DIFFUSION & PERFUSION r MRI.ppt

2
DIFFUSION
 Random, microscopic, translational movement
of molecules in a medium.
Brownian motion.
 Depends on the temperature, type of particles
& the environment.
 The brownian motion in living tissues is
measured quantitatively by applying specific
MR gradient sequences.

3
• Diffusion is the
random thermal
motion of molecules.
• With MRI, we can
measure the
magnitude and
direction of the
diffusion of water
molecules in vivo.

4
DIFFUSION COEFFICIENT
 Diffusion coefficient (D) measures the
diffusivity of a particle in a medium.
 D is the distance traveled by a molecule in unit
time.
 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.

5
TYPES
 Isotropic  In homogenous fluids of infinite
extent diffusion is a random, unlimited
phenomenon.
 Anisotropic  in organized media with
asymmetric structure the diffusion might be
more restricted in one direction than the other.

6
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
resolution.
 Molecular mobility also create changes the
conventional sequences, but these are also
affected by variations in the MR environment
& complex rotational motion.

7
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.

8
WATER
 DWI is based mainly on the diffusion of water
in tissues.
 Water diffuses freely across the capillaries &
the cellular intestitium.
 Also diffuses across cell membranes & tissue
compartments.
 Pure water at 37*C diffuses at a rate of
0.003mm2/ s.

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RESTRICTED DIFFUSION
 Tissues- Diffusion is restricted & less random.
 Due to  High viscosity of bulk water in the
tissues which contain large molecules like
protein.
 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
boundaries.

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 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.

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Diffusion weighted image
 Areas of restricted
diffusion appears
hyper intense 
Bright.
 Areas of
unrestricted
diffusion appears
hypo intense 
Dark.

12
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
magnetization.
 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
sequence.

13
 In MR imaging the motion of water
molecules by diffusion through a
magnetic field gradient results in
irreversible signal loss through
intra-voxel dephasing.

14
 This signal attenuation has the form of an
exponential decay.
 As the diffusion increases there is an
exponentially greater signal loss in in the MR
signal.
 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
technique.

15
 Various techniques to sensitize MR sequence
to diffusion.
 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
precession.

16
 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
gradient pulse.
 Followed by a registration of how far the
molecules has moved during a specified time
period.
 Reduction of the MR signal is more for
molecules that has been subject to a larger
displacement.
 Following the two measurements, it is
possible to determine the diffusion rate,
expressed in terms of the diffusion coefficient.

17
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

18
ECHO PLANAR IMAGING
 The sequences used in DWI are deliberately
sensitized to motion by the addition of large
gradients.
 Bulk motions lead to widely dispersed artifacts
 Macroscopic motion artifact.
 Best way to limit motion artifacts - single shot
technique.
 EPI is a technique to record an image within a
single shot.

19
 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
scheme.

20
ADC mapping
 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
pure water.
 This decrease becomes more prominent with
passing time as more no: of molecules
encounter the obstacles.

21
 An ADC map is the quantitative image
of the calculated ADC values for each
voxel.
 An area of restricted diffusion appears 
low D  Appears dark on ADC map.
 Corresponding DWI  Bright.

23
ANISOTROPIC DIFFUSION
 3 Dimensional process.
 Molecular mobility may not be the same in all
the directions.
 Due to 1. Physical arrangement of the medium.
2. Asymmetric arrangement of the
obstacles.
 Muscle fibres & neurons- water with in &
outside cell membranes diffuse more rapidly
than across the membranes.

24
• When there is an
oriented fibre
structure, the
diffusing water
molecules will move
preferentially parallel
to the fibre direction.

25
 This results in difference in the
measured diffusion coefficients when
the diffusion gradient is applied in
different directions.
 Structures with Faster diffusion- dark.
Slower diffusion- bright.

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Anisotropy in cerebral white matter
 Directional variations in the arrangement of
white matter fibres in the cerebrum.
 Axial sections-Projection fibrecranio-caudal
-Commisural fibretransverse
-Association fibreAP
 Different D and different appearance for
different white matter fibres in the same
section.

27
Myelin diagram
 Water moves more
faster along the
fibres than across it.

28
 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.

29
 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
children.

30
Anisotropy in cerebral white matter

31
DIFFUSION TENSOR IMAGING
 The means to most accurately represent the
diffusion properties of a tissue.
 D/T anisotropy diffusion is sensitive to
directionality.
 The most precise depiction of diffusion is a
vector with both direction & magnitude.
 A tensor completely describes the diffusion
properties of a tissue.

32
 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.

33
 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.

35
FIBRE TRACTOGRAPHY
 DTI can further separate distinct axonal
pathways based on their fiber orientation
by determining the direction of greatest
diffusivity.
 In white matter tracts containing
coherently organized parallel fibers, the
direction of greatest diffusivity coincides
with the fiber orientation.

36
 Computer
algorithms have
been developed
that can follow
DTI fiber
orientations from
point to point in
the human brain,
creating 3
dimensional maps
of white matter
connectivity.

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ARTIFACTS
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.

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 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
this.
 Only if a hyperintense area shows a
hypointensity on ADC map  Restricted
diffusion.

39
Hyper intensities d/t white matter
anisotropy
 Recognised with experience.
 Bilaterally symmetrical.
 Trace images
Eliminates anisotropy. Combined
DWI so that weightage is applied in
all the 3 cardinal directions.
Creates isotropic images.

40
CLINICAL APPLICATIONS
 Difference in the diffusivity of water
molecules in normal & abnormal tissues are
traced by DWI.
1. CVA
2. Differentiation of cysts and solid tumours
3. White matter abnormalities
4. Inflammatory conditions
5. Measure deep body temperature

41
CEREBRAL ISCHEMIA
 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.

42
TIME gain
 As early as 30mts after the ischemic
insult.
 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.

43
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
weeks.

44
MECHANISM
 Interruption of CBF  Rapid breakdown
of energy metabolism and ion exchange
pumps  Shift of extracellular water to
the intracellular compartment
Cytotoxic edema.
 The IC compartment is more confined
More restricted diffusion.
 Produces a typical "bright spot" on DW
MR images.

45
 Persistence of cytotoxic edema +
Development of vasogenic edema  Cell
membrane disruption.
 Leak of water into the EC compartment.
 Diffusion is now less restricted.
 ADC increases.
 Hyperintensity of DWI decreases 
Isointense.

50
CNS TUMORS
 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
lesions.
 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.

51
DWI  NOT AT ALL
SPECIFIC FOR TUMOR
CHARECTARIZATION.
Overlapping features.

52
GLIOMA
 The signal intensity of gliomas on DWI is
variable.
 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.

53
 Iso / Hypo intense on
T1W images.
 Hyper intense with
adjacent vasogenic
edema on T2W.

54
• Necrotic components
hypointense on the
DWI & peritumoral
vasogenic edema is
isointense [increased
diffusion –dark &
increased T2 values
of edema –bright]
 The peritumoral
edema, cerebrospinal
fluid & necrotic
component of the
tumor are
hyperintense (high
diffusion) on the
ADC map.

55
METASTASIS
 Variable.
 Multiple lessions.
 The necrotic components of metastases show a
marked signal suppression on DW images and
increasedADC values (may be related to
increased free water).

57
 The ring-enhancing mass with central
hypointensity on DW images and an
increase in ADC values suggest necrotic
tumor, most frequently cerebral glioma or
metastasis.

58
LYMPHOMA
 High signal intensity on DW images and
low ADC values may favor the diagnosis
of lymphoma rather than glioma or
metastasis.

60
CEREBRAL ABCESS
 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.

62
 The differential diagnosis includes acute
infarction, which also shows hyperintensity on
DW images and reduced ADC values.
 The ring enhancement in acute ischemic stroke
is unusual.
 ADC values remain low even after 8 hours in
cases cerebral abcess.

63
 Increased signal
intensity on DW
images and a low
ADC value are the
usual pattern in
inflammatory
granulomas.
GRANULOMA

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I/C HAEMORRAGE
 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.

66
MULTIPLE SCLEROSIS
 The signal intensity of multiple sclerosis
on DW images is variable- a/c lesions
show hyper intensity while c/c lesions are
hypointense.
 Also abnormal ADC values may be seen
in normal-appearing white matter of MS
patients .

69
CYSTIC LESIONS
 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.

72
 DWI in itself is not diagonostic of any
disease condition.
 Poor structural resolution.
 Very helpful in differentiating lesions
with similar appearance in the
conventional MR.
 Very early detection of abnormalities.
 Detection of subtle abnormalities.

73
DWI outside CNS
 DWI of the other body parts are difficult.
 Mainly d/t the macroscopic motion of
organs  requiring fast acquisition
schemes.
 Duration of imaging is to be reduced &
larger gradient amplitudes need to be
generated to produce visible diffusion
effects.

74
TEMPERATURE IMAGING
 As temperature increases diffusion
coefficient also increases.
 2.4% change occurs per degree change in
celcius.
 Diffusion MR- real time non invasive
temperature monitoring.
 Study tissue interactions in medical &
surgical laser procedures.

75
Clinical hyperthermia
 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.

76
PERFUSION
 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
dimensionless number.

77
 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
flow.

78
 Perfusion depends on:
1. Micro vascular anatomy & histology of the
organ.
2. Blood micro circulation.
3. Blood tissue exchangers.

79
TERMINOLOGIES USED
1. Cerebral blood flow (CBF)  blood
flow/100gm of tissue/mt.
50-60ml/100g/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
outflow.
3. Cerebral blood volume (CBV) 
Intravascular volume in the region.
4-5ml/100g.
 CBV = CBF × MTT

80
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
corresponding maps.

81
 Areas of decreased perfusion:
Decrease in CBF.
Increase in MTT.
Increase in TTP.
Increase in CBV

82
CONVENTIONAL METHODS
 Micro spheres – trapped before the
capillary level – deposition reflects the
blood flow.
 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.

84
CURRENT METHODS
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
techniques (BOLD).

85
DYNAMIC SUSCEPTIBILITY
CONTRAST
 Administration of contrast as a bolus.
 Passage through the vasculature & the
tissue is imaged using rapid scan
technique.
 Transit time after I/V contrast through
heart to end organ < 20 seconds.
 Para magnetic/Susceptibility contrast
agents - Gd DTPA.

86
 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
magnetic agent.
 Enhance the relaxation rates  Decreases the
relaxation time  Loss of MR signal.
 In area of decreased perfusion this decrease in
signal is low.

87
 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

88
 Gadolinium affects both T1 & T2 relaxation
times.
Low concentrations – T1 shortening
predominates.
High concentrations – T2 effects are
substantial.
 Dyspronium based contrasts – Less T1
relaxation than Gd.
Disadvantage  Invasiveness

89
ARTERIAL SPIN LABELLING
 Second major category of perfusion imaging.
 Endogenous blood water is used as the
diffusible tracer.
 Tag the blood magnetically.
 Spatial saturation pulse  Arterial blood
flowing into an image slice is more
magnetically saturated.

90
 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
tissue.
 Measured & translated into a quantitative
flow data.

91
2 types
1. Continuous Arterial Spin Labeling (CASL)
2. Pulse Arterial Spin Labeling (PASL)
Advantages
 Totally non invasive
 Suitable for repeated measurements  no
additional risk of contrast administration.

92
Disadvantage
 Spins are labeled when they are outside
the imaging slice & must flow into it.
 Involves significant transit time.
 Substantial relaxation occurs  label is
diminished.
 Measured relaxations of the blood &
tissues is less accurate.
 Always residual error.
 DSC more informative.

93
BOLD
 Blood Oxygen Level Dependant technique.
 Intravenous deoxy Hb used as the endogenous
contrast.
 Deoxy Hb is paramagnetic – affects MR
signal.
 Oxy Hb is dia magnetic – Little effect on MR
signal.
MR sequences sensitised to the para magnetism
of deoxy Hb forms the BOLDtechnique.

94
 Deoxy Hb level changes with metabolic
processes.
 BOLD signal is also a marker of cellular
activity.
 Finds application in functional MRI.
 BOLD signal response to a short neural event
 gradual rise over 5sec  return to the base
line in 15sec.

95
SEQUENCES
 MR pulse sequences sensitive to susceptibility
induced signal loss is referred to as T2*
weighted.
 Ultrafast imaging techniques are used to image
the passage of contrast agent trough the tissue.
 EPI & Turbo FLASH sequences.

96
CLINICAL APPLICATIONS
 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.
 Functional MRI.

97
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
the stroke.
 When performed in series, they can provide
information about the location, extent &
pattern of evolution of the lesion.

98
DIFFUSION-PERFUSION MISMATCH
 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

99
PENUMBRA
 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
promptly instituted.

100
 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
treatment modalities.

103
Comparison
 43-year-old man with
acute onset of left-sided
weakness and visual
changes.
 He was found to have
left homonemous
hemianopia on
examination.
 Unenhanced CT scan
fails to reveal a cortical
infarction

105
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
obstructive CAD.

106
PWI in I/C neoplasms
 Cerebral blood volume maps can be used to
assess neovascularity in tumors.
 Correlates with tumor grade and malignant
histology.
 High grade tumors marked increase in rCBV
than low grade tumors.

107
 If the CBV anywhere with in the tumour
is >2 times that of white matter = high
grade & if <1.5 times =low grade.

109
 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
residual function.

110
Differentiate radiation necrosis from
tumor recurrence
 Both show enhancement following contrast
administration in conventional MR imaging.
 In perfusion weighted images RN will not
have any signal (decreased perfusion) – appear
dark.
 Tumour recurrence  capillary proliferation
appear as hyperintense foci.

112
FUNCTIONAL MRI
 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
efficiency.
 Higher field strengths are preferred for fMRI.
 Signal intensity increases directly with the
magnetic field strength.

113
 The purpose of fMRI is to determine which
areas of the brain are active during specific
tasks.
 The tasks can involve language, memory,
vision, motion, imagined movement, speaking,
or attention.
 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
increases.
 The increase in blood flow increases the
signal in the EPI image.

114
 fMRI of a subject
flexing his hand.
The motor strip on
the corresponding
side is activated
during the task
(the color key -
indicates the
extent of brain
activation).

115
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.

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DIFFUSION & PERFUSION r MRI.ppt