Random, microscopic, translational movement
of molecules in a medium.
Depends on the temperature, type of particles
& the environment.
The brownian motion in living tissues is
measured quantitatively by applying specific
MR gradient sequences.
• Diffusion is the
motion of molecules.
• With MRI, we can
direction of the
diffusion of water
molecules in vivo.
Diffusion coefficient (D) measures the
diffusivity of a particle in a medium.
D is the distance traveled by a molecule in unit
This is a characteristic of the molecule &
contributes to the tissue characterization.
Human tissue D - 0.2×10-3mm2/s in the
corpus callosum to 3×10-3mm2/s in CSF.
Isotropic In homogenous fluids of infinite
extent diffusion is a random, unlimited
Anisotropic in organized media with
asymmetric structure the diffusion might be
more restricted in one direction than the other.
Diffusion weighted imaging
Measurement of diffusion – new approach to
tissue characterization & functional studies.
MRI is the only technique available today to
evaluate diffusion with accuracy and spatial
Molecular mobility also create changes the
conventional sequences, but these are also
affected by variations in the MR environment
& complex rotational motion.
Unique features of DWI
Directly reflects molecular mobility.
Relates only to translational motion.
Does not depend on the MR environment.
New source of totally non-invasive
contrast in the field of MRI.
DWI is based mainly on the diffusion of water
Water diffuses freely across the capillaries &
the cellular intestitium.
Also diffuses across cell membranes & tissue
Pure water at 37*C diffuses at a rate of
Tissues- Diffusion is restricted & less random.
Due to High viscosity of bulk water in the
tissues which contain large molecules like
Obstructions to diffusion – cell wall,
membranes, fibres, I/C organelles.
Diffusion distance does not increase infinitely
with time; it saturates when it has reached all
Tissues (normal/abnormal) with different
viscosities or different arrangement of
obstructions presents as different D which is
the source of contrast in DWI.
The obstacles to diffusion results in
measurable restricted diffusion effects.
This allows the study of compartments which
are much too small to be observed by the
conventional MR methods.
RD may not be complete – leak diffusion
parameters may be used to measure the
permeability of these barriers.
Diffusion weighted image
Areas of restricted
DIFFUSION WEIGHTED IMAGING
Diffusion imaging of water is based on the fact
that MR signals are sensitive to motion.
In presence of a magnetic field gradient,
protons carried by moving water molecules
undergo a phase shift of their transverse
These phase shifts are random and widespread
and finally attenuate the MRI signal.
Images are obtained by incorporating strong
magnetic field gradient pulses into an imaging
In MR imaging the motion of water
molecules by diffusion through a
magnetic field gradient results in
irreversible signal loss through
This signal attenuation has the form of an
As the diffusion increases there is an
exponentially greater signal loss in in the MR
Non-DWI the diffusion effects contribute <2%
to the signal attenuation.
Using sequences that are highly susceptible to
the diffusion effects DWI.
Strong pulsed gradients during evolution of
the MR signals generated either by spin echo/
gradient echo, usually using echo planar
Various techniques to sensitize MR sequence
Possible to vary the strength/duration of the
diffusion sensitizing gradients or their
direction to enhance the diffusion effects.
Spin-echo variants Gradient pulse pattern
Stimulated echo sequence
Gradient echo variants Turbo sequence
Steady state free
Diffusion measurements are based on a
labeling procedure where water molecules are
marked with respect to their initial position
through the application of a magnetic field
Followed by a registration of how far the
molecules has moved during a specified time
Reduction of the MR signal is more for
molecules that has been subject to a larger
Following the two measurements, it is
possible to determine the diffusion rate,
expressed in terms of the diffusion coefficient.
b - VALUE
A factor which summarizes the gradient pulse
strength & duration used to generate the
diffusion weighted sequence.
Also represents how sensitive the sequence
will be to the diffusion effects.
As b-value increases the effect of diffusion on
the image increases, ie it denotes the amount
of diffusion weightage.
Clinical imaging 1000sec/mm2
ECHO PLANAR IMAGING
The sequences used in DWI are deliberately
sensitized to motion by the addition of large
Bulk motions lead to widely dispersed artifacts
Macroscopic motion artifact.
Best way to limit motion artifacts - single shot
EPI is a technique to record an image within a
With EPI the entire set of echoes needed to
form an image is collected in a single
acquisition period of 25-100ms.
For this a signal formation is split into a series
of gradient echoes – the interval between each
gradient is typically a few 100 micro seconds.
EPI can be applied to almost any sequence
ADC –Apparent Diffusion Coefficent.
More accurate representation of the measured
D in biological tissues.
ADC of water is 2-3 times less than the D of
This decrease becomes more prominent with
passing time as more no: of molecules
encounter the obstacles.
An ADC map is the quantitative image
of the calculated ADC values for each
An area of restricted diffusion appears
low D Appears dark on ADC map.
Corresponding DWI Bright.
3 Dimensional process.
Molecular mobility may not be the same in all
Due to 1. Physical arrangement of the medium.
2. Asymmetric arrangement of the
Muscle fibres & neurons- water with in &
outside cell membranes diffuse more rapidly
than across the membranes.
• When there is an
molecules will move
to the fibre direction.
This results in difference in the
measured diffusion coefficients when
the diffusion gradient is applied in
Structures with Faster diffusion- dark.
Slower diffusion- bright.
Anisotropy in cerebral white matter
Directional variations in the arrangement of
white matter fibres in the cerebrum.
Axial sections-Projection fibrecranio-caudal
Different D and different appearance for
different white matter fibres in the same
When measurements are made parallel to the
direction of the fibres, diffusion is faster
Higher measured D Dark.
Also due to the facilitated transport favoured
by the highly oriented intra-axonal micro
structures like micro tubules & micro filaments
in relation to the axoplasmic transport.
Diffusion measured across the myelin fibres is
less Brighter images.
Due to the decreased water mobility through
the successive lipid layers.
Applications in the study of myelin fibre
orientation in disorders like multiple sclerosis
& abnormal white matter myelination in
DIFFUSION TENSOR IMAGING
The means to most accurately represent the
diffusion properties of a tissue.
D/T anisotropy diffusion is sensitive to
The most precise depiction of diffusion is a
vector with both direction & magnitude.
A tensor completely describes the diffusion
properties of a tissue.
Each element in a tensor represents a
measured diffusion coefficient with
directional indices & represents how
directionally dependant/ how anisotropic
each voxel is compared to its neighbors.
If measurements are performed in six or
more directions, it is possible to analyze
and visualise the diffusion anisotropy.
The method allows for estimation of the
degree of diffusion expressed as the
fractional anisotropy (FA) index.
Color maps can be used for visualizing
the direction of white matter fiber tracts.
DTI can further separate distinct axonal
pathways based on their fiber orientation
by determining the direction of greatest
In white matter tracts containing
coherently organized parallel fibers, the
direction of greatest diffusivity coincides
with the fiber orientation.
that can follow
point to point in
the human brain,
of white matter
T2 shine through:
DWI involves substantial T2 weighting.
Areas of T2 prolongation may result in
the carry over of the hyperintense signal
to the corresponding DWI.
Comes into picture while dealing with
conditions where abnormal areas are
extremely bright on T2WI.
Here it becomes difficult to determine
whether a bright area on DWI is due to
this effect or due to restricted diffusion.
ADC maps are helpful in differentiating
Only if a hyperintense area shows a
hypointensity on ADC map Restricted
Hyper intensities d/t white matter
Recognised with experience.
Eliminates anisotropy. Combined
DWI so that weightage is applied in
all the 3 cardinal directions.
Creates isotropic images.
Difference in the diffusivity of water
molecules in normal & abnormal tissues are
traced by DWI.
2. Differentiation of cysts and solid tumours
3. White matter abnormalities
4. Inflammatory conditions
5. Measure deep body temperature
Major application of DWI is to detect CVA at a
very early stage.
Changes in the D occurs with minutes after the
interruption of blood flow; where all other
conventional imaging modalities usually fail.
Tissue damage reversible reperfusion /
neuron tissue protection therapy.
As early as 30mts after the ischemic
With CT & T2W MR infarcts are
detected usually after 24 hrs.
Acute ischemic lesions are characterized
by high signal intensity on DW images
and low ADC values.
ADC IN ISCHEMIA
ADC values.—It is accepted that ADC
values decline rapidly after the onset of
ischemia and subsequently increase.
Peak signal reduction-between 8-32 hrs.
Remains low for 3 –5 days.
Then increases –reaches baseline in 1-4
Interruption of CBF Rapid breakdown
of energy metabolism and ion exchange
pumps Shift of extracellular water to
the intracellular compartment
The IC compartment is more confined
More restricted diffusion.
Produces a typical "bright spot" on DW
Persistence of cytotoxic edema +
Development of vasogenic edema Cell
Leak of water into the EC compartment.
Diffusion is now less restricted.
Hyperintensity of DWI decreases
Mainly to differentiate solid tumors from
cystic lesions with high protein content.
Some complicated cystic lesions may have
appearance similar to solid tumors in T1 & T2.
DWI demonstrates the fluid nature in such
Tumor cellularity is a major determinant of
ADC values of brain tumors.
DWI and ADC maps cannot distinguish
neoplastic cell infiltration from peritumoral
edema in patients with malignant disease.
DWI NOT AT ALL
SPECIFIC FOR TUMOR
The signal intensity of gliomas on DWI is
Solid component of the lesion appears hyper-
intense where as necrotic elements are hypo-
intense on DWI.
ADC values cannot be used in individual cases
to differentiate glioma types reliably.
Iso / Hypo intense on
Hyper intense with
edema on T2W.
• Necrotic components
hypointense on the
DWI & peritumoral
vasogenic edema is
diffusion –dark &
increased T2 values
of edema –bright]
fluid & necrotic
component of the
diffusion) on the
The necrotic components of metastases show a
marked signal suppression on DW images and
increasedADC values (may be related to
increased free water).
Cerebral abcess show a central hyperintensity
on DW images with reduced ADC values
Hyperintensity in cavities is ascribed to
restricted diffusion in the presence of pus.
Surrounding areas of vasogenic edema show
high ADC & appear hyper intense.
The differential diagnosis includes acute
infarction, which also shows hyperintensity on
DW images and reduced ADC values.
The ring enhancement in acute ischemic stroke
ADC values remain low even after 8 hours in
cases cerebral abcess.
Diffusion-weighted image shows
hypointensity in central part of
hemorrhage ie high ADC values.
Hyperintensity in region of edema d/t
high restricted diffusion & low ADC.
Areas of increased signal with in the
lesion may be seen which are d/t focal
susceptibility artifact caused by
paramagnetic effects of blood products.
The signal intensity of multiple sclerosis
on DW images is variable- a/c lesions
show hyper intensity while c/c lesions are
Also abnormal ADC values may be seen
in normal-appearing white matter of MS
Epidermoid & arachnoid cysts are almost
isointense to cerebrospinal fluid on T1,
T2 and proton density images.
Difficult to differentiate.
DW images epidermoid tumors show
high signal intensity and are easily
differentiated from cerebrospinal fluid or
arachnoid cysts of low signal.
DWI in itself is not diagonostic of any
Poor structural resolution.
Very helpful in differentiating lesions
with similar appearance in the
Very early detection of abnormalities.
Detection of subtle abnormalities.
DWI outside CNS
DWI of the other body parts are difficult.
Mainly d/t the macroscopic motion of
organs requiring fast acquisition
Duration of imaging is to be reduced &
larger gradient amplitudes need to be
generated to produce visible diffusion
As temperature increases diffusion
coefficient also increases.
2.4% change occurs per degree change in
Diffusion MR- real time non invasive
Study tissue interactions in medical &
surgical laser procedures.
Adjunctive in the treatment of cancer.
Limited use in deeper tissues d/t
ineffective temperature control.
MR diffusion can act as an effective
temperature probe on such cases.
Perfusion is the flow of blood through the
capillary circulation of an organ/tissue
quantified in terms of flow rate.
ml / 100g / min.
Densities of blood & tissue are similar
(1mg/ml) perfusion expressed as a
Differs from bulk flow.
Refers to the delivery of oxygen &
nutrients to the tissue.
Cerebral AV malformation – high blood
flow but perfusion deficit.
In healthy capillaries perfusion ∞ blood
Perfusion depends on:
1. Micro vascular anatomy & histology of the
2. Blood micro circulation.
3. Blood tissue exchangers.
1. Cerebral blood flow (CBF) blood
flow/100gm of tissue/mt.
2. Mean transit time (MTT) The
average time taken by a particle tracer
to traverse the capillary circulation.
Difference b/w arterial inflow & venous
3. Cerebral blood volume (CBV)
Intravascular volume in the region.
CBV = CBF × MTT
4. Time to peak (TTP) Time from
contrast injection to peak enhancement
of the ROI.
These quantitative data are converted to
images either on the grey scale or can
be colour coded to attain the
Areas of decreased perfusion:
Decrease in CBF.
Increase in MTT.
Increase in TTP.
Increase in CBV
Micro spheres – trapped before the
capillary level – deposition reflects the
Pure I/V tracers – enter the capillaries but
do not cross the wall – determine the
blood flow rate.
Diffusible tracers – exchanged with the
tissue – monitoring the concentration
with time – perfusion.
In vivo measurement of perfusion:
1. Dynamic susceptibility contrast (DSC) -
monitoring a tracer.
Gadolinium based agents.
2. Arterial spin labelling (ASL) – using
endogenous blood water.
3. Blood oxygen level dependant
Administration of contrast as a bolus.
Passage through the vasculature & the
tissue is imaged using rapid scan
Transit time after I/V contrast through
heart to end organ < 20 seconds.
Para magnetic/Susceptibility contrast
agents - Gd DTPA.
Exogenous I/V tracers.
Presence of para magnetic materials in a
magnetic field increases the field strength in
their immediate vicinity.
Local MF heterogeneity Spin dephasing of
the proton spins in close relation to the para
Enhance the relaxation rates Decreases the
relaxation time Loss of MR signal.
In area of decreased perfusion this decrease in
signal is low.
Numerical integration & analysis of the
signal changes gives a quantitative
measure of perfusion.
The susceptibility effect of the para
magnetic contrast agent on the MR
signal depends on:
1. Pulse sequence
2. Integrity of the blood brain barrier
3. Type of contrast agent
Gadolinium affects both T1 & T2 relaxation
Low concentrations – T1 shortening
High concentrations – T2 effects are
Dyspronium based contrasts – Less T1
relaxation than Gd.
ARTERIAL SPIN LABELLING
Second major category of perfusion imaging.
Endogenous blood water is used as the
Tag the blood magnetically.
Spatial saturation pulse Arterial blood
flowing into an image slice is more
Appropriate RF pulse sequence water
protons in the arterial blood is
magnetically labeled prior to their entry
into the capillaries.
Labeled water protons exchange with
tissue water at the capillary level.
Alter the magnetic properties of the
Measured & translated into a quantitative
1. Continuous Arterial Spin Labeling (CASL)
2. Pulse Arterial Spin Labeling (PASL)
Totally non invasive
Suitable for repeated measurements no
additional risk of contrast administration.
Spins are labeled when they are outside
the imaging slice & must flow into it.
Involves significant transit time.
Substantial relaxation occurs label is
Measured relaxations of the blood &
tissues is less accurate.
Always residual error.
DSC more informative.
Blood Oxygen Level Dependant technique.
Intravenous deoxy Hb used as the endogenous
Deoxy Hb is paramagnetic – affects MR
Oxy Hb is dia magnetic – Little effect on MR
MR sequences sensitised to the para magnetism
of deoxy Hb forms the BOLDtechnique.
Deoxy Hb level changes with metabolic
BOLD signal is also a marker of cellular
Finds application in functional MRI.
BOLD signal response to a short neural event
gradual rise over 5sec return to the base
line in 15sec.
MR pulse sequences sensitive to susceptibility
induced signal loss is referred to as T2*
Ultrafast imaging techniques are used to image
the passage of contrast agent trough the tissue.
EPI & Turbo FLASH sequences.
Evaluation & management of acute stroke.
Characterisation of tumors.
Evaluation of tumor perfusion before & after
anti angiogenesis treatment.
Evaluation of neurodegenerative conditions
such as Alzheimer's disease.
PERFUSION IN A/C STROKE
Information about the perfusion status of the
brain is available.
The decline in signal intensity diminishes as
contrast material passes through the infarcted
area and returns to normal as it exits this area.
DWI and PWI, together have the ability to
detect very early changes ie, within minutes of
When performed in series, they can provide
information about the location, extent &
pattern of evolution of the lesion.
The diffusion-perfusion mismatch is the
difference in size between lesions captured by
DWI and PWI.
Diffusion abnormality is in the ischaemic core.
With arterial occlusion brain regions with
decreased diffusion & decreased perfusion –
represent nonviable tissue or infarct core.
Proximal occlusion results in mismatch more
than distal ones
Region with normal diffusion & abnormal
perfusion is the ischaemic penumbra.
The region of incomplete ischemia that lies
next to the core of the infarction.
The ischemic penumbra is regarded as an area
that is viable but is under ischemic threat.
Can be saved if appropriate intervention is
The viability of this region could extend up to
48 hours after the onset of stroke.
Determining the volume of the ischemic
penumbra may be very useful in identifying
patients who would benefit from thrombolytic
& neuroprotective therapy.
Evaluation of the effectiveness of these
43-year-old man with
acute onset of left-sided
weakness and visual
He was found to have
Unenhanced CT scan
fails to reveal a cortical
MR perfusion in CAD
MR perfusion images during hyperemia and at
rest. There is decreased signal in anterior and
inferior walls during hyperemia only,
suggesting decreased perfusion resulting from
PWI in I/C neoplasms
Cerebral blood volume maps can be used to
assess neovascularity in tumors.
Correlates with tumor grade and malignant
High grade tumors marked increase in rCBV
than low grade tumors.
If the CBV anywhere with in the tumour
is >2 times that of white matter = high
grade & if <1.5 times =low grade.
Maps of CBV used to delineate the normal
cortex adjacent to tumours.
Helps in preoperative planning to delineate the
tumor margin better.
Post op it helps the surgeon to know the
Differentiate radiation necrosis from
Both show enhancement following contrast
administration in conventional MR imaging.
In perfusion weighted images RN will not
have any signal (decreased perfusion) – appear
Tumour recurrence capillary proliferation
appear as hyperintense foci.
Perfusion weighted EPI is obtained while the
subject performs a mental/behavioral task.
Pre-surgical planning to delineate the areas
needed to perform the important tasks.
Reduce morbidity & improve surgical
Higher field strengths are preferred for fMRI.
Signal intensity increases directly with the
magnetic field strength.
The purpose of fMRI is to determine which
areas of the brain are active during specific
The tasks can involve language, memory,
vision, motion, imagined movement, speaking,
During an fMRI, high-speed MR images are
repeatedly acquired of a subject’s brain while
the subject performs a task such as flexing the
fingers of one hand.
Since the brain region that controls the task is
now working, the blood flow to that region
The increase in blood flow increases the
signal in the EPI image.
fMRI of a subject
flexing his hand.
The motor strip on
side is activated
during the task
(the color key -
extent of brain
The pattern of brain activation associated with
hand movement changes after a stroke. fMRI
with movement of the affected hand shows
recruitment of both sides of the brain as an
adaptive response to the injury.