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Contrast-Enhanced MRI
for Tissue Perfusion
Hsiao-Wen Chung (鍾孝文), Ph.D., Professor
Dept. Electrical Engineering, National Taiwan Univ.
Dept. Radiology, Tri-Service General Hospital
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Perfusion MRI with Gd
• I have to assume that you are familiar
with T1 contrast agents in MRI (Gd-
DTPA or the like)
– although I never taught relaxation
mechanism & contrast agent …
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What Is Perfusion ?
• Microcirculation, blood flow ...
• Not angiography though
• Capillary blood flow at tissue site
– Exchange of nutrients/wastes
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Meaning of Perfusion
?
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To “See” Capillary Flow
• Capillary diameter : 0.005 mm
– Current imaging does not see
(resolution limitation)
• Meaningless to see single capillary
– “Overall” evaluation of nutrient
exchange at tissue site
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Perfusion & Tracer
• Tracer kinetics
• Inject tracer into blood vessel
– Often intravenous injection
• Blood flow extrapolated by
following the tracer
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Tracer Distribution (a Time Function)
?
wash-in
wash-out
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What Does Curve Tell ?
• No obvious change in signal: ischemia,
upstream occlusion …
• Large change: abnormal blood volume …
• Slow wash-in: upstream narrowing (stenosis),
collateral flow …
• Slow wash-out: tortuous vessels, increased
permeability …
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Perfusion from Tracer-Time Curve
Two typical types of ischemia
Time
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Normal tissue
Low blood volume
Long transit time
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Perfusion Maps
• Get time curve for every pixel
• Calculate blood volume, transit
time, blood flow for every pixel
• Map perfusion parameters back
to form new images
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Perfusion from Tracer-Time Curve
Fairly close although not too accurate
area ~ blood volume
width ~ transit time
height ~ blood flow
Time
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Distribution of Cerebral Blood Volume
Allows rapid lesion/normal comparison
Siemens Vision+ 1.5T
0.2 mM/Kg Gd-DTPA
EPI (TR=1000, TE=60)
128x128, 3 slices
Bright means more
blood
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Distribution of Mean Transit Time
Allows rapid lesion/normal comparison
Siemens Vision+ 1.5T
0.2 mM/Kg Gd-DTPA
EPI (TR=1000, TE=60)
128x128, 3 slices
Bright means slower
passage
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Typical Perfusion Imaging
• (Not necessarily MRI)
• Intravenous tracer injection
• Dynamic image scanning
• Calculate perfusion parameters
• Form parameter images
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Perfusion MRI
• Contrast + dynamic scan
– T1-weighted
– T2*-weighted
• Arterial spin labeling
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Perfusion MRI
• Contrast + dynamic scan
– T1-weighted
– T2*-weighted
• Arterial spin labeling
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Ha ! Too Simple !
• Intravenous Gd-DTPA injection
• T1WI scanned many times
• Gd flows in brightened, flows out
darkened
• … not that straightforward though
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Capillary Permeability
• Contrast has relatively large chelate
that may not enter tissue rapidly
• In the case of low blood volume
fraction, T1 enhancement very small
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What Is Chelate Then ?
• Molecule that surrounds the
heavy metal ion
• Isolate toxicity
• Avoid heavy metal poisoning
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Gd-DTPA (Magnevist) Structure
Safe and still effective in enhancing relaxation
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Some FDA Approved Gd Chelates
Still large compared capillary permeability
Gd-DTPA (Magnevist) Gd-DOTA (Dotarem)
Gd-DTPA-BMA (Omniscan) Gd-HP-DO3A (Prohance)
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Diffusible Tracer
But not completely freely diffusible
capillary wall
DTPA DTPA
DTPA
capillary wall
ca
pilla
ry
DTPA
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T1 Effect Restricted within Capillaries
Low volume fraction small T1 enhancement
capillaries
image voxel
tissue
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Capillary Permeability
• Contrast has relatively large chelate
that may not enter tissue rapidly
• In the case of low blood volume
fraction, T1 enhancement very small
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Solution
• Extend image scan to permit multiple
(actually many) circulations
• Contrast gradually enters/leaves tissue
• T1WI continuously follow for ~10 min
– Scan & injection do not need to be fast
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Example: Breast
• Malignant tumor often contains
highly permeable neovasculature
– Called “angiogenesis”
• Perfusion MRI uses wash-in & wash-
out information for tumor malignancy
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Normal vs. Tumor Signal-Time Curves
min min
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Parameter Calculation
• Brix model (1991)
• Signal-time curve consists of 3
major parameters
• Blood volume, exchange rate,
(kidney) excretion rate
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Brix Perfusion Model (1991)
Assumption: exchange rate in equilibrium
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No Mean Transit Time
• Very long dynamic scan used
• How fast contrast agent passes
the tissue cannot be examined
• “Equilibrium phase”
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Clinical Applications
• Brain tissue with disrupted BBB
• Pituitary gland
• Femoral head, hip joint
• Breast imaging …
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That’s Low Blood Volume
• What about high blood volume fraction ?
• Example: lung
– Almost all air & capillaries (alveoli)
– Blood the only MR signal source
• Obvious signal change during first-pass
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But T1WI Scan Time …
• Gradient echo: tens of seconds
• Spin echo: some minutes
• One circulation: ~22 sec
• T1WI often too slow for first-pass
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First-Pass T1 Perfusion
• Only for specific tissue (lung)
• New fast-scan T1WI technique
• Limited slice coverage
• Rapid (bolus) contrast injection
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Lung Perfusion MRI Example
Pre-contrast Post-contrast
0 10 20 30 40 50 60-5
0
5
10
15
20
25
30
35
wash-in wash-out
2nd pass
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Parameter Calculation
• Gamma-variate function
• Signal-time curve consists of 2
major parameters
• Blood volume, mean transit time
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Perfusion from Tracer-Time Curve
Fairly close although not too accurate
area ~ blood volume
width ~ transit time
height ~ blood flow
Time
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ntr
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on
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Perfusion Parameters
• Blood volume = integration of
(area under) first-pass curve
• Mean transit time = normalized
first-moment (centroid)
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Plus Variations in “Arrival Time”
Most normal perfusion curves are like this
Time
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on
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No Permeability
• Very short time in first-pass
transit little contrast leakage
– First-pass: 10-15 sec
– Complete circulation: ~22 sec
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Diffusible Tracer
But not completely freely diffusible
capillary wall
DTPA DTPA
DTPA
capillary wall
ca
pilla
ry
DTPA
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About Injection Speed …
Ideal vs. nonideal bolus injection
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Mean Transit Time from the Curve
Gd in “upstream + tissue” both considered
Fast wash-in? Fast upstream?
Slow wash-in? Slow upstream?
Time
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Gd Signal-Time Curve
• Upstream & tissue combined
• De-convolution to obtain pure
tissue perfusion … (complicated)
– Like “x = z/y” from “xy = z”
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Clinical Applications
• Tumor angiogenesis
• Pulmonary stenosis
• Pulmonary embolism
• Other lung perfusion evaluation
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Healthy Male Lung Perfusion
rMTT rPBV
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Lung Cancer
rMTT rPBV
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Pulmonary Stenosis
rMTT rPBV
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Note: Lung MRI
• Lung MRI itself is challenging
– Low proton density, short T2
• Sequence with TE < 1 ms needed
• Shown are research examples
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Note: First-Pass Gd
• Contrast (& blood) just “passes”
the tissue capillaries
• Don’t know if “enters” tissue
• Blood flow unequal to perfusion
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Another Example: Liver
• Malignant tumor: recruit vessels
in hepatic artery territory
• Blood from portal vein fine
• Dynamic Gd imaging for hepatic
arterial & portal venous phases
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Hepatocellular Carcinoma MRI
Pre Gd Arterial phase
VIBE MIP Portal venous phase
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Note: Perfusion?
• Fast dynamic imaging doesn’t
show blood perfuse into tissue
• Sometimes just properly called
dynamic contrast-enhanced MRI
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Perfusion MRI
• Contrast + dynamic scan
– T1-weighted
– T2*-weighted
• Arterial spin labeling
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Intravascular Contrast
• Contrast simply does not leave
low-volume-fraction capillaries
– Brain (blood-brain barrier)
• Use first-pass T2* perfusion MRI
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Diffusible & Non-diffusible Tracer
Contrast agent completely non-diffusible
capillary wall
DTPA DTPA
DTPA DTPA
capillary wall
ca
pilla
ry
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T1 Effect Restricted within Capillaries
Low volume fraction small T1 enhancement
capillaries
image voxel
tissue
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2 Effects of Gd Contrast
• T1: shortened bright on T1WI
– Within vessel, small range
• T2*: shortened dark on T2*WI
– Near vessel, wide range
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Unpaired Electron of Gd Distorts Bo
Larmor freq altered for nearby protons
Bo
H2O
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MR Contrast Agents
• Gd: paramagnetic agent
– Shorten T1 (with Gd presence)
– Distorts Bo homogeneity
(wherever “close to” Gd)
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Range of T1 Influence
Confined within capillaries with intact BBB
capillary
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range of Bo alteration
Range of T2* Influence
About 62% water molecules affected
capillary
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T2* Perfusion MRI
• Use paramagnetic susceptibility
of Gd to distort Bo & shorten T2*
• Dynamic susceptibility-contrast
perfusion-weighted MRI
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T2*WI in Brain Perfusion
• Ideal first-pass perfusion MRI
• Fast scan + T2* weighting EPI
– 6+ slices each second
• Bolus Gd injection
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Signal Changes as a Function of Time
5 sec 6 sec 7 sec 8 sec
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Signal Changes as a Function of Time
9 sec 11 sec 13 sec 15 sec
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Signal Changes as a Function of Time
17 sec 19 sec 21 sec 23 sec
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Signal Changes as a Function of Time
5 sec 11 sec 17 sec 23 sec
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Wash-in & Wash-out of T2*WI Curve
Signal drops when Gd arrives
Time
Sig
na
l in
ten
sit
y
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Parameter Calculation
• Gamma-variate function
– Same as first-pass T1
• Blood volume, mean transit time
• After conversion from T2* to [Gd]
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Wash-in & Wash-out of T2*WI Curve
Signal drops when Gd arrives
Time
Sig
na
l in
ten
sit
y
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Perfusion from Tracer-Time Curve
Fairly close although not too accurate
area ~ blood volume
width ~ transit time
height ~ blood flow
Time
Tra
ce
r c
on
ce
ntr
ati
on
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Perfusion Parameters
• Blood volume = integration of
(area under) first-pass curve
• Mean transit time = normalized
first-moment (centroid)
• Same as first-pass T1
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Plus Variations in “Arrival Time”
Most normal perfusion curves are like this
Time
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Parameter Names …
• rCBV = cerebral blood volume
• rMTT = mean transit time
• rCBF = cerebral blood flow
• “r” for “relative”
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Why Only Relative?
Inter-subject comparison not allowed
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Intra-Subject Perfusion Map Depiction
rCBV rMTT rCBF
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T2* Brain Perfusion MRI
• Good sensitivity
– 30 ~ 60% signal change
• First-pass suffices short scan
• Routinely used clinically
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Clinical Applications
• Ischemic stroke
– Infarct, therapeutic decision
• Brain tumor
– Angiogenesis, biopsy guide
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Perfusion MRI for Ischemic Stroke
Angio CT T1+Gd
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Perfusion MRI for Ischemic Stroke
DWI (b=1000) ADC map
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Perfusion MRI for Ischemic Stroke
rMTT map rCBV map
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Ischemic Stroke
• Diffusion negative: cytotoxic
edema not commenced yet
• Likely reversible process
• Large CBV + long MTT: collateral
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Diagnosis Affects Therapy
rCBV
13 hr after
IA rtPA
5-hr onset
rMTT
rCBV
rMTT
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Perfusion MRI for Glioma
T2 FLAIR rCBV map
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Perfusion MRI for Glioma
F/U at 7 months
F/U at 1 year
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Note: DSC Perfusion MRI
• Also first-pass transit only
• Contrast (& blood) just “passes”
the tissue capillaries
• Blood flow unequal to perfusion
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Note: Abnormal Curves
• Signal drop without returning to baseline ?
– Gd does not flow out ??
• Tortuous vessels? Permeable vessels?
Microvascular structure?
• Still under debate & investigation
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Perfusion MRI for Glioma
T1WI + Gd rCBV map
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Gd Concentration-Time Curve
Likely reflect tortuous neovasculature
0
0.2
0.4
0.6
0.8
1
1.2
0 20 40 60
Time after bolus arrival (seconds)
Co
ntr
ast con
ce
ntr
ation
(arb
itra
ry u
nits)
lesion
normal
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Gd Perfusion MRI
• Contrast + dynamic scan
– T1-weighted equilibrium phase
– T1-weighted first-pass
– T2*-weighted first-pass
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Which Method to Use?
• Depends on tissue capillary
characteristics
– Brain T2*WI used routinely
• Not necessarily for other tissues
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Perfusion MRI
• Contrast + dynamic scan
– T1-weighted
– T2*-weighted
• Arterial spin labeling
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Perfusion MRI with ASL
• Arterial spin labeling
– RF pulse to “label” the blood
– No injection needed
• We’ll leave it for other semesters!
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Contrast-Enhanced MRI
for Tissue Perfusion
Hsiao-Wen Chung (鍾孝文), Ph.D., Professor
Dept. Electrical Engineering, National Taiwan Univ.
Dept. Radiology, Tri-Service General Hospital
