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Evolution of Cerebral Infarct Volume Assessed by Diffusion-Weighted Magnetic Resonance Imaging
Maarten G. Lansberg, MD;
Michael W. O'Brien, MD, PhD;
David C. Tong, MD;
Michael E. Moseley, PhD;
Gregory W. Albers, MD
Arch Neurol. 2001;58:613-617.
ABSTRACT
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Background Knowledge of the natural evolution of ischemic brain lesions may be
a crucial aspect in the assessment of future stroke therapies.
Objective To establish daily changes of ischemic cerebral lesion volume using
diffusion-weighted magnetic resonance imaging.
Design Prospective cohort study.
Setting Referral center.
Patients and Methods Serial magnetic resonance imaging scans were performed in consecutive
untreated stroke patients. The baseline scan was obtained within 48 hours
after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7
days, and 30 days after baseline. Lesion volumes were measured on each scan
by 2 independent observers.
Main Outcome Measure Daily change in lesion volume.
Results A total of 112 magnetic resonance imaging scans were obtained in 24
patients. An early increase in lesion volume was seen in all patients. Maximum
lesion volume was reached at a mean of 74 hours. Lesion volumes increased
by a mean (± SEM) of 21% ± 12% during day 2 and 10% ±
12% during day 3. No significant change occurred during day 4. During days
5, 6, and 7, statistically significant mean (± SEM) decreases of 6%
± 8%, 3% ± 4%, and 4% ± 5%, respectively, were observed.
Conclusions Ischemic lesions follow a relatively consistent pattern of growth during
the first 3 days and subsequent decrease in size. These data in conjunction
with data regarding the evolution of lesion volume during the first 24 hours
after symptom onset may be useful in the design of pilot studies of therapies
for acute stroke.
INTRODUCTION
SEVERAL neuroprotective agents that have shown promising results in
animal stroke models have not demonstrated beneficial effects in clinical
stroke trials.1, 2, 3
Potential explanations for differing results in animals vs humans may be the
more uniform infarct volumes and the possibility of initiating treatment soon
after or even before stroke onset in animal models. Differences in collateral
circulation between rodents and humans may be the reason why trials of neuroprotective
agents in humans have not been successful.3
Another reason may be the use of different study end points. Animal studies
typically use lesion volume as the primary outcome measure, whereas most clinical
trials use a clinical stroke scale score. Unless the treatment dramatically
affects clinical outcome, large trials are required to demonstrate efficacy
using clinical scales. Most recent clinical stroke trials may not have been
of sufficient size to detect a treatment effect on clinical stroke scales.2
Although the most important end point in acute stroke trials is clinical
outcome, an ancillary outcome measure may be useful if it can demonstrate
a treatment effect in smaller clinical trials. Lesion volume evolution assessed
by diffusion-weighted magnetic resonance imaging (MRI) (DWI) could be used
as such an ancillary measure. Diffusion-weighted MRI is an imaging technique
that can identify ischemic brain tissue in the hyperacute phase of stroke.4, 5 The noninvasive nature of the technique
facilitates the acquisition of multiple scans at different times, allowing
ischemic lesion volumes to be followed up over time.
In several animal models, a treatment effect of neuroprotective agents
has been demonstrated using DWI and subsequently confirmed by pathological
assessment.6, 7 The clinical relevance
of reducing ischemic lesion expansion is not known. It is a reasonable but
unproven assumption that attenuating lesion expansion will prevent ischemic
but viable brain tissue from undergoing irreversible damage and that this
may result in clinical benefits. The strong positive correlation in animal
stroke models between early lesion size on DWI and histological infarct size
indicates a direct relationship between DWI lesion volume and final infarct
volume.4, 6, 7, 8, 9
In humans, similarly good correlations have been reported between early lesion
size on DWI and final infarct volume on T2-weighted MRI.10, 11, 12
These studies have also shown a positive correlation between early DWI lesion
size and final National Institutes of Health Stroke Scale (NIHSS) score. This
suggests that attenuation of early increases in DWI lesion volumes may result
in smaller final infarct volumes and lower final NIHSS scores. Therefore,
DWI lesion size measured after administration of a treatment may be a good
surrogate end point for pilot studies of therapies for acute stroke.
To optimize the design of clinical stroke trials using DWI, efforts
are under way to establish the natural course and variability of the evolution
of ischemic lesion volumes in patients with acute stroke. The goal of this
study was to describe the early changes in DWI lesion volumes in untreated
stroke patients.
SUBJECTS AND METHODS
PATIENT ELIGIBILITY
Between January 1, 1997, and May 31, 1998, all patients who presented
to the Stanford Stroke Center, Stanford University Medical Center, Stanford,
Calif, with a presumed diagnosis of acute stroke underwent screening by a
stroke neurologist for eligibility to participate in this longitudinal MRI
study. Eligible patients were aged at least 18 years and presented for evaluation
within 48 hours of symptom onset. Potential patients had to be able to comply
with the MRI procedures and have a score of 1 or more on the NIHSS. Exclusion
criteria included (1) enrollment in an investigational trial of a neuroprotective
agent; (2) stroke treatment with thrombolytic therapy; (3) level-of-consciousness
score of 3 on the NIHSS (responds only with reflex motor or autonomic effects
or totally unresponsive, flaccid, and reflexless); (4) severe coexisting disease
that limits life expectancy or may interfere with the conduct of the study;
and (5) no acute ischemic lesion consistent with the presenting symptoms identifiable
on the baseline DWI scan.
STUDY PROCEDURES
A baseline MRI scan was obtained within 48 hours of symptom onset, and
follow-up MRI scans were obtained at 12 to 48 hours, 3 to 4 days, 5 to 7 days,
and 30 days after the baseline examination. Scans were cancelled or delayed
if scan time was not available or if requested by the patient or their family.
The NIHSS score was determined by a certified neurologist at the time of the
baseline scan. The study was approved by the Stanford University Human Subjects
Committee. Informed consent was obtained from each patient or from an appropriate
family member.
MRI VARIABLES AND DATA PROCESSING
Magnetic resonance imaging was performed by echo planar imaging using
a 1.5-T Signa Magnet (General Electric, Milwaukee, WI). The whole-brain echo
planar imaging–DWI examination acquired 16 slices (slice thickness,
5 mm; 2.5-mm gap between slices; repetition time, 6000 milliseconds; echo
time, 110 milliseconds; field of view, 24 cm; matrix size, 128 x128
pixels; b values, 0 and 849 s/mm2). The DWI images were acquired
in x, y, and z planes and were processed off-line to generate trace-apparent
diffusion coefficient maps and isotropic DWI images.
Lesion volumes were determined on the DWI image for the acute scans
and on the echo planar imaging T2-weighted (b = 0) image for the 30-day scans.
On the baseline MRI scan, the acute lesion was identified by means of high
signal on the DWI image and hypointensity on the apparent diffusion coefficient
map in a region that was consistent with the clinical presentation. Lesion
volume was determined with the aid of an image analysis software program (MRVision,
Menlo Park, Calif) on a computer workstation (Sun Microsystems, Palo Alto,
Calif). Lesion areas were outlined and measured for each slice. If multiple
lesions were present in the same hemisphere, they were outlined separately.
The area measurements were used to calculate lesion volume. Lesion volume
at each time was determined by 2 independent observers, whose results were
averaged. Lesion volumes at 1, 2, 3, 4, 5, 6, 7, and 25 days after symptom
onset were calculated by linear interpolation. After analysis of the data
to determine the median time to maximal lesion volume, lesion volumes at each
time were expressed as a fraction of the volume at 72 hours (closest 24-hour
time to the time of maximal lesion volume) to control for the large variation
in lesion volumes among patients. Mean percentage of changes in lesion volume
were determined for each 24-hour period.
STATISTICAL ANALYSIS
Statistical analyses were performed using commercially available software
(SigmaStat; Jandel, San Rafael, Calif). Mean lesion volumes, SDs, and SEMs
were calculated for each 24-hour period. The paired t
test was used to assess the changes in lesion volume for each 24-hour period.
RESULTS
Twenty-seven patients were enrolled in the study. Three patients died
before the end of the study and are excluded from this analysis. A total of
112 scans were obtained in the 24 patients (average, 4.7 scans per patient)
included in this analysis. The median time from symptom onset to the baseline
MRI scan was 23 hours (range, 8-48 hours). Thirteen patients received their
baseline scan within the first 24 hours; 11, between 24 and 48 hours. The
median time until the final MRI scan was 31 days (range, 26-72 days).
At enrollment, the patients' median age was 73 years (range, 37-93 years)
and the median NIHSS score was 5 (range, 1-24). In 17 patients, the infarction
involved the middle cerebral artery territory; 2 of these were deep subcortical
infarcts. One patient had an infarct that involved the middle and the anterior
cerebral artery distribution, and 6 patients had an infarct in the posterior
cerebral artery.
All lesions initially expanded and subsequently shrank during the course
of the study. Figure 1 shows an
example of the initial increase and subsequent decrease in lesion size. The
mean (± SEM) lesion volume on the baseline DWI scan was 25 ±
32 cm3. Maximum lesion volume was observed at a median of 74 hours
(range, 43-170 hours) after symptom onset. The mean (± SEM) maximum
lesion volume was 31.4 ± 37.1 cm3. Figure 2A displays the mean lesion volumes at each time for patients
with a baseline scan obtained within 24 hours after symptom onset (n = 13)
and for patients with a baseline scan obtained between 24 and 48 hours after
symptom onset (n = 11). The mean lesion volume was smaller in the group of
patients with baseline scans obtained within 24 hours compared with the group
with baseline scans obtained between 24 and 48 hours; this difference was
not statistically significant (t test; P = .13). However, the pattern of evolution was similar for both groups.
This is also illustrated in Figure 2B, where lesion volumes are expressed as fractions of the volumes at 72 hours
(the time point closest to the time of maximal lesion volume), and the curves
for both groups overlap.
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Figure 1. From left to right, the same slice
of the T2-weighted magnetic resonance image (MRI) (top row) and diffusion-weighted
MRI (bottom row) at 8 hours, 43 hours, 3 days, 5 days, and 30 days after symptom
onset in a patient with a right parietal infarct. Lesion volumes for this
patient at the 5 times are 8.0, 12.8, 12.2, 9.0, and 5.5 cm3, respectively.
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Figure 2. A, Mean lesion volume and SEM
at 24-hour increments for the first week after stroke onset and at 25-day
follow-up. B, Mean lesion volume and SEM at 24-hour increments for the first
week after stroke onset and at 25-day follow-up expressed as a percentage
of the lesion volume at 72 hours. The circles represent data for patients
with a baseline scan within 24 hours of symptom onset (n = 13); the triangles,
data of patients first undergoing scanning between 24 and 48 hours after symptom
onset (n = 11).
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The mean daily percentage of change in lesion volume is shown in Figure 3. Lesions significantly increased
in size by a mean (± SEM) of 21% ± 12% (P<.01) during day 2 and an additional 10% ± 12% (P<.01) during day 3. No significant change occurred during day 4.
During days 5, 6, and 7, statistically significant decreases in lesion volume
by a mean (± SEM) of 6% ± 8% (P<.01),
3% ± 4% (P<.1), and 4% ± 0% (P<.01), respectively, were observed. A further decrease
of 34% ± 22% (P<.01) was seen from days
7 through 25, representing a mean daily change of 3% ± 3%, assuming
that the rate of change was uniform each day.
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Figure 3. Mean daily changes in lesion volume
for the first 25 days after stroke onset. Lesion volumes increase substantially
during days 2 and 3, do not change during day 4, and decrease gradually after
day 4. The data for day 2 are based on 13 patients; for all subsequent days,
on 24 patients. Error bars indicate SEM.
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COMMENT
This study describes the daily changes of DWI lesion volume in untreated
stroke patients. The data show a relatively consistent pattern of volume change
in this population. The DWI lesion volumes typically increase substantially
during the first 3 days after stroke onset, plateau during day 4, and slowly
decrease in size during the next 3 to 4 weeks.
Our finding of the early expansion of DWI lesion volumes agrees with
the results of others. Sorensen et al13 reported
that final infarct volumes were larger than baseline DWI lesion volumes in
8 of 9 patients who underwent scanning within 10 hours after symptom onset.
Baird et al14 compared acute DWI lesion volume
with follow-up T2-weighted lesion volume and found evidence that substantial
enlargement of human cerebral ischemic lesions can occur beyond the first
24 hours after symptom onset. Both groups of investigators speculated, based
on data from perfusion-weighted MRI, that the observed early lesion growth
represented recruitment of tissue at risk into the infarct. Schwamm et al15 published the time course of DWI lesion evolution
in a smaller series of stroke patients. They found a progressive increase
in lesion volume in most patients in the first days after symptom onset, with
maximum DWI lesion volume typically occurring after 3 days.
Expansion of DWI lesion volume likely reflects 2 pathophysiological
processes: an increase in ischemic brain tissue injury and the formation of
vasogenic edema. The largest increase in ischemic brain injury likely occurs
during the first hours after stroke onset,8, 9
whereas formation of edema may play a more important role during the following
2 to 3 days.16, 17 The increase
in lesion volume during the second and third days, however, could also reflect
a prolonged period when the ischemic core expands into surrounding tissue.
This hypothesis is supported by the observation in positron emission tomographic
studies that ischemic but viable tissue may be present up to 48 hours after
stroke onset.18, 19 The decrease
in lesion volume between 4 and 25 days after symptom onset is likely explained
by a combination of resolution of edema16, 17
and a decrease in inflammatory infiltration. Reversal of some penumbral ischemia
and atrophy of the infarct may also be contributing factors. Mean lesion volume
at 25 days was somewhat smaller than the 24-hour volume. In studies that obtained
the baseline scan sooner after symptom onset, final T2-weighted lesion volume
has been larger than baseline DWI lesion volume.13, 14, 15
The use of MRI findings as a surrogate end point for studies of therapies
for acute stroke is in its infancy. For this surrogate to be useful, lesion
volume assessed by means of MRI must be shown to be correlated to clinical
outcome. Our study is of insufficient size to determine the correlation between
lesion volume and clinical stroke scale scores. Previous studies have found
a good correlation between lesion volume as assessed by DWI and clinical outcome
as assessed by clinical stroke scales.10, 11, 12
More recently, a moderate correlation has been reported between computed tomographic
lesion volume and NIHSS score.20 It is generally
believed that lesion location is an important factor that weakens the correlation
between lesion volume and clinical stroke scale score. For example, a comparison
of lesion volumes in patients with equal NIHSS scores has shown significantly
larger lesions in patients with a right hemisphere stroke compared with patients
with a left hemisphere stroke.21
The established correlation between DWI lesion volume and clinical stroke
scale scores makes DWI lesion volume a potentially good end point for pilot
trials of therapies for acute stroke. If pilot trials do not demonstrate any
evidence of a treatment effect, much larger trials powered for clinical end
points may be avoided. The optimal timing of the MRI scans and the best imaging
sequences for clinical trials remain to be determined. Our data demonstrate
that ischemic lesions follow a consistent pattern of evolution, despite large
variation in lesion volumes among patients. Therefore, the change in lesion
volume over time is likely to be a much more sensitive end point than absolute
lesion volume at any specific time. To determine change in lesion volume,
the acquisition of at least 2 scans in each patient is required. The first
scan should be acquired before or immediately after the initiation of treatment
to demonstrate the baseline lesion. At present, DWI appears to be the most
suitable imaging modality for this purpose, because ischemic lesions can be
visualized using DWI before they become apparent using conventional imaging
techniques.13, 22, 23, 24
Because DWI lesion volumes change rapidly in the acute phase of stroke, it
is essential that the time from symptom onset to performance of the baseline
scan be well matched between treatment and control groups.
The follow-up scan, ideally, should provide an accurate measure of the
final infarct volume. The lesion volume on a chronic T2-weighted scan is generally
believed to be a reasonable reflection of final infarct volume. Early DWI
lesion volume has been shown to correspond well with lesion volume on later
T2-weighted MRI10, 11, 12
as well as with infarct volume at autopsy4, 6, 7, 8, 9
and may therefore be used as a surrogate measure of final infarct volume.
Because DWI lesion volumes typically increase until day 3 and plateau during
day 4, infarct volumes may be best estimated by means of DWI performed approximately
3 to 4 days after symptom onset. However, at this time, both cytotoxic and
vasogenic edema contribute to the size of the maximum DWI lesion, resulting
in an overestimation of the infarct volume. In contrast, the T2-weighted MRI
lesion volume at a later time may underestimate the actual volume because
of atrophy. If treatment of an acute stroke has an impact on early lesion
growth, then DWI lesion volume, obtained a few days after treatment is begun,
might be as suitable a study end point as late T2-weighted lesion volume.
Logistically, a second scan at 3 to 4 days, when many stroke patients are
still in the hospital or in the rehabilitation unit, may be more convenient
than a follow-up scan several weeks or months after symptom onset.
This study has several limitations. The MRI scans were not obtained
at exact 24-hour increments. However, because linear interpolation and no
extrapolation was used for volume estimations, we expect that the introduced
error is relatively small. Another limitation is that no data points were
collected between the 5- to 7-day scan and the late follow-up. The calculated
mean daily changes in lesion volume of 3% assume a uniform change in lesion
volume during this period. Further studies are necessary to describe the evolution
of lesion volume during this period in more detail. Patients presenting very
early after stroke onset were typically excluded because they were treated
with recombinant tissue-type plasminogen activator or investigational neuroprotective
agents. Volume changes occurring during the first day after symptom onset
could, therefore, not be addressed. Further studies investigating the change
in lesion volume during the first 24 hours in untreated patients would be
very valuable. The most dramatic increases in lesion volume may be observed
during this time, and sample size calculations for acute stroke studies may
thus yield even smaller numbers than those that could be calculated based
on the data in this study. In addition, the change in lesion volume during
the first 24 hours is more likely to reflect expansion of the ischemic region
and less likely to reflect the formation of potentially reversible cerebral
edema, and most clinical stroke trials now initiate treatment very early after
stroke onset. Efforts are currently under way to establish the pattern of
evolution during the first 24 hours after symptom onset and, from these data,
to estimate required sample sizes for placebo-controlled studies of hypothetical
stroke treatments.
CONCLUSIONS
The results of this study demonstrate that ischemic lesions follow a
relatively consistent pattern of volume evolution with a significant increase
in size during days 2 and 3, no change during day 4, and subsequently a slow
decrease in volume. These data suggest that DWI lesion volume may be a sensitive
measure of the efficacy of agents that attenuate early lesion expansion and
may be a useful end point in preliminary trials of stroke therapies.
AUTHOR INFORMATION
Accepted for publication February 28, 2000.
The study was supported by Janssen Pharmaceuticals and grants RO1NS35959
and RO1NS34866 from the National Institutes of Health, Bethesda, Md. Dr Lansberg
was supported by grants from the Dutch Heart Association, The Hague, the Netherlands;
Dutch Brain Association, The Hague; VSB Fund, Utrecht, the Netherlands; and
Philips Medical Instruments, Eindhoven, the Netherlands.
Statistical review by Kala Mehta, DSc, Johns Hopkins School of Public
Health, Baltimore, Md. We are grateful to the patients who gave their time
to participate in this study, to Stephanie Kemp for the logistical organization
of the study, to Juan Ali, MD, for data acquisition, and to Tobias Neumann-Haefelin,
MD, for his valuable advise during the preparation of this manuscript.
From the Stanford Stroke Center, Stanford University Medical Center,
Stanford, Calif.
Corresponding author: Gregory W. Albers, MD, Stanford Stroke Center,
701 Welch Road, Building B, Suite 325, Palo Alto, CA 94304-1705.
REFERENCES
| |
1. Grotta J. Why do all drugs work in animals but none in stroke patients? II: neuroprotective
therapy. J Intern Med. 1995;237:89-94.
ISI
| PUBMED
2. Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology. 1997;49(suppl):S66-S69.
3. del Zoppo G. Clinical trials in acute stroke. Neurology. 1998;51(suppl):S59-S61.
4. Moseley ME, Cohen Y, Mintorovitch J, et al. Early detection of regional cerebral ischemia in cats. Magn Reson Med. 1990;14:330-346.
ISI
| PUBMED
5. Albers GW. Diffusion-weighted MRI for evaluation of acute stroke. Neurology. 1998;51(suppl):S47-S49.
6. Lo EH, Matsumoto K, Pierce AR, Garrido L, Luttinger D. Pharmacologic reversal of acute changes in diffusion-weighted magnetic
resonance imaging in focal cerebral ischemia. J Cereb Blood Flow Metab. 1994;14:597-603.
ISI
| PUBMED
7. Yenari MA, Palmer JT, Sun GH, de Crespigny A, Mosely ME, Steinberg GK. Time-course and treatment response with SNX-111, an N-type calcium
channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted
MRI. Brain Res. 1996;739:36-45.
FULL TEXT
|
ISI
| PUBMED
8. Minematsu K, Li L, Fisher M, Sotak CH, Davis MA, Fiandaca MS. Diffusion-weighted magnetic resonance imaging. Neurology. 1992;42:235-240.
FREE FULL TEXT
9. Knight RA, Dereski MO, Helpern JA, Ordidge RJ, Chopp M. Magnetic resonance imaging assessment of evolving focal cerebral ischemia:
comparison with histopathology in rats. Stroke. 1994;25:1252-1262.
ABSTRACT
10. Lovblad KO, Baird AE, Schlaug G, et al. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic
resonance imaging correlate with clinical outcome. Ann Neurol. 1997;42:164-170.
FULL TEXT
|
ISI
| PUBMED
11. Barber PA, Darby DG, Desmond PM, et al. Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted
MRI. Neurology. 1998;51:418-426.
FREE FULL TEXT
12. Tong DC, Yenari MA, Albers GW, O'Brien M, Marks MP, Moseley ME. Correlation of perfusion- and diffusion-weighted MRI with NIHSS score
in acute (<6.5 hour) ischemic stroke. Neurology. 1998;50:864-870.
FREE FULL TEXT
13. Sorensen AG, Buonanno FS, Gonzalez RG, et al. Hyperacute stroke. Radiology. 1996;199:391-401.
FREE FULL TEXT
14. Baird AE, Benfield A, Schlaug G, et al. Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted
magnetic resonance imaging. Ann Neurol. 1997;41:581-589.
FULL TEXT
|
ISI
| PUBMED
15. Schwamm LH, Koroshetz WJ, Sorensen AG, et al. Time course of lesion development in patients with acute stroke. Stroke. 1998;29:2268-2276.
FREE FULL TEXT
16. Bell BA, Symon L, Branston NM. CBF and time thresholds for the formation of ischemic cerebral edema,
and effect of reperfusion in baboons. J Neurosurg. 1985;62:31-41.
ISI
| PUBMED
17. O'Brien MD. Ischemic cerebral edema: a review. Stroke. 1979;10:623-628.
FREE FULL TEXT
18. Heiss WD, Huber M, Fink GR, et al. Progressive derangement of periinfarct viable tissue in ischemic stroke. J Cereb Blood Flow Metab. 1992;12:193-203.
ISI
| PUBMED
19. Marchal G, Beaudouin V, Rioux P, et al. Prolonged persistence of substantial volumes of potentially viable
brain tissue after stroke. Stroke. 1996;27:599-606.
FREE FULL TEXT
20. Saver JL, Johnston KC, Homer D, et al. Infarct volume as a surrogate or auxiliary outcome measure in ischemic
stroke clinical trials. Stroke. 1999;30:293-298.
FREE FULL TEXT
21. Woo D, Broderick JP, Kothari RU, et al for the NINDS t-PA Stroke Study Group. Does the National Institutes of Health Stroke Scale favor left hemisphere
strokes? Stroke. 1999;30:2355-2359.
FREE FULL TEXT
22. van Everdingen KJ, van der Grond J, Kappelle LJ, Ramos LM, Mali WP. Diffusion-weighted magnetic resonance imaging in acute stroke. Stroke. 1998;29:1783-1790.
FREE FULL TEXT
23. Lutsep HL, Albers GW, DeCrespigny A, Kamat GN, Marks MP, Moseley ME. Clinical utility of diffusion-weighted magnetic resonance imaging in
the assessment of ischemic stroke. Ann Neurol. 1997;41:574-580.
FULL TEXT
|
ISI
| PUBMED
24. Singer MB, Chong J, Lu D, Schonewille WJ, Tuhrim S, Atlas SW. Diffusion-weighted MRI in acute subcortical infarction. Stroke. 1998;29:133-136.
FREE FULL TEXT
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