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Diagnostic Imaging Methods

in Central Nervous System


Disorders
P. Danilo J. Lagamayo, MD
Headache:
Primary:
Migraine
Cluster
Tension
Secondary:
Increased Intracranial Pressure:
Neoplasms
Abscess
Granulomas
Meningeal Irritations:
Meningitis
Subarachnoid Hemorrhage
Vascular Disorders:
Stroke
Malformations
Arteritis
Head Trauma:
Concussion
Hematoma
Other Cranio-Facial Pains:
Trigeminal Neuralgia
Incidence of Primary Brain
Tumors:
- 6 persons / 100,000
population / year
- about 1 in 12 primary brain
tumors occur in children
under 15 years old.
Clinical Presentation of Brain
Tumors:
Focal neurologic deficit
Increase intracranial
pressure: -
Headache that is more severe in AM
- Nausea / Vomiting
- Diplopia
- Papilledema
- Ontundation &
Lethargy (ominous) Focal
neurologic signs and symptoms:
- seizure, seen in about ½ of
Clinical Presentation of Brain
Tumors: (II) Non-localizing
findings: - fatigue
- malaise
- impotense
-
glactorrhea -
growth failure
- macrocephaly in young children
Pathological Classification of
Intracranial Tumors:
Neuroepithelial:
Astrocytes -
Astrocytoma
Oligodendrocytes - Oligodendroglioma
Ependymal cells
& Choroid Plexus-
Ependymoma
Choroid Plexus Papilloma Neurons -
Gangliomas,
Gangliocytomas,
Neuroblastomas
Pineal cells - Pineocytomas
Pineoblastomas
Poorly differentiated
Pathological Classification of
Intracranial Tumors: (cont.)
Meninges - Meningioma
Nerve sheet cells -
Neuroma
- Neurofibroma Blood vessels
- Hemangioblastomas Germ cells
- Germinoma
- Teratoma Tumors
of malde-
velopmental origin -
Craniopharyngioma
- Epidermoid/Dermoid
cyst
Pathological Classification of
Intracranial Tumors:
Anterior pituitary gland
- Pituitary adenoma
- Adenocarcinoma
Local extension
- Chordoma from adjacent
- Glomus jugulare tumors
- Chondroma
- Chondrosarcoma
- Cylindroma
Incidence of Tumors:
Glioblastoma - - - - - - - - -
55% Astrocytoma - - - - - - - - -
20.5% Ependymoma - - - - - - - -
6% Medulloblastoma - - - - - -
6% Oligodendroglioma _ - - -
5% Choroid Plexus
Papilloma 2%
Other less common entities:
Neuronal tumors –
Gangliocytomas,
ganglioglioma Embryonal
– PNET Pineal
Region – germ cell
Primary Imaging
Methods for Diagnosis of
CNS tumors:
- MRI
- CT scan
- Angiography
Advantages of CT Scan
- Wide availability;
- Can accommodate life support systems;
- Fast imaging methods
- Can show bone structures and their
pathologic changes like fractures;
- Cheap.
Disadvantages of CT Scan
• Cannot demonstrate soft tissue detail of
the sella turcica, the brain stem and the
cerebellum;
• Not very sensitive to white matter lesions;
• Cannot differentiate encephalomacic
lesions of hemorrhage from infarcts;
• Uses ionizing radiation and cannot be
used on pregnant patients.
Advantages of MRI
• Unaffected by the thick bone encasement of the
calvarium in the posterior fossa and the sellar
turcica;
• Accurate determination of the age and evidence
of hemorrhage;
• More sensitive for detection of white matter
lesion;
• Ability to perform multiplanar imaging;
• Does not use radiation and can be safely used
on pregnant patients.
Disadvantages of MRI
• Longer time needed to complete an
examination;
• Needs patient cooperation, e.g. patient
must not move during an imaging
sequence that can take anywhere from 1
minute to as long as 7 minute;
• Any metal implement is not allowed into
the MR room.
Disavantages of MRI
• Cannot image patients with:
– Pacemakers
– Neurostimulators
– Newly applied vascular clips
– Vacular clips with ferromagnetic materials
(steel or iron)
– Metal foreign bodies in the orbit
– Claustrophobic patients
– Patients who need extensive life support
Causes of Low Signal
Intensity in Tumors in T2WI:
Paramagnetic effects
- Iron with dystrophic Ca
or necrosis -
Ferritin/hemosiderin from prior bleed
- Deoxy hgb in acute bleed
- Intracellular met hgb in early
subacute bleed - Melanin (or other
free radicals)
Causes of Low Signal
Intensity in Tumors in T2WI
(cont.):
Low spin density
- Calcifications
- Scant cytoplasm
(high
nucleus:cytoplasm ratio) -
Dense Cellularity
Fibrocollagenous stroma
Macromolecule content
Very high (non-
paramagnetic) protein content
Causes of High Signal Intensity
in Tumors in T1WI:
Paramagnetic effects from hemorrhage
- Subacute – chronic
blood (met hgb) Paramagnetic
materials w/out hemorrhage
- Melanin
- Naturally occuring ions associated with
necrosis of calcification:
Manganese, Iron, Copper
Non-paramagnetic effects
- Very high
(non-paramagnetic) proteins - Fat
-
Requirements for contrast
enhancement:
- absence of blood-brain barrier
- adequate delivery of contrast
material - extracapillary interstitial
space to
accommodate contrast
- appropriate contrast dosage
- spatial resolution
- imaging parameters to
allow contrast detection
- time for
Mechanism for contrast
enhancement in CNS tumors:
Formation of capillaries with
deficient blood-brain barrier rather
than the destruction of blood-barrier is
presumed as the mechanism for tumor
enahcement.
The capillaries of metastatic
tumors to the brain has no blood-brain
barrier since these tumors come from
elsewhere and not from the brain.
Type of enhancement:
-immediate or delayed
- evanescent or
persistent - dense
and homogenous -
minimal or irregular

Note: Lack of tumor enhancement do


not signify lack of tumor.
Effects of Tumor Necrosis on
Signal Intensity:

Short relaxation times Hemorrhage


Liberation of
cellular iron Release
of free radicals
Proteinaceous debris
Prolong relaxation Cystic change with
increased times
water
Frequently Cystic Tumors
Colloid cyst
Craniopharyngioma
Desmoplastic infantile ganglioma
Dermoid
Ependymoma (supratentorial and spinal)
Epidermoid
Ganglion cell tumors
Glioblastoma (cystic necrosis)
Hemangioblastoma
Pilocytic astrocytoma
Pleomorphic xanthoastrocytoma
Rathke cleft cyst
Magnetic Resonance Criteria for Cystic
Lesions
Morphology Sharply demarcated, round
smooth
Signal Intensity Isointense to cerebrospinal fluid
on all spin echo images (tumor
cysts can be hyperintense due to
↓ T1)
Fluid-debris levels Intracellular blood-cyst fluid
(bleed into necrotic Intracellular blood-extracellular
or cystic regions) blood
Motion of intra- Lesion emanates ghost images
lesional fluid along phase-encoding axis
Intralesional signal loss
(especially on steady-state
sequences)
Hemorrhagic Tumors
Primary brain tumors
Glioblastoma/anaplastic asctrocytoma
Anaplastic
oligodendroglioma/oligodendroglioma
Ependymoma
Teratoma
Metastatic disease
Melanoma
Renal cell carcinoma
Choriocarcinoma
Lung carcinoma
Breast carcinoma
Thyroid carcinoma
Intratumoral Hemorrhage vs. Benign
Intracranial Hematomas
Intratumoral hemorrhage:
- Markedly heterogenous, related to:
Mixed stages of blood
Debris-fluid (intracellular-extracellular blood) levels
Edema + tumor + necrosis with blood
- Identification of nonhemorrhagic tumor component
- Delayed evolution of blood breakdown products
- Absent, diminished, or irregular ferritin/hemosiderin
-Persistent surrounding high intensity on long TR images
(i.e., tumor/edema) and mass effect, even in late stages
Intratumoral Hemorrhage vs.
Benign Intracranial Hematomas
Benign hemorrhage:
- Shows expected signal intensities of acute,
subacute or chronic blood,
depending on stage of hematoma

- No abnormal nonhemorrhagic mass


- Follows expected orderly progression
- Regular complete ferritin/hemosiderin rim
- Complete resolution of edema and mass
effect in chronic stages
Intratumoral Melanin vs. Hemorrhage
Signal intensity
(relative to gray matter)
T1-weighted T2-weighted
Image Image
Amelanotic tumor ↓ sl. ↑
Melanotic tumor ↑↑ = or sl. ↓
Early subacute blood
(intracellular methemoglobin) ↑↑ ↓↓
Late subacute blood
(extracellular methemoglobin) ↑↑ ↑↑
ssification of Astrocyctic Brain Tum

Diffuse (infiltrative) Localized (circumscribed)


Astrocytoma Pilocytic astrocytoma
Anaplastic astrocytoma Pleomorphic
Glioblastoma multiforme xanthoastrocytoma
Subependymal giant cell
astrocytoma
Diffuse Astrocytic Brain
NeoplasmsAnaplastic astrocytoma
Astrocytoma
Typical site(s) of Cerebral hemisphere Cerebral hemisphere
origin (adult) (adult)
Brainstem (child) Brainstem (child)
Cerebellum (young adult)
Signal intensity Homogeneous; high Some heterogeneity
characteristics(on intensity
T2-weighted
image) Not seen Unusual
Vascular flow voids Variable; irregular Common; irregular
Contrast
enhancement 7-8 yr 2-3 yr
Prognosis (median
survival, if
available)
Diffuse Astrocytic Brain Neoplasms
Glioblastoma Gliomatosis
Typical site(s) of Cerebral hemisphere Cerebral hemisphere
origin (adult) (young
or middle-aged adult)

Signal intensity Markedly heterogeneous;


characteristics(on hemorrhage and Ill-defined; high intensity
T2-weighted necrosis common
image) Common
Vascular flow voids Rare
Common; irregular
Contrast Uncommon
enhancement 12 mo
Prognosis (median Estimated as months
survival, if
available)
atric Supratentorial Hemispheric Neopla
Juvenile pilocytic Ganglioglioma
astrocytoma
Signal intensity Sharply demarcated; Sharply demarcated;
characteristics commonly cystic commonly cystic
(on
T2-weighted Common; dense Common; irregular
image)
Contrast Rare Rare
enhancement Uncommon Common
Hemorrhage Excellent Excellent
Calcification
Prognosis
atric Supratentorial Hemispheric Neopla

Pleomorphic Embryonal tumor


xanthoastrocytoma (e.g., cerebral
neuroblastoma)
Signal intensity Sharply demarcated Markedly
characteristics with subjacent cyst heterogeneous
(on
T2-weighted Common in solid Common; irregular
image) portion
Contrast Rare Common
enhancement Uncommon Common
Hemorrhage Variable Poor
Calcification
Prognosis
iatric Supratentorial Hemispheric Neopla

DNT
Signal intensity Sharply demarcated
characteristics heterogeneous
(on
T2-weighted Unknown
image)
Contrast Rare
enhancement Common
Hemorrhage Excellent
Calcification
Prognosis
ntraventricular Masses
Tumor type Typical location
Central neurocytoma Lateral (attached to septum pellucidum)
Ependymoma Fourth, lateral
Subependymoma Lateral, fourth
Oligodendroglioma Lateral
Pilocytic astrocytoma Lateral, third, or fourth
Meningioma Lateral (atrium)
Choroid plexus tumor Lateral (atrium) or third in children, fourth in adults
Epidermoid Any ventricle
Subependymal giant Lateral
cell
astrocytoma Third
Colloid cyst Any ventricle
Arachnoid cyst
ntraventricular Masses
Tumor type Intensity characteristics Contrast enhancement
on T2-weighted images
Central neurocytoma Isointense to gray matter Usually dense
Ependymoma Heterogeneous Heterogeneous
Subependymoma Hyperintense to gray None
Oligodendroglioma matter
Pilocytic astrocytoma Heterogeneous Variable; irregular
Meningioma Hyperintense to gray Dense
matter
Choroid plexus tumor Dense
Isointense to gray matter
Epidermoid None
Heterogeneous
Subependymal giant Generally enhance
cell astrocytoma Slightly hyperintense to
CSF
Colloid cyst Limited enhancement at
Hyperintense to gray periphery
matter
Arachnoid cyst None
Hyperintense to gray
matter Isointense to CSF
Posterior Fossa Tumors in
Childhood
Juvenile pilocytic
astrocytoma
Medulloblastoma

Signal intensity Sharply demarcated; Homogeneous; low to


characteristics commonly cystic moderate intensity
(on T2-WI)
Contrast Common in solid
enhancement portion (mural nodule) Common; dense
Calcification Uncommon Uncommon
Hemorrhage Rare Uncommon
Tendency to seed Extremely low High
CSF pathways
Prognosis >90% 10-yr survival 50% 5-yr survival
(estimated
survival)
Posterior Fossa Tumors in
Childhood
Ependymoma Diffuse pontine glioma
Signal intensity Markedly heterogeneous Ill-defined; high intensity
characteristics
(on T2WI)
Contrast Common; irregular Variable
enhancement
Calcification Common Rare
Hemorrhage Common Common
Tendency to seed Low to moderate Low
CSF pathways
Prognosis 65-70% 5-yr survival <1-2% 5-yr survival
(estimated
survival)
ineal Region Tumors
Germinoma Teratoma Pineoblastoma
Age; sex Child; male Child; male Child; none
predilection
Pineal vs. Pineal Pineal Pineal
parapineal
Signal intensity Homogeneous Strikingly Homogeneous
(heterogeneous (but often heterogeneous (unless
vs. hemorrhagic) hemorrhagic)
homogeneous)
Hemorrhage Common Typical Common
Calcification Rare Typical Common
Brain edema or Common Variable Common
invasion
Tendency to Yes Variable Yes
metastasize
Enchancement Dense Variable Dense
Prognosis Excellent Variable Poor
neal Region Tumors
Pineocytoma Glioma Meningioma

Age; sex Adult; none Child; none Adult; none


predilection
Pineal vs. Pineal Parapineal Parapineal
parapineal (usually) (usually)
Signal intensity Variable Homogeneous Homogeneous
(heterogeneous (usually)
vs.
homogeneous)
Hemorrhage Common Rare Rare
Calcification Common Common Common
Brain edema or Uncommon Primarily Occasional
invasion midbrain
Tendency to No Variable No
metastasize
Enchancement Dense Variable Dense
Prognosis Variable Variable Excellent
Magnetic Resonance Findings in
Extraaxial Mass Lesions
Suggestive Definitive
Peripheral, broadly based Cerebrospinal fluid cleft
along calvarium between
Overlying bone changes brain and lesion
Vessels interposed between
Enhancement of adjacent brain
and lesion
meninges
Cortex between mass and
Displacement of brain from
(edematous) white matter
skull
Dura (meninges) between
(epidural) mass and brain
Stroke: a new,
often acute,
loss of

neurologic
function
secondary
to
parenchymal
ischemia or
Main Etiologies for
Symptomatology of Stroke:
1. Cerebral Infarction
2. Intraparenchymal
Hemorrhage
3. Subarachnoid
Hemorrhage
Role of Imaging in Stroke:
1. Rule out hemorrhage
2. Rule other causes
of stroke syndrome
3. Help assess
etiology in known
ischemic infarction
The Normal Brain:
To sustain the normal
brain, a normal mean
regional cerebral blood
flow (rCBF) must be
maintained at about

54 (± 12 ml) /
100 g / min
The Normal Brain:

The threshold for


cerebral ischemia is
approximately at:
23 ml / 100 g
/min.
Autoregulation plays a very
important role in maintaining
intracerebral blood flow.

This mechanism can be


temporarily lost in ischemia
leaving the control of blood
flow to peripheral flow
volumes.
Ischemic Strokes:
1. Large Artery or Atherosclerotic
Infarction
2.
Cardioembolic Infarction
3. Small Vessel Infarction
4. Venous Infarction
The Abnormal
Brain:
Between cerebral
blood flow rate of:

15 & 20 ml / 100
gm / min.,
ischemic brain injury
begins w/ loss of
neurologic function,
noted as flattening of
the
electroencephalogram
The Abnormal
Brain:
Blood flow values
below:

10 ml / 100 gm /
min.,
may lead to
infarction within a
few minutes.
The Ischemic Brain:
There are two ischemic changes
thresholds, one occurring at blood
flow range of 15-20 ml / 100 gm
/ min., resulting to loss of electrical
function and another one at 10ml /
100 gm / min. , resulting to loss of
cell polarizaton.
PENUMBRA
Heterogeneity in brain injury has been
documented in an infarcted zone.
Blood flow to an infarcted zone is said to
have:
A. a central region or core of very low
flow that results in rapid cell demise
and
B. a peripheral penumbra where decline
in flow is more moderate and cell
death is not immediate.
PENUMBRA
The penumbra is thought to
represent salvageable tissues that
may go on to infarction.

If blood flow is normalized at an


adequate time, the brain cells will
normalize.
Imaging in stroke:
Most commonly used imaging method
non-contrast CT scan but MRI is fast
catching-up.
CT scan is commonly used in stroke
due to:
- Widespread and ready availability;
- Ease of hemorrhage detection;
- Compatibility with monitoring
equipment;
- Rapid scanning techniques for
unstable patients.
Emergent evaluation in Acute
Stroke:
Goals:
- Confirm cause of deficit is stroke
related.
- Assess possible reversibility of
the lesion.
- Determine most likely etiology.
- Predict likelihood of immediate
complications.
- Begin appropriate treatment.
Emergent Evaluation in Acute
Stroke:
Opportunities for Intervention:
- Before any clinical symptoms.
- After transient ischemic attack or
minor stroke.
- During acute ischemic stroke.
- Before a recurrence.
Imaging Signs of Hyperacute
Infraction:
1. Hyperdense LMCA sign
2. Loss of gray-white matter
differentiation
3. Sulcal effacement.
4. Loss of insular ribbon.
5. Obscurred lentiform nucleus.
Lacunar Infarction:
- Not larger than 1.5 cm

- Deep gray
matter

- Brain stem

- Deep hemispheric
Cardioembolic Infarction
- Relative stasis resulting to mural
thrombus, ex.: M.I., atrial fib.,
ventricular aneurysm
- Valvular heart disease
resulting to vegetation or from
prosthesis - Cardiac tumors

- Congenital HD,
ex.: right to left shunt
Watershed Infarction:
- Boundary zone infarct
- Internal carotid stenosis
or occlusion
- Systemic
hypotension - Embolic
events
Hemorrhagic Infarction:
- Hemorrhagic transformation results
to petechial hemorrhage or
frank hematoma -
Anticoagulant therapy
- Thrombolytic agents
- More common in cardioembolic strokes
- Larger cardioembolic strokes are
more likely to bleed
Temporal Evolution of Infarction on
CT Scan:
0 – 4 hrs. Normal to subtle hypodensity
± sulcal effacement

1 – 7 days Mass effect peaks at 3 – 4 days

1 – 8 weeks Contrast enhancement

Days to Hypodensity
months/ yrs
Acute to Subacute Infarction
Changes:
1. Vasogenic Edema
that later on wanes
2. Enhancement -
(Luxury perfusion)
3. Petechial hemorrhage
Hypertensive Hemorrhage
In hypertensives, hyalinization within
the walls of small cerebral vessels
results in
microaneurysms
that are less than 1.0 mm in size,
(Charcot & Bouchard),
that tend to arise from perforating
vessels that will later on bleed.
Some of the Causes of ICH:
Hypertension
Amyloid Vasculopathy
Aneurysm
A-V malformation
Neoplasm
Coagulation disorders, e.g.
hemophilia
Aticoagulants
Vasculitis
Drug abuse e.g. cocaine
Trauma
Idiopathic
Hypertension accounts for 40-50%
of deaths from non-traumatic
hemorrhage in an autopsy series.
In young (less than 40 y/o)
normotensive patients, cause
remains unknown but cryptic AVM
is a suspect.
Why is there a need to measure
hemorrhage size?
Volume of the hemorrhage is a
strong indicator of the 30 day
survival of the patient.
Methods of measuring ICH
Volume:
A. Direct volume measurement in
the CT Scan system or in a
work station;
B. Planimetry
C. Application of the formula for
the sphere:
Volume = 4/3 π (r)3
D. ABC/2 method
Among different methods of volume
measurements, the direct volume
measurement in the CT scanner is the
most accurate but this would depend
on the cooperation of the facility
operators.
Once the patient data is deleted from
the memory file of the system, the
direct volume measurement can no
longer be applied on the data in the
hard copy (film).
In older model CT Scan where volume
measurement is not available, an
alternative method is possible by using
the area of the hemorrhage:
Volume in cubic cm =
Area x slice thickness (millimeters)
1000
ABC/2 Method:
Kothari, et. al., has developed a simple
bedside method of ICH volume
determination with the following
formula:

ICH volume = A x B x C
2
ABC/2 Method (continued):
Step 1: The largest dimension of the
hemorrhage is determined in the
series of CT slices, then the
largest diameter of the hematoma
is measured and labeled - A;
Step 2: On the same slice, the largest
diameter of hemorrhage 90o to A is
determined and labeled – B.
ABC/2 Method (continued):
Step 3: “C” or the cephalocaudal
dimention of the hemorrhage is
determined by comparing the rest
of the CT slices to the largest
hemorrhage on the scan.
If the hemorrhage area is 75 % of
the largest hemorrhage area =
one (1) slice for determining C;
ABC/2 Method (continued):
Step 3: If the area was 25 to 75% of the
slice where the hemorrhage was
largest, the slice is considered
as one-half a hemorrhage slice;

If the area was less than 25 % of


the largest hemorrhage, this is
not considered as a hemorrhage
slice.
When the CT slice thickness is smaller
than the table movement, as will be
commonly encountered in CT slices of
the posterior fossa, there will necessarily
be the presence of inter-slice gaps.
To remedy this, use the table movement
measurement for thickness of the slice
instead of the actual slice thickness to
calculate for volume.
1 2

3 4
A
(2)
B

“1” slice
ABC/2 Method:
(A x B x C ) ÷ 2 = Volume in cc
A = 4.0 cm
B = 2.6 cm
C = 2.5 cm
(4.0 x 2.6 x 2.5) ÷ 2 = 13 cc
Actual computation directly done
in the CT scan = 13.3 cc
Reliability & Reproducibility of the ABC/2 Method of
Measuring Intraparenchymal Hemorrhage Volume

Reader No. Intraclass Difference From P† Mean Time per


Correlatio Planimetric,* Measurement,‡
n cm3 s
1 (Neurosurgery 20 .99 -2.0 ± 1.2 .11 35
faculty)
2 (Neurosurgery 20 .99 0.6 ± 3.0 .85 40
resident)
3 (Emergency 20 .99 0.8 ± 1.3 .55 33
physician)
4 (Nurse) 20 .99 -2.5 ± 1.5 .07 31
Interrater reliability (readers 1-4): Interclass correlation = .99
Intrarater reliability (reader 3): Interclass correlation = .99 (P=.19)

* Mean±SE difference from planimetric measurement.


† Difference from planimetric measurement.
‡ Mean time to determine hemorrhage volume per CT scan with the ABC/2 technique
Mean Hemorrhage Volumes
Hemorrhage Volume, cm3

Location No. Planimetric ABC/2 R2

Deep 83 23.0 ± 2.7 23.5 ± 2.9 .94


Lobar 21 44.6 ± 8.4 49.9 ± 9.9 .96
Brain 8 13.6 ± 7.2 12.3 ± 6.3 .99
Stem
Cerebellar 6 19.6 ± 4.3 24.4 ± 5.9 .78
Total 118 26.0 ± 2.6 27.5 ± 2.9 .96
Hemorrhage volumes are mean ± SE.
Temporal Evolution of ICH

Biochemical Clinical Stage Approximate Time


Form of Appearance
Immediately to first
OxyHg in RBCs Hyperacute
several hours
DeoxyHg in
Acute Hours to days
RBCs
MetHg in RBCs Early subacute First several days
Extracellular Subacute to
Days to months
MetHg chronic
Ferritin and
Remote Days to indefinitely
Hemosiderin
Temporal Evolution of ICH

Biochemical Intensity on Intensity on


Form T1WI T2WI

OxyHg in RBCs ≈ 

DeoxyHg in
≈,  
RBCs
MetHg in RBCs  
Extracellular
 
metHg
Ferritin and
≈,  
hemosiderin
Acute Infarction findings in MRI:
1. Lesion in arterial distribution
2. High intensity in Proton
density or in T2 FLAIR
3. Gyral swelling / sulcal
effacement 4. Absent arterial flow void
5. Subcortical white matter
hypointensity 6. Intravascular
contrast enhancement
Diffusion weighted imaging:
-Signal attenuation is noted in areas of free
diffusion -
Signal intensity is increased in areas of
restricted diffusion with decrease in apparent
diffusion coefficient in brain tissue
- Decrease in
diffusion of water in early ischemia is due
to shift of water from extracellular to
intracellular