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(Stroke. 1999;30:2043-2052.)
© 1999 American Heart Association, Inc.
Original Contributions |
Pathophysiological Topography of Acute Ischemia by Combined Diffusion-Weighted and Perfusion MRI
From the Departments of Neurology (D.G.D., P.A.B., R.P.G., M.P., S.M.D.) and Radiology (P.M.D, Q.Y., T.L., B.M.T.), The Royal Melbourne Hospital, University of Melbourne, Australia.
Correspondence and reprint requests to Prof Stephen Davis, Director of Neurology, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia. E-mail sdavis{at}ariel.its.unimelb.edu.au
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Abstract |
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Background and Purpose—Combined echoplanar MRI diffusion-weighted imaging (DWI), perfusion imaging (PI), and magnetic resonance angiography (MRA) can be used to visualize acute brain ischemia and predict lesion evolution and functional outcome. The appearance of a larger lesion by PI than by DWI quantitatively defines a mismatch of potential clinical importance. Qualitative lesion variations exist in the topographic concordance of this mismatch. We examined both the topographic heterogeneity and relative frequency of mismatched patterns in acute stroke using these MRI techniques.
Methods—Acute DWI, PI, and MRA studies of 34 prospectively recruited patients with supratentorial ischemic lesions scanned within 24 hours of stroke onset (range 2.5 to 23.3 hours, 12 patients <6 hours) were analyzed.
Results—Ischemic lesions were predominantly in the middle cerebral artery (MCA) territory (94%), with DWI lesions most commonly affecting the insular region. Mismatched patterns with PI lesion larger than DWI lesion occurred in 21 patients (62% overall), in all 4 patients imaged within 3 hours, and in 44% of patients imaged after 18 hours. A patient with a large PI but no DWI lesion and severe clinical deficit at 2.5 hours after stroke onset recovered completely. Regional variations in DWI and PI lesion loci were found, inferring site of proximal MCA occlusion, embolic pathogenesis, and regional arterial reperfusion.
Conclusions—Analysis of the topographic concordance of PI and DWI lesions in acute stroke reveals regional PI lesions without concomitant DWI lesions, which do not necessarily progress to infarction but may suggest stroke pathogenesis and site of current arterial occlusion. Location of DWI lesions may suggest an earlier site of arterial occlusion and regions of maximal perfusion deficit.
Key Words: cerebral ischemia • echo-planar imaging • diffusion • perfusion
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Early thrombolytic treatment of acute ischemic stroke may significantly improve prognosis by reestablishing arterial flow in a region of hypoperfusion.1 Thrombolytic therapy is currently recommended only in patients who present within 3 hours of stroke onset and without significant CT abnormalities indicative of hemorrhage or major infarction. Unfortunately, benefit is not universal even within this time window,1 and there is experimental and clinical evidence to suggest that in some cases, treatment after longer delays might be beneficial.2 3 There is therefore a need for techniques that refine current patient selection criteria to identify those with clinically significant regions of potentially salvageable ischemic tissue at any time after infarction onset.
Perfusion (PI) and diffusion-weighted (DWI) MRI techniques can detect both tissue hypoperfusion and usually irreversible injury in acute infarction.4 5 6 7 8 A single imaging session can therefore rapidly visualize and quantify the presence, extent, and evolution of acute ischemia-associated changes. These measures correlate quantitatively with short-term and long-term functional deficits,7 which indicates their utility for predicting clinical course. They can also depict regions around the infarction core (as defined by areas of impaired diffusion on DWI images) where perfusion is reduced on PI but tissue diffusion is near normal.7 Such regions may be a surrogate marker of the true ischemic penumbra, as originally defined physiologically.7 9 10 Reperfusion, including reperfusion after thrombolysis, into these areas may prevent transition to infarction.11 In addition, magnetic resonance angiography (MRA) allows rapid visualization of proximal large cerebral arterial patency and predicts the presence of large perfusion deficits and the presence of lesions that appear larger on PI than on DWI.12
There are 6 possible regional concordance combinations of acute PI and DWI, which have been divided into putative "penumbral" and "nonpenumbral" patterns on the basis of the mismatch between PI and DWI lesion volume.7 Evolution is reported only in those cases with mismatch patterns in which PI lesion volume is larger than DWI lesion volume.7 13 14 Hence, the presence of a PI>DWI mismatch is likely to be an independent predictor of benefit from thrombolysis. One small trial using tissue plasminogen activator supports this contention,11 although larger-scale trials are required.15 16 In combination, PI, DWI, and MRA techniques allow accurate specification of the state of the hemodynamic perturbations in an individual patient's infarction and may lead to more rational targeting of therapy, so that benefit is maximized and adverse events are avoided.15 16
Our previous work has described quantitative correlations of these MRI methods and clinical deficits acutely and serially,7 12 17 but qualitative aspects of lesion concordance may also be relevant to therapy. In the present study, we therefore examined the concordance of DWI, PI, and MRA lesions and their clinical consequences in patients scanned within 24 hours of infarction onset with serial studies included in cases in which pathophysiology could be further elucidated. We aimed to identify patterns that might be clinically useful in the examination and treatment of an acute stroke patient. We were particularly interested in determining whether PI and DWI lesions were usually concentric, as suggested by the quantitative core-penumbra model described above, and whether the likely stroke mechanism could be inferred by imaging alone (eg, embolism or border-zone or deep-perforator occlusion).
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Patients
Patients were prospectively recruited from the Stroke Service of the Royal Melbourne Hospital as previously described.7 12 They were included if they presented within 24 hours of sudden onset of a focal neurological deficit consistent with hemispheric ischemic stroke. Stroke onset was defined as the last time the patient was known to be without neurological deficit.
Exclusion criteria were the presence of cerebral hemorrhage, preexisting significant nonischemic neurological deficits (including dementia or extrapyramidal disease), or a history of prior stroke that would hamper interpretation of clinical and radiological data. There were no age, sex, handedness, or prior therapy exclusions. The study was performed with the approval of our institution's Ethics Committee, and written informed consent was obtained from all patients or their next of kin.
Imaging Protocol
MRI scans were obtained with a 1.5-T echoplanar imaging
(EPI)–equipped whole-body scanner (Signa Horizon SR 120, General
Electric) according to a protocol optimized to obtain high-quality
images as rapidly as possible in ill and potentially uncooperative
patients. Sequences were always performed in the same order, with an
initial T1-weighted sagittal localizer (T1-W), the diffusion-weighted
sequence, then the perfusion sequence, a proton-density (PD) and
T2-weighted (T2-W) fast-spin double-echo sequence (TR/TE/TE 3500/10/60
ms), and other studies as previously described.7 Similar
slice positions were used to facilitate comparisons. The acute DWI, PI,
and MRA studies are reported here, although later studies are mentioned
if relevant.
Diffusion Imaging
DWI was performed with a multislice, single-shot, spin-echo EPI
sequence with imaging time of either 1 minute 23 seconds or 2 minutes
10 seconds. The rapid acquisition times made cardiac or respiratory
gating and special head restraint unnecessary. Slice thickness was
6 mm with a 1-mm gap. The number of slices was set to include the
entire brain (average of 15 slices). Matrix size was 256x128, and
field of view was 40x20 cm. The remainder of the protocol for the
first 27 patients was as described previously.7 In the
final 7 patients recruited for the study, DWI sequences used TR/TE of
10 000/100 ms. The diffusion gradient strength was varied between 0
and 22 mT/m, resulting in 3 b values from 0 to 1000
s/mm2.18 The diffusion gradient was
applied in 3 orthogonal directions (x, y, and z), and an average of
these measurements was calculated that yielded isotropic
images19 and a trace of the diffusion tensor, which may
minimize the effects of diffusion anisotropy.20
Perfusion Imaging
The initial 18 patients were imaged according to the protocol
described previously.7 Perfusion images were obtained in
subsequent patients by dynamic first-pass bolus tracking of gadolinium
diethylenetriamine penta-acetic acid (Gd-DTPA) with an EPI gradient
echo sequence (TR/TE 2000/70 ms). The Gd-DTPA bolus (0.1 to 0.2
mmol/kg) was administered by a power injector (Spectris MR Injector,
MEDRAD) over 3 to 5 seconds via an 18-gauge antecubital fossa cannula.
The concentration time curve obtained was processed on a voxel-by-voxel
basis to determine an observed or relative mean transit time (rMTT)
map, where the rMTT is related to the sum of the true mean transit time
plus injection time.21 No arterial input
function was used, which made the rMTT maps equivalent to time-to-peak
maps. We found that in addition to giving the most visually distinct
perfusion-deficit border, as previously reported,7 13 the
rMTT map also resulted in perfusion deficits of greater volume than
other hemodynamic parameters, which
suggests it was more representative of the maximum
anatomic extent of perfusion impairment. In addition, rMTT maps give
individual voxels scalar values, which allows delineation of regional
variations in perfusion within each image. Imaging time was 1 minute 21
seconds.
Magnetic Resonance Angiography
Magnetic resonance angiograms were obtained by use of a 2D
phase-contrast sequence in the region of the Circle of Willis with slab
thickness of 10 mm (1-mm gap) and velocity encoding speeds of 70
cm/s. Gradients were applied in all 3 orthogonal directions: TR/TE of
25/7.5 ms; flip angle of 30°; matrix of 256x128; field of view
20x20 cm; and the 2 excitations. Imaging time was 1 minute 50
seconds.12
Data Analysis
Postprocessing of MR images was performed with customized
commercial software based on AVS (Advanced Visualization Systems) and
an Indigo 2 workstation (Silicon Graphics Inc). Quantitative
analysis methods used in our institution have been reported
previously.7 The present study used DWI and PI images
at the same levels for qualitative comparisons. Isotropic DWI images at
the maximum diffusion sensitivity were used to differentiate
hyperintense lesions from surrounding normal tissue. We compared the
spatial extent and conformation of DWI with rMTT lesions. MRA studies
were examined independently by 2 neuroradiologists blinded to other
imaging and clinical data and were evaluated for presence and site of
vessel occlusion. Statistical analyses were descriptive, with
mean and SD for demographic data, and correlations were tested by use
of Pearson product moment correlation coefficients.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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A total of 41 patients were studied between September 1996 and June 1998. Seven patients were excluded; 3 had cerebral venous sinus thrombosis; 1 each had lobar hemorrhage, pontine infarct, or postseizure paresis; and an additional patient was excluded because of technical difficulties. Paired DWI and PI studies were available for the remaining 34 patients (21 men and 13 women aged 69.1±12.7 years [range 37 to 90 years]).7 MRA was performed in 27 of these patients; results of examinations of 26 of these patients have been reported previously with respect to correlations with lesion volumes in cases in which the lesion was in the middle cerebral artery (MCA) territory,12 and 1 additional patient with an anterior cerebral artery territory lesion is reported here.
MRI studies were performed in the 34 patients at a mean of 11.8±7.2 hours (range 2.5 to 23.3 hours, 12 <6 hours, and 4 <3 hours). There were 32 patients with MCA territory lesions (94%), of whom 1 had additional anterior cerebral artery (ACA) territory involvement. The remaining 2 patients had either isolated ACA or posterior cerebral artery (PCA) territory lesions.
Abnormalities of DWI and/or PI were seen in all subjects
(Table
). Conventional MRI
sequences (T1-W, T2-W, and PD sequences), however, showed either no
lesion or underestimation of lesion extent compared with DWI and PI
lesions. Patients scanned later in the 24-hour time window were more
likely to show abnormalities on conventional scans. Lesions were
present on MRA examinations in 12 patients (44%), with major
vessel occlusions in 8 patients (MCA in 7 patients, ACA in 1
patient).
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Clinicoradiological Correlations
The arterial territories depicted by DWI and PI
lesions showed good correspondence with acute clinical deficits. Motor
abnormalities were always contralateral to the MRI lesions. Isolated
left facial weakness was associated with DWI and PI lesions in the
right insular region in 1 patient. Of 4 patients with hemiparesis and
dysarthria (but without aphasia or neglect), all had lesions only on
DWI (2 each with subcortical or small cortical lesions). One
patient with isolated right distal arm paresis had a small DWI lesion
involving the left motor cortex.
Of 16 patients with aphasia, DWI and PI lesions were seen in the left
MCA (15) or PCA (1) territory. One patient with adynamic mute state
showed bilateral ACA territory lesions (Figure 1). The right ACA territory was
hypoperfused, but the left side showed hyperperfusion, as evidenced by
reduced rMTT values; together, this suggested earlier ACA stem
occlusion and partial reperfusion by the time of scanning. Unilateral
spatial neglect or inattention was associated with right-sided DWI and
PI lesions.
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Frequency of Lesions
The frequency of the 6 possible combined DWI and PI lesion
variations (patterns 1 through 6) is shown in the Table
. The
mismatch patterns in which the perfusion lesion was of larger volume
than the diffusion lesion (PI>DWI patterns 1 and 5) were the commonest
subtype overall (61.7%). Only 1 patient showed a large perfusion and
no diffusion lesion (pattern 5). This patient, designated N.A., showed
dramatic resolution of all clinical deficits within 2 hours and
concomitant resolution of perfusion deficit when scanned at 3 days
(Figure 2).
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Patterns in which the perfusion deficit was smaller than the diffusion lesion or absent were seen less commonly (38.3%). In patients with patterns 3 or 4 (all but 1 of whom were scanned after 10 hours), some reperfusion was presumed to have occurred by the time of scanning.
Mismatch PI>DWI patterns were seen at all scan times up to 23 hours
from onset. All 4 patients scanned within 3 hours had this type of
mismatch (3 with pattern 1 and 1 patient [N.A.] with pattern 5). Of
the 12 patients scanned within 6 hours, 9 showed PI>DWI patterns, 2
showed equal diffusion and perfusion deficits (pattern 2), and 1 had
DWI without PI lesion (pattern 4). The proportion of PI>DWI patterns
decreased with scan delay, constituting 75.0% before 6 hours, which in
the following 6-hour periods decreased to 71.4%, 50.0%, and 44.4%
(Figure 3). Hence, although PI>DWI
patterns were more common at an earlier time of scanning, the time to
scan alone could not be used to exclude them. Significant reperfusion
(pattern 3 or 4) was unusual in patients scanned before 10 hours.
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Topography of PI>DWI lesions
The anatomic extent and magnitude of DWI and PI lesions were
compared in the 20 patients with PI>DWI mismatch pattern 1. In 17
patients, the PI lesion contained most or all of the DWI lesion or
lesions, which conforms to the expected model in which DWI lesions
develop within the region of hypoperfusion. Of these, 14 had PI lesions
within tributaries of the main or distal branches of the MCA territory
(hereafter called MCA DWI within PI lesion patients), including 1 with
an additional ipsilateral distal ACA territory lesion. In 1 patient,
the lesion was solely in ACA territory, and 2 others involved
border-zone regions.
Ten of the 14 MCA DWI within PI lesion patients had MRA studies. All but 2 had either occlusion of the MCA stem6 or of more distal branches.2 The 2 patients with normal MRA examinations were not distinguishable from the others on the basis of any discernible diffusion or perfusion lesion characteristics. It remains possible that better-quality MRA examinations might have delineated additional abnormalities.
In the MCA DWI within PI lesion patients, the size of the DWI lesion varied markedly relative to the PI lesion. However, there was no significant relationship between time of scan after onset and either size of DWI lesion (Pearson product moment correlation r=0.17, P=0.56) or ratio of DWI to PI lesion volume (r=0.08, P=0.78). Thus, DWI lesions were not significantly smaller if the MRI study was performed earlier after stroke onset, which implies that time alone was not the major determinant of transition to DWI lesion.
Specific anatomic regions appeared preferentially susceptible to DWI
lesions. Twelve MCA DWI within PI lesion patients had DWI lesions
involving the insula (eg, Figures 4 and 5). In these cases, there was extension
of the DWI abnormality beyond the MCA insular arteries into distal MCA
arterial tributaries in 6 patients. In 10 of these 12
cases, MRA studies had been performed, of which 8 were abnormal (6 MCA
occlusions, 2 more-distal branch occlusions). Another patient, scanned
at 4 hours, showed a curvilinear external capsule DWI lesion medial to
the insula and lateral to the lenticulostriate territory (Figure 6A). The lenticulostriate territory was
affected by DWI abnormality in 2 patients, either in continuity with
insular region lesion (Figure 5) or as the sole territory with
DWI abnormality (Figure 7).
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None of the 14 patients with insular, capsular, or lenticulostriate DWI
abnormalities showed PI lesions proximal to their DWI lesions, which
suggests the DWI lesion developed at the site of MCA occlusion. Two
patients showed normal perfusion in the proximal abnormal DWI region
(eg, Figure 7) suggestive of reperfusion, despite more lateral
PI abnormalities in regions consistent with distal MCA
tributaries. Both of these were clinically considered of embolic
pathogenesis due to atrial fibrillation. At follow-up scanning, neither
showed infarction beyond the initial DWI lesions, which indicates the
distal PI lesions had reperfused without evolution to infarction.
In the majority of patients, the regional severity of rMTT abnormality
at the time of scanning did not appear to directly correlate with the
site of DWI lesion. Ten patients showed relatively uniform PI lesions,
including those within the region of the DWI lesion. However, 2
patients showed inhomogeneity of rMTT abnormality within the PI
lesion, with slowest transit times colocalizing with the DWI
lesions (Figure 4A and Figure 8).
These core rMTT lesions were surrounded by regions of lesser but still
abnormal perfusion without DWI lesions. Patency of the MCA on MRA was
shown in 1 patient (Figure 4A), but in the other patient (Figure 8), reduced MCA flow and distal occlusions were found. Hence, in
these 2 patients, the DWI lesion appeared to be developing only where
hypoperfusion was maximal, which suggests a quantitative regional
correlation.
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Two PI>DWI pattern patients showed regional hyperperfusion as
evidenced by hypointense regions on the rMTT maps (Figures 1 and 5). In 1 patient, the hyperperfused area was within the MCA
territory between 2 areas of hypoperfusion and was colocalized with
this patient's DWI abnormality (Figure 5), which had not
enlarged when reimaged 3 days later. Cardioembolic pathogenesis was
suspected in the setting of atrial fibrillation. The other patient
showed hypoperfusion in the right ACA territory and hyperperfusion in
the left ACA territory with occlusion of the right ACA on MRA (Figure 1). A DWI lesion was present only in the right ACA
territory, even at follow-up imaging, but pathogenesis was not
determined. Anatomic observations suggested these were not artifactual
in nature. Their locations were limited to recognized
arterial territories and were contiguous with vascular
territories affected by regional hypoperfusion, ie, distal branches of
the MCA or the common trunk of the ACA, which suggests a common
pathogenesis.
Mismatch between DWI and PI lesions at their margins was common. There
were 2 MCA DWI within PI lesion patients who had DWI lesions on
inferior slices without corresponding PI abnormalities at
these levels. On the other hand, DWI lesions were not present on
all imaged levels at which PI lesions were observed. Six of the MCA DWI
within PI lesion patients had at least 2 imaged levels with PI lesion
but no DWI lesion. These were seen both above and below the DWI lesion
and at any scan time (range 4 to 21.7 hours from stroke onset), so that
this was not just an early phenomenon (eg, Figure 7). Scanning
at just these levels would have missed the DWI lesions.
The 2 patients with presumed border-zone lesions showed small, patchy, deep-white-matter DWI lesions within the border-zone region of MCA, ACA, and PCA territories. In 1 of these patients, the DWI lesions lay within wedge-shaped cortically based PI lesions with apices toward the lateral ventricles.22 The second patient had poor-quality perfusion images related to low cardiac output, which markedly delayed and attenuated the signal intensity–time curve so that conclusions about PI lesion extent were not possible.
Topography of Other Lesions
In the 13 patients with non-PI>DWI patterns, 5 had DWI lesions in
the deep white matter with minimal or no concomitant PI lesions. Four
of these patients showed multiple lesions consistent with
partial internal border-zone infarction and clinical histories
consistent with systemic hypoperfusion.23 24 The
fifth nonpenumbral patient was presumed to have single lenticulostriate
territory deep-perforator occlusion.
Small, superiorly situated, peripheral cortical MCA territory DWI lesions with no perfusion deficit were seen in 4 patients. These were all left sided and had minor or circumscribed functional impairments, such as an isolated contralateral brachial paresis, consistent with occlusions of a single small MCA branch.
The remaining 4 patients had patterns consistent with cortical
arterial territory ischemia. Two showed insula
involvement (eg, Figure 6B) and variable branches of MCA
territory DWI lesions, and 1 had PCA territory involvement.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Concordance analysis of combined diffusion and perfusion MRI in acute stroke has revealed several novel findings of clinical interest. Clinicoradiological correlations confirm that in addition to quantitative correlations with clinical scale scores,7 individual MRI lesion loci relate appropriately to clinical syndromes. These techniques can therefore augment other modalities in correlative studies elucidating brain-behavior relationships acutely.
Patterns with PI>DWI are likely to be found in the early hours after stroke onset but may also be seen up to 24 hours. The greater efficacy of thrombolytic treatment with earlier administration1 2 25 26 27 is likely to be influenced by the frequency of significant volumes of salvageable hypoperfused tissue, for which we believe PI>DWI patterns are markers. Although our study supports the vast majority of patients having PI>DWI patterns throughout the first 24 hours of stroke,28 29 the fact that benefit from early thrombolysis is no more than 30%1 3 suggests other factors must interact (eg, apoptosis, DWI lesion size or site, and rapidity of reperfusion).15 30 31
Individual deviations from the theoretical topography of an
infarct-core DWI lesion wholly within a larger perfusion lesion were
commonly seen. MRI images are but a snapshot of a complex dynamic state
with evolution based on the individual's unique anatomic and vascular
constraints, as well as the responsible
pathophysiological cause. Thus, there was a
spectrum of lesions, from perfusion without diffusion abnormality
(N.A., Figure 2)32 through diffusion lesion cores
mostly contained within perfusion abnormalities, perfused diffusion
lesions in the distributions of proximal arterial branches
but with distal cortical-branch perfusion deficits (eg, Figure 7), and other patterns in which diffusion lesions were larger
than concomitant perfusion deficits. Each of these patterns may have
implications for clinical decision making.
Recognition of pattern 5, in which there is PI deficit only (Figure 2), is particularly instructive. Although uncommon, this likely
represents a pure perfusion deficit (ie, tissue at risk but not
committed to infarction) at the time of scanning. Our single patient
showed spontaneous resolution of clinical and perfusion deficits within
hours of imaging, consistent with a spectacular shrinking
deficit syndrome. Another patient, with similar isolated perfusion
deficit only, subsequently failed to improve clinically or
radiologically,33 and transition to infarction in 3 other
patients has been described recently.32 In contrast, our 2
patients with proximal DWI lesion and distal PI lesions in MCA
tributaries did not evolve to distal infarction. We believe these 2
clinical courses lie at the extremes of a spectrum of possible outcomes
in such patients that probably is influenced by the intensity and
persistence of hypoperfusion, as well as by other factors. Transition
to eventual infarction (as represented by early DWI
lesions) is not made inevitable by the presence of a PI lesion. Thus,
the absence of a DWI lesion is not a "false-negative"
finding,34 even in profound ischemia, but an
important marker of persisting viability. The presence of this pattern
at any time after onset of ischemia may argue for
revascularization therapy.
The main findings in the present study relate to the topographic
lesion deviations from the prototypic central core and hypoperfused
periphery, which suggests the likely site of arterial
occlusion, prior or current locus of maximal hypoperfusion, and
pathogenesis. The clearest demonstration of the likely site of
arterial occlusion was seen in patients with DWI lesions in
the territories of the perforating branches of the horizontal segment
of the MCA (Figures 4 through 7). These involved the
arteries that sequentially arise from the MCA to supply the
lenticulostriate, external capsular, and insular
regions.35 36 Such lesions suggested arterial
obstruction at their origin sufficient to cause probable transition to
infarction at some time before scanning. Some of these regions with DWI
lesions but not contained within PI lesions indicated proximal
reperfusion. In support of this contention were the few patients with
additional PI lesions in more-distal cortical branches of the MCA (eg,
Figure 7) and clinical evidence of sources of emboli that
implied dissolution and dislodgement of clot. However, the situation in
this patient (Figure 7) was complex, because MRA showed MCA
occlusion, which implies that collateral flow was supplying much of the
overlying cortical mantle. Although a PI>DWI mismatch existed (with
overall volume of PI greater than DWI lesion), there was no overlap in
these lesions, with additional reperfusion only possible within the PI
lesion. This patient's final infarct did not include these cortical
branches, unlike other similar acute patients,32 which
again emphasizes the parlous but not committed state of tissue with PI
but no DWI deficit. In such patients, prediction of net benefit from
thrombolysis may be complex.
The insular region was frequently involved by DWI or PI lesions or both
(Figure 4). Where no MCA arterial territory proximal
to insular branches was involved, the site of arterial
occlusion could be inferred and was frequently confirmed on MRA (80%
of cases). The fact that 2 patients had no occlusions on MRA despite
insular PI lesions suggested occlusions in branches beyond the
resolution of MRA sequences used in the present study.
Abnormalities of the "insular ribbon" on CT scans have been
reported previously to predict contiguous MCA
infarction.36 Similar logic would apply to DWI
abnormalities seen in the lenticulostriate territory (Figure 7),
consistent with prior proximal occlusion theories of the
mechanism of striatocapsular infarction.37 38
The high frequency of DWI lesions in the proximal MCA territories may
relate to the severity of perfusion deficits. In 2 patients, there was
direct evidence for colocalization of the most severe hypoperfusion and
the development of diffusion lesions (Figure 4A and Figure 8). In 1 of these patients, the appropriate MRA occlusions were
consistent with the expected maximal hypoperfusion furthest
from collateral supplies. However, in the majority of patients with
PI>DWI mismatch, DWI lesions occurred within regions of
homogeneous hypoperfusion, which suggests that perfusion
abnormalities had been more severe or were present longer in these
regions before scanning, or perhaps that the DWI lesions were emerging
in selectively vulnerable tissue. Additional research is required to
investigate these alternatives.
Topographic appearance also suggested likely stroke pathophysiology in
selected patients. In 2 patients, we were able to identify border-zone
mechanisms.22 Lacunar infarction was recognized as a
pattern with matching PI and DWI lesions in central white matter.
Embolic pathogenesis was suggested where multiple sites of occlusion
occurred with the presence of PI lesions in regions supplied by
cortical arterial branches and separate proximal DWI
lesions (eg, Figure 7). The reperfusion inferred by the presence
of isolated proximal DWI lesions strongly suggests that the initial
proximal occlusion had lysed or fragmented, perhaps lodging downstream
in the regions represented by the multiple
divisional-branch PI lesions. Embolic pathogenesis was also suggested
by the single case with both MCA and distal ipsilateral ACA territory
perfusion lesions, consistent with origin from a cardiac
valvular lesion. Moreover, the uncommon finding of focal
hyperperfusion, as observed in 2 patients, in arterial
territories contiguous or within those affected by other PI or DWI
lesions also suggested fragmentation of prior occlusions. The mechanism
of such focal hyperperfusion is unknown but did not appear to be
nonnutritional or "luxury" perfusion, because later DWI lesions did
not develop.39 Future prospective trials should clarify
the predictive value of patterns suggestive of embolic fragmentation
for subsequent reperfusion.
Imaging at the periphery of PI>DWI mismatched lesions showed variability, which might confound limited radiological assessments. Perfusion abnormalities without concomitant DWI lesions were seen at the margins of lesions in 43% of patients with the most common PI>DWI pattern. This combination of lesions resembled pattern 5. In addition, 2 patients showed the opposite pattern, with DWI lesion but no PI abnormality in slice levels at the inferior lesion margin. This pattern may relate to focal reperfusion as discussed above, with early, more-proximal occlusion, or other mechanisms.40 41 42 In both cases, less than complete infarct imaging might lead to erroneous inferences about the pattern of perfusion-to-diffusion mismatch.30
We conclude that consideration of the qualitative features of DWI and PI studies is an important area of future study, particularly where revascularization therapies are being considered. Variations in the patterns of abnormalities, which are present within minutes of infarction onset, may refine clinical decisions regarding pathophysiology, including decisions for patients who present beyond currently accepted therapeutic time windows.
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Acknowledgments |
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This study was supported in part by grants 980771 and 970323 from the NHMRC, Australia; the National Stroke Foundation, Australia; the Neurological Foundation of New Zealand, VJ Chapman Research Fellowship (P.A.B.); and by proprietary research support from GE Medical Systems (Q.Y.).
Received May 21, 1999; revision received July 16, 1999; accepted July 16, 1999.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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