individuals (dash line) is equal between left and
right hemisphere with peaks and dips characteristic pattern of ICP waveform. After
a presence of small mass in right hemisphere, the ICP of contralateral hemisphere
is higher than normal condition. Moreover, ICP waveform of contralateral side still
performs peaks and dips features and synchronization of peak with ICP of normal
condition. However, ICP level of injured hemisphere become lower than normal con-
dition. The peaks and dips characteristic pattern of ICP waveform is smoothed out
or become dampened ICP waveform. Also, the synchronization of ICP peak value
between normal condition and injured hemisphere is distorted.
Intracranial Pressure in Left vs Right Hemisphere
15
Left−ICP
Right−ICP
ICP at Normal
14
13
ICP (mmHg)
12
11
10
8
3 3.5 4 4.5 5 5.5 6 6.5 7
Time (sec.)
Figure 6.11: After small mass lesion placing in right cerebral hemisphere, left hemi-
sphere (dark blue) has higher ICP than right hemisphere (green). Dash black wave-
form represents ICP in normal condition (without mass lesion).
As presented in Figure 6.12, the midline is displaced forward to positive value after
intracranial system reaching new equilibrium. It means that the midline shifts forward
to the lesion hemisphere after placing small mass. The displacement of midline also
113
0.4
Midline Shift
Midline Displacement (mm)

0.35
0.3
0.25
0.2
0.15
0.1
0.05
−0.05
−0.1
0 1 2 3 4 5 6 7
Time (sec.)
Figure 6.12: After small mass lesion placing in right cerebral hemisphere, positive
displacement of midline refers to midline shift to right hemisphere which has lower
ICP.
agrees with ICP level between left and right hemisphere which midline shifts to lower
ICP side.
Cerebral blood flow through intracranial artery in both side of hemisphere is com-
pared as illustrated in Figure 6.13. An appearance of small mass lesion brings about
the lower blood flow into intracranial artery of lesion side compared to contralateral
hemisphere. For blood flow through contralateral artery (Figure 6.13 (upper)), no
significant change of blood flow waveform is found. The less pulsatile outflow with
phase shift indicates that buffering function of Windkessel mechanism still performs
effectively in non-lesion hemisphere. In contrast, blood outflow after passing intracra-
nial artery of lesion side (Figure 6.13 (lower)) shows the breakdown of intracranial
Windkessel mechanism which cannot convert pulsatile blood inflow into less pulsatile
outflow to cerebral capillaries. As a result of high pulsatile outflow to capillary bed, it
can be indicated that the proportion between arterial expansion and brain expansion
become lower in the patient with mass effect. This predicted result also agrees with
MRI data in hydrocephalic patient as shown in Figure 3.4(b). Also, smaller phase
shift of outflow waveform (reflected wave) after inflow waveform is observed in lesion
hemisphere.
114
40
Left Cerebral Blood Flow
Flow(ml/s)
35
30
25
20
15
10
−5
3 3.5 4 4.5 5 5.5 6 6.5 7
Right Cerebral Blood Flow

25
Flow(ml/s)
20
15
10
−5
3 3.5 4 4.5 5 5.5 6 6.5 7
Time (sec.)
Figure 6.13: After small mass lesion placing in right cerebral hemisphere, cerebral
blood flow to the right hemisphere (thick green) becomes greatly lower. Also, the
high pulsatility with shorter delay of right cerebral blood outflow (thin green) after
systolic peak of arterial inflow is observed. However, no significant change of blood
inflow (thick dark blue) and outflow waveform (thin dark blue) over left hemisphere
is observed.
As presented in Figure 6.14, the observation of systolic expansion of cerebral

artery shows that smaller arterial expansion in lesion side compared to the contralat-
eral hemisphere. The phase difference of systolic arterial expansion between lesion
and contralateral side are clearly observed. The constriction of cerebral artery in the
injured hemisphere leads to increased arterial resistance which decreases arterial com-
pliance. This breakdown of Windkessel mechanism which causes marked reduction
of cerebral blood flow, is presented as high pulsatile blood outflow and shorter phase
lag between inflow and outflow waveforms on lesion hemisphere. Hence, this pre-
dicted results can be used to describe the failure of intracranial volume compensatory
mechanism.
6.2.2 Large mass lesion

In this case, large volume of mass (about 30% of total volume of one hemisphere)
is still placed in right hemisphere. As presented in Figure 6.15, the predicted ICP
of lesion side is higher than contralateral hemisphere in case of large mass lesion.
115
Left vs Right Arterial Expansion
2
Left Arterial Expansion
Right Arterial Expansion
Arterial Expansion (mm)

1.8
1.6
1.4
1.2
0.8
0.6
0.4
3 3.5 4 4.5 5 5.5 6 6.5 7
Time (sec.)
Figure 6.14: After small mass lesion placing in right cerebral hemisphere, systolic
expansion of artery in lesion hemisphere (green) becomes significantly lower compared
to non-lesion side (dark blue).
This simulated ICP result agree with the most of clinical case reports in the patient
with severe TBI. The predicted ICP waveform of lesion side is flatten out which is
similar to the predicted ICP derived from the case of small mass lesion. Hence, the
dampened ICP waveform might be used as the indicator of vascular compression in
that hemisphere.
For large mass lesion, the midline is displaced forward to negative zone after
reaching equilibrium as shown in Figure 6.16. It means midline shift over its center
line to contralateral side which has lower ICP. This predicted result also agrees with
an appearance of midline shift on CT scan commonly observed in patients who suffer
from severe hematoma or tumor.
As illustrated in Figure 6.17, the significant reduction of cerebral blood flow on
both hemisphere after placing large mass lesion, especially, the markedly decreased
cerebral blood flow on the lesion hemisphere (Figure 6.17 (lower)) is found. The
cessation of cerebral blood flow on the lesion hemisphere after short period of time
(about 5 seconds) brings about brain ischemia on that side. This observation enhance
that to remove tumor or hematoma promptly after a severe TBI is required, otherwise
116
Intracranial Pressure in Left vs Right Hemisphere
14
Left−ICP
Right−ICP
13
ICP (mmHg)
12
11
10
8
9 10 11 12 13 14 15
Time (sec.)
Figure 6.15: After large mass lesion placing in right cerebral hemisphere, left hemi-
sphere (dark blue) has lower ICP than right hemisphere (green). The dampened ICP
waveform over lesion hemisphere is also observed.
Midline Shift
Midline Displacement (mm)
0.2
−0.2
−0.4
−0.6
−0.8
−1
0 1 2 3 4 5 6 7
Time (sec.)
Figure 6.16: After large mass lesion placing in right cerebral hemisphere, negative dis-
placement of midline represent the displacement of midline forward to left hemisphere
which has lower ICP.
117
40
Left Cerebral Blood Flow
Flow(ml/s)
35
30
25
20
15
10
−5
0 1 2 3 4 5 6 7 8 9 10
Right Cerebral Blood Flow

40
Flow(ml/s)
35
30
25
20
15
10
−5
0 1 2 3 4 5 6 7 8 9 10
Time (sec.)
Figure 6.17: After large mass lesion placing in right cerebral hemisphere, cerebral
blood flow to both hemisphere becomes lower. Especially, on the lesion side, blood
flow to the right hemisphere (thick green) ceases after 5 seconds.
the reduction of cerebral blood flow will further result in secondary brain ischemia
and eventually serious neurological disorders.
The cerebral blood flow on lesion side is lower than contralateral side which results
from the greater restriction of arterial expansion on lesion side as shown in Figure 6.18.
This observation is identical to predicted result derived from the case of small mass
lesion. The distortion of arterial outflow waveform (Figure 6.17 (Upper)) might be
resulted from the displacement of midline to contralateral hemisphere which restricts
the arterial expansion as well.
As presented in Figure 6.19, the expansion of cerebral capillary is distorted after
placing large mass lesion compared to normal condition. The capillary expansion
which usually refers to brain expansion are restricted to both hemisphere. Especially,
the severe compression of capillary in the lesion hemisphere is presented. This pre-
dicted result shows that compression of brain parenchyma called brain herniation
after severe TBI can be observed in both hemisphere with more damage on the lesion
side.
118
Left vs Right Arterial Expansion
1.8 Left Arterial Expansion

1.6
1.4
1.2
0.8
0.6
0.4
0.2
3 3.5 4 4.5
Time (sec.)
5 5.5 6 6.5 7
Figure 6.18: After large mass lesion placing in right cerebral hemisphere, arterial
expansion of artery in lesion hemisphere (green) is severely restricted and becomes
lower than the expansion of artery in contralateral hemisphere (dark blue).
Left vs Right Capillary Expansion

0.06
Normal Condition
Left Capillary
Right Capillary
Capillary Expansion (mm)
0.055
0.05
0.045
0.04
0.035
0.03
0.025
0.02
7 7.5 8 8.5
Time (sec.)
9 9.5 10 10.5 11
Figure 6.19: After large mass lesion placing in right cerebral hemisphere, capillary
in both hemisphere becomes more restriction compared to normal condition (dash
black). Especially, the marked restriction of capillary in lesion hemisphere (green) is
observed.
119
6.3 Case of Treatment by using a Medical Balloon
A medical balloon is used as alternative treatment method to make recovery of cere-
bral blood flow in the patient with neurosurgical condition. In this section, balloon
is inserted in the right hemisphere which the side that mass lesion is presented. As
shown in Figure 5.9, three different balloon cycles is simulated including augmenta-
tion, reduction, and inversion along cardiac cycle. To observe the dynamic response
of intracranial system and especially the cerebral blood flow improvement after us-
ing medical balloon with intermittent-pumping cycle, both cases of intracranial mass
lesion are simulated.
6.3.1 Small mass lesion

After inserting balloon into lesion hemisphere and performing all three balloon cycles,
inversion cycle of balloon provides the most improvement of global cerebral blood flow.
As shown in Figure 6.20, for the most improvement of cerebral blood flow, the peak of
inversion cycle should be synchronous with the peak of initial cardiac output (Figure
6.20 (lower)), not with the peak of ICP waveform.
Inversion vs Cardiac Output

15
10
Left−ICP
5 Right−ICP
Inversion
−5
3 3.5 4 4.5 5 5.5 6 6.5 7
400
Flow after passing Aorta
350 Cardiac Output
Flow(ml/s)
300
250
200
150
100
50
0
3 3.5 4 4.5 5 5.5 6 6.5 7
Time (sec.)
Figure 6.20: Inversion (blue) should do synchronously with cardiac output (thick red)
to obtain most cerebral blood flow improvement. ICP response in left (dark blue)
and right (green) cerebral hemisphere along inversion cycle are also plotted.
120
Small Mass Lesion Treatment
ICP (mmHg)
3.5 4 4.5 5 5.5 6 3.5 4 4.5 5 5.5 6
Time (sec.) Time (sec.)
Figure 6.21: Intracranial pressure in left Figure 6.22: Intracranial pressure in left
(dark blue) and right (green) hemisphere (dark blue) and right (green) hemisphere
with small mass lesion after inversion treatment
As shown in Figure 6.22, the ICP waveform of non-lesion side (left hemisphere)
after inversion treatment is similar to ICP waveform with in the case of small mass
lesion (Figure 6.21). However, the dampened ICP waveform of the lesion side (right
hemisphere) is likely transformed into peaks and dips ICP waveform after inversion
cycle of balloon.
In non-lesion hemisphere, arterial blood inflow/outflow waveform in case of small
mass lesion (Figure 6.23 (upper)) and during inversion treatment (Figure 6.24 (up-
per)) are almost identical. However, the inversion cycle can increase arterial blood
inflow to lesion hemisphere with undesirable high pulsatile outflow as shown in Figure
6.24 (lower).
The comparison of arterial expansion in both hemispheres between case of small
mass lesion and after inversion treatment is presented in Figure 6.25 and Figure
6.26 respectively. Inversion cycle of balloon which is synchronous with the initial
cardiac cycle provides the additional expansion of artery on the lesion hemisphere.
Furthermore, the larger arterial lumen diameter can decrease the flow resistance which
allows additional blood flow to intracranial space.
As presented in Table 6.1, average value of ICP, cerebral blood flow (Qbrain) and
121
Left Cerebral Blood Flow Left Cerebral Blood Flow
Flow(ml/s)
3.5 4 4.5 5 5.5 6 3.5 4 4.5 5 5.5 6
Right Cerebral Blood Flow Right Cerebral Blood Flow
Flow(ml/s)
3.5 4 4.5 5 5.5 6 3.5 4 4.5 5 5.5 6
Figure 6.23: Cerebral blood flow to the left Figure 6.24: Cerebral blood flow to the left
(thick dark blue) and right (thick green) (thick dark blue) and right (thick green)
hemisphere with small mass lesion hemisphere after inversion treatment
Small Mass Lesion Treatment

Left Arterial Expansion

3.5 4 4.5 5 5.5 6 3.5 4 4.5 5 5.5 6
Time (sec.) Time (sec.)
Figure 6.25: Expansion of left cerebral Figure 6.26: Expansion of left cerebral
artery (dark blue) and right (green) cere- artery (dark blue) and right (green) cere-
bral artery with small mass lesion bral artery after inversion treatment
122
Table 6.1: Comparison table of ICP, cerebral blood flow (Qbrain) and flow to hands
(Qhand) during normal condition, with small mass lesion and after inversion treat-
ment
blood flow to hand (Qhand) during normal condition, with small mass lesion, and
after inversion treatment are compared. The percentage change column represents the
percentage difference between the case of mass lesion and after treatment by inversion
cycle. As mentioned earlier in case of small mass lesion, average ICP of non-lesion
hemisphere (ICP,L) becomes higher and lesion hemisphere (ICP,R) becomes lower
compared to normal condition. After inversion treatment, the small increase in ICP
of lesion hemisphere brings about the small increase in total ICP (L+R/2). Moreover,
a presence of small mass lesion results in marked reduction of cerebral blood flow
to lesion hemisphere (Qbrain,R) which leads to decreased global cerebral blood flow
(L+R/2). The inversion cycle of balloon can significantly increase cerebral blood flow
on lesion side about 21.6% improvement which can improve global cerebral blood flow
by 6%. However, the inversion treatment cannot recover cerebral blood flow to normal
condition. Since the mathematical model assumes that blood will flow to the hand
if blood cannot flow into the intracranial space, the amount of blood flows to each
hand and each intracranial hemisphere has inversely proportional relationship.
123
Inversion vs Cardiac Output
15
10
Left−ICP
5 Right−ICP
Inversion
−5
−10
−15
11 11.5 12 12.5 13 13.5 14 14.5 15
400
Blood Flow After Passing Acsending Aorta
Flow(ml/s)
350 Cardiac Output
300
250
200
150
100
50
0
11 11.5 12 12.5 13 13.5 14 14.5 15
Time (sec.)
Figure 6.27: Inversion (blue) should do nearly synchronously with cardiac output
(thick red) to obtain most cerebral blood flow improvement. ICP response in left (dark
blue) and right (green) cerebral hemisphere along inversion cycle are also plotted.
6.3.2 Large mass lesion

Similarly, from all of balloon cycles perform in large mass lesion case, the most im-
provement of cerebral blood flow is also provided by inversion cycle of balloon. In this
case, however, the peak of inversion cycle is not precisely synchronous with the peak
of initial cardiac cycle. As shown in Figure 6.27, the small delay of inversion cycle
after initial cardiac cycle brings about the most cerebral blood flow improvement for
the case of large mass lesion.
In addition, ICP response for large mass lesion (Figure 6.28) is compared to the
case of inversion treatment by using a medical balloon (Figure 6.29). After inversion
treatment, the ICP waveform of non-lesion side (left hemisphere) is converted to wider
pulse and higher ICP level. On lesion side (right hemisphere), the predicted ICP
waveform is converted from flatten-out waveform to larger ICP pulse along inversion
cycle of balloon.
In case of large mass lesion, blood flow into both intracranial arteries is decreased.
Especially, the lack of blood supply into the lesion hemisphere as presented in Figure
6.30 (lower). After balloon insertion (Figure 6.31), inversion cycle can increase blood
124
Large Mass Lesion Treatment
ICP (mmHg)
10 11 12 13
Time (sec.) 10 11 12
Time (sec.)
13
Figure 6.28: Intracranial pressure in left Figure 6.29: Intracranial pressure in left
(dark blue) and right (green) hemisphere (dark blue) and right (green) hemisphere
with large mass lesion after inversion treatment
flow to both hemispheres which recovers blood supply on the lesion hemisphere from
loss of blood flow to continuous flow. However, high pulsatile outflow to capillary bed
is observed which is unfavorable condition.
In Table 6.2, the existence of large mass lesion results in an increase of ICP level on
the lesion side (ICP,R) over the non-lesion hemisphere (ICP,L). Cerebral blood flow on
both hemispheres (Qbrain) are reduced significantly in the case of large mass lesion.
Furthermore, the cessation of blood supply to lesion hemisphere (Qbrain,R) is also
observed. Inversion treatment can greatly improve blood flow on lesion side which
gain 94% improvement of global cerebral blood flow (L+R/2). However, cerebral
blood flow is still far from normal condition.
125
Left Cerebral Blood Flow Left Cerebral Blood Flow
Flow(ml/s)
6.5 7 7.5 8 8.5 9 11.5 12 12.5 13 13.5 14
Right Cerebral Blood Flow Right Cerebral Blood Flow
Flow(ml/s)
6.5 7 7.5 8 8.5 9 11.5 12 12.5 13 13.5 14
Figure 6.30: Cerebral blood flow to the left Figure 6.31: Cerebral blood flow to the left
(thick dark blue) and right (thick green) (thick dark blue) and right (thick green)
hemisphere with large mass lesion hemisphere after inversion treatment
Table 6.2: Comparison table of ICP, cerebral blood flow (Qbrain) and flow to hands
(Qhand) during normal condition, with large mass lesion, and after inversion treat-
ment
126
6.4 Discussion
To convert the pulsatile nature of blood flow created by pumping action of heart into
less pulsatile and continuous outflow to capillary bed is major function of Windkessel
mechanism. This buffering function is mainly provided by the elasticity of artery
and flow resistance which has different physiological properties in various parts of
arterial system. In this mathematical model, the dynamical relationship of blood
flow, pressure and vascular expansion in human major arterial system and intracranial
system is studied based on Windkessel mechanism.
For normal condition, the effective Windkessel mechanism not only provides the
arterial blood outflow with less pulsatility but the phase shift after inflow waveform
is also another characteristic feature. The predicted results have well agreement with
clinical data in many aspects such as pulsatile waveform and phase relationship in
both major arteries to lower limbs and intracranial space. In addition, the simulation
reveals the time delay of arterial blood pressure at femoral artery which usually
selected as site of blood pressure monitoring after ICP signal. For intracranial space,
the dynamic of intracranial contents is also based on Windkessel mechanism under
the constraint of Monro-Kellie doctrine. Arterial blood inflow with delay of systolic
expansion of arteries is the major source to drive out the intracranial dynamics.
Systolic expansion of intracranial arteries which synchronous with arterial outflow
leads to ICP pulsation, venous contraction and delay of capillary dilation. Moreover,
bilaterally interhemispheric balance of ICP and cerebral blood flow are normally
observed in healthy individuals.
For neurosurgical condition, this mathematical model demonstrates the change of
intracranial dynamic secondary to the mass effect condition. Furthermore, the simu-
lation results show that different size of mass lesion lead to vastly different intracranial
dynamics response. Especially, the interhemispheric asymmetry of ICP and cerebral
blood flow between lesion and non-lesion hemisphere is observed in term of level and
waveform. An appearance of large mass lesion brings about the higher of ICP on
127
the lesion hemisphere compared to contralateral side (and vice versa in case of small
mass lesion). In response to the interhemispheric ICP gradient, midline shifts forward
over center line to the lower ICP hemisphere. In my opinion, interhemispheric ICP
gradient may not be observed if no blockage of subarachnoid space as mentioned by
Langfitt et al. [92, 94]. However, most case of severe neurosurgical disorders are asso-
ciated with the blockage CSF flow and pressure communication pathway which follow
by the interhemispheric imbalance of ICP. In addition, peaks and dips ICP waveform
of the lesion hemisphere is flatten out into dampened ICP waveform. For cerebral
blood flow, a presence of mass lesion results in the reduction of global cerebral blood
flow and a marked reduction of regional blood flow also on the lesion hemisphere.
Arterial blood outflow waveform shows the higher pulsatility and shorter phase lag
after inflow waveform. Also, a larger size of mass lesion leads to greater reduction of
regional and global cerebral blood flow. Hence, it can be concluded that the inter-
hemispheric ICP gradients and reduction of global and regional cerebral blood flow
depend on the size of mass lesion which agree with many animal experimentation and
clinical case reports. Moreover, the observation of the arterial expansion shows that
reduction of CBF results from the smaller expansion of arterial lumen diameter. As
a result of restriction of arterial expansion, flow resistance is increased which reduces
arterial volume compensatory capacity (arterial compliance). This situation can ex-
plain the failure of intracranial Windkessel mechanism that the pulsatile energy from
cardiac output cannot be filtered into nearly pulseless outflow.
According to simulation results, many observations can be used as the indicator
to predict the failure of intracranial Windkessel mechanism which is highly useful for
real-time patient monitoring. Higher amplitude of arterial outflow and venous out-
flow compared to healthy individuals is the fundamental indicator that artery cannot
convert pulsatile inflow into steady outflow. Also, the smaller difference in amplitude
between arterial inflow and outflow or venous outflow can be another indicator by
using blood flow waveform. In the patient with space-occupying lesion, the reduction
of cerebral blood flow due to the restriction of artery is typically found. However,
128
because of high pulsatile arterial outflow, capillary expansion which provided by the
arterial outflow is still relatively high compared to arterial expansion. In other words,
the lower proportion between arterial expansion and capillary expansion (usually re-
ferred as brain expansion) indicates the problem of Windkessel buffering function.
Moreover, the shorter phase lag between the peak of arterial blood inflow and arterial
outflow is commonly observed in the patient with Windkessel mechanism problem.
For practical monitoring, arterial outflow might be replaceable by capillary outflow,
venous outflow, or ICP signal because they perform almost identical timing. Nor-
mally, the ICP waveform perform peaks and dips feature. Dampened ICP waveform
might be used to indicate the compression of vascular bed and brain herniation in
that hemisphere. The breakdown of Windkessel mechanism also relates to cardiac
afterload as mentioned in Section 3.1. The failure of volume compensatory mecha-
nisms usually result in high pulsatility and much earlier venous return to heart which
can increase work load of the heart. High systolic blood pressure and blood flow
velocity are responded to increased heart afterload. In the future, the cardiac action
that respond to the change of venous return might be included in the mathematical
model. Hence, the change of arterial blood pressure at femoral artery and peak-to-
peak difference in timing of blood flow or ICP might be used as another indicator to
respond to the change of blood pressure and flow velocity respectively.
The simulation results show that the intermittent action of medical balloon can im-
prove the cerebral blood flow in patient with decreased cerebral blood flow due to mass
effect. Inversion cycle is the only technique that can improve CBF and should operate
approximately at the same time with the peak of initial cardiac output. However, the
high pulsatility arterial blood outflow to capillary bed is an undesirable result. More-
over, cerebral blood flow cannot be restored to normal level because balloon insertion
also occupies the finite volume of intracranial space. Hence, the technique to recover
cerebral blood flow by balloon insertion might not be recommended to the patient
who already loads with intracranial space occupation or decreased intracranial com-
pliance. To make recovery of cerebral blood flow and volume compensatory capacity,
129
Occlusion/Vasospasm
Reduction of
Cerebral Blood Flow
NPH Breakdown of
Windkessel Mechanism Reduction of Reduction of
Arterial Expansion Capillary Expansion
TBI Mass Effect
Reduction of Reduction of
Squeezing force Squeezing force
Ventricular Enlargement at Choriod Plexus at Venticles
(Hydrocephalus)
Collection of CSF
in Ventricles
Obstructive Hydrocephalus
Figure 6.32: Developmental cycle of hydrocephalus
surgical treatment or shunting placement is still a practical solution. However, the

balloon might be used for a short period of time to stimulate cerebral blood flow in the
patient with extremely low cerebral blood flow after lesion removal. Furthermore, the
medical balloon might be conjointly used during surgical shunting because shunting
can provide a little extra space to compensate for the space occupied by balloon.
This mathematical model is one of the useful tool to predict a possible outcome of
patients who suffer from the failure of volume compensatory mechanisms due to space-
occupying mass lesion. Moreover, I believe that the enlargement of cerebral ventricles
referred to hydrocephalus might be considered as the mass effect because the enlarge-
ment of ventricles also occupy the finite volume of intracranial space. Especially, the
130
behavior of unilateral dilation of ventricle (called unilateral or monoventricular hydro-
cephalus) as presented in Figure 2.13 might be able to understand from the simulation
results of unilateral mass lesion. In my opinion, the cause of hydrocephalus might be
described as the malfunction of intraventricular CSF flow due to the abnormalities of
intracranial dynamics. As mentioned earlier, the systolic expansion of arteries is the
major source to drive out the intracranial dynamics and intraventricular CSF flow.
Also, choroid plexus is the major site of CSF formation and stimulate the pulsatile
CSF flow in ventricular system induced by systolic arterial expansion. Hence, the in-
traventricular CSF flow requires two consecutive squeezing forces provided by arterial
and capillary expansion which can be divided into two stages. For the first stage, the
large systolic expansion of artery will squeeze choroid plexus to drive out the CSF
flow. For the second stage, the small expansion of capillary provides the additional
force on lateral ventricles for CSF flow to the third and fourth ventricle and then
to SAS. The development of hydrocephalus might be expressed as the inadequate of
squeezing force exerting on choroid plexus and ventricles which can be explained in
the aspect of developmental cycle as illustrated in Figure 6.32. The developmental
cycle of hydrocephalus shows that any abnormalities in the cycle can be the cause
that will develop to hydrocephalus. For example, the marked reduction of cerebral
blood flow which may result from vascular occlusion or vasospasm decrease the pul-
satile volume of blood into the cranium and reduce the expansion of intracranial
artery and capillary. Also, the effective timing to compress the choroid plexus and
ventricles is distorted due to the phase shift of vascular expansion especially capillary.
Thus, the squeezing force that drive out CSF to SAS cannot be provided sufficiently.
When the CSF cannot be squeezed out from the ventricles, the accumulation of CSF
within ventricle might be occurred. If the treatment is not provided, the collection
of CSF will dilate the ventricles. Furthermore, the ventricular enlargement can be
considered as the mass effect by occupying the intracranial space. After that, the vol-
ume compensatory capacity will be exhausted and the Windkessel mechanism will be
break-downed. The failure of Windkessel mechanism will further reduce the cerebral
131
blood flow and then proceed into the cycle. The enlargement of ventricle affects the
intracranial Windkessel mechanism in two aspects. First, ventricle dilation occupies
the intracranial space which can be considered as the mass effect as mentioned above.
Second, the compression of elastic ventricles is normally provided by the expansion of
capillary. Hence, the enlargement of ventricles not only resists the expansion of capil-
lary but also leads to the loss of absorbing function of ventricles which normally acts
as one of pulsatile absorber in the intracranial space. As a result, the breakdown of
intracranial Windkessel mechanism is developed. The developmental cycle of hydro-
cephalus also can be used to classify the cause of hydrocephalus due to other factors.
For example, the ventricular obstruction of CSF flow pathway referred to obstruc-
tive hydrocephalus brings about the collection of CSF in ventricles. An appearance
of brain hematoma observed in the patients with TBI can be classified as hydro-
cephalus secondary to head injury which considered as the mass effect. Moreover, the
development of NPH in the elderly as the result of aging or arteriosclerosis might be
explained by the gradual loss of arterial compliance which restricts arterial expansion
and eventually causes the failure of Windkessel mechanism. Also, the blockage of
CSF flow pathway for communication between intracranial SAS and compliant spinal
theca in lumber region can be considered as the breakdown of Windkessel mechas-
nism in the developmental cycle because of the loss of volume compensatory capacity.
Hence, to study the effect of ventricular dynamic on intracranial system related to
the development of hydrocephalus, the ventricular system should be included in the
mathematical model in the future.
According to the developmental cycle of hydrocephalus, the treatment of hydro-
cephalus should focus on preventing or breaking up the cause of development. For
example, to remove the space occupying mass lesion by surgery is the practical ap-
proach for the patients with TBI. In the patients with NPH who require the im-
provement of arterial compliance, vasodilating drug might be the suitable choice for
restoring arterial compliance. Shunting is still the appropriate treatment procedure
to recover the intracranial volume compensatory capacity which may either result
132
from the intracranial occupation due to mass effect or the blockage of CSF flow path-
way between intracranial and compliant spinal SAS. To remove the collection of CSF
in lateral ventricles, an endoscopic third ventriculostomy (ETV) by bypassing CSF
from the third ventricle flow directly to SAS might be the most effective solution. Ca-
dence action of the medical balloon is another treatment option for hydrocephalus.
As shown in the simulation results, the inversion cycle of balloon can increase the
pulsatile volume of cerebral blood provided by the greater expansion of artery. A
sufficient arterial expansion will provide the capable force acting on choroid plexus
for the intraventricular CSF pulsation. Furthermore, the augmentation cycle directly
exerted the squeezing power on choroid plexus might be the alternative therapy to
treat hydrocephalus which requires further studies. However, the insertion of balloon
inside intracranial space may occupy the finite volume of cranium. The collaboration
of shunting while the balloon is in use may eliminate this space occupying problem.
133
Chapter 7
Summary and Conclusions
7.1 Summary
In this dissertation, by simulating through the mathematical model, the high pulsatile
nature of blood flow major human arterial system can be converted into less pulsatil-
ity which results from the effectiveness of Windkessel mechanism. The Windkessel
mechanism is provided by the buffering function obtained from vascular elasticity
and flow resistance. For intracranial space, not only the vascular elasticity acts as
pulsatile absorber but the intracranial compliance which defined by volume compen-
satory mechanism also together provides compliance to overall intracranial system.
The interactive relationship among major intracranial contents is presented. This
observation clarifies the intracranial system in term of dynamics along the cardiac
output which pulsatile arterial blood flow is the major driving force. Also, the de-
mand and compensation in volume of intracranial contents according to Monro-Kellie
doctrine is well satisfied.
An appearance of unilateral mass lesion brings about the variation of intracranial
dynamics because the mass lesion occupies the finite volume of intracranial space.
Especially, the interhemispheric asymmetry of intracranial pressure (ICP) and cere-
bral blood flow are presented. Also, the displacement of midline (midline shift) is
observed. The predicted show that higher ICP would be on either the lesion or non-
134
lesion hemisphere depends on the size of mass lesion. However, cerebral blood flow
of the lesion side is always lower than the contralateral side because of the collapsing
of cerebrovascular bed. In term of waveform and timing, the significantly interhemi-
spheric different of signals is also observed. This can be used to categorize between
the normality and abnormality of intracranial Windkessel mechanism using signal
analysis. For useful of real-time patient monitoring, many observations can be used
as the indicator to predict the failure of intracranial Windkessel mechanism including
waveform, amplitude, timing and phase shift.
To hypothesize the cause of hydrocephalus, the failure of intracranial Wind-
kessel mechanism might be the good explanation especially for communicating hydro-
cephalus. However, I believe that the failure of intracranial Windkessel mechanism
can be both cause and result of hydrocephalus.
Neurosurgical disorders are typically related to decreased cerebral blood flow. In
order to recover cerebral blood flow, the medical balloon insertion with intermittent
action is used as the alternative treatment method. According to the simulation re-
sults, the inversion action of balloon can increase the cerebral blood flow by increasing
the arterial expansion. For the most improvement, the inversion cycle should do ap-
proximately synchronously with the initial cardiac output. However, cerebral blood
flow cannot be restored to normal level because balloon insertion also occupies the
intracranial space. Thus, the balloon might be recommended to use for a short period
of time to stimulate cerebral blood flow in the patient with extremely low cerebral
blood flow after lesion removal or conjointly used with shunting to provide the extra
space to compensate for the space occupation of balloon
This pulsatile mathematical modeling is the useful tool to understand the hemo-
dynamics and intracranial system based on Windkessel mechanism. In addition,
improved understanding of its mechanism and abnormalities can help to explore the
cause and effect of intracranial disorders. This observation can also enlighten the
medical professionals to direct future protection and treatment strategies against this
related clinical condition properly.
135
7.2 Recommendations for Future Development
The following list contains feasible development for the further studies:
• Investigation on the effect of another neurosurgical conditions on intracranial

system
• Addition of ventricular system into model to study the dynamics of ventric-

ular system and to investigate the dilation of ventricles in the patients with
hydrocephalus
• Incorporation of cardiac response to the dynamical change of intracranial system

such as the earlier return of venous flow due to decreased intracranial compliance
• Simulation of the alternative treatment method to improve cerebral blood flow

or restore effectiveness of intracranial Windkessel mechanism
136
Appendix A
Parameters for the Model of

Hemodynamics and Intracranial
System
Table A.1: Parameters for the Model of Hemodynamics

and Intracranial System
Parameter value
Dynamic viscosity of blood, µblood (kg/cm.s) 10−5
Density of blood, ρblood (kg/cm3 ) 0.001
Heart rate, ω (rad/s) 2.3π - 2.4π
Radius of intracranial artery’s outlet, xout (cm) 0.5
Total volume of left hemisphere, VL (ml) 75
Total volume of right hemisphere, VR (ml) 75
Cross-sectional area of midline, Amid (cm2) 15
Midline tissue’s stiffness, kmid (kg/s2 ) 1000
Mass of midline, mmid (kg) 0.1
Volume of small mass lesion, Vlesion,S (ml) 4
Volume of large mass lesion, Vlesion,L (ml) 25
Initial radius of blood vessel, x0,vessel (cm)
Ascending aorta 1.5
Descending aorta 1.2
Common iliac artery 1
External iliac artery 0.7
Femoral artery 0.5
Common carotid artery 1.2
137
Parameter value
Subclavian artery 1
Intracranial artery, x0,art 0.7
Intracranial capillary, x0,cap 0.2
Intracranial vein, x0,vein 1
Length of blood vessel, lvessel (cm)
Ascending aorta 15
Descending aorta 40
External iliac artery 10
Femoral artery 20
Common carotid artery 25
Subclavian artery 25
Intracranial artery 3
Intracranial capillary 5
Intracranial vein 5
Stiffness of blood vessel, kvessel (N/m, kg/s2 )
Ascending aorta 1800
Descending aorta 2300
Femoral artery 2000
Intracranial artery, keq,art 600
Intracranial capillary, kcap 1000
Intracranial vein, keq,vein 800
Pressure in blood vessels outlet, Pout (mmHg)
Ascending aorta 85
Descending aorta 80
Femoral artery 60
Intracranial artery, keq,art 40
Intracranial capillary, kcap 25
138
Parameter value
Intracranial vein, keq,vein 15
139
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MATHEMATICAL MODEL FOR HEMODYNAMIC AND

INTRACRANIAL WINDKESSEL MECHANISM

Submitted in partial fulfillment of the requirements

Dissertation Advisor: Dr. Kenneth A. Loparo

Department of Electrical Engineering & Computer Science

CASE WESTERN RESERVE UNIVERSITY

SCHOOL OF GRADUATE STUDIES

We hereby approve the thesis/dissertation of

Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

3 Associated Intracranial System 38

6 Simulation Results 103

7 Summary and Conclusions 134

A Parameters for the Model of Hemodynamics and Intracranial Sys-

2.1 Characteristics of various types of blood vessels in humans [10]. . . . 14

4.1 Summary of the equivalent between pulsation of CSF and oscillations

1.1 Current and projected numbers of patients with hydrocephalus, aged

3.1 The concept of Windkessel mechanism. The air reservoir (chamber)

4.1 (a) Two-element Windkessel model, (b) Three-element Windkessel model

1.1 Motivation and Literature Survey

• to elaborate hemodynamics through human major arterial system and intracra-

• to compare intracranial dynamics response for different intracranial conditions

• to assess the possibility of medical balloon insertion with cadence action in

• to provide the hypothesis of the cause of hydrocephalus related to intracranial

• Based on Windkessel mechanism, hemodynamics through major arterial system

• The effect of unilateral mass lesion on intracranial dynamic especially interhemi-

• The abnormalities of intracranial Windkessel mechanism due to space occupying

• The cause of hydrocephalus especially communicating hydrocephalus is hypoth-

• Chapter 2: Review of Physiology

• Chapter 3: Associated Intracranial System

• Chapter 4: Review of Windkessel Model and the Model of Intracra-

• Chapter 5: Mathematical Model

• Chapter 6: Simulation Results

• Chapter 7: Summary and Conclusions

• Appendix: Parameters for the Model of Hemodynamics and Intracra-

2.1 The Cardiovascular System

2.1.2 Vascular System

of progressively smaller diameters, referred to as arteries, arterioles, and capillaries.

toregulation”. The autoregulation reacts to a variation of systemic arterial pressure

Arteries of Head, Neck and Upper Limbs

Arteries of Abdomen and Lower Limbs

2.2 Intracranial Space

Formation, Flow, and Absorption of Cerebrospinal Fluid

2.2.3 Cerebral Blood Flow

A unique characteristic of the cerebral circulation is that it all envelopes within

2.3 Pathological Conditions

2.3.2 Traumatic Brain Injury

An epidural or extradural hematoma (Figure 2.9) is a collection of blood results from

Figure 2.9: Axial noncontrast CT demonstrates an epidural hematoma [199].

A subdural hematoma is a collection of blood commonly caused by a rupture of

meningitis or head trauma [134].

Associated Intracranial System

Pump Chamber Nozzle

Heart Elastic Artery Peripheral Resistance

Figure 3.2: Pressure-dependent arterial compliance [103]

The development of magnetic resonance imaging (MRI) technique in the past

3.3 Intracranial Compliance

As shown in Figure 3.7, the exponential pressure-volume curve can be simplified

where P0 and P are initial and peak pressure level respectively.

Magnetic resonance imaging (MRI) is also non-invasive flow-based method for

3.4 Interhemispheric Pressure Gradients

Significant interhemispheric ICP gradient ranging from 5 to 14 mmHg was ob-

3.5 Effect of Neurosurgical Disorders on Cerebral

evated ICP was produced by expansion of balloon which placed in supratentorial