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(Stroke. 1999;30:1263-1270.)
© 1999 American Heart Association, Inc.
Original Contributions |
Reperfusion in a Gerbil Model of Forebrain Ischemia Using Serial Magnetic Resonance FAIR Perfusion Imaging
From the Department of Medical Physics and Bioengineering, University College London (G.S.P., D.L.T., R.J.O.), and The Royal College of Surgeons Unit of Biophysics, Institute of Child Health, University College London Medical School, (D.L.T., F.C., M.F.L., M.D.K., D.G.G.), London, UK.
Correspondence to Gaby Pell, RCS Unit of Biophysics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. E-mail g.pell{at}medphys.ucl.ac.uk
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Abstract |
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Background and Purpose—Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer.
Methods—Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period.
Results—On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum.
Conclusions—The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.
Key Words: animal models • cerebral ischemia, transient • magnetic resonance imaging • perfusion • reperfusion
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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After a stroke, reperfusion may occur spontaneously or via an interventional technique, such as thrombolysis. Animal studies of reperfusion after global ischemia have demonstrated that an impaired level of cerebral blood flow (CBF) may develop on recirculation.1 In models of focal ischemia, a varied range of flow levels have been observed on reperfusion.2 A few studies have suggested that a period of compromised blood flow after recirculation may not be pathogenic.3 4 Clinical reports of the pathogenesis of CBF impairment after reperfusion are limited,5 6 and this may reflect the time delay before most patients can be scanned. Because the use of thrombolytic therapy for the treatment of stroke is becoming more widespread, it is important to be able to understand any detrimental effects of recirculation. An aim of this study was to use the MRI techniques of perfusion and diffusion imaging to gain further insight into postreperfusion vascular and tissue status.
Two major categories of defects in circulation that follow a period of transient global ischemia have been characterized over the past 30 years. The first of these is known as the "no-reflow phenomenon,"7 in which areas of the brain fail to reperfuse. The alternative pattern is that of hyperemia followed by hypoperfusion.8
Many studies have been carried out that have aimed to characterize and follow the postischemic disturbances in circulation that occur after a period of transient global ischemia. An ideal study of postischemic reperfusion would track the time course of these changes in a single animal and would offer good regional differentiation, because a heterogenous reflow might be expected. Previous investigations have used methods of perfusion quantification such as autoradiography using [14C]-iodoantipyrine,9 [3H]-nicotine,10 or [14C]-butanol11 ; hydrogen clearance12 ; xenon clearance13 ; and the technique of laser-Doppler flowmetry.14 All of these methods suffer from limitations in their application to such studies. For example, hydrogen clearance relies on the invasive placement of electrodes and provides measurements that are localized to the cortical volume in their immediate vicinity. The technique of xenon clearance is limited in spatial resolution and is susceptible to errors due to partial volume effects and high volumetric flow rates.15 Autoradiography, although displaying good spatial resolution, is invasive and does not permit longitudinal observations in a single animal. We have therefore implemented a technique for perfusion quantification that offers the relatively high spatial and temporal resolution of MRI.
The principal use of MRI is to obtain structural images of brain tissue. Recently, flow-sensitive implementations of the technique have been reported that allow quantitative maps of cerebral perfusion to be obtained.16 These techniques utilize the magnetic labeling of the water spins of inflowing blood or static tissue in the image voxel by the saturation or inversion of one with respect to the other. The flow-sensitive alternating inversion recovery (FAIR) technique was implemented in this study.17 Perfusion MRI was combined in this study with diffusion imaging, which provides measurements of the apparent diffusion coefficient (ADC) of tissue water. A reduction of the ADC is believed to be consistent with the development of cellular energy failure and the resultant cell swelling.18 19 20
The purpose of this study was to use a combination of quantitative perfusion and diffusion imaging in an investigation of postischemic recirculation. A modification of the FAIR method was implemented that enabled a time-course study of cerebral perfusion with improved time efficiency. These techniques were used in an investigation of the reperfusion deficits that occur following a transient period of total forebrain ischemia in a gerbil model.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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Adult Mongolian gerbils (n=8; weight, 60 to 70 g; B&K Universal Ltd, Hull, UK) were used in this study. The animals were anesthetized with 2% halothane. Anesthesia was subsequently maintained with a mixture of 1.5% halothane and 0.4 L/min of oxygen that was supplied via a nose cone, and the gerbils were allowed to breathe spontaneously throughout the study. The common carotid arteries were carefully dissected away from the vagus nerves. Nylon snares (Ethilon 2/0, Ethicon) were placed around both arteries and attached to individually controlled manual screw systems to allow remote bilateral occlusion with the animal in the magnet.21 Before the animal was placed inside the magnet bore, the mechanics of the occlusion procedure were verified. Body temperature was recorded with a rectal thermometer and maintained at between 37°C to 38°C by blowing warm air into the magnet bore. Respiratory rate and ECG were also monitored. All procedures were in accordance with institutional and governmental guidelines.
Experimental Protocol
The experimental protocol commenced with a period of control
imaging. Bilateral occlusion was then initiated by tightening the
snares around the common carotid arteries. This state was maintained
for 4 minutes. The snares were then opened to begin the reperfusion
phase. Perfusion and diffusion imaging were continued for at least 3
hours.
MRI Methods
MRI measurements were performed on a 2.35-T horizontal bore
magnet (Oxford Instruments) interfaced to an SMIS console. The
radiofrequency (RF) pulses were transmitted with a volume coil of
length 6.5 cm. The signal was received with a separate 3-cm-diameter
surface coil.
FAIR Perfusion Imaging
Full analyses of the theory of FAIR imaging have been
reported elsewhere.17 22 Briefly, the technique relies on
the modification of the rate of tissue T1 (spin-lattice) relaxation as
a direct consequence of inflowing blood water spins. Manipulation of
the fundamental Bloch equations enables the following expression for
the apparent T1, T1app, in the presence of flow
to be obtained:
 | (1) |
is the blood-brain partition
coefficient.16 The apparent change in the relaxation
time can be probed by suitable application of inversion pulses that
initiate the process of T1 relaxation. Two images are acquired in FAIR:
a flow-sensitive image due to its preceding slice-selective inversion,
and a relatively flow-insensitive image which is preceded by a
non–slice-selective inversion pulse. The subtracted signal intensity
is manipulated with the use of parameters obtained during
an inversion recovery fit to obtain the flow in standard units
(milliliters per 100 grams per minute). The FAIR technique used an adiabatic FOCI T-shape inversion pulse23 for improved inversion slice definition. Bipolar gradient pulses were applied simultaneously along each gradient direction to eliminate signal contamination from fast-moving arterial spins.16 FAIR was implemented with a spin-echo echo-planar imaging sequence (TE=35 ms; imaging slice thickness, 2.3 mm; inversion slice thickness, 6 mm; image matrix size, 64x128; field of view, 27.5x55 mm). Images were obtained in the coronal plane. Slice-selective and non–slice-selective acquisitions were interleaved.
During the control phase of the experiment, a slice-selective inversion
recovery set was acquired (recovery time, 
=6500 ms) at 7 inversion
times (TI) (200 to 2500 ms). For 20 averages, this procedure lasted 22
minutes. The data were fitted for the parameters
T1app, 
0, and
M0 using the standard inversion recovery
relationship (where 0 is the degree of
inversion and M0 represents the
equilibrium magnetization per unit mass of the tissue). These
parameters are required for the quantification of
perfusion.
For the time-course measurements of CBF, a reduced repetition time
between the averaged acquisitions was used for rapid CBF mapping
(TI=1300 ms, =1500 ms). To preserve the accuracy of CBF
quantification in this situation, a series of global (half-passage
adiabatic) saturation pulses were applied at the start of each recovery
period.22 Previous experimentation had confirmed that
perfusion values obtained with this implementation of FAIR were in
excellent agreement with flows obtained with the more time-consuming
biexponential fitting procedure.22 During the control
period and acute phases of the experiment (occlusion and approximately
1 hour after reperfusion), 30 interleaved averages for each pair of
selective and nonselective images provided a time resolution for CBF
measurements of 2.8 minutes. During the later period of reperfusion,
the number of averages was increased in order to increase the
signal-to-noise ratio of the images with a 10-minute time resolution.
The control values of M0 and
0 and the longitudinal tissue relaxation time,
T1, were used to obtain perfusion measurements directly from each
subtraction image. Previous studies in which inversion recovery data
sets were acquired at approximately half-hour intervals during the
reperfusion period had demonstrated that the values of these
parameters did not change during this phase at our field
strength (n=2; data not shown). A value for the T1 of blood,
T1a, of 1500 ms was obtained by extrapolation of
published data acquired at other field strengths.
The transmitter coil inflow time, 
, must be taken into account to
determine CBF in the situation of an RF coil that does not provide
complete coverage of the body. This defines the time subsequent to the
application of the inversion pulse, after which blood spins will begin
to enter the imaging slice from outside the RF transmitter
coil.22 24 A value for this time was experimentally
determined in a control experiment by obtaining values for the
magnetisation difference while varying the recovery time. Comparison of
the data with the theoretical relationship of these 2 variables
enabled a value for of 1800 ms to be estimated.22
Diffusion MRI
Measurements of the trace of the diffusion tensor, denoted
trace(D), were obtained in 5 of the animals during the control period
and at approximately half-hour intervals during the postreperfusion
phase. The trace(D) is a rotationally invariant measure of the
diffusion tensor, and a number of sequences have been devised that
enable its acquisition by a single scan. The single-shot
trace(D)-weighted echo-planar imaging sequence25 used in
this study was implemented with the following parameters:
TE=110 ms; TR=1000 ms; number of averages=30; b values=0; and 1187
s/mm2.
Image and Data Analysis
Perfusion values were calculated pixelwise by importing the data
into IDL (Floating Points Systems). The relevant reduced repetition
time equation for the magnetisation difference provides a nonlinear
expression for the CBF. An iterative root-finding routine was used to
solve the equation for flow, thus providing a CBF map from each
subtraction image (selective-nonselective). Four regions of interest
were drawn on these perfusion maps in the left and right hemispheres of
the slice, in both the cortex and the corpus striatum. All values are
presented as mean±SD. Statistical analyses of the
factorial (regionxgroup) within-subjects data were performed by
mixed-model regression analysis using appropriate random
effects models. A value of P<0.05 was considered to
indicate statistical significance.
To characterize certain features of the flow response during the acute
phase of the reperfusion, a suitable random-coefficients model was
fitted to the first hour of the reperfusion data. Maximum likelihood
nonlinear mixed model regression was performed with use of an SAS macro
(NLINMIX, supplied by R. Wolfinger, SAS Institute, Cary,
NC).26 A detailed models comparison study was not
performed. Instead, an exponentially damped polynomial model was
adopted of the form
 | (2) |
, ß0,
ß1, and are random
coefficients.27 This model was selected since it is
economical in the number of coefficients and provides an adequate
description of the zero-time and asymptotic behavior
[f(0)
f(
)]. |
Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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CBF measurements were obtained with the reduced repetition time implementation of FAIR. Equation A11 in Reference 2222 was used to obtain CBF maps from each subtraction image, because the conditions
<
and TI< that define this equation were satisfied in our experiment.
The mean preocclusion blood flow measurements were, in the right
cerebral hemisphere, 155±27 mL/100 g/min in the cortex and 132±26
mL/100 g/min in the striatum; and in the left hemisphere, 161±25
mL/100 g/min in the cortex and 129±26 mL/100 g/min in the striatum
(n=8).
Representative perfusion maps are displayed in Figure 1
. After recirculation had been
initiated, a marked variability in the response to recirculation became
obviously apparent on visual inspection. Based on these observations,
the responses observed in the cerebral hemispheres of each animal were
assigned to 2 groups (groups A and B). The group response reflected the
characterization of the reperfusion time course in each hemisphere. In
each of the 8 animals, at least 1 cerebral hemisphere displayed an
early transient recovery of CBF that was followed by a period of
hypoperfusion. Hemispheres that showed this response were assigned to
group B. In 4 of the 8 animals, a side-to-side difference became
apparent and the group B hemisphere was accompanied by the observation
in the contralateral hemisphere of a permanent immediate
renormalization of the flow (Figure 1, panel a); these
hemispheres were assigned to group A. Each of the 4 animals thereby
provided 1 group A and 1 group B hemisphere. The other 4 animals
displayed a bilateral group B response (Figure 1, panel b). The
complete data set of 8 animals, therefore, provided 4 group A
hemispheres and 12 group B hemispheres. Figure 2 shows the time-course of the CBF values
for the data sets in each of the 2 groups.
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Table 1 details the control
and occlusion flows for group A and group B data. Mixed model
regression analysis of the pre-occlusion data showed a
significant regional (cortex versus striatum) difference
(P=0.01) while the difference between the 2 groups (group A
versus group B) was not significant. There was no significant regional
or group differences in the flow values measured during the occlusion
phase.
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Time-Course CBF Data: Group A (Immediate Normalization)
This response of immediate normalization of the flow never
occurred in both cerebral hemispheres of the same animal. On
recirculation, the blood flow recovered to a value close to the
pre-occlusion level. In order to characterize the initial recovery and
the subsequent flow response, an exponentially damped polynomial was
fitted to the first hour of the postreperfusion data (Equation 2
). To
test for regional differences, 2 such models were compared, one of
which is a full model and consists of a separate set of coefficients
for the cortical and striatal regions; the second model is a reduced
model and assumes a common set of coefficients for the 2 regions. The
difference between the models was not significant (log-likelihood
ratio, 
24); the reduced,
region independent model was therefore adopted. The calculated mean
time-dependent behavior is shown in Figure 3. The level of the initial recovery on
reperfusion was provided by the peak of the fitted model. A value of
146 mL/100 g/min at 11.7 minutes after reperfusion (ie, at 15.7 minutes
after occlusion) was thereby obtained. This maximal flow is 8% lower
and 12% higher than the preocclusion levels in the cortex and
striatum, respectively. At the end of the 1-hour period, the CBF
reached an asymptotic level of 126 mL/100 g/min.
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By 3 hours after reperfusion, the measured CBF values were 140±16 mL/100 g/min and 122±15 mL/100 g/min in the cortical and striatal regions, respectively. These values are not significantly different from the preischemic CBF measurements (paired t test).
Time-Course CBF Data: Group B (Recovery Followed by
Hypoperfusion)
This response occurred in 50% of the animals as a unilateral
response and in the other animals as a bilateral response; in the
latter situation, regional data were averaged over the 2 cerebral
hemispheres. On initiation of recirculation, the blood flow recovered
and, at approximately 5 minutes of reflow, reached a maximal level. A
period of hypoperfusion then followed. An exponentially damped
polynomial was fitted to the first hour of the postreperfusion data
(Equation 2). The likelihood ratio test comparing a full,
region-dependent coefficients model with the restricted common
coefficients model was not significant. Therefore, a common
coefficients model was chosen to provide an adequate description of the
data. The maximal level of the initial recovery on reperfusion was
provided by the peak of the fitted model (Figure 3). A value of
80 mL/100 g/min at 4.9 minutes after reperfusion (ie, 8.9 minutes after
occlusion) was thereby obtained. This flow is 49% lower and 38% lower
than the mean preocclusion levels in the cortex and striatum
respectively and, therefore, the mean response is not suggestive of a
period of true reactive hyperemia. The calculated mean flow
subsequently dropped to an asymptotic level during this 60-minute
period of 13 mL/100 g/min.
At approximately 60 minutes after reperfusion, the blood flow
began to recover slowly. The mean slope of the recovery obtained by
linear regression of data collected from 1 hour after reperfusion until
the end of the experiment was significantly different from zero with
values of 9.8±2.6 (mL/100 g/min)/h and 9.4±4.6 (mL/100 g/min)/h in
the cortical and the striatal regions (P
0.0002). By 3
hours after reperfusion, the CBF had reached a level of 35±9 mL/100
g/min and 37±14 mL/100 g/min in the cortex and striatum,
respectively.
Diffusion Trace(D) Data: Group A (Immediate Normalization)
Trace(D) measurements were obtained in 5 animals, 2 of which
displayed a side-to-side asymmetry on recirculation. No occlusion data
were acquired. The postreperfusion trace(D) values in the cerebral
hemispheres which displayed a group A response, were very similar to
the preischemic values and remained at a relatively
constant level. However, a statistical comparison could not be
performed due to the limited number of observations.
Diffusion Trace(D) Data: Group B (Recovery Followed by
Hypoperfusion)
Figure 4 displays the temporal
profiles of the trace(D) data for this response. The 5 animals
displayed the group B response in one or both hemispheres. Linear
regression of the postreperfusion trace(D) values with time in each
animal indicated a generally decreasing trend. In the cortex, 4 of the
5 data sets exhibited a negative slope, but the average slope was not
significantly different from zero (mean
slope=-1.4±3.2x10-7
[mm2/s] min-1). In the
striatal region, a negative linear trend was obtained in all of the
data sets, and the average slope was significantly different from zero
(mean slope=-3.0±2.4x10-7[mm2/s]
min-1; P=0.05). The values predicted
by the regression lines of the trace(D) at the time of the first
postreperfusion measurement (35 minutes) were 0.75±0.06 and 0.79±0.04
(x10-3) mm2/s in the
2 regions. These values are not statistically different from the
preocclusion level (paired t test). The regression slopes
were used to obtain the mean change in the trace(D) values during the
observation period, denoted 35–180. The
values of 35–180 were -0.021±0.019 (2.7%
of control level) and -0.043±0.04
(x10-3) mm2/s
(5.7%) in the cortical and striatal regions, respectively.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferencesIntroduction References |
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The principal findings of this investigation were the demonstration of the benefits of using rapid FAIR imaging in a time-course study of perfusion, the observation of the 2 flow patterns of reflow, and the regional trends in the diffusion coefficient.
A time-efficient implementation of FAIR was used in this investigation to follow accurately the changes in the blood flow with a time resolution of 2.8 minutes. This method has offered significant advantages over invasive techniques of perfusion measurement that do not permit longitudinal studies in the same animal. In its current implementation, single-slice acquisitions were used. The FAIR technique can, however, be extended to multiple-slice implementations, although certain issues relating to the quantification become problematic.24 The serial measurements of flow have enabled distinct discrimination of the 2 group responses to reperfusion. The increased power of the statistical analysis of longitudinal data used in this study has facilitated this differentiation and has permitted examination of possible regional differences in the response. It has also been possible to take into account the interanimal variability within the 2 patterns of reflow. Moreover, the changing flows have been mapped with a higher temporal resolution than offered by other techniques that provide serial, quantitative flow measurements. Because the immediate recovery and subsequent decrease in CBF on reperfusion occur over approximately 15 minutes, the acute phase of recirculation may be difficult to characterize with these other techniques.
The mean global preocclusion CBF value obtained with FAIR was 144±21 mL/100 g/min. This control flow is in general agreement with figures quoted in previous work with gerbil models.10 28 29 30 On reperfusion, the initial return, in all cases, of the CBF to values close to the preocclusion level precludes the presence of a general no-reflow phenomenon. There was no indication of any immediate focal impairments in CBF on reperfusion even in the striatum, which has been shown to be one of the subcortical regions that is susceptible to no-reflow.8 9
The immediate and permanent recovery of perfusion that was observed unilaterally in a number of animals (group A response) was unexpected. On 4 occasions, at the conclusion of the experiment, the animal was removed from the magnet and the snares were examined. The pulsation of the arterial flow proximal and distal to the snares was checked for consistency. At the end of every study, a postmortem examination was carried out to verify that the snares were fully open and that the external diameter of sections of the carotid arteries proximal and distal to the snares was constant. No evidence of an unsuccessful occlusion or reperfusion was thereby found. It has been noted31 that there is a variability in the number and the size of the small communicating blood vessels between the vertebrobasilar and the carotid circulations in the gerbil. The degree of collateral circulation that originates from the unoccluded vertebral supply might therefore be the cause of the observed side-to-side asymmetry on reperfusion. Previous studies32 have noted the side-to-side variations in the vasculature of the circle of Willis in gerbils.
The postischemic impairment in reflow that was observed in this study (group B response) followed the pattern of an initial recovery of flow, a delayed period of hypoperfusion, and then a slow recovery in the direction of the preocclusion level. The diffusion trace(D) measurements after reperfusion suggested a decreasing trend with time. However, further work is required to confirm this diffusion response with more animals. The diffusion coefficient and the longitudinal relaxation time, T1, are sensitive to temperature33 34 but the nonselective, T1-weighted FAIR data provided no evidence of temperature-related changes. The decreasing trend in the trace(D) values may reflect a process of progressive cell swelling during the phase of hypoperfusion. This trend was especially apparent in the striatal regions, which suggests a regional difference in susceptibility to injury. A similar regional pattern was observed in a recent study of hypoxia-ischemia in the rat.35 The magnitude of the decline in the trace(D) values observed in the striatum was substantially smaller than the change typically observed during acute ischemia. This observation is consistent with the CBF remaining close to the flow threshold for diffusion changes. Our laboratory has demonstrated the existence of a flow threshold of approximately 20 mL/100 g/min in the gerbil.19 These findings suggest that further work must be performed to elucidate whether the regional ADC change during the hypoperfusion period contributes to any long-term, deleterious effects of recirculation. In previous studies of the ADC changes that occur after reperfusion, several distinct responses have been observed, including immediate normalization36 and a delayed decline related to secondary energy failure.37
The CBF during the period of delayed hypoperfusion (group B response) dropped to an unexpectedly low level based on previous similar studies. It has been suggested that, paradoxically, shorter periods of ischemia result in a more pronounced degree of postischemic hypoperfusion.1 For example, 30 minutes of total forebrain ischemia in the gerbil resulted in a delayed drop in flow that represented approximately 40% of the control level (hydrogen clearance technique for CBF measurement),38 while after 5 minutes of ischemia in a similar gerbil model, the CBF fell to a value that was approximately 15% of the preocclusion flow (autoradiography technique).39 This relationship between the duration of the period of ischemia and the severity of hypoperfusion has however, not been verified in a single study.
It is also probable that the flow is being underestimated by the FAIR
measurement during the period of compromised perfusion. The first
postreperfusion measurement of the diffusion coefficient displayed no
significant change, and this indicates that the level of flow is above
the threshold for diffusion changes.19 The underlying
cause of the inaccuracy in the flow measurement is the effect of the
reduction in the blood flow on the validity of certain assumptions of
the FAIR model. The reduced blood flow will increase the significance
of the transit time, 
, during which blood originating from within
the inversion slab will move into the imaging slice.40
This duration exists as a result of the increased width of the
selective inversion slice relative to the imaging slice, which is
necessary to eliminate effects from imperfect edges of the inversion
and the imaging pulse profiles. The effects of are not normally
considered when analyzing FAIR data, because this time is expected to
be insignificant for normal levels of flow. However, the impairment of
flow during the period of hypoperfusion will increase the transit and
inflow times. If these increased times are not taken into account in
the FAIR quantification model, the technique will provide
underestimated flow values. The sensitivity of the flow measurements to
a changing transit time or inflow times can be theoretically
determined. For example, with our combination of parameters
and for a real flow of 20 mL/100 g/min, the transit and inflow times
would both need to rise by approximately 300 ms to induce an
underestimation in the measured flow value of 5 mL/100 g/min. Improved
inversion and imaging slice profiles are being investigated in our
laboratory with a view to reducing the effect of the transit time on
the quantification.
In conclusion, we have demonstrated the use of noninvasive FAIR perfusion imaging in following regional CBF changes with a high time resolution in a longitudinal study of reperfusion. On initiation of recirculation after 4 minutes of total forebrain ischemia, the blood flow in the cerebral hemispheres either returned to the preocclusion level or displayed a pattern of initial recovery followed by hypoperfusion. The combined measurements of CBF and the diffusion trace suggest a period during the reperfusion phase when intervention may be necessary to ameliorate recovery. The ability to follow and characterize a time course of events with quantitative mapping of cerebral perfusion has obvious potential in the investigation of stroke.
Received December 8, 1998; revision received February 16, 1999; accepted March 26, 1999.
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Editorial Comment
Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico
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Measurement of cerebral blood flow noninvasively has been an elusive goal since Kety and Schmidt1 first measured blood flow. In this article the authors describe the flow-sensitive alternating inversion recovery (FAIR) method that spin-labels flowing blood and follows it through a tissue region.2 With the aid of computer algorithms, they have shortened the acquisition times, making flow maps in several minutes. Technical requirements are still daunting. Echo-planar instruments and specially designed pulse sequences are required. However, as with other MR methods, clinical applications should follow.
Diffusion-weighted imaging (DWI) shows the state of water in tissue.3 When cells are swollen, reducing the extracellular space, the diffusion coefficient falls. Because the changes in diffusion are highly sensitive and very rapid, the diffusion imaging has shown early development of edema after an ischemic event.4 The present report combines the DWI with FAIR and provides a unique view of the relationship of flow to diffusion constants.
Using the well-established gerbil model of ischemia, they occluded the carotids for 4 minutes within the magnet.5 Several patterns of flow occurred after the release of the occlusions. Some animals had no change in flow, while others showed hyperemia followed by decreased flow ("no-reflow").6 Variability was seen in the flow patterns between hemispheres in the same animal. To overcome the variability, hemispheres were grouped according to flow rather than by animal. The data showed that the poorly perfused hemispheres had a slight fall in diffusion coefficients rather than the expected significant change. They suggest that the lack of correlation is due to an underestimation of true values when flow is impaired. The strength of this report lies in the methodology rather than in new physiological data. In fact, more work will be needed to clarify the potential errors in the measurements.
Characterization of the state of the tissue after a stroke is critical for the use of thrombolytics and fibrolytics that have entered clinical use. Selecting patients that have potentially salvageable brain tissue and do not have an increased risk for hemorrhage is a major challenge.7 8 Quantification of blood flow, measurements of diffusion constants, and biochemical measurements with spectroscopy provide a 3-dimensional view.9 Speeding up the acquisition of MR data will add a time dimension. This report adds another step in the rapid advance in MR methods. It should provide information about tissue viability that will guide therapies.
Received December 8, 1998; revision received February 16, 1999; accepted March 26, 1999.
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[Abstract/Free Full Text]
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