Advanced MRI

Advanced MR Imaging (2)
Advanced MR Imaging
g g
● Perfusion MRI
● Functional MRI
©louwutao@gmail.com
Advanced MR Imaging
g g
Perfusion MRI
Perfusion MRI
● Perfusion
¾ The delivery of oxygen and nutrients to the cells via
capillaries
ill i
¾ Identified with blood flow which is measured in milliliters
per minute per 100g of tissue
Perfusion MRI
● Perfusion MRI
¾ Methods
Exogenous tracers
● Dynamic Susceptibility Contrast (DSC
DSC-MRI)
● Dynamic
D i CContrast
t tE Enhanced
h d (DCE
DCE MRI)
DCE-MRI)
Endogenous tracers
● Arterial spin labeling (ASL
ASL MRI)
ASL-MRI)
¾ Applications
Stroke
Tumors
Perfusion MRI
● Brain Perfusion Techniques
Dynamic
y Susceptibility
p y Contrast ((DSC
DSC))
● Measurable Parameters
¾ Cerebral Blood Flow (CBF) – The amount of blood moving
through a given amount of tissue per unit time
¾ Cerebral Blood Volume (CBV) – The amount of blood in a given
amount of tissue at any time
¾ Mean Transit Time (MTT) – The average time it takes for the
blood to flow through a unit brain volume
Dynamic
y Susceptibility
p y Contrast ((DSC
DSC))
● Non
Non-deconvolution
deconvolution Approach
¾ Directly employ fitted curves of the concentration of contrast in
volume of interest
Time-to-peak (TTP)
Mean transit time (MTT)
Cerebral blood volume (CBV)
( )
Time-concentration curve
In normal brain tissue, vessel

autoregulation maintains CBF
at 50-60 mL/100g/min.
In irreversible cell
death, CBF<20% of
normal CBF
(Peter Adamczyk, and David S Liebeskind)

Dynamic
y Contrast Enhanced MRI ((DCE))
¾ Widely applied in clinical oncology

¾ Contrast agents
Commonly used gadolinium-based e.g. Gd
Gd--DTPA
Baseline Acquisition
Injection - T1 Map
- 3 Baseline images
- Imaging for ~ 5-10 min including
baseline
Redistri
bution
Dynamic
¾ Tofts Model
Bolus injection
j of contrast
agent (Gd-DTPA)
Plasma Ktrans Extravascular Extracellular

Space (EES)
Cp(t)
Ce(t)
⎧C e (t ) → contrast concentrat ion in EES

Kidneys C(t ) = ⎨
⎩C p (t ) → contrast concentrat ion in blood plasma
K trans ⋅( t −τ )
−
C(t ) = K ∫ C (τ )e
t
trans
p
ve
dτ
0
Dynamic
¾ ROI-based experiment of Tofts model
Normal Lesion
permeability-surface area Product: Ktrans 0.014 0.029
extra-cellular extra-vascular space volume fraction: Ve 0.2 0.5
Arterial Spin
p Labeling
g ((ASL))
● Arterial Spin Labeling (ASL)

¾ Using magnetically labeled arterial blood water protons as
endogenous tracer particles.
particles
¾ Noninvasive, quantitative measurements of cerebral blood
fl
flow (CBF) with
ith relative
l ti insensitivity
i iti it tto permeability
bilit
¾ Don’t require contrast agents
¾ Allowing repeated measurements that may be used to
evaluate multiple interventions
Arterial Spin
p Labeling
g ((ASL))
¾ 1. Tag inflowing arterial blood by

magnetic inversion
¾ 2.
2 Acquire the Tag Image
¾ 3. Repeat experiment without tag
¾ 4. Acquire the Control Image
¾ 5. Subtract: Control Image - Tag Image
Arterial Spin
p Labeling
g ((ASL))
Representative clinical applications of ASL showing hypoperfusion in an acute stroke (A)

and hyperperfusion in a glioblastoma (B).
Arterial Spin
p Labeling
g ((ASL))
A B
Normal ASL CBF maps in a pediatric patient (A) and an adult patient (B).
Diffusion-perfusion
p mismatch
● The combined use of diffusion and perfusion MRI for acute stroke is
based on the concept of the “ischemic penumbra”
● The “ischemic penumbra” is believed to be what can be saved with
prompt treatment
● The combination of diffusion and perfusion MRI offers a means of
visualizing the size off the ischemic penumbra
● Perfusion MRI shows the entire affected territory
● Diffusion MRI shows the already damaged and unrepairable territory
● The penumbra is the difference (the mismatch)
Diffusion-perfusion
p mismatch
Diffusion-perfusion
p mismatch
Diffusion-perfusion
p mismatch
Advanced MR Imaging
g g
Functional MRI
Principle
p of BOLD
● The physiology
- Neuronal activity causes an increase in regional Cerebral Blood
Flow (rCBF).
- There
Th is
i an excess off oxyhemoglobin
h l bi in
i active
ti bbrain
i ti
tissue
● The physics
- Deoxyhemoglobin is paramagnetic Æ T2 decrease
- Oxyhemoglobin is diamagnetic Æ T2 increase
- Paramagnetic objects become magnetized in the presence of a
magnetic field.
- Inhomogeneities in the magnetic field and signal dephasing
● Ph
Physics
i meets t Physiology
Ph i l
- More oxygenated blood when the activation started
- A net decrease in pparamagnetic
g material
- A net increase in signal in activated areas due to less dephasing of
the signal
(Institute of Statistics, National Chiao Tong University, Taiwan)
Principle
p of BOLD
↑neural activity Î ↑ blood oxygen consumption Î ↑ O/D increase Î

↑ T2 signal
fMRI resolution
● Relatively high spatial resolution

● Low temporal resolution
¾ Neural activity within tens to hundreds of ms
¾ Temporal resolution of fMRI = sec
Functional MR Imaging
g g ((fMRI))
● The rise of fMRI
(Smith, Nature, 2012.)
g g ((fMRI))
● Applications
¾ Clinical diagnosis
Presurgical mapping
Risk assessment of invasive brain surgery
Assessment of brain injury
Assessment of patients with disorders of consciousness
¾ Research applications
Mapping brain functions
Detect abnormal neural activity for patients with brain
disease, e.g., Alzheimer's disease, Parkinson's disease
g g ((fMRI))
● Applications
FMRI language mapping in children
(Guibert et al. NeuroImage, 2010)
g g ((fMRI))
● Applications
Resting Functional MRI in Traumatic Brain Injury
(Palacios et al. JAMA Neurol. 2013)

g g ((fMRI))
● Applications
Adolescents with Online Gaming Addiction
©louwutao@gmail.com (Yuan et al. PLOS One, 2013)

g g ((fMRI))
● fMRI Setup
g g ((fMRI))
● Different mode of fMRI

¾ Resting-state fMRI
Mapping of functional networks during rest
¾ Task-based fMRI
Identify subdivisional functions of human brain
Activate neuron by performing different tasks
g g ((fMRI))
● Resting-state fMRI
¾ A scan in which the subject relaxes without falling asleep
and is told not to think about anything in particular while
activation is measured throughout the brain.
I don’t feel
good
The only true resting state?

g g ((fMRI))
● Task-based fMRI
objects
faces
places
● Lateral Occipital (LO) • Parahippocampal Place Area (PPA)

– place-selective
¾ object-selective
• Fusiform Face Area (FFA) or pFs
– face-selective
– ~ posterior fusiform sulcus (pFs)
(Malach, 2002, TICS)
g g ((fMRI))
● Data Analysis
¾ Hypothesis-driven
e.g. general linear model (GLM), dynamic causal model
(DCM)
priori
a i i model
d l off activation
ti ti iis suggested
t d
data is checked to see how closely it matches components of
the model
most commonly used approach
SPM
g g ((fMRI))
● Data Analysis
¾ Data-driven
e.g. Independent Component Analysis (ICA)
no prior hypotheses are necessary
multivariate techniques determine the patterns in the data
that account for the most variance across all voxels
can be
b iinspected
t d tto see if th
there are thi
things h
happening
i iin your
data that you didn’t predict
can be used to identify confounds (e
(e.g.,
g head motion)
need a way to organize the many possible components
g g ((fMRI))
● Functional Connectivity
¾ Areas show correlations in activation
¾ Those areas may or may not be directly interconnected
¾ Why connectivity?
Understanding communications in brain networks
● More interesting than regional activations
● May
M indicate
i di t some abnormal
b l situations
it ti (ASD,
(ASD schizophrenia)
hi h i )
● Connectome!!!
g g ((fMRI))
● Default mode network (DMN)
(Fox & Raichle,

Raichle Nat Rev Neurosci,
Neurosci 2007)
g g ((fMRI))
● ICA in detection of resting-state network
g g ((fMRI))
● Functional Connectivity Reflects Structural Connectivity
g g ((fMRI))
● Altered DMN in AD
ICA-based detection of default-mode network in healthy aging (A) and AD (B).
g g ((fMRI))
● Altered DMN in AD
(Greicius et al., PNAS, 2004)
g g ((fMRI))
● Aberrant DMN in Early Onset Schizophrenia
(Tang et al., PLOS One, 2013)

Studyy Brain as a Network
Graph based network analysis offers new

fundamental insights into global and new integrative
aspects of brain function.
Networks are sets of nodes linked by connections,

connections
mathematically described as GRAPHS. Its structure
can be convenientlyy organized
g as adjacency
j y matrix.
Graph Theory in Brain Network Studies
● What makes such networks complex is not only their

size
i but
b t also
l the
th network’s
t k’ connection
ti t
topology
l and
d
the behavior of the individual network nodes.
● Brain graphs provide a relatively simple and

increasingly popular way of modeling the human
brain connectome, using graph theory to abstractly
define a nervous system as a set of nodes (denoting
anatomical or functional regions) and interconnecting
edges
d (d
(denoting
ti structural
t t l or functional
f ti l connections).
ti )
Brain as a Complex System
● A large number and a great variety of components

¾ Ca
Can be deco
decomposed
posed into
to co
components
po e ts a and
d
interactions, probably on several hierarchical levels
¾ A mixture of order and disorder,
disorder or regularity and
randomness (complex structure and diverse
dynamics)
Brain is a good example of a system that consists of components nested

across multiple hierarchical levels: brain networks
networks, anatomical brain regions
regions,
specialized neural populations, and single neurons
Brain Network Analysis
y
Network
N t k topology
t l analysis
l i
Edge density, Global efficiency, Small-world properties analysis
Cycle probability, Average Global clustering coefficient,
nodal degree characteristic path length,
Small-worldness
Nodal-based analysis S=(C/Crand)/(L/Lrand)
Nodal degree,
Betweenness centrality,
Nodal efficiency, Subgraph-based analysis
Hub identification Local efficiency
Participation coefficients
Network robustness analysis Subgraph centrality
Metrics of Brain Network
Scale Metric Definition
Local Nodal degree The sum of no. of connections
Local clustering coefficient Ratio of no. of existing edges between neighbors and no. of
potential
t ti l connections
ti b
between
t neighbors
i hb
Betweenness centrality Fraction of the number of all shortest paths that pass through a
given node.
Nodal efficiency mean, median,
mean median or harmonic mean of inverse shortest path length
between given node and all other nodes
Complex network analysis aims to characterize brain networks with a small
Global Edge density Proportion of connections relative to no. of potential connections of
number of neurobiologically meaningful
a network and easily computable measures.
Global efficiency Global mean, median of finite entries of the distance matrix (or
inverse distance)
Global clustering coefficient The average of the local clustering coefficient of all nodes.
Regional Subgraph subgraph detected in the correlation matrix at a given threshold
Local efficiency The mean of the finite entries of the inverse distance matrix in
subgraph
Participation coefficients Measure of diversity of inter-subgraphs connections of individual
nodes
(Fortunato, 2010, Latora and Marchiori, 2001, Guimera` et al., 2005).
Structural Brain Networks
White Matter Connectivity

Diffusion tensor imaging (DTI)
Diffusion spectrum imaging (DSI)
Cortical Connectivity – morphological correlation
T1W MRI
Functional Brain Networks
● The human brain can be conceptualized as a complex,

hierarchical network, in which billions of neurons are
precisely organized into circuits, columns, and
f
functional
ti l areas.
● Recent advances in MRI technology have enabled
precise measurements of correlated activity
throughout the brain, leading to the comprehensive
descriptions
p of functional brain networks in humans.
● Examination of functional connectivity become an
important tool to investigate functional changes in
patient populations, healthy aging, and recently also
child development.
Construction of Functional Brain
N t
Network
k
Brain Network Analysis
y in Alzheimer’s Disease
● Structural WM Network (DTI) (Lo et al., 2010)

¾ AD p
patients and controls all have a small-world topology
p gy
¾ AD:
Increase in shortest p
path length
g
Decrease in global efficiency compared with controls
● Functional network ((fMRI)) (Zhao et al., 2012, Sanz-Arigitaetal et
al., 2010)
¾ topological properties were disrupted in AD patients
increased local efficiency
decreased global efficiency
no significant differences were found in cluster coefficient
significant synchronization differences was found in AD

Advanced MRI

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Advanced MRI

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Advanced MR Imaging (2)

● Brain Perfusion Techniques

In normal brain tissue, vessel

(Peter Adamczyk, and David S Liebeskind)

¾ Widely applied in clinical oncology

Plasma Ktrans Extravascular Extracellular

⎧C e (t ) → contrast concentrat ion in EES

¾ ROI-based experiment of Tofts model

● Arterial Spin Labeling (ASL)

¾ 1. Tag inflowing arterial blood by

Representative clinical applications of ASL showing hypoperfusion in an acute stroke (A)

↑neural activity Î ↑ blood oxygen consumption Î ↑ O/D increase Î

● Relatively high spatial resolution

● The rise of fMRI

(Palacios et al. JAMA Neurol. 2013)

©louwutao@gmail.com (Yuan et al. PLOS One, 2013)

● Different mode of fMRI

The only true resting state?

● Lateral Occipital (LO) • Parahippocampal Place Area (PPA)

● Default mode network (DMN)

(Fox & Raichle,

● ICA in detection of resting-state network

● Functional Connectivity Reflects Structural Connectivity

ICA-based detection of default-mode network in healthy aging (A) and AD (B).

● Aberrant DMN in Early Onset Schizophrenia

(Tang et al., PLOS One, 2013)

Graph based network analysis offers new

Networks are sets of nodes linked by connections,

● What makes such networks complex is not only their

● Brain graphs provide a relatively simple and

● A large number and a great variety of components

Brain is a good example of a system that consists of components nested

Scale Metric Definition

Local Nodal degree The sum of no. of connections

Regional Subgraph subgraph detected in the correlation matrix at a given threshold

White Matter Connectivity

● The human brain can be conceptualized as a complex,

● Structural WM Network (DTI) (Lo et al., 2010)

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