2. 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. 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. 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. 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. 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. 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. 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.
9. 9
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.
10. 10
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.
11. 11
Diffusion weighted image
Areas of restricted
diffusion appears
hyper intense
Bright.
Areas of
unrestricted
diffusion appears
hypo intense
Dark.
12. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24
• When there is an
oriented fibre
structure, the
diffusing water
molecules will move
preferentially parallel
to the fibre direction.
25. 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.
26. 26
Anisotropy in cerebral white matter
Directional variations in the arrangement of
white matter fibres in the cerebrum.
Axial sections-Projection fibrecranio-caudal
-Commisural fibretransverse
-Association fibreAP
Different D and different appearance for
different white matter fibres in the same
section.
28. 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. 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.
31. 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. 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. 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. 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. 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.
37. 37
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.
38. 38
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. 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. 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. 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. 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. 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. 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. 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. 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. 51
DWI NOT AT ALL
SPECIFIC FOR TUMOR
CHARECTARIZATION.
Overlapping features.
52. 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. 53
Iso / Hypo intense on
T1W images.
Hyper intense with
adjacent vasogenic
edema on T2W.
54. 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. 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. 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. 58
LYMPHOMA
High signal intensity on DW images and
low ADC values may favor the diagnosis
of lymphoma rather than glioma or
metastasis.
60. 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. 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. 63
Increased signal
intensity on DW
images and a low
ADC value are the
usual pattern in
inflammatory
granulomas.
GRANULOMA
64. 64
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. 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. 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. 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. 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. 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. 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. 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. 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. 78
Perfusion depends on:
1. Micro vascular anatomy & histology of the
organ.
2. Blood micro circulation.
3. Blood tissue exchangers.
79. 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. 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. 81
Areas of decreased perfusion:
Decrease in CBF.
Increase in MTT.
Increase in TTP.
Increase in CBV
82. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.