P A Barber

Royal Melbourne Hospital, Melbourne, Victoria, Australia

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Publications (20)162.25 Total impact

  • Article: Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch.
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    ABSTRACT: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.
    Neurology 09/2010; 75(12):1040-7. · 8.31 Impact Factor
  • Article: Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.
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    ABSTRACT: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. None.
    The Lancet 05/2010; 375(9727):1695-703. · 38.28 Impact Factor
  • Article: Baseline diabetic status and admission blood glucose were poor prognostic factors in the EPITHET trial.
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    ABSTRACT: Previous data have suggested that diabetes and hyperglycemia predict poor outcome following stroke. We studied the prognostic impact of diabetes and admission blood glucose in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). EPITHET was a prospective randomized placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. A preexisting diagnosis of diabetes was noted and baseline serum glucose was measured. Intravenous tPA attenuated infarct growth in non-diabetics, but not in diabetics (p = 0.029). In the tPA treatment group, admission blood glucose was higher among patients with poor functional outcome (p = 0.002). Diabetes and hyperglycemia attenuate the effects of tPA on infarct evolution. Future thrombolytic trials should consider randomizing patients by subgroups based on diabetic status and serum glucose levels.
    Cerebrovascular Diseases 11/2009; 29(1):14-21. · 2.72 Impact Factor
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    Article: Refining the perfusion-diffusion mismatch hypothesis.
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    ABSTRACT: The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day 90-vol)-DWI(Acute-vol)) were also assessed. Mean age was 68+/-11, time to MRI 4.5+/-0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch > or =20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=-0.51; P=0.009). Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.
    Stroke 07/2005; 36(6):1153-9. · 5.73 Impact Factor
  • Article: The value of apparent diffusion coefficient maps in early cerebral ischemia.
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    ABSTRACT: Prediction of the regions of the ischemic penumbra that are likely to progress to infarction is of great clinical interest. Whether lowered apparent diffusion coefficient (ADC) values were present in the ischemic penumbra of patients presenting with acute ischemic stroke and were specific to regions of the penumbra that proceeded to infarction was investigated. Nineteen patients with hemispheric stroke of less than 6 hours' onset and with acute scans showing a perfusion lesion greater than a diffusion lesion (ischemic penumbra) were studied. Scans also were performed subacutely (days 3 to 5) and at outcome (day 90). The outcome scan was used to identify regions of the penumbra that proceeded to infarction. The ADC ratios were significantly reduced (P <.00001) in regions of the penumbra that progressed to infarction on the outcome scan compared with those that remained normal. In regions that showed transition to infarction, the mean ADC ratios were typically 0.75 to 0.90. Intermediate ADC values are present in the ischemic penumbra and are indicative of tissue at risk of infarction.
    American Journal of Neuroradiology 08/2001; 22(7):1260-7. · 2.93 Impact Factor
  • Article: Perfusion magnetic resonance imaging maps in hyperacute stroke: relative cerebral blood flow most accurately identifies tissue destined to infarct.
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    ABSTRACT: In ischemic stroke, perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) provide important pathophysiological information. A PWI>DWI mismatch pattern suggests the presence of salvageable tissue. However, improved methods for distinguishing PWI>DWI mismatch tissue that is critically hypoperfused from benign oligemia are required. We investigated the usefulness of maps of relative cerebral blood flow (rCBF), volume (rCBV), and mean transit time (rMTT) to predict transition to infarction in hyperacute (<6 hours) stroke patients with PWI>DWI mismatch patterns. Semiquantitative color-thresholded analysis was used to measure hypoperfusion volumes, including increasing color signal intensity thresholds of rMTT delay, which were compared with infarct expansion, outcome infarct size, and clinical status. Acute rCBF lesion volume had the strongest correlation with final infarct size (r=0.91, P<0.001) and clinical outcome (r=0.67, P<0.01). There was a trend for acute rCBF>DWI mismatch volume to overestimate infarct expansion between the acute and outcome study (P=0.06). Infarct expansion was underestimated by acute rCBV>DWI mismatch (P<0.001). When rMTT lesions included tissue with moderately prolonged transit times (mean delay 4.3 seconds, signal intensity values 50% to 70%), infarct expansion was overestimated. In contrast, when rMTT lesions were restricted to more severely prolonged transit times (mean delay 6.1 seconds, signal intensity >70%), these regions progressed to infarction in all except 1 patient, but infarct expansion was underestimated (P<0.001). The acute rCBF lesion most accurately identified tissue in the PWI>DWI mismatch region at risk of infarction. Color-thresholded PWI maps show potential for use in an acute clinical setting to prospectively predict tissue outcome.
    Stroke 08/2001; 32(7):1581-7. · 5.73 Impact Factor
  • Article: A three-item scale for the early prediction of stroke recovery.
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    ABSTRACT: Accurate assessment of prognosis in the first hours of stroke is desirable for best patient management. We aimed to assess whether the extent of ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI) could provide additional prognostic information to clinical factors. In a three-phase study we studied 66 patients from a North American teaching hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of Health Stroke Scale (NIHSS) score measured at the time of scanning; and the Barthel Index measured no later than 3 months after stroke. We used logistic regression to derive a predictive model for good recovery. This logistic regression model was applied to an independent series of 63 patients from an Australian teaching hospital, and we then developed a three-item scale for the early prediction of stroke recovery. Combined measurements of the NIHSS score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of stroke recovery. The model was externally validated on the Australian sample with 0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three-item scale. The combination of clinical and MR DWI factors provided better prediction of stroke recovery than any factor alone, shortly after admission to hospital. This information was incorporated into a three-item scale for clinical use.
    The Lancet 07/2001; 357(9274):2095-9. · 38.28 Impact Factor
  • Article: Prediction of the final infarct volume within 6 h of stroke using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime.
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    ABSTRACT: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.
    Cerebrovascular Diseases 02/2001; 11(2):119-27. · 2.72 Impact Factor
  • Article: Comparison of MRI perfusion imaging and single photon emission computed tomography in chronic stroke.
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    ABSTRACT: There have been few direct comparisons between MR perfusion-weighted imaging (PWI) and established perfusion imaging techniques, and none in chronic stroke. We therefore studied 17 chronic hemispheric infarction patients (mean, 90 days) and compared hypoperfusion volumes determined from PWI maps of relative cerebral blood flow (rCBF) and volume (rCBV), and mean transit time (rMTT) with those measured with (99)Tc-HMPAO single photon emission computed tomography (SPECT). Comparisons were also made between infarct size (T(2)-WI) and clinical scales. Correlations were found between lesion location and volume in all three PWI hemodynamic parameter maps with clinical state and lesions on SPECT and T(2)-WI. In 3 patients, rCBF and rCBV lesions extended well beyond the borders of moderate-sized infarctions. We conclude that in chronic stroke, PWI can delineate regions of abnormal perfusion that reflect the degree of functional impairment and structural damage. The finding of peri-infarct hypoperfusion suggests that PWI may have the potential to provide a rapid and non-invasive template against which interventional strategies aimed at promoting functional recovery may be investigated.
    Cerebrovascular Diseases 02/2001; 11(2):128-36. · 2.72 Impact Factor
  • Article: Significance of acute multiple brain infarction on diffusion-weighted imaging.
    Stroke 10/2000; 31(9):2270-1. · 5.73 Impact Factor
  • Article: Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome.
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    ABSTRACT: The prognostic value of the biochemical changes seen with proton MR spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel localization. Nineteen patients had 36 1H MRS studies, 13 patients acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels from the infarct core. Outcome measures were final infarct volume and clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale). Acute lactate/choline ratio correlated more strongly with clinical outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0. 96; p < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of acute lactate/choline ratio with acute DWI lesion volume improved prediction of all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In subacute and chronic infarction, both lactate/choline and NAA/choline ratios continued to correlate with outcome (p < 0.05). At the chronic stage, persistent lactate/choline ratio elevation strongly correlated with outcome measures (r = 0.71 to 0.87). Lactate/choline ratio measured in the acute infarct core by 1H MRS improves the prediction of stroke outcome and provides prognostic information complementary to DWI. Lactate/choline ratio could be used as an additional marker to select patients for acute and chronic therapies.
    Neurology 08/2000; 55(4):498-505. · 8.31 Impact Factor
  • Article: Echoplanar magnetic resonance imaging in acute stroke.
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    ABSTRACT: Echoplanar magnetic resonance imaging (EPI) enables rapid, non-invasive imaging and analysis of cerebral pathophysiology in acute stroke. It represents an important clinical advance over computed tomography (CT) and conventional magnetic resonance (MR) scanning. It can rapidly delineate infarcted cerebral tissue and distinguish acute from chronic stroke. In addition, EPI has the potential to quickly determine the presence and degree of potentially viable brain tissue in the ischaemic penumbra. Thrombolysis is thought to reperfuse the penumbra and hence reduce infarct size. The thrombolytic agent tissue plasminogen activator (t-PA) improves outcome in ischaemic stroke when administered within the first 3 hours of onset. However, there is a significant risk of haemorrhage, and the time window for benefit may well exceed 3 hours in some patients. Hence, by facilitating diagnosis of 'at-risk' tissue in the ischaemic penumbra, a major clinical role of EPI may well become the rational selection of patients for acute interventional stroke therapy.
    Journal of Clinical Neuroscience 02/2000; 7(1):3-8. · 1.25 Impact Factor
  • Article: Serial study of apparent diffusion coefficient and anisotropy in patients with acute stroke.
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    ABSTRACT: We sought to characterize the evolution of apparent diffusion coefficient (ADC) and apparent diffusion anisotropy (ADA) in acute stroke and to evaluate their roles in predicting stroke evolution and outcome. We studied 26 stroke patients acutely (<24 hours), subacutely (3 to 5 days), and at outcome (3 months). Ratios of the ADC and ADA within a region of infarction and the normal contralateral region were evaluated and compared with the Canadian Neurological Scale, Barthel Index, and Rankin Scale. Heterogeneity in ADC and ADA evolution was observed not only between patients but also within individual lesions. Three patterns of ADA evolution were observed: (1) elevated ADA acutely and subacutely; (2) elevated ADA acutely and reduced ADA subacutely; and (3) reduced ADA acutely and subacutely. At outcome, reduced ADA with elevated ADC was observed generally. We identified 3 phases of diffusion abnormalities: (1) reduced ADC and elevated ADA; (2) reduced ADC and reduced ADA; and (3) elevated ADC and reduced ADA. The ADA ratios within 12 hours correlated with the acute Canadian Neurological Scale (r=0.46, P=0.06), subacute Canadian Neurological Scale (r=0.55, P=0.02), outcome Barthel Index (r=0.62, P=0.01), and Rankin Scale (r=-0.77, P<0.0005) scores. Combined ADC and ADA provide differential patterns of stroke evolution. Early ADA changes reflect cellular alterations in acute ischemia and may provide a potential marker to predict stroke outcome.
    Stroke 11/1999; 30(11):2382-90. · 5.73 Impact Factor
  • Article: Pathophysiological topography of acute ischemia by combined diffusion-weighted and perfusion MRI.
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    ABSTRACT: 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. 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. 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. 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.
    Stroke 11/1999; 30(10):2043-52. · 5.73 Impact Factor
  • Article: Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography.
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    ABSTRACT: 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. 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. 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 (kappa=0.88). One patient eligible for thrombolysis on the ECASS CT criteria had major ischemia on DWI. DWI is more sensitive than CT in the identification of acute ischemia and can visualize major ischemia more easily than CT.
    Stroke 11/1999; 30(10):2059-65. · 5.73 Impact Factor
  • Article: Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra.
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    ABSTRACT: In acute ischemic stroke the pattern of a perfusion-imaging (PI) lesion larger than the diffusion-weighted imaging (DWI) lesion may be a marker of the ischemic penumbra. We hypothesized that acute middle cerebral artery (MCA) occlusion would predict the presence of presumed "penumbral" patterns (PI > DWI), ischemic core evolution, and stroke outcome. Echoplanar PI, DWI, and magnetic resonance angiography (MRA) were performed in 26 patients with MCA territory stroke. Imaging and clinical studies (Canadian Neurological Scale, Barthel Index, and Rankin Scale) were performed within 24 hours of onset and repeated at days 4 and 90. MCA flow was absent in 9 of 26 patients. This was associated with larger acute PI and DWI lesions, greater PI/DWI mismatch, early DWI lesion expansion, larger final infarct size, worse clinical outcome (p < 0.01) and provided independent prognostic information (multiple linear regression analysis, p < 0.05). Acute penumbral patterns were present in 14 of 26 patients. Most of these patients (9 of 14) had no MCA flow, whereas all nonpenumbral patients (PI < or = DWI lesion) had MCA flow (p < 0.001). Penumbral-pattern patients with absent MCA flow had greater DWI lesion expansion (p < 0.05) and worse clinical outcome (Rankin Scale score, p < 0.05). Absent MCA flow on MRA predicts the presence of a presumed penumbral pattern on acute PI and DWI and worse stroke outcome. Combined MRA, PI, and DWI can identify individual patients at risk of ischemic core progression and the potential to respond to thrombolytic therapy beyond 3 hours.
    Neurology 04/1999; 52(6):1125-32. · 8.31 Impact Factor
  • Article: Spontaneous reperfusion after ischemic stroke is associated with improved outcome.
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    ABSTRACT: BACKGROUND and The rationale behind thrombolytic therapy in acute ischemic stroke is penumbral salvage by rapid restoration of cerebral blood flow. The relationship, however, between early reperfusion (potentially composed of both nutritional and nonnutritional components) and outcome remains unclear. To establish the relationship between reperfusion parameters and outcome variables (Canadian Neurological Scale, Barthel Index, outcome CT scans), we used 99Tc-hexamethylpropyleneamine oxime (99Tc-HMPAO) single-photon emission CT (SPECT) to examine 41 acute ischemic stroke patients. All patients had at least 2 SPECT studies (24 with 3 studies), and none had been treated with thrombolytic or other acute investigational drugs. A total of 106 studies were performed. Mean time to acute study was 9.2 hours; that for subacute study was 42 hours and for outcome study was 150 days. Hypoperfusion (HP) volumes at each of the 3 time points correlated with outcome clinical state and final infarct size. Both early reperfusion (61% of patients) and nutritional reperfusion alone (56%), which is early reperfusion maintained at outcome, were associated with improvement in clinical state and better functional outcome. Early HP volume change (acute minus subacute HP volume) and total HP volume change (acute minus outcome HP volume) also correlated with clinical improvement and better outcome. This study establishes the benefit of spontaneous reperfusion after ischemic stroke and emphasizes the prognostic value of HP deficit volumes. 99Tc-HMPAO SPECT may be used to screen patients and group them according to perfusion deficit in acute stroke trials, thereby decreasing patient numbers required to show drug effect.
    Stroke 01/1999; 29(12):2522-8. · 5.73 Impact Factor
  • Article: Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI.
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    ABSTRACT: We examined the utility of echoplanar magnetic resonance perfusion imaging and diffusion-weighted imaging (DWI) in predicting stroke evolution and outcome in 18 patients with acute hemispheric infarction. Patients were studied within 24 hours (mean, 12.2 hours), subacutely (mean, 4.7 days), and at outcome (mean, 84 days). Comparisons were made between infarction volumes as measured on perfusion imaging (PI) and isotropic DWI maps, clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale), and final infarct volume (T2-weighted MRI). Acute PI lesion volumes correlated with acute neurologic state, clinical outcome, and final infarct volume. Acute DWI lesions correlated less robustly with acute neurologic state, but correlated well with clinical outcome and final infarct volume. Three of six possible patterns of abnormalities were seen: PI lesion larger than DWI lesion (65%), PI lesion smaller than DWI lesion (12%), and DWI lesion but no PI lesion (23%). A pattern of a PI lesion larger than the DWI lesion predicted DWI expansion into surrounding hypoperfused tissue (p < 0.05). In the other two patterns, DWI lesions did not enlarge, suggesting that no significant increase in ischemic lesion size occurs in the absence of a larger perfusion deficit. Combined early PI and DWI can define different acute infarct patterns, which may allow the selection of rational therapeutic strategies based on the presence or absence of potentially salvageable ischemic tissue.
    Neurology 08/1998; 51(2):418-26. · 8.31 Impact Factor
  • Article: Echoplanar magnetic resonance imaging in acute stroke
    [show abstract] [hide abstract]
    ABSTRACT: Echoplanar magnetic resonance imaging (EPI) enables rapid, non-invasive imaging and analysis of cerebral pathophysiology in acute stroke. It represents an important clinical advance over computed tomography (CT) and conventional magnetic resonance (MR) scanning. It can rapidly delineate infarcted cerebral tissue and distinguish acute from chronic stroke. In addition, EPI has the potential to quickly determine the presence and degree of potentially viable brain tissue in the ischaemic penumbra. Thrombolysis is thought to reperfuse the penumbra and hence reduce infarct size. The thrombolytic agent tissue plasminogen activator (t-PA) improves outcome in ischaemic stroke when administered within the first 3 hours of onset. However, there is a significant risk of haemorrhage, and the time window for benefit may well exceed 3 hours in some patients. Hence, by facilitating diagnosis of ‘at-risk’ tissue in the ischaemic penumbra, a major clinical role of EPI may well become the rational selection of patients for acute interventional stroke therapy.
    Journal of Clinical Neuroscience.
  • Article: Multiple definitions of PWI-DWI mismatch reliably predict infarct growth