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PERFUSION IMAGING
Perfusion
• Perfusion is the process of passage of blood from an arterial supply to venous
drainage through the microcirculation (capillary bed). It is a fundamental
biological function that refers to the delivery of oxygen and nutrients to tissue
by means of blood flow.
• Perfusion normally refers to the delivery of blood at the level of capillaries and
measures in ml/100gm/min.
Common Terms Used in Perfusion Imaging
• Blood Flow: Volume of blood moving through a given volume of tissue per unit time (ml
/100g/min)
• Blood volume : Volume of flowing blood within a vasculature in tissue region (ml per 100 g)
• Mean transit time : Average time taken to travel from artery to vein (Seconds)
• Time to peak enhancement: Time from the beginning of contrast material injection to the
maximum concentration of contrast
Modalities for perfusion analysis
• Computed tomography
• MRI
• Nuclear medicine
CT Perfusion
Introduction
• Perfusion computed tomography (CT) allows functional evaluation of tissue
vascularity.
• It measures the temporal changes in tissue density after intravenous injection of
a contrast medium (CM) bolus using a series of dynamically acquired CT
images.
• The greatest impact of perfusion CT has been on the assessment of patients who
have had strokes, wherein the rapid scan timing and faster image processing
have cemented its role as the modality of choice for evaluation of structural and
functional status of cerebral vasculature.
Principle
• The fundamental principle of perfusion computed tomography (CT) is based on
temporal changes in tissue attenuation after intravenous injection of contrast
material.
• The tissue attenuation depends on the tissue iodine concentration and the
changes in tissue attenuation indirectly reflect tissue vascularity and vascular
physiology.
• Tissue enhancement after intravenous injection of the iodinated CM can be
divided into two phases based on the distribution in the intravascular or
extravascular compartment.
Density = [Iodine] = Blood Flow
Contd…
• In the initial phase, the enhancement is mainly attributable to the distribution of
contrast within the intravascular space and this phase lasts for approximately 40
to 60 seconds from the time of contrast injection.
• In the second phase, contrast passes from the intravascular to the extravascular
compartment across the capillary basement membrane and tissue enhancement
results from contrast distribution between the two compartments.
Contd…
• By obtaining a series of CT images in quick succession in the region of interest
during these two phases, the temporal changes in tissue attenuation after
injection of contrast medium can be recorded.
• The various analytical methods vary from scanner to scanner and among the
commercial vendors. Two most commonly used analytical methods are
Compartmental analysis and Deconvolution analysis.
Mathematical models
• CT perfusion parameters can be analyzed by –
• Compartmental analysis
• Deconvolution analysis
• Both the analytical methods require obtaining time attenuation data from the
arterial input for estimation of tissue vascularity and to correct for inter patient
variations in bolus geometry
Compartmental analysis
• In this kinetic modeling technique, analysis can be undertaken using the single
compartment or double compartment method.
• Single compartment model:
• This method assumes that the intravascular and extravascular spaces are
a single compartment. This model which is based on Fick’s principle
which calculates tissue perfusion based on conservation of mass within
the system.
• It estimates perfusion using the maximum slope of peak height of the
tissue concentration curve normalized to the arterial input function.
Contd…
• Double compartment model:
• This method assumes that the intravascular and extravascular spaces are
separate compartments.
• It estimates capillary permeability and BV using a technique called Patlak
analysis, which quantifies the passage of contrast from intravascular space
into the extravascular space.
Deconvolution analysis
• This CM kinetic modeling is based on the use of arterial and tissue time
concentration curves to calculate the impulse residue function (IRF) for the tissue.
• The IRF is a theoretic tissue curve that is obtained from the direct arterial input,
assuming that the concentration of contrast material in the tissue is linearly
dependent on the input arterial concentration when the BF is constant.
• After accounting for the flow correction, the height of this curve reflects the tissue
perfusion and the area under the curve provides the relative BV estimation. For the
estimation of capillary permeability, a distributed parameter model is used, which is
essentially an extended deconvolution method.
Compartmental vs Deconvolution Analysis
• Results have shown that both the techniques are broadly equivalent, however they differ in
terms of their theoretical assumptions, susceptibility to noise and motion.
• Compartmental analysis assumes that the bolus of CM has to be retained within the organ of
interest at the time of measurement which may result in underestimation of perfusion values
in organs with rapid vascular transit or with large bolus injection.
• Deconvolution assumes that the shape of IRF is a plateau with a single exponential wash-out.
Though this assumption works well for most of the organs, it might not be suitable for organs
such as spleen and kidney which have complex microcirculations. Hence, it is preferable to use
compartmental analysis for organs with complex circulatory pathways.
Contd…
• Deconvolution methods are appropriate for measuring lower levels of perfusion
(< 20ml/min/100mg) as they are able to tolerate greater image noise due to
inclusion of the complete time series of images in calculation. This is particularly
beneficial for accurate measurement of lower perfusion values which are
typically seen in tumors following treatment response. However, the inclusion of
all the acquired images for calculation introduces possibilities of image
misregistration due to motion of the patient.
• Whereas, compartmental analysis uses three images for perfusion measurement:
base line image, the image immediately before and after the time of maximal rate
of contrast tissue enhancement and hence patient motion are rarely of
significance.
Contd…
• The deconvolution method, being less sensitive to noise, allows the use of lower
tube current and permits scanning with higher temporal resolution for the
dynamic cine acquisition.
• For the compartmental model, the presence of the image noise results in
miscalculation of perfusion values; hence, a higher tube current with low image
frequency is preferred for the dynamic study.
• However, Deconvolution analysis is probably the most commonly used
algorithm for dynamic CT perfusion data postprocessing because of its
advantages over other methods, namely the absence of unrealistic assumptions
about venous outflow and the ability to use lower intravenous infusion rates.
Contrast Medium
• As there is a linear relation between iodine concentration and tissue
enhancement, a higher concentration of CM is preferred (iodine 370 mgI/ml).
• Volume : 40 to 70 ml
• Rate : 3.5 to 10 ml/s
Perfusion CT protocols
• Variety of the perfusion CT protocols have been proposed, typically depending
upon the target organ, mathematic modeling technique, CT scan configuration
and clinical objective
• typical perfusion CT protocol consists of a baseline unenhanced acquisition,
followed by a dynamic acquisition performed sequentially after intravenous
injection of CM.
• Scan delay for the cine acquisition from the start of the CM injection is
determined by the CM circulation time to the region of interest. For most body
applications, a scan delay of 5 to 10 seconds is considered suitable (5–8 seconds
for neck/chest/abdomen studies and 10–15 seconds for studies of the pelvis and
extremities).
Contd…
• Unenhanced CT Acquisition:
• This baseline unenhanced CT acquisition provides wide coverage to include
the organ of interest and basically serves as a localizer to select the
appropriate tissue area to be included in the contrast enhanced dynamic
imaging range.
Contd…
• Dynamic CT Acquisition:
• The dynamic acquisition study includes a first pass study, delayed study, or both
depending on the pertinent physiological parameters that need to be analyzed.
• The first pass study comprises images acquired in initial cine phase for approximately 40
to 60 seconds.
• For first pass study for deconvolution method, image acquisition is done every 1 second,
whereas for the compartment method, image acquisition is done every 3 to 5 seconds.
• Delayed phase ranging from 2 to 10 minutes is supplemented after the first pass study. It
is acquired every 10 seconds for 2 minutes after the first pass study for a deconvolution
method based study and every 10 to 20 seconds for compartment model
Technique of CT Perfusion
• Step I involves acquisition of unenhanced CT images to cover the entire region of
interest.
• Step II involves selection of the slice for dynamic imaging. The selected slices should
be chosen to cover the maximum tumor area. The total tumor coverage area is 2 cm
for 16MDCT and 4 cm for 64MDCT and up to 9 cm for 128 MDCT scanner.
• Step III involves contrast enhanced dynamic image acquisition.
• Step IV involves post-processing of CT data to generate colored perfusion maps of
blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability
surface area product. Time attenuation curves showing the enhancement
characteristics of the artery and tumor during the first pass and delayed phase of
perfusion CT acquisition can be obtained.
Post Processing
• Steps in CT Perfusion Data Postprocessing:
• Freehand/automated placement of an ROI over an input artery to obtain the arterial
time-attenuation curve or arterial input function
• Freehand/automated placement of an ROI over an input vein to obtain the venous
time-attenuation curve
• Analysis of arterial and tissue time attenuation curves to obtain the mean transit time
• Calculation of cerebral blood volume from the area under the curve in a parenchymal
pixel divided by the area under the curve in an arterial pixel
• Calculation of cerebral blood flow by using the central volume principle
(CBF=CBV/MTT)
• The steps involved in the
postprocessing of CT perfusion data
include the placement of ROIs in an
arterial pixel (arrow in a,1) and a
venous pixel (arrow in b,2) and the
generation of a time attenuation curve
(c) for each ROI. The curves are then
used to formulate color-coded CT
perfusion maps. Most commonly
selected artery is ACA and vein is
superior sagittal sinus.
Time density curve (TDC)
Normally by convention, all color maps
are coded RED for higher values and
BLUE for lower values.
NCCT (A), CTP parametric maps, CBF
(B), CBV(C), MTT(D), Demonstrate
normal symmetric brain perfusion.
CT perfusion in acute ischemic stroke
• A stroke, or cerebrovascular accident, is defined as an abrupt onset
of a neurologic deficit that is attributable to a vascular cause.
• Acute cerebral ischemia may result in a central irreversibly infarcted
tissue core surrounded by a peripheral region of stunned cells that
is called a penumbra.
• The ischemic penumbra is the part of the brain that is sandwiched
between brain regions committed to die and those that receive
enough blood to communicate and that the cells in the ischemic
penumbra could survive if the blood flow is restored.
• Perfusion CT imaging is a functional imaging modality to
differentiate between the infarcted core and the ischemic penumbra.
Contd…
• CT perfusion maps of cerebral blood volume (a)
and cerebral blood flow (b) show, in the left
hemisphere, a region of decreased blood volume
(white oval) that corresponds to the ischemic core
and a larger region of decreased blood flow (black
oval in b) that includes the ischemic core and a
peripheral region of salvageable tissue. The
difference between the two maps (black oval-white
oval) is the penumbra.
• The penumbra phase generally begins when blood
flow falls below 20 mL/100 g/min and electrical
communication between neurons cease with
infarction not occurring until blood flow falls
below 10 or 12 mL/100 gm/min.
CBV CBF
CT perfusion in oncology
• There has been a gradual increase in the utility of perfusion CT in oncology, with
a wide spectrum of clinical applications, including:
• Lesion characterization (differentiation between benign and malignant
lesion)
• Identification of occult malignancies
• Vascularity
• Monitoring therapeutic response of various treatment regimens, including
chemoradiation and antiangiogenic drugs.
Other application of CT perfusion
• Hepatic CT perfusion : In case of HCC, Metastatic diseases and focal liver
lesions.
• CT perfusion in pancreatic neoplasm
• CT perfusion in colorectal cancers
• CT perfusion in prostate cancers
• CT perfusion in lymphomas
• CT perfusion in brain , neck tumors
(A)HCC in liver (1-ROI in the tumor,
2,3-volume of interest in the normal
liver parenchyma).
(B) Higher BF values in the tumor in
comparison with normal liver
parenchyma.
(C)Higher BV values in the tumor.
(D)Lower TTP values in the tumor.
(E) Lower PMB values in the tumor.
(F) Higher ALP in the tumor.
(G)Lower PVP values in the tumor.
(H)Higher HPI values in the tumor.
(I) Perfusion parameters calculation.
Radiation dose in brain perfusion CT
• The overall effective dose required for dynamic CT (2.0–3.4 mSv) is only slightly
higher than that required for routine head CT (1.5–2.5 mSv).
• Imanishi et al. encountered 3 patients with transient bandage-shaped hair loss
after 2 DSA and 2perfusion CT. It was estimated that they received a radiation
dose of more than 3–5 Gy to the skin
Dose Management recommendation by AAPM
• 80 kV should be used to increase iodine signal brightness
• Low dose per single scan (i.e. one tube rotation) is critical, since repeated
scanning will result in a relatively high cumulative dose
• Time interval between scans, and hence the total number of scans over the exam
duration, should be set carefully, taking into account the analysis algorithm
(some approaches require relatively dense data points)
• Dose (tube current) modulation should not be used, as it may interfere with the
calculation of the BV and BF parameters
MR PERFUSION
Introduction
• Perfusion MRI is sensitive to microvasculature and has been widely used for variety of
clinical applications including classification of tumors, identification of stroke regions
and characterization of other diseases.
• Two main perfusion MRI approaches:
1. using exogenous contrast agent
• dynamic susceptibility contrast (DSC)-MRI
• dynamic contrast-enhanced (DCE)-MRI
2. without the use of contrast agent
• arterial spin-labeling (ASL)
DSC-MRI
• Exploits the T2* susceptibility effects of gadolinium.
• This technique utilizes very rapid imaging to capture the first pass of contrast agent,
k/a Bolus Tracking MRI.
• After the bolus of contrast agent is injected, hemodynamic signals of DSC-MRI
depends on T2 or T2* relaxation time and transiently decrease because of increasing
susceptibility effect.
• Signal loss resulting from passage of the contrast agent bolus on T2* weighted images
can be used to calculate the change in contrast concentration occurring in each pixel.
• These data can be used to produce calculated estimates of cerebral blood volume
(CBV), mean transit time (MTT) and cerebral blood flow (CBF).
Image acquisition
• Data is acquired by using a fast imaging technique, such as single or multishot EPI to
produce a temporal resolution of approximately 2 seconds.
• The imaging sequence may be gradient echo which will maximize T2* weighting or a spin
echo approach can be used which will minimize the signal contribution from large vessels.
• Series of at least five pre-contrast images should be collected to improve the estimation of
the signal intensity baseline during analysis.
• Standard contrast dose (0.1 mmol/kg) at 3-7ml/s is adequate in most cases although double
dose of gadolinium (0.2mmol/Kg) may be used to improve signal to noise ratio.
• Successive images of the region of interest (ROI) are then acquired during the first pass of
contrast material.
Data analysis
• Based on the assumption that the contrast agent remains within the vascular space
throughout the examination acting as a blood pool marker, only applicable in brain where
there is no contrast leakage due to the BBB.
• The drop in T2* signal is computed on a voxel-by-voxel basis and used to construct a
time-versus intensity curve
• The degree of signal drop is then assumed to be proportional to the tissue concentration
of gadolinium, so that relative concentration-time curves can be obtained
• “Relative” refers to the fact that an arterial input function is not used in the calculation of
CBV, and therefore, precise quantification of cerebral blood volume is not performed
Figs A to C: Figure shows data analysis in DSC perfusion.
(A)Time-versus MR signal intensity curve where signal intensity decrease during passage of contrast agent bolus and
is measured from a series of MR images.
(B) Tissue concentration-versus time curve where change in the relaxation rate (ΔR2*) is calculated from signal
intensity, and a baseline subtraction method is applied to measured data.
(C)Corrected ΔR2* curve after leakage correction
A B C
Problems with DSC MRI
• There are several major problems/ errors with the DSC MRP, which have led to a
number of major modifications of the analysis approach in an attempt to
produce more accurate quantitative estimates of blood flow. Three main
problems with the technique include:
1. Contrast recirculation
2. Contrast leakage
3. Bolus dispersion.
Contrast recirculation
• Analysis assumes that the bolus passes through the voxel and that the
concentration of contrast then returns to zero.
• However, the contrast re-circulates through the body and a second re-circulation
peak is seen following the first.
• Errors in measurement of CBV are due to the presence of both first pass and
recirculating contrast in the vessels during the later part of the bolus passage.
• The error can be approached by use of gamma fitting technique, which also
smoothes the data, effectively reducing noise and eliminates the contamination
of the first pass bolus due to contrast agent recirculation.
Signal intensity–time curve
showing marked signal intensity
decrease during arrival of the
contrast agent, followed by
partial recovery of the signal
intensity loss. A second decrease
in signal intensity (arrow) is due
to recirculation.
Contrast leakage
• Leakage of contrast into the interstitial space will cause signal changes.
• High permeability in regions of severe blood-brain barrier breakdown (e.g. high-grade
neoplasm) leads to extravasation of contrast material into the interstitium, which
increases signal above baseline due to the T1 shortening effects of gadolinium. This
leads to significant underestimation of CBV.
• Susceptibility based imaging helps to separate these relaxivity and susceptibility based
effects to reduce or eliminate contrast leakage effect.
Contrast leakage
• Techniques with reduced T1 sensitivity, such as low flip angle gradient echo
based sequences and increase the repetition time (TR), or uses a dual echo
technique or use pre-enhancement [preinject an additional small dose of
gadolinium (0.05 mmol/kg) to presaturate the interstitium, effectively elevating
the baseline before the dynamic acquisition], which effectively removes
relaxivity effects.
• Newer contrast materials, which can act as ‘blood pool’ agents (such as
gadobenate dimeglumine and monocrystalline iron oxide nanoparticles) may
reduce this problem.
• Each approach offers a perfect solution and the choice of method must be based
on individual analysis task to be undertaken.
Signal intensity–time
curve showing contrast
leakage and signal above
baseline due to the T1
shortening effects of
gadolinium
Bolus dispersion and the measurement of absolute CBF
• To measure the absolute CBF it is assumed that the technique can produce
quantitative measurements of CBV and MTT.
• However, the use of the area under the curve to estimate CBV results in relative
measurement that allows comparison of CBV between tissues rather than producing
an absolute measurement.
• In addition, the measurement of CBF also requires accurate estimation of MTT
(calculated from the width of the contrast bolus). The width of the contrast bolus is
affected by the arterial input function (AIF), changes in bolus width (due to regional
alterations in flow) and physical bolus broadening (due to dispersive effects).
Hemodynamics of contrast agent obtained
with dynamic susceptibility contrast MRI
signal intensity time course (in arbitrary
units), for voxel. Series images are acquired
before, during, and after injecting contrast
agent. While passing through
microvasculature, bolus of contrast agent
produces decreases in magnetic resonance
signal intensity.
DSC MR perfusion. (B) Perfusion analysis is performed by placing an ROI on the enhancing mass in the perfusion
sequence (ROI #2, purple) and comparing it with the contralateral white matter (ROI #1, green). (C) The time course
of the perfusion curves demonstrates the left frontal mass to have a loss of signal from the susceptibility effect of
the gadolinium contrast of a greater magnitude than the contralateral white matter, signifying elevated relative
cerebral blood volume, with less than 50% return to baseline for the perfusion curve of the mass, characteristic of
extra-axial, nonglial tumors such as meningiomas.
DCE-MRI
• This is the other exogenous contrast based method. DCE MR perfusion, also widely
referred to as “permeability” MRI. The resulting signal intensity–time curve reflects a
composite of tissue perfusion, vessel permeability, and extravascular-extracellular
space.
• After the bolus of contrast agent is injected, hemodynamic signal of DCE-MRI
depend on T1 relaxation time, and increase because of T1 shortening effect associated
with paramagnetic contrast agent.
• DCE-MRI uses rapid and repeated T1W images to measure the change in signal
induced by paramagnetic tracer in the tissue with change in time.
• The main advantage is that tumor leakiness (enhancement) is used for data analysis
rather than considering it as an artifact as in DSC MRP.
Contd…
• The DCE MRP is based on a two-compartmental pharmacokinetic model.
DSC-MRP: Two-compartment model demonstrates the exchange of contrast between
plasma and extravascular-extracellular space
Image acquisition
• The general steps in acquisition of DCE MRP are:
1. perform baseline T1 mapping
2. acquire DCE MRP images,
3. convert signal intensity data to gadolinium concentration
4. determine the vascular input function, and
5. Perform pharmacokinetic modeling
• This is usually scanned with T1W in 2D or 3D
• lower dose of gadolinium is administered (typically a single dose of 0.1
mmol/kg) at a lower rate (2 mL/sec) and repetitive acquisitions are then made
through the lesion at longer intervals, typically every 15 to 26 seconds.
Data analysis
• Quantification of the contrast enhancement effect can be performed using a
variety of techniques like:
1. simple measures of the rate of enhancement
2. complex pharmacokinetic analyses.
Simple analysis technique
• quantification of enhancement is done by directly comparing the signal intensity
curves from ROI.
• the enhancement curve is poorly reproducible and most of these signal intensity
based methods remain sensitive to variations between acquisition systems as
there is a non-linear relationship between contrast concentration and signal
intensity.
Pharmacokinetic analysis technique
• With pharmacokinetic modeling of DCE MR perfusion data, several metrics are
commonly derived:
• the transfer constant (ktrans),
• the fractional volume of the extravascular extracellular space (ve),
• the rate constant (kep, where kep = ktrans / ve), and
• the fractional volume of the plasma space (vp)
Contd...
• The most frequently used metric in DCE MRP is ktrans.
• It can have different interpretations depending on blood flow and permeability.
• In situations, in which there is very high permeability, the flux of gadolinium-based
contrast agent is limited only by flow, and thus ktrans mainly reflects blood flow;
whereas
• if there is very low permeability, the gadolinium-based contrast agent cannot leak
easily into the extravascular-extracellular space, and thus ktrans mainly reflects
permeability.
Problems with DCE MRI
• The measurement of ktrans with pharmacokinetic analysis techniques have few
disadvantages, which includes:
1. partial volume averaging effects
2. long acquisition time
3. flow dependency of ktrans.
Contd…
Partial volume averaging:
• The pharmacokinetic analysis technique assumes that samples taken from voxels in blood
vessels will represent blood concentration changes whereas voxels within the target tissue
will represent extravascular contrast leakage.
• However, this assumption is incorrect and voxels within the target tissue are actually likely to
represent a mixture some of which will have significant intravascular contrast content.
• This will result in overestimation of ktrans in these voxels which can be seen as areas of
apparently high permeability in areas of normal brain.
• This problem can be approached by excluding any voxel which produces values over a
certain threshold (1.2/ min) as being vascular in origin or more complex pharmacokinetic
models.
Contd…
Long acquisition time:
• The measurement takes a considerable period of time (at least 5 min)
• There is little or no misregistration of data in brain perfusion and can be easily corrected
by data co-registration. However, in other areas of the body which are affected by
respiratory motion, there is significant misregistration and respiratory gating techniques
markedly limit the image acquisition strategy and the temporal sampling rate which can
be achieved.
• This can be approached by modifying the pharmacokinetic model and describing only
the first passage of the contrast bolus.
• This technique also eliminates the problems with partial volume averaging described
above and produces highly reproducible parametric maps of both ktrans and CBV.
Contd…
Flow dependency of ktrans:
• The measurements of ktrans will be markedly affected by flow to the voxel as well
as the permeability and surface area of the vascular endothelium.
• There is limitation, in areas where there is contrast leakage and the blood flow is
inadequate to replenish contrast at adequate rate; as a result plasma contrast
concentration decreases and ktrans will reflect local blood flow.
Hemodynamics of contrast agent
obtained with dynamic contrast-
enhanced MRI signal intensity time
course (in arbitrary units), for voxel.
Time course of enhancement is depended
on physiological parameters of
microvasculature in lesion, and on
volume fractions of various tissue
compartments. For bolus injection of
contrast agent into blood circulation,
there is always initial increase in its
concentration in plasma.
Arterial Spin Labeling (ASL)
• Arterial-spin labeling (ASL) is an alternative technique of performing MR perfusion
without the use of an intravenous contrast agent.
• ASL gives absolute values of perfusion of tissue by blood.
• This technique utilizes arterial water as an endogenous diffusible tracer which is
usually achieved by magnetically labeling incoming blood.
• ASL is completely non-invasive, using no injection of contrast agent or ionizing
radiation and is repeatable for studying normal or abnormal physiology and its
variation with time.
Contd…
• ASL requires the subtraction of two images, one in which the incoming blood
has been magnetically labeled (k/a label or tag image) and the other in which no
labeling has occurred (k/a control or reference image).
• The signal difference is the ASL signal which removes the static tissue signal and
gives the signal related to flow (perfusion) only.
Contd….
Principle of ASL:
• First, "control" images are acquired
through the area of interest
• Next, "tagging" pulse(s) are applied to a
slab of tissue proximally (upstream) from
the imaging volume that inverts the
magnetization of water molecules in this
slab
• The area of interest is re-imaged, and
data from the newly "tagged" images are
subtracted from the "control" images on a
pixel-by-pixel basis.
Contd….
Principle of ASL:
• The Static tissue are identical in both
images but the magnetization of
inflowing blood is different because of
“tagging”
• The final subtracted image is
thus perfusion-weighted
Contd…
• All arterial spin labeling (ASL) pulse sequences consist of two components:
1. a preparation module to magnetically label/tag flowing blood, and
2. a readout module to generate paired images of the target tissue under "control" and
"tagged" conditions. ASL methods may be classified as to how each of these
modules is constructed.
• Main pattern of perfusion-diffusion
mismatch, perfusion-weighted imaging >
diffusion-weighted imaging, in a patient
with acute stroke. Extensive area of
prolonged time to peak (TTP) and small
diffusion-weighted imaging (DWI) lesion
in deep middle cerebral artery (MCA)
territory, with a complete proximal MCA
occlusion on magnetic resonance
angiography (MRA) (reprint from Muir
KW et al Lancet Neurol 2006; 5: 755-68 with
permission). ADC: Apparent diffusion
coefficient; FLAIR: Fluid-attenuated
inversion-recovery.
• Source : AJR January 2013
Comparison of CTP and MRP
CTP MRP
Linear relation of signal changes with
contrast concentration; quantitative
maps
Nonlinear relation of signal changes
with gadolinium concentration;
nonquantitative maps
Higher spatial resolution Lower spatial resolution
More readily available Not as readily available
Decreased sensitivity for detection of
cerebral microbleeds
MRP advantages
Ionizing radiation No ionizing radiation
Limited z-direction coverage Whole-brain coverage
Iodinated contrast–related concerns Gadolinium contrast concerns (NSF)
Non-contrast MR perfusion study.
Complex postprocessing Less labor-intensive postprocessing
Nuclear Medicine
Myocardial perfusion studies
• A myocardial perfusion scan is a type of nuclear medicine procedure which
evaluates the heart’s function and blood flow.
• A stress myocardial perfusion scan is used to assess the blood flow to the heart
muscle (myocardium) when it is stressed by exercise or medication and to
determine what areas of the myocardium have decreased blood flow. This is
done by injecting a radionuclide (thallium or technetium) into a vein in the arm
or hand.
• Indications for stress-MPI:
• Detection of CAD
• Assessing functional significance of coronary stenosis
• Assessing cardiac viability
• Assessing medical therapy of CAD
• Evaluating prognosis and risk stratification
• There are different types of radionuclides. When one type of radionuclide is used,
areas of the myocardium that have blocked or partially blocked arteries will be seen
on the scan as "cold spots," or "defects," because these areas will be unable to take in
the radionuclide into the myocardium. Another type of radionuclide binds to the
calcium that is released when a heart attack occurs, so it will accumulate in area(s) of
injured heart tissue as a "hot spot" on the scan.
• There are two types of stress myocardial perfusion scans, one that is used in
conjunction with exercise (myocardial perfusion scan with exercise) and one that is
used in conjunction with medication (pharmacologic myocardial perfusion scan).
MPI protocol
• Inject …… wait …….. Image
• Repeat with stress : Exercise OR Adenosine , Dobutamine
Dipyridamole, Regadenoson
• Image
Time from injection to imaging
Source : R.Klein MPI image acquisition and processing
v
Renal scintigraphy
• Quantitative evaluation of renal perfusion and renal function.
• Common radiopharmaceuticals used for perfusion scans of the kidney are:
• Glomerular agents like 99mTc DTPA
• Tubular agents like 99mTc MAG3
Cerebral perfusion
• Radiopharmaceuticals commonly
used are :
• Tc99m DTPA, Tc99m glucoheptonate, Tc99m pertechnetate.
• The latter is most widely used owing the fact that it is inexpensive and easy to use.
• The drawback however is the slow renal clearance and the accumulation by the
choroid plexus (so a blocking agent needs to be administered : Potassium
perchlorate orally 30 min before admn.)
Respiratory perfusion
• Commonly used agent is Tc99m Macro Aggregated Albumin (MAA) which
localizes by mechanism of capillary blockade.
• Ventilation agent : Xenon 133
References
• Diagnostic Radiology : Recent Advances and Applied Physics in Imaging
• Moreira, M., Dias, P., Cordeiro, M., Santos, G. and Fernandes, J. (2010). A
Framework for Cerebral CT Perfusion Imaging Methods Comparison. Lecture
Notes in Computer Science, pp.141-150.
• Jahng, G., Li, K., Ostergaard, L. and Calamante, F. (2014). Perfusion Magnetic
Resonance Imaging: A Comprehensive Update on Principles and
Techniques. Korean Journal of Radiology, 15(5), p.554.
• Saini, S., Rubin, G. and Kalra, M. (2008). MDCT. Milano: Springer.
Perfusion imaging: CT, MRI, Nuclear Medicine- Avinesh Shrestha

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Perfusion imaging: CT, MRI, Nuclear Medicine- Avinesh Shrestha

  • 2. Perfusion • Perfusion is the process of passage of blood from an arterial supply to venous drainage through the microcirculation (capillary bed). It is a fundamental biological function that refers to the delivery of oxygen and nutrients to tissue by means of blood flow. • Perfusion normally refers to the delivery of blood at the level of capillaries and measures in ml/100gm/min.
  • 3. Common Terms Used in Perfusion Imaging • Blood Flow: Volume of blood moving through a given volume of tissue per unit time (ml /100g/min) • Blood volume : Volume of flowing blood within a vasculature in tissue region (ml per 100 g) • Mean transit time : Average time taken to travel from artery to vein (Seconds) • Time to peak enhancement: Time from the beginning of contrast material injection to the maximum concentration of contrast
  • 4. Modalities for perfusion analysis • Computed tomography • MRI • Nuclear medicine
  • 6. Introduction • Perfusion computed tomography (CT) allows functional evaluation of tissue vascularity. • It measures the temporal changes in tissue density after intravenous injection of a contrast medium (CM) bolus using a series of dynamically acquired CT images. • The greatest impact of perfusion CT has been on the assessment of patients who have had strokes, wherein the rapid scan timing and faster image processing have cemented its role as the modality of choice for evaluation of structural and functional status of cerebral vasculature.
  • 7. Principle • The fundamental principle of perfusion computed tomography (CT) is based on temporal changes in tissue attenuation after intravenous injection of contrast material. • The tissue attenuation depends on the tissue iodine concentration and the changes in tissue attenuation indirectly reflect tissue vascularity and vascular physiology. • Tissue enhancement after intravenous injection of the iodinated CM can be divided into two phases based on the distribution in the intravascular or extravascular compartment. Density = [Iodine] = Blood Flow
  • 8. Contd… • In the initial phase, the enhancement is mainly attributable to the distribution of contrast within the intravascular space and this phase lasts for approximately 40 to 60 seconds from the time of contrast injection. • In the second phase, contrast passes from the intravascular to the extravascular compartment across the capillary basement membrane and tissue enhancement results from contrast distribution between the two compartments.
  • 9. Contd… • By obtaining a series of CT images in quick succession in the region of interest during these two phases, the temporal changes in tissue attenuation after injection of contrast medium can be recorded. • The various analytical methods vary from scanner to scanner and among the commercial vendors. Two most commonly used analytical methods are Compartmental analysis and Deconvolution analysis.
  • 10.
  • 11. Mathematical models • CT perfusion parameters can be analyzed by – • Compartmental analysis • Deconvolution analysis • Both the analytical methods require obtaining time attenuation data from the arterial input for estimation of tissue vascularity and to correct for inter patient variations in bolus geometry
  • 12. Compartmental analysis • In this kinetic modeling technique, analysis can be undertaken using the single compartment or double compartment method. • Single compartment model: • This method assumes that the intravascular and extravascular spaces are a single compartment. This model which is based on Fick’s principle which calculates tissue perfusion based on conservation of mass within the system. • It estimates perfusion using the maximum slope of peak height of the tissue concentration curve normalized to the arterial input function.
  • 13. Contd… • Double compartment model: • This method assumes that the intravascular and extravascular spaces are separate compartments. • It estimates capillary permeability and BV using a technique called Patlak analysis, which quantifies the passage of contrast from intravascular space into the extravascular space.
  • 14. Deconvolution analysis • This CM kinetic modeling is based on the use of arterial and tissue time concentration curves to calculate the impulse residue function (IRF) for the tissue. • The IRF is a theoretic tissue curve that is obtained from the direct arterial input, assuming that the concentration of contrast material in the tissue is linearly dependent on the input arterial concentration when the BF is constant. • After accounting for the flow correction, the height of this curve reflects the tissue perfusion and the area under the curve provides the relative BV estimation. For the estimation of capillary permeability, a distributed parameter model is used, which is essentially an extended deconvolution method.
  • 15. Compartmental vs Deconvolution Analysis • Results have shown that both the techniques are broadly equivalent, however they differ in terms of their theoretical assumptions, susceptibility to noise and motion. • Compartmental analysis assumes that the bolus of CM has to be retained within the organ of interest at the time of measurement which may result in underestimation of perfusion values in organs with rapid vascular transit or with large bolus injection. • Deconvolution assumes that the shape of IRF is a plateau with a single exponential wash-out. Though this assumption works well for most of the organs, it might not be suitable for organs such as spleen and kidney which have complex microcirculations. Hence, it is preferable to use compartmental analysis for organs with complex circulatory pathways.
  • 16. Contd… • Deconvolution methods are appropriate for measuring lower levels of perfusion (< 20ml/min/100mg) as they are able to tolerate greater image noise due to inclusion of the complete time series of images in calculation. This is particularly beneficial for accurate measurement of lower perfusion values which are typically seen in tumors following treatment response. However, the inclusion of all the acquired images for calculation introduces possibilities of image misregistration due to motion of the patient. • Whereas, compartmental analysis uses three images for perfusion measurement: base line image, the image immediately before and after the time of maximal rate of contrast tissue enhancement and hence patient motion are rarely of significance.
  • 17. Contd… • The deconvolution method, being less sensitive to noise, allows the use of lower tube current and permits scanning with higher temporal resolution for the dynamic cine acquisition. • For the compartmental model, the presence of the image noise results in miscalculation of perfusion values; hence, a higher tube current with low image frequency is preferred for the dynamic study. • However, Deconvolution analysis is probably the most commonly used algorithm for dynamic CT perfusion data postprocessing because of its advantages over other methods, namely the absence of unrealistic assumptions about venous outflow and the ability to use lower intravenous infusion rates.
  • 18. Contrast Medium • As there is a linear relation between iodine concentration and tissue enhancement, a higher concentration of CM is preferred (iodine 370 mgI/ml). • Volume : 40 to 70 ml • Rate : 3.5 to 10 ml/s
  • 19. Perfusion CT protocols • Variety of the perfusion CT protocols have been proposed, typically depending upon the target organ, mathematic modeling technique, CT scan configuration and clinical objective • typical perfusion CT protocol consists of a baseline unenhanced acquisition, followed by a dynamic acquisition performed sequentially after intravenous injection of CM. • Scan delay for the cine acquisition from the start of the CM injection is determined by the CM circulation time to the region of interest. For most body applications, a scan delay of 5 to 10 seconds is considered suitable (5–8 seconds for neck/chest/abdomen studies and 10–15 seconds for studies of the pelvis and extremities).
  • 20. Contd… • Unenhanced CT Acquisition: • This baseline unenhanced CT acquisition provides wide coverage to include the organ of interest and basically serves as a localizer to select the appropriate tissue area to be included in the contrast enhanced dynamic imaging range.
  • 21. Contd… • Dynamic CT Acquisition: • The dynamic acquisition study includes a first pass study, delayed study, or both depending on the pertinent physiological parameters that need to be analyzed. • The first pass study comprises images acquired in initial cine phase for approximately 40 to 60 seconds. • For first pass study for deconvolution method, image acquisition is done every 1 second, whereas for the compartment method, image acquisition is done every 3 to 5 seconds. • Delayed phase ranging from 2 to 10 minutes is supplemented after the first pass study. It is acquired every 10 seconds for 2 minutes after the first pass study for a deconvolution method based study and every 10 to 20 seconds for compartment model
  • 22. Technique of CT Perfusion • Step I involves acquisition of unenhanced CT images to cover the entire region of interest. • Step II involves selection of the slice for dynamic imaging. The selected slices should be chosen to cover the maximum tumor area. The total tumor coverage area is 2 cm for 16MDCT and 4 cm for 64MDCT and up to 9 cm for 128 MDCT scanner. • Step III involves contrast enhanced dynamic image acquisition. • Step IV involves post-processing of CT data to generate colored perfusion maps of blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product. Time attenuation curves showing the enhancement characteristics of the artery and tumor during the first pass and delayed phase of perfusion CT acquisition can be obtained.
  • 23. Post Processing • Steps in CT Perfusion Data Postprocessing: • Freehand/automated placement of an ROI over an input artery to obtain the arterial time-attenuation curve or arterial input function • Freehand/automated placement of an ROI over an input vein to obtain the venous time-attenuation curve • Analysis of arterial and tissue time attenuation curves to obtain the mean transit time • Calculation of cerebral blood volume from the area under the curve in a parenchymal pixel divided by the area under the curve in an arterial pixel • Calculation of cerebral blood flow by using the central volume principle (CBF=CBV/MTT)
  • 24. • The steps involved in the postprocessing of CT perfusion data include the placement of ROIs in an arterial pixel (arrow in a,1) and a venous pixel (arrow in b,2) and the generation of a time attenuation curve (c) for each ROI. The curves are then used to formulate color-coded CT perfusion maps. Most commonly selected artery is ACA and vein is superior sagittal sinus.
  • 26.
  • 27. Normally by convention, all color maps are coded RED for higher values and BLUE for lower values. NCCT (A), CTP parametric maps, CBF (B), CBV(C), MTT(D), Demonstrate normal symmetric brain perfusion.
  • 28. CT perfusion in acute ischemic stroke • A stroke, or cerebrovascular accident, is defined as an abrupt onset of a neurologic deficit that is attributable to a vascular cause. • Acute cerebral ischemia may result in a central irreversibly infarcted tissue core surrounded by a peripheral region of stunned cells that is called a penumbra. • The ischemic penumbra is the part of the brain that is sandwiched between brain regions committed to die and those that receive enough blood to communicate and that the cells in the ischemic penumbra could survive if the blood flow is restored. • Perfusion CT imaging is a functional imaging modality to differentiate between the infarcted core and the ischemic penumbra.
  • 29. Contd… • CT perfusion maps of cerebral blood volume (a) and cerebral blood flow (b) show, in the left hemisphere, a region of decreased blood volume (white oval) that corresponds to the ischemic core and a larger region of decreased blood flow (black oval in b) that includes the ischemic core and a peripheral region of salvageable tissue. The difference between the two maps (black oval-white oval) is the penumbra. • The penumbra phase generally begins when blood flow falls below 20 mL/100 g/min and electrical communication between neurons cease with infarction not occurring until blood flow falls below 10 or 12 mL/100 gm/min. CBV CBF
  • 30.
  • 31. CT perfusion in oncology • There has been a gradual increase in the utility of perfusion CT in oncology, with a wide spectrum of clinical applications, including: • Lesion characterization (differentiation between benign and malignant lesion) • Identification of occult malignancies • Vascularity • Monitoring therapeutic response of various treatment regimens, including chemoradiation and antiangiogenic drugs.
  • 32. Other application of CT perfusion • Hepatic CT perfusion : In case of HCC, Metastatic diseases and focal liver lesions. • CT perfusion in pancreatic neoplasm • CT perfusion in colorectal cancers • CT perfusion in prostate cancers • CT perfusion in lymphomas • CT perfusion in brain , neck tumors
  • 33. (A)HCC in liver (1-ROI in the tumor, 2,3-volume of interest in the normal liver parenchyma). (B) Higher BF values in the tumor in comparison with normal liver parenchyma. (C)Higher BV values in the tumor. (D)Lower TTP values in the tumor. (E) Lower PMB values in the tumor. (F) Higher ALP in the tumor. (G)Lower PVP values in the tumor. (H)Higher HPI values in the tumor. (I) Perfusion parameters calculation.
  • 34. Radiation dose in brain perfusion CT • The overall effective dose required for dynamic CT (2.0–3.4 mSv) is only slightly higher than that required for routine head CT (1.5–2.5 mSv). • Imanishi et al. encountered 3 patients with transient bandage-shaped hair loss after 2 DSA and 2perfusion CT. It was estimated that they received a radiation dose of more than 3–5 Gy to the skin
  • 35.
  • 36. Dose Management recommendation by AAPM • 80 kV should be used to increase iodine signal brightness • Low dose per single scan (i.e. one tube rotation) is critical, since repeated scanning will result in a relatively high cumulative dose • Time interval between scans, and hence the total number of scans over the exam duration, should be set carefully, taking into account the analysis algorithm (some approaches require relatively dense data points) • Dose (tube current) modulation should not be used, as it may interfere with the calculation of the BV and BF parameters
  • 38. Introduction • Perfusion MRI is sensitive to microvasculature and has been widely used for variety of clinical applications including classification of tumors, identification of stroke regions and characterization of other diseases. • Two main perfusion MRI approaches: 1. using exogenous contrast agent • dynamic susceptibility contrast (DSC)-MRI • dynamic contrast-enhanced (DCE)-MRI 2. without the use of contrast agent • arterial spin-labeling (ASL)
  • 39. DSC-MRI • Exploits the T2* susceptibility effects of gadolinium. • This technique utilizes very rapid imaging to capture the first pass of contrast agent, k/a Bolus Tracking MRI. • After the bolus of contrast agent is injected, hemodynamic signals of DSC-MRI depends on T2 or T2* relaxation time and transiently decrease because of increasing susceptibility effect. • Signal loss resulting from passage of the contrast agent bolus on T2* weighted images can be used to calculate the change in contrast concentration occurring in each pixel. • These data can be used to produce calculated estimates of cerebral blood volume (CBV), mean transit time (MTT) and cerebral blood flow (CBF).
  • 40. Image acquisition • Data is acquired by using a fast imaging technique, such as single or multishot EPI to produce a temporal resolution of approximately 2 seconds. • The imaging sequence may be gradient echo which will maximize T2* weighting or a spin echo approach can be used which will minimize the signal contribution from large vessels. • Series of at least five pre-contrast images should be collected to improve the estimation of the signal intensity baseline during analysis. • Standard contrast dose (0.1 mmol/kg) at 3-7ml/s is adequate in most cases although double dose of gadolinium (0.2mmol/Kg) may be used to improve signal to noise ratio. • Successive images of the region of interest (ROI) are then acquired during the first pass of contrast material.
  • 41. Data analysis • Based on the assumption that the contrast agent remains within the vascular space throughout the examination acting as a blood pool marker, only applicable in brain where there is no contrast leakage due to the BBB. • The drop in T2* signal is computed on a voxel-by-voxel basis and used to construct a time-versus intensity curve • The degree of signal drop is then assumed to be proportional to the tissue concentration of gadolinium, so that relative concentration-time curves can be obtained • “Relative” refers to the fact that an arterial input function is not used in the calculation of CBV, and therefore, precise quantification of cerebral blood volume is not performed
  • 42. Figs A to C: Figure shows data analysis in DSC perfusion. (A)Time-versus MR signal intensity curve where signal intensity decrease during passage of contrast agent bolus and is measured from a series of MR images. (B) Tissue concentration-versus time curve where change in the relaxation rate (ΔR2*) is calculated from signal intensity, and a baseline subtraction method is applied to measured data. (C)Corrected ΔR2* curve after leakage correction A B C
  • 43.
  • 44. Problems with DSC MRI • There are several major problems/ errors with the DSC MRP, which have led to a number of major modifications of the analysis approach in an attempt to produce more accurate quantitative estimates of blood flow. Three main problems with the technique include: 1. Contrast recirculation 2. Contrast leakage 3. Bolus dispersion.
  • 45. Contrast recirculation • Analysis assumes that the bolus passes through the voxel and that the concentration of contrast then returns to zero. • However, the contrast re-circulates through the body and a second re-circulation peak is seen following the first. • Errors in measurement of CBV are due to the presence of both first pass and recirculating contrast in the vessels during the later part of the bolus passage. • The error can be approached by use of gamma fitting technique, which also smoothes the data, effectively reducing noise and eliminates the contamination of the first pass bolus due to contrast agent recirculation. Signal intensity–time curve showing marked signal intensity decrease during arrival of the contrast agent, followed by partial recovery of the signal intensity loss. A second decrease in signal intensity (arrow) is due to recirculation.
  • 46. Contrast leakage • Leakage of contrast into the interstitial space will cause signal changes. • High permeability in regions of severe blood-brain barrier breakdown (e.g. high-grade neoplasm) leads to extravasation of contrast material into the interstitium, which increases signal above baseline due to the T1 shortening effects of gadolinium. This leads to significant underestimation of CBV. • Susceptibility based imaging helps to separate these relaxivity and susceptibility based effects to reduce or eliminate contrast leakage effect.
  • 47. Contrast leakage • Techniques with reduced T1 sensitivity, such as low flip angle gradient echo based sequences and increase the repetition time (TR), or uses a dual echo technique or use pre-enhancement [preinject an additional small dose of gadolinium (0.05 mmol/kg) to presaturate the interstitium, effectively elevating the baseline before the dynamic acquisition], which effectively removes relaxivity effects. • Newer contrast materials, which can act as ‘blood pool’ agents (such as gadobenate dimeglumine and monocrystalline iron oxide nanoparticles) may reduce this problem. • Each approach offers a perfect solution and the choice of method must be based on individual analysis task to be undertaken. Signal intensity–time curve showing contrast leakage and signal above baseline due to the T1 shortening effects of gadolinium
  • 48. Bolus dispersion and the measurement of absolute CBF • To measure the absolute CBF it is assumed that the technique can produce quantitative measurements of CBV and MTT. • However, the use of the area under the curve to estimate CBV results in relative measurement that allows comparison of CBV between tissues rather than producing an absolute measurement. • In addition, the measurement of CBF also requires accurate estimation of MTT (calculated from the width of the contrast bolus). The width of the contrast bolus is affected by the arterial input function (AIF), changes in bolus width (due to regional alterations in flow) and physical bolus broadening (due to dispersive effects).
  • 49. Hemodynamics of contrast agent obtained with dynamic susceptibility contrast MRI signal intensity time course (in arbitrary units), for voxel. Series images are acquired before, during, and after injecting contrast agent. While passing through microvasculature, bolus of contrast agent produces decreases in magnetic resonance signal intensity.
  • 50. DSC MR perfusion. (B) Perfusion analysis is performed by placing an ROI on the enhancing mass in the perfusion sequence (ROI #2, purple) and comparing it with the contralateral white matter (ROI #1, green). (C) The time course of the perfusion curves demonstrates the left frontal mass to have a loss of signal from the susceptibility effect of the gadolinium contrast of a greater magnitude than the contralateral white matter, signifying elevated relative cerebral blood volume, with less than 50% return to baseline for the perfusion curve of the mass, characteristic of extra-axial, nonglial tumors such as meningiomas.
  • 51. DCE-MRI • This is the other exogenous contrast based method. DCE MR perfusion, also widely referred to as “permeability” MRI. The resulting signal intensity–time curve reflects a composite of tissue perfusion, vessel permeability, and extravascular-extracellular space. • After the bolus of contrast agent is injected, hemodynamic signal of DCE-MRI depend on T1 relaxation time, and increase because of T1 shortening effect associated with paramagnetic contrast agent. • DCE-MRI uses rapid and repeated T1W images to measure the change in signal induced by paramagnetic tracer in the tissue with change in time. • The main advantage is that tumor leakiness (enhancement) is used for data analysis rather than considering it as an artifact as in DSC MRP.
  • 52. Contd… • The DCE MRP is based on a two-compartmental pharmacokinetic model. DSC-MRP: Two-compartment model demonstrates the exchange of contrast between plasma and extravascular-extracellular space
  • 53. Image acquisition • The general steps in acquisition of DCE MRP are: 1. perform baseline T1 mapping 2. acquire DCE MRP images, 3. convert signal intensity data to gadolinium concentration 4. determine the vascular input function, and 5. Perform pharmacokinetic modeling • This is usually scanned with T1W in 2D or 3D • lower dose of gadolinium is administered (typically a single dose of 0.1 mmol/kg) at a lower rate (2 mL/sec) and repetitive acquisitions are then made through the lesion at longer intervals, typically every 15 to 26 seconds.
  • 54. Data analysis • Quantification of the contrast enhancement effect can be performed using a variety of techniques like: 1. simple measures of the rate of enhancement 2. complex pharmacokinetic analyses.
  • 55. Simple analysis technique • quantification of enhancement is done by directly comparing the signal intensity curves from ROI. • the enhancement curve is poorly reproducible and most of these signal intensity based methods remain sensitive to variations between acquisition systems as there is a non-linear relationship between contrast concentration and signal intensity.
  • 56. Pharmacokinetic analysis technique • With pharmacokinetic modeling of DCE MR perfusion data, several metrics are commonly derived: • the transfer constant (ktrans), • the fractional volume of the extravascular extracellular space (ve), • the rate constant (kep, where kep = ktrans / ve), and • the fractional volume of the plasma space (vp)
  • 57. Contd... • The most frequently used metric in DCE MRP is ktrans. • It can have different interpretations depending on blood flow and permeability. • In situations, in which there is very high permeability, the flux of gadolinium-based contrast agent is limited only by flow, and thus ktrans mainly reflects blood flow; whereas • if there is very low permeability, the gadolinium-based contrast agent cannot leak easily into the extravascular-extracellular space, and thus ktrans mainly reflects permeability.
  • 58. Problems with DCE MRI • The measurement of ktrans with pharmacokinetic analysis techniques have few disadvantages, which includes: 1. partial volume averaging effects 2. long acquisition time 3. flow dependency of ktrans.
  • 59. Contd… Partial volume averaging: • The pharmacokinetic analysis technique assumes that samples taken from voxels in blood vessels will represent blood concentration changes whereas voxels within the target tissue will represent extravascular contrast leakage. • However, this assumption is incorrect and voxels within the target tissue are actually likely to represent a mixture some of which will have significant intravascular contrast content. • This will result in overestimation of ktrans in these voxels which can be seen as areas of apparently high permeability in areas of normal brain. • This problem can be approached by excluding any voxel which produces values over a certain threshold (1.2/ min) as being vascular in origin or more complex pharmacokinetic models.
  • 60. Contd… Long acquisition time: • The measurement takes a considerable period of time (at least 5 min) • There is little or no misregistration of data in brain perfusion and can be easily corrected by data co-registration. However, in other areas of the body which are affected by respiratory motion, there is significant misregistration and respiratory gating techniques markedly limit the image acquisition strategy and the temporal sampling rate which can be achieved. • This can be approached by modifying the pharmacokinetic model and describing only the first passage of the contrast bolus. • This technique also eliminates the problems with partial volume averaging described above and produces highly reproducible parametric maps of both ktrans and CBV.
  • 61. Contd… Flow dependency of ktrans: • The measurements of ktrans will be markedly affected by flow to the voxel as well as the permeability and surface area of the vascular endothelium. • There is limitation, in areas where there is contrast leakage and the blood flow is inadequate to replenish contrast at adequate rate; as a result plasma contrast concentration decreases and ktrans will reflect local blood flow.
  • 62. Hemodynamics of contrast agent obtained with dynamic contrast- enhanced MRI signal intensity time course (in arbitrary units), for voxel. Time course of enhancement is depended on physiological parameters of microvasculature in lesion, and on volume fractions of various tissue compartments. For bolus injection of contrast agent into blood circulation, there is always initial increase in its concentration in plasma.
  • 63. Arterial Spin Labeling (ASL) • Arterial-spin labeling (ASL) is an alternative technique of performing MR perfusion without the use of an intravenous contrast agent. • ASL gives absolute values of perfusion of tissue by blood. • This technique utilizes arterial water as an endogenous diffusible tracer which is usually achieved by magnetically labeling incoming blood. • ASL is completely non-invasive, using no injection of contrast agent or ionizing radiation and is repeatable for studying normal or abnormal physiology and its variation with time.
  • 64. Contd… • ASL requires the subtraction of two images, one in which the incoming blood has been magnetically labeled (k/a label or tag image) and the other in which no labeling has occurred (k/a control or reference image). • The signal difference is the ASL signal which removes the static tissue signal and gives the signal related to flow (perfusion) only.
  • 65. Contd…. Principle of ASL: • First, "control" images are acquired through the area of interest • Next, "tagging" pulse(s) are applied to a slab of tissue proximally (upstream) from the imaging volume that inverts the magnetization of water molecules in this slab • The area of interest is re-imaged, and data from the newly "tagged" images are subtracted from the "control" images on a pixel-by-pixel basis.
  • 66. Contd…. Principle of ASL: • The Static tissue are identical in both images but the magnetization of inflowing blood is different because of “tagging” • The final subtracted image is thus perfusion-weighted
  • 67. Contd… • All arterial spin labeling (ASL) pulse sequences consist of two components: 1. a preparation module to magnetically label/tag flowing blood, and 2. a readout module to generate paired images of the target tissue under "control" and "tagged" conditions. ASL methods may be classified as to how each of these modules is constructed.
  • 68.
  • 69. • Main pattern of perfusion-diffusion mismatch, perfusion-weighted imaging > diffusion-weighted imaging, in a patient with acute stroke. Extensive area of prolonged time to peak (TTP) and small diffusion-weighted imaging (DWI) lesion in deep middle cerebral artery (MCA) territory, with a complete proximal MCA occlusion on magnetic resonance angiography (MRA) (reprint from Muir KW et al Lancet Neurol 2006; 5: 755-68 with permission). ADC: Apparent diffusion coefficient; FLAIR: Fluid-attenuated inversion-recovery.
  • 70.
  • 71.
  • 72.
  • 73. • Source : AJR January 2013
  • 74. Comparison of CTP and MRP CTP MRP Linear relation of signal changes with contrast concentration; quantitative maps Nonlinear relation of signal changes with gadolinium concentration; nonquantitative maps Higher spatial resolution Lower spatial resolution More readily available Not as readily available Decreased sensitivity for detection of cerebral microbleeds MRP advantages Ionizing radiation No ionizing radiation Limited z-direction coverage Whole-brain coverage Iodinated contrast–related concerns Gadolinium contrast concerns (NSF) Non-contrast MR perfusion study. Complex postprocessing Less labor-intensive postprocessing
  • 76. Myocardial perfusion studies • A myocardial perfusion scan is a type of nuclear medicine procedure which evaluates the heart’s function and blood flow. • A stress myocardial perfusion scan is used to assess the blood flow to the heart muscle (myocardium) when it is stressed by exercise or medication and to determine what areas of the myocardium have decreased blood flow. This is done by injecting a radionuclide (thallium or technetium) into a vein in the arm or hand.
  • 77. • Indications for stress-MPI: • Detection of CAD • Assessing functional significance of coronary stenosis • Assessing cardiac viability • Assessing medical therapy of CAD • Evaluating prognosis and risk stratification
  • 78. • There are different types of radionuclides. When one type of radionuclide is used, areas of the myocardium that have blocked or partially blocked arteries will be seen on the scan as "cold spots," or "defects," because these areas will be unable to take in the radionuclide into the myocardium. Another type of radionuclide binds to the calcium that is released when a heart attack occurs, so it will accumulate in area(s) of injured heart tissue as a "hot spot" on the scan. • There are two types of stress myocardial perfusion scans, one that is used in conjunction with exercise (myocardial perfusion scan with exercise) and one that is used in conjunction with medication (pharmacologic myocardial perfusion scan).
  • 79. MPI protocol • Inject …… wait …….. Image • Repeat with stress : Exercise OR Adenosine , Dobutamine Dipyridamole, Regadenoson • Image
  • 80. Time from injection to imaging Source : R.Klein MPI image acquisition and processing
  • 81.
  • 82. v
  • 83.
  • 84. Renal scintigraphy • Quantitative evaluation of renal perfusion and renal function. • Common radiopharmaceuticals used for perfusion scans of the kidney are: • Glomerular agents like 99mTc DTPA • Tubular agents like 99mTc MAG3
  • 85. Cerebral perfusion • Radiopharmaceuticals commonly used are : • Tc99m DTPA, Tc99m glucoheptonate, Tc99m pertechnetate. • The latter is most widely used owing the fact that it is inexpensive and easy to use. • The drawback however is the slow renal clearance and the accumulation by the choroid plexus (so a blocking agent needs to be administered : Potassium perchlorate orally 30 min before admn.)
  • 86. Respiratory perfusion • Commonly used agent is Tc99m Macro Aggregated Albumin (MAA) which localizes by mechanism of capillary blockade. • Ventilation agent : Xenon 133
  • 87. References • Diagnostic Radiology : Recent Advances and Applied Physics in Imaging • Moreira, M., Dias, P., Cordeiro, M., Santos, G. and Fernandes, J. (2010). A Framework for Cerebral CT Perfusion Imaging Methods Comparison. Lecture Notes in Computer Science, pp.141-150. • Jahng, G., Li, K., Ostergaard, L. and Calamante, F. (2014). Perfusion Magnetic Resonance Imaging: A Comprehensive Update on Principles and Techniques. Korean Journal of Radiology, 15(5), p.554. • Saini, S., Rubin, G. and Kalra, M. (2008). MDCT. Milano: Springer.

Hinweis der Redaktion

  1. Through the TDC, parameters can be extracted to characterize the hemodynamic blood flows in the brain along time. The usual parameters are Cerebral Blood Flow (CBF), Cerebral Blood Volume (CBV), Mean Transit Time (MTT) and Time To Peak (TTP). CBV is the percentage of blood per unit volume of tissue. MTT is the time between the inflow and outflow blood flow in the tissue. TTP is the time elapsed between the injection of the contrast material and the appearance of a maximum concentration in the blood vessels
  2. Hepatic blood flow (BF), representing the flow rate through vasculature; Hepatic blood volume (BV), representing the volume of flowing blood; Time to peak (TTP), defined as the time from arrival of the contrast medium in major arterial vessels to the peak enhancement; Permeability (PMB), representing the total flow from plasma to interstitial space; Arterial liver perfusion (ALP), representing the flow rate through arterial vasculature; Portal venous perfusion (PVP), representing the flow rate through venous vasculature and Hepatic perfusion index (HPI), defined as the ratio between arterial liver perfusion and total liver perfusion.
  3. Arrival Time (AT, to) is the interval between intravenous contrast injection and its first detection in tissue (or in a large feeding artery). Time to Peak (TTP) is typically defined as the time from initial contrast injection to peak (maximal) signal loss within the organ of interest Negative Enhancement Integral (NEI) is the total area ("integral") under the signal intensity curve during first pass of gadolinium, sometime known by its synonym, Area Under Curve (AUC). NEI reflects the total amount of contrast transiting through the regional vascular system and is roughly proportional to blood volume. Mean Time to Enhance (MTE) represents the average time for the entire bolus of injected contrast to pass through a region of tissue. Absolute values of MTE are therefore highly dependent on the shape (compactness) of the arriving contrast bolus and to a lesser degree on tissue perfusion. Although frequently confused, it is important to recognize that MTE is not the same as Mean Transit Time (MTT), which reflects the average time for a single contrast molecule (not the entire bolus) to pass through tissue. Percent Baseline at Peak (PBP) and Percent Signal Recovery (PSR) are defined respectively as the ratios of signal intensity at minimum (peak) or during the recirculation phase (recovery) divided by their initial (baseline) values.
  4. Since, the algorithm for calculation of rCBV assumes a constant baseline, the area above baseline is interpreted by the algorithm as negative blood volume, and subtracted from the area below baseline caused by the drop in T2* signal.
  5. Since, the algorithm for calculation of rCBV assumes a constant baseline, the area above baseline is interpreted by the algorithm as negative blood volume, and subtracted from the area below baseline caused by the drop in T2* signal.
  6. Ktrans is an index characterizing the diffusive influx of gadolinium contrast across the vascular endothelium.  and the rate constant for efflux of gadolinium contrast back into plasma from the tissue extracellular space (kep).
  7. Ktrans is an index characterizing the diffusive influx of gadolinium contrast across the vascular endothelium.  In addition to Ktrans, additional tissue specific parameters may be estimated by DCE including: the volume fraction of the extravascular extracellular space (ve) in tissue, the volume fraction of plasma in tissue (vp), and the rate constant for efflux of gadolinium contrast back into plasma from the tissue extracellular space (kep).
  8. A fourth ASL method, still largely confined to research centers, is known as VSASL (Velocity-Selective Arterial Spin Labeling). Unlike the other ASL methods, VSASL tags blood based on its velocity, not spatial location. 
  9. Decreased flow in Rt MCA territory
  10. Spgr- spoiled gradient Mprage – magnetization prepared rapid acquisition gradient echo Flash-fast low angle shot MRI FFE- fast field echo
  11. Myocardial perfusion scan with exercise : A myocardial perfusion scan with exercise is used to determine what areas of the heart muscle (myocardium) demonstrate decreased blood flow during exercise. This is done by injecting a radionuclide (thallium or technetium) into a vein in the arm or hand during exercise. After the radionuclide has been injected and has circulated through the blood stream, the patient is imaged using a gamma camera. Any areas of the myocardium that have blocked or partially blocked arteries during exercise will be seen on the scan as "cold spots," or "defects," because these areas will be unable to absorb the radionuclide into the myocardium. A second set of scans is taken some hours later, at rest. The resting phase is done in order to compare the results with the exercise phase to see if areas that do not get adequate blood flow while exercising are able to absorb the radionuclide during rest. Myocardial perfusion scan with pharmacologic intervention : A pharmacologic myocardial perfusion scan is used when the physician has determined that exercise on a treadmill is not an appropriate choice due to the person’s medical condition. In this situation, a medication is given that causes the coronary arteries to dilate. This dilation of the coronary arteries increases blood flow and is very similar to the response of the arteries during exercise.
  12. Rest scan is needed only if there doubt otherwise only a stress scan is sufficient less radiation dose less work Stress first protocol is required 2 day protocol not 1 day protocol (tracer crosstalk and recovery from stress) Thalium chloride
  13. Mercapto acetyl tri glycine MAG3
  14. Normally radiopharmaceuticals used for brain imaging don’t traverse the BBB. Thus the radioactivity noted on normal brain images doesn’t lie within the brain itself but rather in the overling soft tissue and calvarium and blood pool accumulations in head like sagittal and transverse sinus; however in cerebral pathologies like neoplasm, infarction or inflammatory processes, there is alteration in the BBB allowing the passage of some radioactive tracers into the region of abnormality. Thi allows dentificaton of lesions in the external imaging as hot spots of greater than normal activity. Less than normal activity in case of stroke alzheimers cold spots. Technique: In 2 phases : Dynamic/angiographic study Rapid sequential acquisition if images after the arrival of bolus of contrast in the cerebral hemisphere which constitutes a quantitative measure of brain perfusion. Static images : after 1 hr to record distribution of radiopharmaceutical in brain inc abnormal conc of the agent.