| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 1999;30:2059-2065.)
© 1999 American Heart Association, Inc.
Original Contributions |
Identification of Major Ischemic Change
Diffusion-Weighted Imaging Versus Computed Tomography
From the Departments of Neurology (P.A.B., D.G.D., R.P.G., S.M.D.) and Radiology (P.M.D., Q.Y., T.L., B.M.T.), Royal Melbourne Hospital, and the Departments of Medicine (G.A.D., B.M.T., S.M.D.) and Public Health and Community Medicine (D.J.), University of Melbourne (Australia).
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—Thrombolytic therapy is not recommended in patients with CT changes of recent major infarction, which has been defined as reduced attenuation or cerebral edema involving >33% of the middle cerebral artery territory (European Cooperative Acute Stroke Study [ECASS] criteria). Diffusion-weighted imaging (DWI) is more sensitive than CT in detecting acute ischemia, and the combination of DWI, MR perfusion imaging, and MR angiography provides additional information from a single examination. We sought to determine whether DWI could identify the presence and extent of major ischemia as well as CT in hyperacute stroke patients.
Methods—Seventeen suspected hemispheric stroke patients were studied with both CT and DWI within 6 hours of symptom onset. None received thrombolytic therapy. The scans were examined separately by 2 neuroradiologists in a blinded fashion for ischemic change and cerebral edema, graded as normal, <33%, or >33% of the MCA territory. Final diagnosis of stroke was determined with the use of standard clinical criteria and T2-weighted imaging at day 90.
Results—Sixteen of 17 patients had a final diagnosis of stroke.
Acute ischemic changes were seen in all 16 on DWI (100%
sensitivity) and in 12 of 16 on CT (75% sensitivity). DWI identified
all 6 patients with major ischemia on CT, with excellent
agreement between the 2 imaging techniques (
=0.88). One patient
eligible for thrombolysis on the ECASS CT criteria had
major ischemia on DWI.
Conclusions—DWI is more sensitive than CT in the identification of acute ischemia and can visualize major ischemia more easily than CT.
Key Words: magnetic resonance imaging, diffusion-weighted • stroke, ischemic • tomography, x-ray computed
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Thrombolytic therapy with tissue plasminogen activator (tPA) improves outcome if given within 3 hours of ischemic stroke onset.1 However, not all treated patients obtain benefit, and avoidance of tPA has been recommended in patients with CT evidence of major infarction because of the increased risk of hemorrhagic transformation.2 3 A number of acute stroke therapy trials, beginning with the European Cooperative Acute Stroke Study (ECASS) I, have defined major infarction as parenchymal hypointensity or cerebral edema exceeding one third of the middle cerebral artery (MCA) territory on CT.4 5 6 7 8 9 Such change is associated with worse acute neurological state and worse outcome and may identify patients less likely to respond to t-PA.10 11
CT has been the investigation of choice for the triage of stroke patients. The early ischemic changes of parenchymal hypointensity and cerebral edema on CT correspond to an increase in the intracellular and extracellular water components of affected brain tissue.12 13 However, these changes are subtle, and CT is frequently normal in the first hours after stroke onset.14 15 Thus, in the emergency setting, CT is still primarily used to exclude intracerebral hemorrhage.15 16
Significant advantages are offered by newer rapid MR techniques, particularly diffusion-weighted imaging (DWI),17 18 19 20 21 22 which has a high sensitivity and specificity for ischemic stroke.22 23 24 Increased DWI signal intensity is evident within minutes of the onset of ischemic injury and occurs as the result of a reduction in the apparent diffusion coefficient of water and the development of cytotoxic edema.25 Acute DWI lesions can also be clearly delineated from surrounding normal brain tissue and from areas of old infarction.17 18 20 While very early restoration of blood flow to an ischemic region may lead to a reversal of DWI lesions in animal studies,26 there has been only 1 human case report in which the initial DWI lesion was very small.27 We suggest that DWI lesions remain useful markers of tissue that is likely to die without prompt intervention.
The therapeutic time window for thrombolytic and other acute stroke therapies is likely to vary between patients,28 29 and not all patients will respond equally well to therapies regardless of time from symptom onset. When DWI is used in combination with MR perfusion imaging (PI), different lesion patterns may be identified from which predictions can be made concerning stroke evolution and likely outcome.29 30 31 32 Such DWI/PI patterns may provide a template on which a more rational selection of acute stroke therapy can be based.29 30 32 33 34 35 36 37 38 39 40 However, the use of both CT and MRI is time consuming and expensive.
In this prospective serial study we compared the sensitivity and positive predictive value of CT and DWI for detecting early infarction. We also determined whether DWI could identify all cases of major ischemia as defined by the ECASS criteria (>33% MCA territory).4 5 The purpose of the study was to decide whether DWI, as part of a single-modality acute ischemia protocol, can be used together with accepted clinical criteria to screen and select stroke patients for thrombolytic therapy.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We studied 17 consecutive patients (9 men; mean age, 68.5±12.8 years) presenting to the Royal Melbourne Hospital with suspected acute hemispheric cerebral infarction (9 right sided) and who had DWI and CT studies within 6 hours of stroke onset. This was defined as the time the patient was last known to be without neurological deficit. This time window was used because there is evidence to suggest that some patients treated between 3 and 6 hours may benefit from thrombolytic therapy.4 5 In addition, we and others have found that hypoperfused tissue at risk of infarction may persist beyond 3 hours.29 32 41 None of the patients were treated with thrombolytic therapy, although 11 patients were enrolled in trials of putative neuroprotective agents. Patients had T2-weighted imaging (T2-WI) performed at 90 days. A final diagnosis of stroke was made on the basis of the standard clinical criteria in conjunction with T2-WI studies. The study was performed with the approval of our institution's Ethics Committee, and written informed consent was obtained from the patient or next of kin.
Only patients with symptoms and signs consistent with hemispheric ischemic stroke were included because these are the most frequent stroke subtypes and are the easiest to study with combined DWI and PI. Other exclusion criteria were preexisting significant nonischemic neurological deficits (including dementia or extrapyramidal disease) or a history of prior stroke, which would hamper interpretation of clinical and radiological data. Seven of the 17 patients have been previously described in 2 studies investigating the utility of echo-planar PI and DWI and MR angiography (MRA).29 32
The Canadian Neurological Scale (CNS), a validated neurological
impairment scale,42 was performed just before the acute
imaging studies. Outcome clinical assessments were performed on the
same day as the final MR study and consisted of a repeated CNS score,
the Barthel Index (BI), and the modified Rankin Scale
(RS).43 The BI is a validated functional disability scale,
and the RS is a validated handicap scale. Outcome was dichotomized into
excellent or poor outcome, with excellent outcome defined as RS score
of 
1 (normal or no significant disability despite symptoms), as in
the National Institute of Neurological Disorders and Stroke and ECASS
II studies,1 5 BI 
95, or CNS score of 11.5. All clinical
assessments were performed by a neurologist or neurology resident
trained in their administration and without knowledge of the imaging
results.
All CT scans were obtained with the use of a high-resolution CT scanner (General Electric 9800, General Electric Co) with contiguous 1-cm transaxial slices. MR scans were obtained with the use of a 1.5-T echo-planar imaging (EPI)–equipped whole body scanner (Signa Horizon SR 120, General Electric). Sequences were always performed in the same order, with an initial T1-weighted sagittal localizer, diffusion-weighted sequence, MR spectroscopy, perfusion sequence, a proton density and T2-weighted fast-spin double-echo sequence (repetition time [TR], 3500 ms; echo time [TE], 10 ms; TE, 60 ms), EPI spin-echo sequence, phase-contrast MRA, and finally a contrast-enhanced T1-weighted sequence. Similar slice positions were used to facilitate comparisons. Only the DWI, MRA, and T2-WI are reported here, with a total "table time" for all 3 sequences of approximately 15 to 20 minutes. Apparent diffusion coefficient of water maps were generated but were not required for this analysis.
DWI was obtained with the use of a multislice, single-shot, spin-echo EPI sequence. Slice thickness was 6 mm with a 1-mm gap; the number of slices was set to include the whole brain (average of 15), with a matrix size of 256x128 and field of view of 40x20 cm. The remainder of the protocol in the first 10 patients was as previously described, resulting in 5 b values of increasing magnitude from 0 to 1200 s/mm2 applied in 3 orthogonal directions.29 In the remaining 7 patients, the protocol was modified with a TR/TE of 10 000/100 ms and 3 b values of increasing magnitude from 0 to 1000 s/mm2.44 Analyses were performed from the average of the measurements taken in the x, y, and z orthogonal directions. This gave the trace of the diffusion tensor, which is reported to minimize the effects of diffusion anisotropy.45 Imaging time was up to 2 minutes and 10 seconds.
MR angiograms were obtained with a 2-dimensional, 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, with TR/TE of 25/7.5 ms; flip angle, 30°; matrix, 256x128; field of view, 20x20 cm; and number of excitations, 2. Imaging time was 1 minute and 50 seconds.
Postprocessing of MR images was performed with customized software based on a commercial image analysis application (Advanced Visualization Systems), using an Indigo 2 workstation (Silicon Graphics Inc). Acute lesion volumes were measured on DWI and outcome T2-WI studies. The quantitative analysis methods of the acute DWI and T2-WI lesion volumes and analysis of the MRAs have been previously described and are reproducible with good intraobserver and interobserver agreement.29 32 Volumetric analysis of the CT studies was not performed because the often subtle CT changes of early ischemia make accurate measurement difficult.
The CT and DWI images were presented separately and individually to 2 neuroradiologists who were blinded to clinical details and the results of the other imaging study. In the CT and DWI studies in which there was disagreement, the scans were jointly reanalyzed, and a final decision was reached by consensus. The CT scans were examined for evidence of intracerebral hemorrhage, the hyperdense middle cerebral artery sign (HMCAS), parenchymal hypodensity, and cerebral edema. The HMCAS was defined as a part of the MCA that was denser than other parts of the vessel or any other visualized vessel of similar size as shown by unenhanced CT, in which density could not be attributed to calcification. Parenchymal hypodensity was defined as increased radiolucency of cerebral tissue relative to other parts of the same structure or to its contralateral counterpart. Cerebral edema was defined as a circumscribed effacement of cortical sulci, compression of ventricles, and shift of midline structures. The presence of edema and parenchymal hypodensity were noted and graded (normal, <33%, or >33% of MCA territory), as previously reported in the ECASS I and II trials.4 5
The isotropic DWI scans were examined for evidence of intracerebral hemorrhage and parenchymal hyperintensity. Cerebral edema was defined as in the CT scans. The extent of the parenchymal hyperintensity and cerebral edema was also graded (normal, <33%, or >33% of MCA territory).
Demographic and time of scan data are presented as mean±SD values. Dependent variables were compared with nonparametric techniques except when normality of data could be proven, in which case parametric equivalents were preferred, and are presented as mean difference with 95% CIs. Results were considered statistically significant at the 5% level.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
There was a mean time of 3 hours and 18 minutes (±1 hour and 30 minutes) to the acute CT scan and 4 hours and 1 minute (±1 hour and 1 minute) to the DWI scan (mean difference, 0.7 hours; 95% CI, -0.3 to 1.7 hours; P=0.16). Fourteen patients had outcome T2-WI studies (83.5±25.5 days; range, 29.3 to 125.0). Two patients had died by day 90 as a result of complications related to their strokes and were assigned CNS and BI scores of 0 and RS scores of 5. One patient was unable to tolerate the MRI. All 3 patients without an outcome MRI had T2-WI studies performed at 3 to 5 days. We have previously shown that there is no significant difference in infarct volumes measured in the subacute and outcome periods29 and have therefore carried the subacute T2-WI lesion volumes in these 3 patients forward. The mean acute CNS score was 5.8±2.8 (range, 1.5 to 11.0). The outcome clinical scores were as follows: CNS, 7.8±3.9; BI, 55.3±38.0; and RS, 2.9±1.7.
Interobserver agreement between the 2 neuroradiologists on both the
extent of parenchymal hypointensity and cerebral edema on the CT scans
occurred in 13 of 17 patients (76%) (=0.44; P=0.03).
With the DWI studies, the interobserver agreement regarding the extent
of parenchymal hyperintensity and cerebral edema was greater, occurring
in 15 of 17 patients (88%) (=0.76; P=0.0006).
There was no evidence of hemorrhage on any of the CT scans
performed. In contrast, small hypointense lesions consistent
with petechial hemorrhage were seen in the DWI scans of
patients 1 and 3 and were confirmed on other MR sequences performed.
Both of these patients had evidence of major ischemia on DWI
and CT (Table
).
|
The HMCAS was seen on CT in 5 of 17 patients (29%). Occlusion of the
M1 segment of the MCA was seen on MRA in 6 patients (35%). The HMCAS
was seen in conjunction with MCA stem occlusion on MRA in 4 patients;
however, 2 had MCA stem occlusion on MRA with no evidence of a HMCAS
(Table
). A fifth patient with a HMCAS was unable to tolerate an
MRA. Thus, CT was unable to identify all cases of occlusion on MRA. In
addition, 5 of 6 patients with MCA occlusion on MRA had evidence of
major ischemia on DWI, while only 2 of 5 patients with a HMCAS
had evidence of major ischemia on CT. This difference was not
significantly different (P=0.20, Fisher exact test),
possibly because of the small patient numbers.
A final diagnosis of stroke was made in 16 of 17 patients on the basis of standard clinical criteria and imaging results. The remaining patient (patient 13) presented with sudden onset of a left upper limb monoparesis. An initial diagnosis of ischemic stroke was made, and he was admitted to the stroke unit. Normal acute imaging studies prompted further investigation, which led to a final diagnosis of a brachial plexopathy. However, because of his initial treatment as a stroke patient, he has been included in this analysis.
Hyperintense lesions on DWI consistent with acute
ischemia were seen in all 16 patients with a final diagnosis of
stroke, giving a sensitivity and positive predictive value for DWI of
100%. Changes consistent with ischemia were seen on CT
in 12 of 16 stroke patients, giving a sensitivity of 75%. All 12
patients with CT changes of ischemia had a final diagnosis of
stroke, giving a positive predictive value of 100%. Thus, 25% of
patients with a final diagnosis of stroke had normal CT scans, all of
whom had evidence of ischemia on DWI. This difference in
ischemia detection rate is significant (relative difference,
0.24; 95% CI, 0.0 to 0.50; McNemar 
2=4.00;
P<0.05). Thus, DWI is better able than CT to detect signs
of ischemia in the first 6 hours after stroke onset. The
Figure shows CT and MRA/DWI studies in
patient 17.
|
The ECASS criteria of major ischemia were then applied to
the CT studies and extended to DWI. Evidence of ischemia
involving >33% of the MCA territory (major ischemia) was
detected in 6 patients by CT and 7 patients by DWI (difference, 0.06;
95% CI, -0.11 to 0.23; McNemar 2=1.0;
P=0.32). Thus, there was no difference in the detection of
major ischemia between CT and DWI in the first 6 hours after
stroke onset. In addition, there was excellent agreement between the 2
imaging modalities (=0.88; P=0.0001). However, the
hyperintense DWI ischemic lesions were visually more distinct
and easier to identify than the ischemic lesions on CT.
In 1 patient (patient 2), the CT scan was normal despite evidence of major ischemia on DWI. The CT scan in this particular case was performed at 2 hours after symptom onset, while the DWI was performed at 4 hours. It is therefore possible that the ischemic changes seen on the DWI developed in the 2 hours after the CT scan was performed. This patient subsequently died.
We then examined the relationship between the presence of major ischemia on both CT and DWI with the final infarct size (T2-WI) and clinical outcome, which was dichotomized into excellent and poor. The presence of major ischemia on DWI was associated with larger final infarct size (mean volume difference, 83.5 cm3; 95% CI, 21.3 to 153.2 cm3; P=0.01) and worse clinical outcome (CNS, Z=2.65, P=0.008; BI, Z=2.12, P=0.03; RS, Z=1.67, P=0.10; Wilcoxon signed rank test).
Similarly, patients with major ischemia on acute CT had worse clinical outcome (CNS, Z=2.83, P=0.005; BI, Z=2.33, P=0.02; RS, Z=1.90, P=0.058; Wilcoxon signed rank test). There were also trends in those with major ischemia on CT to have larger acute DWI volumes (mean volume difference, 42.9 cm3; 95% CI, -9.6 to 91.5 cm3; P=0.08) and larger final infarct size (mean volume difference, 71.7 cm3; 95% CI, -2.4 to 145.9 cm3; P=0.06).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
DWI was able to detect major ischemia, defined as ischemic changes involving >33% of the MCA territory, as well as CT. However, these changes were more easily visualized on DWI than CT. The presence of major ischemia on DWI was also associated with a larger final infarct size and worse functional outcome. We and others29 40 46 have previously found that acute DWI lesion volumes are correlated with both acute neurological state and eventual stroke outcome. However, to our knowledge, this is the first study to show an association between major ischemic change on DWI and stroke outcome.
In a report by von Kummer et al,10 the extent of hypointensity on acute CT correlated with both acute and outcome clinical states. This group also found that the beneficial effect of tPA treatment is most pronounced in patients with ischemic changes on CT involving <33% of the MCA territory. Those with normal CT scans or evidence of major ischemia obtained no benefit from tPA and had an increased risk of fatal hemorrhage. Thus, the presence and extent of ischemic changes appear to have significant implications for prognosis and treatment and should therefore be determined as rapidly as possible.
There was greater interobserver agreement regarding the extent of
ischemia on DWI than CT. Hyperintense ischemic lesions
on DWI were comparatively easy to identify and grade. In contrast,
early ischemic changes on CT are often subtle and can be
difficult to appreciate.10 47 One of the reasons for this
superiority of DWI over CT in the detection of acute ischemia
is the significantly greater contrast-to-noise ratio for
DWI.24 As a result, the reliability and reproducibility of
CT in the detection and estimation of the degree of ischemic
change is controversial. von Kummer et al10 found an
interobserver agreement on the extent of parenchymal hypointensity of
86%, but the chance-adjusted agreement was low (=0.36). Similarly,
Marks et al11 found an interobserver agreement on the
estimation of the extent of MCA territory ischemia of 72%,
with pairwise coefficients of 0.44 to 0.65. These results are
similar to those of the present study. However, in all 3 studies,
CT scans have been read by neuroradiologists in the nonacute setting
and are therefore unlikely to represent standard clinical
practice.10
DWI had greater sensitivity in the detection of hyperacute ischemia than CT and had a positive predictive value of 100%. All patients with a final diagnosis of stroke had evidence of ischemia on DWI. In contrast, 25% of stroke patients had normal acute CT scans. These results confirm the high sensitivity of DWI to hyperacute ischemia in earlier investigations, which has ranged from 94% to 100%.22 24 Previous studies have also found that DWI is superior to T2-weighted and proton-density MR sequences in the detection of ischemia.23 24
In this study there was only 1 DWI scan in which there was no evidence of ischemia. This was a true-negative result since the patient was subsequently found to have a brachial plexopathy. This patient was the only subject in this series without a final diagnosis of stroke. The absence of false-negative DWI scans in this study was likely to be the result of the exclusion of patients with suspected brain stem ischemia, which may not be identified on acute DWI studies.22 Most of the stroke patients admitted to our institution have CT scans soon after they arrive in the emergency department. Those with intracerebral pathology other than ischemic stroke, such as hemorrhage or space-occupying lesions, are not studied with DWI. Consequently, we are unable to comment on the specificity of DWI, which in previous investigations of hyperacute stroke patients has ranged from 86% to 100%.22 24
The sensitivity of CT for ischemia in this study was 75%, which is similar to that found in previous studies of patients imaged in the hyperacute stage with modern CT scanners. In the study by Gonzalez et al,24 the sensitivity of CT was lower at 45%; however, in this report patients were only included in the analysis if initial CT findings were inconclusive. The sensitivity of CT for ischemia is low in the first 2 hours from stroke onset and increases with time, so that it is 58% in patients imaged within 5 hours and 82% to 88% in patients imaged within 6 hours.16 48 49
Ten of 17 patients had CT before DWI, with CT performed at a mean of 42 minutes before DWI. In 2 patients, this difference was >3 hours. It is therefore possible that ischemic changes on DWI in these 10 patients may have developed after the CT. Randomizing patients to either CT or DWI as the first imaging study may have avoided this potential bias. Unfortunately, the MRI scanner at our institution is in routine clinical use, and not all patients could be studied when we wished. The greater availability of CT, combined with the requirement to perform 2 imaging studies within 6 hours of stroke onset, meant that patients were usually studied with CT first.
In addition, 11 of 17 patients were treated with neuroprotective agents. At this stage treatment assignation is unknown. This may temper our conclusions as to the relationship between the presence of major ischemia and stroke outcome. However, therapy was commenced after both imaging studies had been obtained in all but 2 patients. This would therefore have little effect on the comparisons between the acute CT and DWI studies.
The CT sign of a hyperdense MCA was inferior to MRA in identifying MCA occlusion. The presence of the HMCAS is associated with severe brain ischemia and poor functional outcome. However, while the HMCAS may identify patients who may benefit from tPA, it has no significant independent prognostic value when compared with acute clinical state and early CT changes.50 Of interest, the Pro-urokinase in Acute Cerebral Thromboembolism (PROACT) trial has found that intra-arterial thrombolysis is of benefit in patients with occlusion of the MCA.9 We have previously shown that the absence of MCA blood flow on MRA predicts the presence of a region of hypoperfusion that is of greater volume than the diffusion-weighted lesion and as such may identify hypoperfused tissue at risk of infarction.32 We suggest that the positive results of the PROACT trial may in part be a result of the selection and treatment of only patients with MCA occlusion and therefore those with greater likelihood of having potentially salvageable penumbral tissue.
None of the patients studied had intraparenchymal hematoma. However, 2 patients had small areas of hypointensity consistent with minor petechial hemorrhage on the MR studies. Neither of these patients had a history of hypertension, and the areas of hypointensity occurred within the region of infarction. Changes consistent with hemorrhage were not seen on CT, possibly as the result of partial volume effects. With the advent of thrombolytic therapy for acute ischemic stroke, the detection of hyperacute hemorrhage has become critical. There is increasing evidence that multimodal MRI, particularly susceptibility-weighted sequences, are as reliable as CT in the detection of acute intraparenchymal hemorrhage.51 52 53 At higher field strengths, a hypointense rim is characteristically seen surrounding a central isointense or heterogeneous region of hyperacute hematoma on T2-WI and to a lesser extent T1-WI. This rim is thought to be the result of a transitional stage in which there is rapid deoxygenation of hemoglobin within erythrocytes at the periphery of the hematoma. This causes an increase in magnetic susceptibility with resultant signal loss, best seen on gradient echo susceptibility-weighted sequences and echo-planar MRI T2-WI.51 However, it remains to be proven that MRI is as sensitive as CT in the detection of acute hemorrhage.
In summary, this study has shown that DWI is able to identify the presence of early infarction with greater sensitivity than CT. In addition, DWI can visualize major ischemia more easily than CT. Should the ability of MRI to identify acute hemorrhage be confirmed in further studies, it could safely replace CT in the investigation of stroke patients being considered for thrombolytic therapy. This hypothesis requires further investigation with randomized controlled trials.
|
Acknowledgments |
|---|
This study was supported by the National Health and Medical Research Council, the National Stroke Foundation, and the Neurological Foundation of New Zealand, VJ Chapman Research Fellowship (Dr Barber). We wish to thank the residents, nurses, and radiographers of the Royal Melbourne Hospital for their invaluable assistance in the performance of this study.
|
Footnotes |
|---|
Reprint requests to Professor Stephen Davis, Director of Neurology, Royal Melbourne Hospital, Parkville, Vic 3050, Australia.
Received May 10, 1999; revision received July 9, 1999; accepted July 9, 1999.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. The National Institute of Neurological Disorders and Stroke rt-PA Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–1587.
2. Adams HP, Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Kwiatkowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 1996;27:1711–1718.
3.
Report of the Quality Standards Subcommittee of the
American Academy of Neurology. Practice advisory:
thrombolytic therapy for acute ischemic stroke:
summary statement. Neurology. 1996;47:835–839.
4.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von
Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH, Henerici M.
Intravenous thrombolysis with recombinant
tissue plasminogen activator for acute
hemispheric stroke: the European Cooperative Acute Stroke Study
(ECASS). JAMA. 1995;274:1017–1025.
5. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P, for the Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet. 1998;352:1245–1251.[Medline] [Order article via Infotrieve]
6.
Grond M, Stenzel C, Schmulling S, Rudolf J, Neveling
M, Lechleuthner A, Schneweis S, Heiss W. Early intravenous
thrombolysis for acute ischemic stroke in a
community-based approach. Stroke. 1998;29:1544–1549.
7. Hamilton SA, on behalf of the Standard Treatment with Activase to Reverse Stroke (STARS) Investigators. Post approval experience with intravenous t-PA for treatment of acute stroke: a phase IV multicenter, prospective, monitored study. Cerebrovasc Dis. 1999;9:125. Abstract.
8. Albers GW, Clark WM, for the ATLANTIS Study Investigators. The ATLANTIS rt-PA (alteplase) acute stroke trial: final results. Cerebrovasc Dis. 1999;9:126. Abstract.
9. Furlan AJ, Higashida R, Weshler L, Schultz G, for the PROACT Investigators. PROACT II: recombinant prourokinase (r-ProUK) in acute cerebral thromboembolism: initial trial results. Stroke. 1999;30:234. Abstract.
10.
von Kummer R, Allen KL, Holle R, Bozzao L, Bastianello
S, Manelfe C, Bluhmki E, Ringleb P, Meier D, Hacke W. Acute stroke:
usefulness of early CT findings before thrombolytic
therapy. Radiology. 1997;205:327–333.
11.
Marks MP, Holmgren EB, Fox A, Patel S, von Kummer R,
Froehlich J. Evaluation of early computed tomographic findings in acute
ischemic stroke. Stroke. 1999;30:389–392.
12.
Garcia JH. Experimental ischemic stroke: a
review. Stroke. 1984;15:5–14.
13. Unger E, Littlefield J, Gado M. Water content and water structure in CT and MR signal changes: possible influence in detection of early stroke. AJNR Am J Neuroradiol. 1988;9:687–691.[Abstract]
14.
Truwit CL, Barkovich AJ, Gean-Marton A, Hibri N, Norman
D. Loss of the insular ribbon: another early sign of acute middle
cerebral artery infarction. Radiology. 1990;176:801–806.
15.
Gilman S. Imaging of the brain: first of two parts.
N Engl J Med. 1998;338:812–820.
16. von Kummer R, Nolte PN, Schnittger H, Thron A, Ringelstein EB. Detectability of cerebral hemisphere ischaemic infarcts by CT within 6 h of stroke. Neuroradiology. 1994;38:31–33.
17. Moseley ME, Cohen Y, Mintorovitch J, Chileuitt L, Shimizu Z, Kucharczyk J, Wendland MF, Weinstein PR. Early detection of cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med. 1990;14:330–346.[Medline] [Order article via Infotrieve]
18. Moseley ME, Kucharczyk J, Mintorovitch J, Cohen Y, Kurhanewicz J, Derugin N, Asgari H, Norman D. Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats. AJNR Am J Neuroradiol. 1990;11:423–429.[Abstract]
19.
Warach S, Chien D, Li W, Ronthal M, Edelman R. Fast
magnetic resonance diffusion-weighted imaging of acute human stroke.
Neurology. 1992;42:1717–1723.
20. Mintorovitch J, Moseley ME, Chileuitt L, Shimizu Z, Cohen Y, Weinstein PR. Comparison of diffusion- and T2-weighted MRI for the early detection of cerebral ischemia and reperfusion in rats. Magn Reson Med. 1991;18:39–50.[Medline] [Order article via Infotrieve]
21. Warach S, Gaa J, Siewert B, Wielopolski P, Edelman R. Acute human stroke studied by whole brain echoplanar diffusion-weighted magnetic resonance imaging. Ann Neurol. 1995;37:231–141.[Medline] [Order article via Infotrieve]
22. Lovblad K, Laubach H, Baird AE, Curtin F, Schlaug G, Edelman R, Warach S. Clinical experience with diffusion-weighted MR in patients with acute stroke. AJNR Am J Neuroradiol. 1998;19:1061–1066.[Abstract]
23.
van Everdingen KJ, van der Grond J, Kappelle LJ, Ramos
LMP, Mali WPTM. Diffusion-weighted magnetic resonance imaging in acute
stroke. Stroke. 1998;29:1783–1790.
24.
Gonzalez G, Schaefer PW, Buonanno FS, Schwamm L, Budzik
RF, Rordorf G, Wang B, Sorensen AG, Koroshetz WJ. Diffusion-weighted MR
imaging: diagnostic accuracy in patients imaged within 6
hours of stroke symptom onset. Radiology. 1999;210:155–162.
25.
Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis
E, Laval-Jeantet M. MR imaging of intravoxel incoherent motions:
application to diffusion and perfusion in neurologic disorders.
Radiology. 1986;161:401–407.
26.
Minematsu K, Li L, Sotak C, Davis MA, Fisher M.
Reversible focal ischemic injury demonstrated by
diffusion-weighted magnetic resonance imaging. Stroke. 1992;23:1304–1310.
27.
Lecouvet FE, Duprez TPJ, Raymackers JM, Peeters A,
Cosnard G. Resolution of early diffusion-weighted and FLAIR MRI
abnormalities in a patient with TIA. Neurology. 1999;52:1085–1087.
28.
Baron JC, von Kummer R, del Zoppo GJ. Treatment of
acute ischemic stroke: challenging the concept of a rigid and
universal time window. Stroke. 1995;26:2219–2221.
29.
Barber PA, Darby DG, Desmond PM, Yang Q, Gerraty RP,
Jolley D, Donnan GA, Tress BM, Davis SM. Prediction of stroke outcome
with echoplanar perfusion- and diffusion-weighted magnetic resonance
imaging. Neurology. 1998;51:418–426.
30.
Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev
MH, Huang-Hellinger FR, Reese TG, Weisskoff RM, Davis TL, Suwanwela N,
Can U, Moreira JA, Copen WA, Look RB, Finkelstein SP, Rosen BR,
Koroshetz WJ. Hyperacute stroke: Evaluation with combined
multisection diffusion-weighted and hemodynamically
weighted echo-planar MR imaging. Radiology. 1996;199:391–401.
31. Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad K, Edelman R, Warach S. Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol. 1997;41:581–589.[Medline] [Order article via Infotrieve]
32.
Barber PA, Darby DG, Desmond PM, Yang Q, Gerraty RP,
Jolley D, Donnan GA, Tress BM, Davis SM. Absent middle cerebral artery
flow predicts the presence and evolution of the ischemic
penumbra. Neurology. 1999;52:1125–1132.
33. Warach S, Wielopolski P, Edelman R. Identification and characterization of the ischemic penumbra of acute human stroke using echoplanar diffusion and perfusion imaging. In: Proceedings of the 12th Annual Scientific Meeting of the Society of Magnetic Resonance Medicine; 1993; Berkeley, Calif. Abstract, p 263.
34. Warach S, Dashe JF, Edelman R. Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging. J Cereb Blood Flow Metab. 1996;16:53–59.[Medline] [Order article via Infotrieve]
35. Koroshetz WJ, Gonzalez G. Diffusion-weighted MRI: an ECG for "brain attack"? Ann Neurol. 1997;41:565–566.[Medline] [Order article via Infotrieve]
36. Zivin JA. Diffusion-weighted MRI for diagnosis and treatment of ischemic stroke. Ann Neurol. 1997;41:567–568.[Medline] [Order article via Infotrieve]
37.
Fisher M, Garcia JH. Evolving stroke and the
ischemic penumbra. Neurology. 1996;47:884–888.
38. Miyabe M, Mori S, van Zijl PCM, Kirsch JR, Eleff SM, Koehler RC, Traystman RJ. Correlation of the average water diffusion constant with cerebral blood flow and ischemic damage after transient middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab. 1996;16:881–891.[Medline] [Order article via Infotrieve]
39.
Rordorf G, Koroshetz WJ, Copen WA, Cramer SC, Schaefer
PW, Budzik RF, Schwamm L, Buonanno FS, Sorensen AG, Gonzalez G.
Regional ischemia and ischemic injury in patients with
acute middle cerebral artery stroke as defined by early
diffusion-weighted and perfusion-weighted MRI. Stroke. 1998;29:939–943.
40.
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.
41.
Marchal G, Beaudouin V, Rioux P, de la Sayette V, Le
Doze F, Viader F, Derlon JM, Baron JC. Prolonged persistence of
substantial volumes of potentially viable brain tissue after stroke: a
correlative PET-CT study with voxel based data analysis.
Stroke. 1996;27:599–606.
42.
Cote R, Battista RN, Wolfson C, Boucher J, Adam J,
Hachinski V. The Canadian Neurological Scale: validation and
reliability assessment. Neurology. 1989;39:638–643.
43. Wade DT. Measurement in Neurological Rehabilitation. Oxford, UK: Oxford Medical Publications; 1994.
44. Stejskal E, Tanner J. Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys. 1965;42:288–292.
45. van Gelderen P, de Vleeschouwer MHM, Des Pres D, Pekar J, van Zijl PCM. Water diffusion and acute stroke. Magn Reson Med. 1994;31:154–163.[Medline] [Order article via Infotrieve]
46. Lovblad K, Baird AE, Schlaug G, Benfield A, Siewert B, Voetsch B, Connor A, Burzynski C, Edelman R, Warach S. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome. Ann Neurol. 1997;42:164–170.[Medline] [Order article via Infotrieve]
47. Bryan RN, Levy LM, Whitlow WD, Killian JM, Preziosi TJ, Rosario JA. Diagnosis of acute cerebral infarction: comparison of CT and MR imaging. AJNR Am J Neuroradiol. 1991;12:611–620.[Abstract]
48.
Horowitz SH, Zito JL, Dinnarumma R, Patel M, Alvir
J. Computed tomographic-angiographic findings within the first
five hours of cerebral infarction. Stroke. 1991;22:1245–1253.
49.
Moulin T, Cattin F, Crepin-Leblond T, Tatu L, Chavot D,
Piotin M, Viel JF, Rumbach L, Boneville JF. Early CT signs in acute
middle cerebral artery infarction: predictive value for subsequent
infarct locations and outcome. Neurology. 1996;47:366–375.
50.
Manelfe C, Larrue V, von Kummer R, Bozzao L, Ringleb P,
Bastianello S, Iweins F, Lesaffre E. Association of hyperdense middle
cerebral artery sign with clinical outcome in patients treated with
tissue plasminogen activator.
Stroke. 1999;30:769–772.
51.
Patel R, Edelman R, Warach S. Detection of hyperacute
primary intraparenchymal hemorrhage by magnetic resonance
imaging. Stroke. 1996;27:2321–2324.
52. Atlas SW, Thulborn KR. MR detection of hyperacute parenchymal hemorrhage of the brain. AJNR Am J Neuroradiol. 1998;19:1471–1507.[Abstract]
53.
Schellinger PD, Jansen O, Fiebach JB, Hacke W, Sartor
K. A standardized MRI stroke protocol: comparison with CT in hyperacute
intracerebral hemorrhage. Stroke. 1999;30:765–768.
This article has been cited by other articles:
 |
|
 |
|
  R. E. Latchaw, M. J. Alberts, M. H. Lev, J. J. Connors, R. E. Harbaugh, R. T. Higashida, R. Hobson, C. S. Kidwell, W. J. Koroshetz, V. Mathews, et al. Recommendations for Imaging of Acute Ischemic Stroke: A Scientific Statement From the American Heart Association Stroke, November 1, 2009; 40(11): 3646 - 3678. [Full Text] [PDF]
|
|
|
|
|
|
O. C. Singer, W. Kurre, M. C. Humpich, M. W. Lorenz, A. Kastrup, D. S. Liebeskind, G. Thomalla, J. Fiehler, J. Berkefeld, T. Neumann-Haefelin, et al. Risk Assessment of Symptomatic Intracerebral Hemorrhage After Thrombolysis Using DWI-ASPECTS Stroke, August 1, 2009; 40(8): 2743 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Butcher, M. Parsons, L. Allport, S. B. Lee, P. A. Barber, B. Tress, G. A. Donnan, S. M. Davis, and for the EPITHET Investigators Rapid Assessment of Perfusion-Diffusion Mismatch Stroke, January 1, 2008; 39(1): 75 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Muir, J. Baird-Gunning, L. Walker, T. Baird, M. McCormick, and S. B. Coutts Can the Ischemic Penumbra Be Identified on Noncontrast CT of Acute Stroke? Stroke, September 1, 2007; 38(9): 2485 - 2490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Rivers, J. M. Wardlaw, P. A. Armitage, M. E. Bastin, T. K. Carpenter, V. Cvoro, P. J. Hand, and M. S. Dennis Persistent Infarct Hyperintensity on Diffusion-Weighted Imaging Late After Stroke Indicates Heterogeneous, Delayed, Infarct Evolution Stroke, June 1, 2006; 37(6): 1418 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P L Tan, D King, C J Durkin, T M Meagher, and D Briley Diffusion weighted magnetic resonance imaging for acute stroke: practical and popular. Postgrad. Med. J., April 1, 2006; 82(966): 289 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A Barber, M D Hill, M Eliasziw, A M Demchuk, J H W Pexman, M E Hudon, A Tomanek, R Frayne, A M Buchan, and for the ASPEC Study Group Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging J. Neurol. Neurosurg. Psychiatry, November 1, 2005; 76(11): 1528 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Alberts, R. E. Latchaw, W. R. Selman, T. Shephard, M. N. Hadley, L. M. Brass, W. Koroshetz, J. R. Marler, J. Booss, R. D. Zorowitz, et al. Recommendations for Comprehensive Stroke Centers: A Consensus Statement From the Brain Attack Coalition Stroke, July 1, 2005; 36(7): 1597 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wardlaw and O. Mielke Early Signs of Brain Infarction at CT: Observer Reliability and Outcome after Thrombolytic Treatment--Systematic Review Radiology, May 1, 2005; 235(2): 444 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Christensen, L. Allport, K. Butcher, and S. Davis Insular Lesions and Hyperglycemia in Acute Stroke Revisited * Response Stroke, February 1, 2005; 36(2): 229 - 230. [Full Text] [PDF]
|
|
|
|
|
|
S. P. Kloska, D. G. Nabavi, C. Gaus, E.-M. Nam, E. Klotz, E. B. Ringelstein, and W. Heindel Acute Stroke Assessment with CT: Do We Need Multimodal Evaluation? Radiology, October 1, 2004; 233(1): 79 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-D. Heiss, J. Sobesky, U. v. Smekal, L. W. Kracht, F.-G. Lehnhardt, A. Thiel, A. H. Jacobs, and K. Lackner Probability of Cortical Infarction Predicted by Flumazenil Binding and Diffusion-Weighted Imaging Signal Intensity: A Comparative Positron Emission Tomography/Magnetic Resonance Imaging Study in Early Ischemic Stroke Stroke, August 1, 2004; 35(8): 1892 - 1898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Inatomi, K. Kimura, T. Yonehara, S. Fujioka, and M. Uchino DWI abnormalities and clinical characteristics in TIA patients Neurology, February 10, 2004; 62(3): 376 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Packard, C. S. Kase, A. S. Aly, and G. D. Barest "Computed Tomography-Negative" Intracerebral Hemorrhage: Case Report and Implications for Management Arch Neurol, August 1, 2003; 60(8): 1156 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Saur, T. Kucinski, U. Grzyska, B. Eckert, C. Eggers, W. Niesen, V. Schoder, H. Zeumer, C. Weiller, and J. Rother Sensitivity and Interrater Agreement of CT and Diffusion-Weighted MR Imaging in Hyperacute Stroke AJNR Am. J. Neuroradiol., May 1, 2003; 24(5): 878 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]
|
|
|
|
|
|
R. P. Gerraty, M. W. Parsons, P. A. Barber, D. G. Darby, P. M. Desmond, B. M. Tress, and S. M. Davis Examining the Lacunar Hypothesis With Diffusion and Perfusion Magnetic Resonance Imaging Stroke, August 1, 2002; 33(8): 2019 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kucinski, O. Vaterlein, V. Glauche, J. Fiehler, E. Klotz, B. Eckert, C. Koch, J. Rother, and H. Zeumer Correlation of Apparent Diffusion Coefficient and Computed Tomography Density in Acute Ischemic Stroke Stroke, July 1, 2002; 33(7): 1786 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Wu, W. J. Koroshetz, L. Ostergaard, F. S. Buonanno, W. A. Copen, R. G. Gonzalez, G. Rordorf, B. R. Rosen, L. H. Schwamm, R. M. Weisskoff, et al. Predicting Tissue Outcome in Acute Human Cerebral Ischemia Using Combined Diffusion- and Perfusion-Weighted MR Imaging Stroke, April 1, 2001; 32(4): 933 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Keir and J. M. Wardlaw Systematic Review of Diffusion and Perfusion Imaging in Acute Ischemic Stroke Stroke, November 1, 2000; 31(11): 2723 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Parsons, T. Li, P. A. Barber, Q. Yang, D. G. Darby, P. M. Desmond, R. P. Gerraty, B. M. Tress, and S. M. Davis Combined 1H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome Neurology, August 22, 2000; 55(4): 498 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. von Kummer, N. J. Beauchamp Jr, P. B. Barker, P. Y. Wang, and P. C. M. vanZijl CT of Acute Cerebral Ischemia Dr Beauchamp and colleagues respond: Radiology, August 1, 2000; 216(2): 611 - 613. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||