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Review
MR Perfusion Imaging of the Brain: Techniques and
Applications
Jeffrey R. Petrella 1 and James M. Provenzale

R imaging has become a powerful


clinical tool for evaluation of brain
anatomy. Its application has recently expanded into evaluation of brain function via assessment of a number of functional
or metabolic parameters. One such parameter
is cerebral perfusion, which describes passage
of blood through the brains vascular network.
MR perfusion imaging refers to several recently developed techniques used to noninvasively measure cerebral perfusion via
assessment of various hemodynamic measurements such as cerebral blood volume, cerebral
blood flow, and mean transit time. These techniques have great potential in becoming important clinical tools in the diagnosis and
treatment of patients with cerebrovascular disease and other brain disorders. Potential applications include the evaluation of tissue at risk
after acute stroke, noninvasive histologic assessment of tumors, evaluation of neurodegenerative conditions such as Alzheimers disease,
as well as assessment of the effects of drugs
used to treat these conditions. The purpose of
this article is to provide an understanding of
basic techniques and applications of MR perfusion imaging and highlight recent developments in this emerging technology.

Techniques

Measurement of tissue perfusion depends


on the ability to serially measure concentra-

tion of a tracer agent in a target organ of interest. Exogenous tracers such as iced saline
solution, iodinated radiographic contrast material, and radionuclides have been used [1,
2]. More recently, with the advent of MR imaging, exogenous tracer agents, such as paramagnetic contrast material, and endogenous
tracer agents, such as magnetically labeled
blood, have been used [3].
To obtain hemodynamic parameters from serial tissue tracer concentration measurements, a
general model of the method by which that
tracer passes through or distributes in the target
organ is required [4]. Such a model must be
based on an understanding of the manner in
which the tracer is infusedthat is, bolus injection versus constant infusion, and on assumptions about the pharmacokinetic properties of
the tracer in the organ of interest. These assumptions include diffusibility from the intravascular
to extravascular space, volume of distribution,
and equilibrium half-life of the tracer.
Exogenous Tracer Methods

Exogenous tracer methods in MR perfusion


imaging use a model that assumes the tracer is
restricted to the intravascular compartment and
does not diffuse into the extracellular space.
Imaging can be performed either dynamically
(rapid imaging over time during a bolus injection) or in the steady state (imaging after a
constant infusion has reached an equilibrium
concentration in the blood).

Dynamic imaging.Dynamic imaging takes


advantage of transient changes in the local magnetic field of the surrounding tissue induced by a
bolus of paramagnetic tracer passing through the
organ capillary network (Fig. 1). These changes
in the local magnetic field can be measured as
signal changes on MR imaging. Ultrafast imaging techniques, such as echoplanar and spiral
MR imaging [5, 6], enable the accurate measurement of rapidly varying signal changes that are
due to the first pass of the bolus with adequate
temporal resolution (<2 sec for coverage of the
entire brain). Signaltime course data can then
be converted to relative tracer tissue concentrationtime course data [3]. Tracer concentration
time curves can then be analyzed to determine
various tissue hemodynamic parameters, such as
tissue blood volume, blood flow, transit time,
and bolus arrival time (Fig. 2). In this article, the
terms cerebral blood volume, cerebral blood
flow, and mean transit time are defined as follows: Cerebral blood volume refers to the volume of blood in a given region of brain tissue,
commonly measured in milliliters per 100 g of
brain tissue. Cerebral blood flow refers to the
volume of blood per unit time passing through a
given region of brain tissue, commonly measured in milliliter per minute per 100 g of brain
tissue. Mean transit time refers to the average
time it takes blood to pass through a given region
of brain tissue, commonly measured in seconds.
Bolus arrival time refers to the time it takes for
an IV-injected bolus of contrast material to arrive

Received July 27, 1999; accepted after revision December 15, 1999.
1

Both authors: Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710. Address correspondence to J. R. Petrella

AJR 2000;175:207219 0361803X/00/1751207 American Roentgen Ray Society

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Petrella and Provenzale

Fig. 1.32-year-old healthy man. Echoplanar images of same


slice show bolus of paramagnetic contrast material passing
through tissues. Imaging was performed at rate of one image
per 1.5 sec. Every fourth image is shown.
A, Echoplanar image obtained at 9 sec.
B, Echoplanar image obtained at 15 sec.
C, Echoplanar image obtained at 21 sec. Note transient drop in
signal intensity in and around major blood vessels (arrows) that
is due to susceptibility effects from bolus.
D, Echoplanar image obtained at 27 sec.
AJR:175, July 2000
E, Echoplanar image obtained at 33 sec.

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MR Perfusion Imaging of the Brain


at a given region of the brain, also commonly
measured in seconds.
These parameters are dependent on the specific features of the bolus injection, including
the amount of contrast material injected, the
injection rate, and the paramagnetic properties
of the contrast agent. In addition, hemodynamic parameters depend on variables within
the subject being imaged, such as total-body
vascular volume and cardiac output. As a result, hemodynamic parameters cannot be directly compared between different subjects
and may even differ between examinations on
the same subject at different times. Nonetheless, semiquantitative or relative values can be
obtained using an internal standard of reference such as normal-appearing gray or white
matter. This allows intra- and intersubject
comparisons. Semiquantitation is valuable for
subcategorizing disease processes, following
disease course, and monitoring the effects of
therapeutic interventions, provided such alterations are local and do not change the hemo-

dynamic parameters of the internal reference.


For example, in the case of stroke, relative hemodynamic measurements can be useful in
monitoring the periinfarct ischemic tissue zone
at risk for infarction as well as in monitoring
the effects of thrombolytic therapy [7, 8]. For
diffuse disease processes, in which the internal
reference may also be affected, absolute quantitation is necessary. Although absolute quantitation of cerebral blood volume and cerebral
blood flow has been attempted using dynamic
MR methods that measure arterial input to the
brain [913], the accuracy of these methods remains unproven [14]. With further improvements in signal-to-noise capability and
improved techniques to determine true arterial
input, quantitation of absolute cerebral blood
volume and cerebral blood flow with dynamic
MR methods may well be feasible.
Determination of relative cerebral blood volume from tracer concentrationtime data is
straightforward and robust, accomplished by integrating the area under the tracer concentration

time curve (Fig. 2). This integration may be performed on the curve data points themselves or
on an analytic fit of the data points [15]. The latter approach has the advantage of eliminating
overestimation from the effects of tracer recirculation, but this approach has the disadvantage of
requiring high signal stability and faster imaging
over time [16]. Determination of relative cerebral blood flow requires more extensive processing of the imaging data and is more adversely
influenced by poor image quality and instability
in the MR signal over time. The processing techniques require deconvolution of an arterial input
function from tissue concentrationtime data to
find the true brain clearance, or mean transit time
through the cerebral capillary bed (mean transit
time). Cerebral blood volume, calculated by integrating the area under the deconvolved tissue
concentrationtime curve, is then divided by
mean transit time to obtain cerebral blood flow
[17]. Alternatively, the initial height of the deconvolved tissue concentrationtime curve may
be taken as the cerebral blood flow, and the mean

Fig. 2.Diagram explaining calculation of relative cerebral blood volume, cerebral blood flow, and mean transit time using dynamic contrast-enhanced T2-weighted technique. Signaltime course data for each voxel is converted to tracer tissue concentrationtime course data using well-characterized relationship between T2* signal intensity and tracer tissue concentration [3]. Maps of relative cerebral blood volume are obtained by determining area below tracer concentrationtime curve. Maps of
relative cerebral blood flow are obtained by determining height of ideal tissue concentrationtime curve, or tissue response function. Maps of mean transit time are obtained by dividing area under tissue response function by its height. To obtain tissue response function, arterial concentrationtime curve, or arterial input function, must
be deconvolved from measured tissue concentrationtime curve. This arterial input function may be derived directly from imaging data. EPI = echoplanar imaging.

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Petrella and Provenzale


transit time may then be calculated as the ratio of
cerebral blood volume to cerebral blood flow
[18] (Fig. 2). Again, image quality and signal
stability over time are important requirements
for reliably calculating relative cerebral blood
flow because the deconvolution technique mentioned previously can amplify noise and artifactually introduce bias [18].
Determination of an accurate arterial input
function is also an important requirement for
calculating relative cerebral blood flow. An arterial input function may be obtained directly
from the imaging data by manually selecting
the voxels from which the arterial input function
will be obtained [19]. This may be aided by narrowing the selection to a small population of
voxels chosen using an automated algorithm
that searches the entire imaging volume for voxels with timeconcentration curves that satisfy
criteria characteristic of arteries, such as a large
peak, early arrival time, and a short mean transit
time [9, 11]. The use of such an algorithm increases reproducibility because it requires less
user interaction. It should be noted, however,
that the exclusive reliance on an automated approach may lead to erroneous selection of an arterial input function. For example, in the case in
which a cerebral hemisphere is being fed by a
diseased middle cerebral artery, deriving the arterial input function from voxels in the diseased
hemisphere would lead to a more accurate result
than deriving the arterial input function from the
voxels in the contralateral hemisphere, even
though the latter may better satisfy criteria for a
normal artery. Voxel-by-voxel determination
of cerebral blood flow, in theory, requires determination of the unique arterial input to each
voxel. Because this is not possible, most methods assume the arterial input is uniform across
the brain and apply a single arterial input function to the entire brain. In the case of a unilaterally diseased middle cerebral artery, this
assumption is violated. Applying an arterial input function chosen from voxels in the normal
contralateral hemisphere may lead to underestimation of cerebral blood flow and false-positive
identification of an ischemic zone.
Dynamic sequences must be ultrafast to
monitor the rapid first-pass transit of a bolus of
contrast agent through the brain, which is on
the order of 18 sec [20]. Either T1- or T2weighted techniques can be used. The T2weighted sequences are more commonly used
in clinical practice. Using these sequences, injection of a paramagnetic contrast agent causes
a transient drop in signal intensity that is due to
the susceptibility effects of the paramagnetic
contrast agent. A single- or dual-slice dynamic

210

study can be performed on a conventional MR


scanner without specialized gradient hardware
[9]. Multislice techniques (up to 30 slices per
second) are available on systems with specialized gradient hardware for echoplanar imaging
or spiral imaging [21]. These techniques can be
either T2-weighted (spin echo) or T2*weighted (gradient echo). The spin-echo technique has the advantage of minimizing artifact
at brainbone and brainair interfaces and is
more sensitive to signal changes from paramagnetic contrast material passing through
small vessels, such as capillaries, rather than
through large vessels, such as cortical veins
[22]. The spin-echo technique has the disadvantage of requiring a larger dose of contrast material, often 1.52.0 times that of a standard dose,
to produce signal changes equivalent to those of
the gradient-echo technique (Aronen H et al.,
presented at the Society of Magnetic Resonance
in Medicine meeting, August 1992). Furthermore, the spin-echo technique may create bias
on serial studies, leading to artificially elevated
cerebral blood volume measurements, if repeated within 2 hr of the initial study. This bias
is caused by a residual contrast material effect
that alters the magnitude of signal change from
baseline [23]. These effects have been shown to
not be significant using a gradient-echo technique [11].
A T1-weighted dynamic technique is another
method by which to measure cerebral hemodynamics [24] and has the advantage of requiring
a smaller contrast material dose and providing
better temporal resolution than the T2- or T2*weighted sequences. The T1-weighted technique measures the relaxivity effects, rather
than the susceptibility effects, of an IV-injected
dose of paramagnetic contrast material. The relaxivity effect of paramagnetic contrast material
refers to the shortening of T1 relaxation time,
leading to higher signal on T1-weighted images, whereas the susceptibility effect refers to
the shortening of T2 and T2* relaxation times,
leading to lower signal on T2- or T2*-weighted
images. Because the relaxivity effects of gadopentetate dimeglumine are much stronger than
the susceptibility effects, the T1-weighted pulse
sequences require a smaller amount of contrast
material (approximately 10%) than the T2- or
T2*-weighted techniques [25], allowing multiple repeated studies. Moreover, the short injection time allowed by a smaller bolus may result
in better quantitation of cerebral blood volume
and cerebral blood flow provided that the temporal resolution of the pulse sequence allows
tracking the bolus over a sufficient number of
time points to extract the corresponding param-

eters [24]. Subsecond imaging times (300900


msec) over an anatomic range of one to two
slices are currently possible with this technique
using fast T1-weighted gradient-echo imaging
[25]. The T2- or T2*-weighted technique requires imaging times on the order of 1.52 sec,
although the anatomic coverage is greater with
echoplanar imaging (811 slices) or spiral imaging (1820 slices) [21, 26]. The disadvantage
of the T1-weighted technique is that leakage
through the bloodbrain barrier may lead to errors in measurements of hemodynamic parameters. Although this may be corrected for in the
calculations, the effects of bloodbrain barrier
breakdown are greater with the T1-weighted
technique than with the T2- or T2*-weighted
technique. Quantitative assessment of permeability through the bloodbrain barrier has been
examined using both T1- and T2-weighted
techniques. Further discussion of such techniques can be found in the literature [27, 28].
Steady-state imaging.In addition to the
more commonly used T1- and T2- or T2*weighted dynamic perfusion imaging techniques, a T1-weighted steady-state technique
may be used to estimate absolute cerebral
blood volume with high spatial resolution
across the entire brain. This method assumes
the tracer is nondiffusible from the intravascular to extravascular space. With this technique,
a baseline image is obtained before the injection
of the paramagnetic agent, followed by a postinfusion image that is acquired during the steady
state,that is, up to 30 min after the contrast
material has circulated through the body and
reached a point of relative concentration equilibrium. By subtracting the baseline image
from the postcontrast steady-state image and
normalizing the pixel values to those of a pixel
containing only blood, such as in the sagittal
sinus, one can obtain a map of absolute cerebral blood volume in units of volume percent
[29, 30]. This can be converted to the more
conventional units of milliliters per 100 g of
brain by normalizing to the density of brain tissue (1.04 g/ml) and multiplying by 100 [9].
Unfortunately, this approach has a number of
disadvantages. First, because image subtraction
is performed, the resulting images have a low
signal-to-noise ratio. Second, patient movement
between the pre- and postcontrast scans may
affect the accuracy of these measurements.
Third, spurious results can be obtained in areas where the bloodbrain barrier has been
disrupted and the assumption of tracer nondiffusibility has been violated; therefore, the
technique is not useful in many cases of infarction and tumor.

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MR Perfusion Imaging of the Brain


Fig. 3.33-year-old healthy man. Unenhanced sagittal
T1-weighted MR image of brain shows continuous inversion arterial spin-tagging technique. Solid lines depict imaging slice and dashed line depicts tagging
plane where water protons in inflowing arterial blood
are magnetically tagged by radiofrequency inversion
pulse. Quantitative estimates of cerebral blood flow
can be obtained by measuring signal changes between tagged images and baseline untagged images.

Endogenous Tracer Methods

Endogenous tracer methods in MR perfusion imaging use a model that assumes the
tracer freely diffuses from the intravascular
compartment into the tissue compartment. This
model is similar to that used in positron emission tomography and single-photon emission
computed tomography (SPECT) in which a
tracer is administered and the regional accumulation, influenced by regional blood flow and
tracer half-life, is measured [31]. Endogenous
tracer MR perfusion methods take advantage of
signal loss resulting from magnetically labeled
water protons (spins) flowing into the imaging
plane and exchanging with tissue protons. Water protons within inflowing arterial blood are
magnetically labeled (or tagged) by the appli-

cation of a special radiofrequency pulse designed to invert spins in a thick slab proximal to
the slice of interest (Fig. 3). By measuring signal changes between tagged images and
baseline untagged images, qualitative or quantitative images of cerebral blood flow can be obtained (Fig. 4). Inflowing blood may be tagged
continuously or intermittently [31, 32]. Although continuous-labeling techniques afford
twice as much signal contrast compared with
pulsed techniques, they produce substantially
more radiofrequency pulseinduced power
deposition to the subject. This safety consideration can ultimately limit slice coverage and acquisition time.
Spin-tagging techniques suffer inaccuracies
that are due to two major effects. The first is

magnetization transfer effects in the imaging


plane as spins are labeled below the imaging
plane with a radiofrequency pulse. During this
time, the spins in the plane of interest experience an off-resonance radiofrequency pulse that
selectively saturates the broad resonance peak
of macromolecular-bound protons. This saturation is then transferred to the free-proton pool,
resulting in as much as a 60% loss in observed
brain signal [33]. To compensate for this effect,
one strategy involves applying a radiofrequency
pulse during the baseline state at an equal distance above the plane of interest [34, 35].
The second inaccuracy is from the loss of
spin labeling during the arterial transit period
due to T1 relaxation as blood moves from the
tagging plane to the imaging plane [31]. These

Fig. 4.33-year-old healthy man. Multiple slices of brain obtained using multislice arterial spin-tagging MR perfusion imaging technique. Images show quantitative cerebral blood
flow maps. Displayed are five of 10 slice locations extending from level of mid lateral ventricle to level of supraventricular white matter. Artifacts from high flow in superior sagittal
sinus are noted anteriorly and, to lesser extent, posteriorly. Total imaging time was approximately 5 min (Courtesy of Yongbi M, Duyn JH, and Yang Y, Bethesda, MD).

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Petrella and Provenzale

Fig. 5.43-year-old man with acute onset of left-sided weakness and visual changes who was found to have left homonmous hemianopsia on examination.
A, Unenhanced CT scan reveals negative finding for cortical infarction.
B, T2-weighted MR image shows increased signal (arrow ) in right calcarine cortex.
C, Diffusion-weighted scan demonstrates larger area of signal abnormality (arrow) involving right occipital lobe, consistent with infarction.
D, Color-coded cerebral blood volume map obtained using dynamic T2-weighted technique shows even larger perfusion deficit than that seen in B and C in right occipital
lobe, including infarction core, and surrounding tissue at risk. Red denotes high cerebral blood volume; blue, low cerebral blood volume.
E, Color-coded mean transit time map obtained using dynamic T2-weighted technique shows prolonged transit time in right occipital lobe, also corresponding to infarct
core, and surrounding tissue at risk. Red denotes prolonged mean transit time; yellow, normal mean transit time.

arterial transit effects may be markedly reduced


by introducing a delay after continuous labeling
[36] or by tagging spins immediately below the
imaging plane using an intermittent pulse to reduce overall transit time [32]. The latter technique, called EPISTAR (echoplanar imaging

212

with signal targeting and alternating radiofrequency), provides only a qualitative map of cerebral blood flow because the relationship between
cerebral blood flow and EPISTAR signal is
complex and depends on differential arterial
transit times, the angle of feeding arteries with

the imaging plane, and inflow effects [37]. This


technique also suffers from low sensitivity and
therefore low flow rates (1025 ml 100 g1
min1) may be difficult to detect.
An alternative to labeling spins proximal to
the imaging plane is to directly label spins in

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MR Perfusion Imaging of the Brain

Fig. 6.66-year-old man with right-sided internal carotid occlusion.


A, Lateral view from conventional arteriogram shows occlusion of right-sided internal carotid artery at origin (arrowhead).
B, Intracranial MR angiogram reveals no visible flow within intracranial portion of right-sided internal carotid artery until cavernous segment (arrow), where there is reconstitution of right hemispheric circulation via cross-filling (black arrowheads) from Circle of Willis and from external carotid artery (white arrowheads) collaterals.
C, Baseline mean transit time map reveals mildly prolonged transit times (arrows) in right cerebral hemisphere.
D, After vasodilatory challenge with acetazolamide, map shows transit time in right hemisphere has normalized, suggesting maintenance of cerebrovascular reserve capacity from adequate collateral circulation.

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Petrella and Provenzale

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Fig. 7.24-year-old woman with previously treated high-grade cerebral neoplasm


(anaplastic ependymoma) with an enhancing lesion on follow-up examination. Biopsy
revealed radiation necrosis.
A, Contrast-enhanced axial T1-weighted image shows area of abnormal enhancement in right frontoparietal deep white matter.
B, Color-coded cerebral blood volume map obtained using dynamic T2-weighted
technique illustrates low cerebral blood volume in area of abnormal contrast enhancement seen in A. Red denotes high cerebral blood volume; blue, low cerebral
blood volume.
C, Overlay of color-coded cerebral blood volume map on T1-weighted image with cerebral blood volume map thresholded so only voxels with cerebral blood volume values equal to or higher than that of gray matter are depicted. Note that area of
enhancement in right frontoparietal deep white matter has low cerebral blood volume
relative to gray matter, consistent with radiation necrosis.

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MR Perfusion Imaging of the Brain


the imaging plane itself using a slice-selective
inversion-recovery technique and thereafter
measure signal increases from unlabeled inflowing spins. In this case, the unlabeled spins
have complete longitudinal magnetization and
the T1-relaxation effects that are due to arterial transit are eliminated. Thus, signal
changes are indirectly related to cerebral
blood flow. By applying an alternating global
inversion-recovery pulse along with the sliceselective pulse and comparing the two conditions, one can measure signal changes that are
caused solely by inflowing blood. These
signal changes are more directly related to
absolute cerebral blood flow. The FAIR (flowsensitive alternating inversion-recovery) technique [38] is one example of this method. A
multislice version of FAIR has recently
been developed using imaging [39].
Clinical Applications
Exogenous Tracer Methods

Stroke.Probably the widest application of


exogenous tracer methods in MR perfusion imaging has been in the assessment of cerebral ischemia. A number of investigators have
suggested that in the setting of an acute stroke,
perfusion imaging in combination with diffusion imaging can help identify surrounding viable ischemic tissue at risk (the so-called
ischemic penumbra) [7, 40]. Specifically, it has
been hypothesized that the area of decreased cerebral blood volume, decreased cerebral blood
flow, or prolonged mean transit time in the ischemic region represents both the infarct core
as well as reversible surrounding ischemic tissue at risk, whereas the area of abnormal diffusion represents only the irreversibly ischemic
infarct core. The mismatch between the perfusion and diffusion abnormality is thought to
represent the potentially salvageable ischemic
tissue at risk for infarction (Fig. 5). Identification of the presence of salvageable tissue surrounding an infarct has taken on critical
importance given the availability of recently approved thrombolytic and neuroprotective agents
[41]. Because these therapeutic agents are not
without risk, it is necessary to select patients
with reversibly ischemic tissue who are likely to
benefit from this therapy. In the setting of subacute infarction, it is possible to evaluate for the
presence of luxury perfusion, characterized by
increased cerebral blood volume, surrounding
the infarct core. In such cases, it is important to
distinguish between cerebral blood volume and
cerebral blood flow because cerebral blood volume may be increased adjacent to a recently
infarcted area, whereas cerebral blood flow

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may be decreased because of prolonged transit


times [8].
MR perfusion imaging is useful not only in
the assessment of stroke, but also in the assessment of stroke risk. Under normal circumstances, the brain has an autoregulatory
mechanism for maintaining adequate cerebral
oxygenation in the face of decreasing cerebral
perfusion pressure, which allows normal blood
flow despite fluctuations in systemic pressure.
This mechanism may be impeded in patients
with hemodynamically significant carotid artery
stenosis who are at high risk for stroke. The ability to maintain an autoregulatory response
to hemodynamic stress has been termed cerebrovascular reserve capacity. Areas of the brain
supplied by a markedly stenotic or occluded artery, in which vasodilatation has already occurred to maintain adequate flow, lack
cerebrovascular reserve capacity. As a result,
when a pharmacologic vasodilatory challenge is
administered, minimal vasodilatory response occurs. Assessment of response to vasodilatory
challenge has therefore also been used as an indirect means of measuring cerebrovascular reserve capacity. Perfusion MR imaging may be
used to assess cerebral blood volume or cerebral
blood flow before and after a vasodilatory challenge using agents such as carbon dioxide or the
carbonic anhydrase inhibitor, acetazolamide
[1012]. In addition to a poor response to a vasodilatory challenge, perfusion imaging may
show other abnormalities in the cerebral hemisphere ipsilateral to a severe carotid stenosis or
occlusion, such as delayed bolus arrival time and
prolonged mean transit time [42, 43] (Fig. 6).
Brain tumors.Another area in which MR
perfusion imaging may be useful is in the evaluation of brain tumors. Dynamic imaging is
performed using either T1-weighted or T2- or
T2*-weighted technique [44]. Cerebral blood
volume maps can be used to assess neovascularity in tumors, which is thought to correlate
with tumor grade and malignant histology. Because of selective sensitivity to small vessels,
the T2-weighted technique may be preferred
over the T2*-weighted technique [22]. Cerebral
blood volume maps may aid in early evaluation
of therapeutic agents, especially of a new class
of drugs aimed at suppressing growth of tumor
blood vessels. These maps can also potentially
be used to localize areas of tumor more likely to
yield positive results on stereotactic biopsy and
to noninvasively differentiate radiation necrosis
from recurrent tumor in circumstances in which
conventional MR findings are equivocal [45,
46] (Figs. 7 and 8). Similar techniques have
evolved for differentiating radiation necrosis

from recurrent tumor on the basis of differences


in bloodbrain barrier permeability. For detailed
discussions of these methods, the reader is referred to the literature [28, 47].
Other disorders.In addition to evaluation
of ischemia and tumors, MR perfusion imaging
has been applied to the study of various other
neurologic and psychiatric disorders, such as
dementia and migraine headaches [48]. The effects of psychoactive drugs, such as cocaine,
have been studied as well (Kaufman MJ et al.,
presented at the International Society of Magnetic Resonance in Medicine, April 1996). In
the case of migraine headaches, decreases in
cerebral blood volume and cerebral blood flow
have been seen during the auras compared with
the post-aura state (Sorensen AG et al., presented at the International Society of Magnetic
Resonance in Medicine, April 1996). In the
case of dementia, decreases in cerebral blood
volume in the temporal and parietal lobes of
patients with Alzheimers disease have correlated well with the results of SPECT studies on
the same subjects [49, 50].
Endogenous Tracer Methods

Clinical applications of the endogenous


tracer methods have been limited compared
with those of exogenous methods because of
longer acquisition times and sensitivity to patient motion. Furthermore, although FAIR and
other spin-labeling techniques are capable of
calculating absolute cerebral blood flow in theory, in practice these techniques have not yet
shown sufficient signal-to-noise ratio to validate these measurements, especially in low-flow
states and in white matter. In such situations,
even the theoretical assumptions required to
make absolute flow estimates may break down
because of, for example, the loss of spin labeling from prolonged transit times. Once these
limitations are overcome, however, many clinical applications may be possible.
Stroke.Quantitative MR cerebral blood
flow measurements could potentially be obtained as part of a complete MR evaluation of
stroke in the assessment of tissue viability and
stroke etiology, for example. Previous work
has suggested that tissue viability, in the setting of acute stroke, is related to the degree and
duration of ischemia [51, 52]. The degree of
ischemia has been assessed in the past through
quantitative regional cerebral blood flow measurements using positron emission tomography and 133 Xe SPECT, and thresholds of
cerebral blood flow measurements have been
established below which tissue viability is unlikely. The role of hypoperfusion as the pri-

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Fig. 8.29-year-old woman with previously treated high-grade astrocytoma with


an enhancing lesion on follow-up examination. Biopsy revealed recurrent tumor.
A, Contrast-enhanced axial T1-weighted image depicts area of abnormal enhancement in left frontal lobe periventricular white matter.
B, Color-coded cerebral blood volume map obtained using dynamic T2-weighted
technique illustrates areas of moderate to high cerebral blood volume in area of
abnormal contrast enhancement seen in A. Red denotes high cerebral blood volume; blue, low cerebral blood volume.
C, Overlay of color-coded cerebral blood volume map on T1-weighted image with
cerebral blood volume map thresholded so only voxels with cerebral blood volume values equal to or higher than that of gray matter are depicted. Note area of
enhancement in left frontal lobe periventricular white matter reveals areas of
moderate to high cerebral blood volume, consistent with recurrent tumor.

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MR Perfusion Imaging of the Brain

B
Fig. 9.33-year-old healthy man. Comparison of finger-tapping activation task using arterial spin-tagging and blood oxygenation leveldependent (BOLD) techniques. (Reprinted with permission from [38])
A, t test activation maps (red) superimposed on T2*-weighted images using multislice FAIR (flow-sensitive alternating inversion-recovery) technique; FAIR is sensitive to
increases in local cerebral blood flow during task.
B, t test activation maps (red) superimposed on T2*-weighted images using BOLD technique, which is sensitive to changes in blood oxygenation. Note patterns of activation similar
to those in A.

TABLE 1

Advantages and Disadvantages of Current MR Perfusion Imaging Techniques

Technique

Advantages

Disadvantages

Current Applications

Exogenous tracer
Dynamic contrast imaging
T2- or T2*-weighted
Short imaging times
Largest clinical experience

T1-weighted

Steady-state imaging
T1-weighted

FAIR

Stroke
Neoplasms
Neuropsychiatric disorders
Drug effects
Neoplasms

Better spatial resolution


Lower doses of contrast material

Limited to single slice


Relative rather than absolute
measurements

Absolute cerebral blood volume


High spatial resolution

Inaccurate if breakdown of bloodbrain


Only situations in which no bloodbrain
barrier
barrier breakdown
Cerebral blood volume measurements only Potentially neuropsychiatric disorders
Sensitive to motion between scans

Endogenous tracer
Continuous labeling
Flow-induced inversion Absolute cerebral blood flow

Pulsed labeling
EPISTAR

Relative rather than absolute


measurements

Shorter arterial transit times,


increasing signal-to-noise ratio

Inaccurate for long arterial transit times

Cerebral blood flow values are not


absolute
Angle between imaging slice and feeding
arteries may cause inaccuracies
Absolute cerebral blood flow
Angle between imaging slice and feeding
Accurate for long arterial transit times
arteries may cause inaccuracies

Potential assessment of tissue viability in


acute stroke
Mapping of blood flow changes during
functional activation studies
Mapping of blood flow changes during
functional activation studies

Mapping of blood flow changes during


functional activation studies

Note.EPISTAR = echoplanar imaging with signal targeting and alternating radiofrequency; FAIR = flow-sensitive alternating inversion recovery.

AJR:175, July 2000

217

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Petrella and Provenzale


mary cause of stroke can also be examined
using quantitative MR measurements of cerebral blood flow in patients with potential border-zone or watershed infarctions [53].
Clinical research.Another major benefit
of absolute quantitation of cerebral blood flow
is in clinical research, which depends on accurate inter- and intrasubject comparisons. Intrasubject comparisons are useful in following
the natural history of a disease process or in
assessing the effect of therapeutic interventions in conditions such as stroke, neoplasms,
and neurocognitive disorders such as dementia, especially in cases when no normal areas
of internal reference are available. Intersubject
comparisons of cerebral blood flow between
different patient populations may allow assessment of drug efficacy or may be a useful
tool in investigating disease mechanisms.
Functional brain mapping.A third major
benefit of absolute quantification of cerebral
blood flow is in the area of functional MR brain
mapping. Cerebral activation is usually determined through qualitative assessment of local
changes in deoxyhemoglobin concentration.
This phenomenon, in which local differences in
cerebral blood oxygenation levels are related to
the degree of neuronal activity, is known as the
blood oxygenation leveldependent (BOLD)
effect. The BOLD effect is based on close coupling of neuronal activity to hemodynamic response in the brain [54]. Although BOLD
changes are more sensitive to cerebral activation
than absolute cerebral blood flow changes,
BOLD changes are dependent on a number of
other physiologic variables and MR parameters
[38, 55]. Direct measurement of cerebral blood
flow changes during cerebral activation may enable better localization of neuronal activity than
measurement of BOLD changes and may allow
more physiologically meaningful comparison
of activation between different brain regions
[38] (Fig. 9). Quantitative cerebral blood flow
changes during motor and working memory
tasks have been measured with the arterial spintagging technique and yield results similar to
those obtained with other techniques such as
133Xe SPECT and positron emission tomography [56, 57].
Conclusion

In summary, MR perfusion imaging is an


emerging clinical tool that enables assessment
of regional cerebral hemodynamics using a variety of techniques (Table 1). The most common
clinically applicable technique uses rapid T2- or
T2*-weighted imaging to monitor the first pass

218

of a bolus injection of exogenous paramagnetic


contrast material. Using tracer analysis techniques, one may obtain semiquantitative or relative cerebral blood flow, cerebral blood volume,
and mean transit time maps. Spin-tagging techniques use magnetically labeled blood as an endogenous contrast agent and may enable
absolute quantitation of cerebral blood flow.
These techniques are gaining increasing use and
have the potential to become an important clinical tool in the diagnosis and treatment of patients with cerebrovascular disease, neoplasms,
and other disorders.
Acknowledgments

We thank Joseph Frank and Alan


McLaughlin at the National Institutes of
Health for their helpful comments and Jimmie Wong and Luiz Celso H. Cruz for assistance in preparing the figures.

11.

12.

13.

14.
15.

16.

17.

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