Baseline Diffusion-weighted Imaging Lesion Research Articles

Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds.

Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions. Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.org; NCT00715533). We built a fully automated lesion segmentation algorithm using a fixed ADC threshold (≤620 × 10-6 mm2/s) to delineate the baseline DWI lesion and analyzed its performance compared to manual assessments. Diagnostic capabilities of best possible ADC thresholds were investigated using receiver operating characteristic curves. Influential patient factors on ADC thresholding techniques' performance were studied by conducting multiple linear regression. 108 acute ischemic stroke patients were selected for analysis. The median Dice coefficient for the algorithm was 0.43 (IQR 0.20-0.64). Mean ADC values in the DWI lesion (β = -0.68, p < 0.001) and DWI lesion volumes (β = 0.29, p < 0.001) predicted performance. Optimal individual ADC thresholds differed between subjects with a median of ≤691 × 10-6 mm2/s (IQR ≤660-750 × 10-6 mm2/s). Mean ADC values in the DWI lesion (β = -0.96, p < 0.001) and mean ADC values in the brain parenchyma (β = 0.24, p < 0.001) were associated with the performance of individual thresholds. The performance of ADC thresholds for delineating acute stroke lesions varies substantially between patients. It is influenced by factors such as lesion size as well as lesion and parenchymal ADC values. Considering the inherent noisiness of ADC maps, ADC threshold-based automated delineation of very small lesions is not reliable.

Collateral estimation by susceptibility-weighted imaging and prediction of functional outcomes after acute anterior circulation ischemic stroke

To determine the value of susceptibility-weighted imaging (SWI) for collateral estimation and for predicting functional outcomes after acute ischemic stroke. To identify independent predictors of favorable functional outcomes, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline diffusion-weighted imaging (DWI) lesion volume, site of steno-occlusion, SWI collateral grade, mode of treatment, and successful reperfusion were evaluated by multiple logistic regression analyses. A total of 152 participants were evaluated. A younger age (adjusted odds ratio (aOR), 0.42; 95% confidence interval (CI) 0.34 to 0.77; P < 0.001), a lower baseline NIHSS score (aOR 0.90; 95% CI 0.82 to 0.98; P = 0.02), a smaller baseline DWI lesion volume (aOR 0.83; 95% CI 0.73 to 0.96; P = 0.01), an intermediate collateral grade (aOR 9.49; 95% CI 1.36 to 66.38; P = 0.02), a good collateral grade (aOR 6.22; 95% CI 1.16 to 33.24; P = 0.03), and successful reperfusion (aOR 5.84; 95% CI 2.08 to 16.42; P = 0.001) were independently associated with a favorable functional outcome. There was a linear association between the SWI collateral grades and functional outcome (P = 0.008). Collateral estimation using the prominent vessel sign on SWI is clinically reliable, as it has prognostic value.

Early successful reperfusion after endovascular therapy reduces malignant middle cerebral artery infarction occurrence in young patients with large diffusion-weighted imaging lesions.

Malignant middle cerebral artery infarction (MMI) is a severe complication of acute ischaemic stroke (AIS). The aim of our study was to assess whether successful reperfusion after endovascular therapy (EVT) in AIS with clinical and imaging predictors of MMI decreased its occurrence. Data were collected between January 2014 and July 2018 in a monocentric prospective AIS registry of patients treated with EVT. Patients selected were <65years old with severe anterior circulation AIS with a National Institutes of Health Stroke Scale score >15, baseline Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score≤6 and baseline diffusion-weighted imaging lesion volume >82mL within 6h of symptom onset. Successful reperfusion was defined as a Thrombolysis in Cerebral Ischemia score≥2b. Occurrence of MMI was the primary endpoint. A total of 66 EVT-treated patients were included in our study. MMI occurred in 27 patients (41%). In unadjusted analysis, successful reperfusion was associated with fewer MMIs (31.8% vs. 65.0%; P=0.015) and with more favorable outcome at 3months (50% vs. 20%; P=0.023). In multivariate analysis, successful reperfusion was associated with an adjusted odds ratio (95% confidence intervals) of 0.35 (0.10-1.12) for MMI and 2.77 (0.84-10.43) for 3-month favorable outcome occurrence. Early successful reperfusion performed in patients with AIS with clinical and imaging predictors of MMI was associated with decreased MMI occurrence. Reperfusion status might be considered in evaluating the need for craniectomy in patients with early predictors of MMI.

Does Diffusion Lesion Volume Above 70 mL Preclude Favorable Outcome Despite Post-Thrombolysis Recanalization?

Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ≤4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal. We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ≤2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes. Median (interquartile range) DWI lesion volume was 22 mL (10-60), and median onset time to imaging was 116 minutes (86-151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09-20.32]; P=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2-47.6] versus 8.5 mL [4.3-31.1]; P=0.17; and 19.6% [10.9-62.8] versus 8.7% [3.9-16.5], respectively; P=0.049). Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal.

Dynamic Evolution of Diffusion-Weighted Imaging Lesions in Patients With Minor Ischemic Stroke.

Diffusion-weighted imaging (DWI) lesion volume on magnetic resonance imaging is increasingly being used as a surrogate outcome measure in clinical trials. We aimed to characterize the evolution of DWI lesion volumes within 30 days of symptom onset after minor stroke. Minor stroke patients with DWI lesions on magnetic resonance imaging within 48 hours of symptom onset were prospectively followed with magnetic resonance imaging brain scan at 7 and 30 days. Change in the lesion volume was defined as the difference between day 30 Fluid-Attenuated Inversion Recovery and baseline DWI lesion volumes. Three patterns of infarct evolution were observed: reduction (72 [63%]), no change (26 [23%]), and growth (16 [14%]). Patients with infarct reduction at 30 days had larger baseline DWI lesion volumes (2.5 [0.9-8.5] mL) than those with stable infarcts (0.5 [0.3-0.9] mL; P=0.01). Complete DWI reversal at day 30, was seen in only 6 (5.3%) patients. The most common pattern of infarct evolution in patients with minor stroke is a reduction in volume, but complete resolution is uncommon.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Early Diffusion-Weighted Imaging Reversal After Endovascular Reperfusion Is Typically Transient in Patients Imaged 3 to 6 Hours After Onset

The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient. MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed. A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion. Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

Pilot Study of Intravenous Glyburide in Patients With a Large Ischemic Stroke

Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours. Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3). RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.

Granulocyte Colony–Stimulating Factor in Patients With Acute Ischemic Stroke

Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. http://www.clinicaltrials.gov. Unique identifier: NCT00927836.

Arterial Spin–Labeled Perfusion Imaging to Predict Mismatch in Acute Ischemic Stroke

We assigned a threshold to arterial spin-labeling (ASL) perfusion-weighted images (PWI) from patients with acute ischemic stroke and compared them with dynamic susceptibility contrast perfusion images to examine whether mismatch can be determined. Pseudocontinuous ASL was combined with dynamic susceptibility contrast PWI in 23 patients with acute ischemic stroke. Scans were obtained within 24 hours of symptom onset. PWI volumes were defined by ASL cerebral blood flow (<15, <20, and <25 mL/100 g per minute) and dynamic susceptibility contrast-mean transit time (MTT) thresholds (>10 s) that show a strong association with cerebral blood flow <20 mL/100 g per minute in Xenon CT studies. Agreement between the ASL-diffusion-weighted imaging and MTT-diffusion-weighted imaging mismatch and the correlation between penumbra salvage and infarct growth, defined as the difference between the baseline PWI and the baseline diffusion-weighted imaging lesion, respectively, and the final infarct volume were assessed. The lesion volumes defined by MTT>10 s and ASL<20 mL/100 g per minute showed an excellent correlation. There was 100% agreement on the mismatch status between MTT>10 s and ASL<20 mL/100 g per minute. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by ASL<20 mL/100 g per minute and MTT>10 s. In acute ischemic stroke, PWI lesions based on ASL threshold of <20 mL/100 g per minute can provide a reliable estimate of mismatch in correspondence at MTT threshold of >10 s.

Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke

There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥ 4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality. Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02). In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation.

A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA)

Higher body temperature is a prognostic factor of poor outcome in acute stroke. Our aim was to study the relationship between body temperature, HT (haemorrhagic transformation) and biomarkers of BBB (blood-brain barrier) damage in patients with acute ischaemic stroke untreated with rtPA (recombinant tissue-type plasminogen activator). We studied 229 patients with ischaemic stroke <12 h from symptom onset. Body temperature was determined at admission and every 6 h during the first 3 days. HT was evaluated according to ECASS II (second European Co-operative Acute Stroke Study) criteria in a multimodal MRI (magnetic resonance imaging) at 72 h. We found that 55 patients (34.1%) showed HT. HT was associated with cardioembolic stroke (64.2% against 23.0%; P<0.0001), higher body temperature during the first 24 h (36.9°C compared with 36.5°C; P<0.0001), more severe stroke [NIHSS (National Institutes of Health Stroke Scale) score, 14 (9-20) against 10 (7-15); P=0.002], and greater DWI (diffusion-weighted imaging) lesion volume at admission (23.2 cc compared with 13.2 cc; P<0.0001). Plasma MMP-9 (matrix metalloproteinase 9) (187.3 ng/ml compared with 44.2 ng/ml; P<0.0001) and cFn (cellular fibronectin) levels (16.3 μg/ml compared with 7.1 μg/ml; P=0.001) were higher in patients with HT. Body temperature within the first 24 h was independently associated with HT {OR (odds ratio), 7.3 [95% CI (confidence interval), 2.4-22.6]; P<0.0001} after adjustment for cardioembolic stroke subtype, baseline NIHSS score and DWI lesion volume. This effect remained unchanged after controlling for MMP-9 and cFn. In conclusion, high body temperature within the first 24 h after ischaemic stroke is a risk factor for HT in patients untreated with rtPA. This effect is independent of some biological signatures of BBB damage.

Acute Perfusion and Diffusion Abnormalities Predict Early New MRI Lesions 1 Week After Minor Stroke and Transient Ischemic Attack

Transient ischemic attack and minor stroke are associated with high ischemic recurrence in the first week. We prospectively studied the correlation between baseline diffusion/perfusion deficits and development of new ischemic lesions. Patients with transient ischemic attack and those with minor stroke (n=50) underwent MRI at admission. Acute perfusion-weighted imaging deficit (Tmax+2-second delay) and diffusion-weighted imaging (DWI) lesion volumes were measured planimetrically. Follow-up scans were examined for new DWI/fluid-attenuated inversion recovery lesions at Days 7 and 30. Twenty-eight patients (56%) had acute DWI lesions. New DWI lesions developed in 9 of 50 patients (18%) at 1 week and 11 of 50 (cumulative 22%) at 4 weeks. Patients with new infarcts were more likely to have baseline DWI lesions (χ²=8.264, P=0.003). Baseline DWI lesion volume was significantly larger in those who developed new lesions at Day 7 (median, 13.2 mL; interquartile range, 12 versus median 0.1 mL; interquartile range, 2 mL; P<0.001) and Day 30 (11.1 mL; interquartile range, 13 mL versus 0.1 mL; interquartile range, 13 mL; P<0.001). Thirty-eight patients had baseline perfusion-weighted imaging. Patients with recurrent lesions were more likely to have baseline perfusion deficits (χ²=19.5, P<0.0001). All new lesions developed within the baseline hypoperfused regions. Baseline DWI lesion volume predicted new lesion development at day 7 (OR, 1.17 per mL; CI, 1.05 to 1.30; P=0.005) and Day 30 (OR, 1.39 per mL; CI, 1.03 to 1.26; P=0.009) by regression analysis. Early recurrence of stroke is much more likely in patients with larger baseline DWI and perfusion-weighted imaging lesions. MRI lesion "recurrence" appears to be related to completion of the natural history of the original cerebrovascular syndrome rather than de novo events in most patients.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: Report of the Therapeutics and Technology Subcommittee of the American Academy of Neurology

Objective: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusionweighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. Methods: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. Results and Recommendations: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U). Neurology ® 2010;75:177–185

Stromal-Derived Factor-1α Correlates With Circulating Endothelial Progenitor Cells and With Acute Lesion Volume in Stroke Patients

Endothelial progenitor cells (EPC) are important participants of neovascularization and are mobilized through signaling with stromal-derived factor (SDF-1α), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and stem cell factor. The association between EPC levels and these growth factors (GF) in acute stroke has not been previously established. We aimed to determine the association between EPC and these GF, and to elucidate a relationship between these GF and stroke severity in acute stroke patients. Seventeen patients were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified using CD34, CD133, and VEGF-R2 markers. Plasma VEGF, SDF-1α, granulocyte colony-stimulating factor, and stem cell factor were determined by enzyme-linked immunosorbent assay on days 1 and 3, and brain MRI was performed at baseline and on days 1 and 5 after the stroke onset. Levels of SDF-1α strongly (r=0.6) correlated with the numbers of EPC subsets CD133(+)VEFG-R2(+) (P<0.004), CD34(+)VEGF-R2(+) (P<0.01), and CD34(+)CD133(+)VEGF-R2(+) (P<0.01) on day 1. Stem cell factor strongly (r=0.5) correlated with CD133(+)VEGF-R2(+) (P<0.05). SDF-1α moderately inversely (r=-0.49) correlated with baseline diffusion-weighted imaging lesion volumes (P<0.04). Median levels of SDF-1α (1561 pg/mL) increased (P<0.04) on day 3 compared to day 1 (1379 pg/mL). Similarly, VEGF at day 3 (95 pg/mL) increased (P<0.03) compared to day 1 (64 pg/mL). These results indicate that SDF-1α and stem cell factor correlate with an increase in EPC early in ischemic stroke patients.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch

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.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke [RETIRED

To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

Relative Energy Index of Microembolic Signal Can Predict Malignant Microemboli

Microembolic signals (MES) found on transcranial Doppler range from harmless air bubbles to large, solid, particulate emboli from the heart and large vessels. The presence of MES is not always associated with poor clinical outcome. The purpose of our study was to determine whether the relative energy index of MES measured by power M-mode Doppler can distinguish malignant from benign MES and to identify patients with worse prognosis. We prospectively collected transcranial Doppler emboli monitoring data from patients with symptomatic carotid stenosis presenting with TIA or ischemic stroke. For each patient, we calculated the relative energy index of MES and categorized those >1.0 as malignant MES. We compared the clinical characteristics, number, and volume of diffusion-weighted imaging lesions, and degree of stenosis and plaque characteristics on CT angiogram of patients with malignant and benign MES. We enrolled 92 patients, 29 with TIA and 63 with stroke, within 48 hours of symptom onset. Twenty-six patients had a total of 319 MES; of these, 82.4% were benign and were 17.6% malignant. Malignant MES traveled further within intracranial vessels than benign MES. The 9 patients with >1 malignant MES had significantly larger baseline diffusion-weighted imaging lesion volume, had a higher prevalence of intraluminal thrombus on CT angiogram of the neck and plaque ulceration, and were more likely to have a poor clinical outcome (modified Rankin Score > or = 2) than those with benign MES (OR, 6.5; 95% CI, 1.47-28.68). The presence of malignant MES led to the institution of more aggressive secondary prevention measures. Power M-mode transcranial Doppler identifies a subgroup of patients with malignant MES. These signals are more frequent in longer arterial trajectory. Patients with malignant MES have larger baseline infarcts, a higher prevalence of intraluminal thrombus or ulcerated plaque in the carotid artery, and worse clinical outcome.

Reliability of Measuring Lesion Volumes in Transient Ischemic Attack and Minor Stroke

Lesion volume measurements in disabling ischemic stroke have excellent reliability, but it is not clear whether this is also true for small lesions. We assessed the reliability of measuring baseline and follow-up lesion volumes in transient ischemic attack and minor stroke. Patients who presented with a transient ischemic attack or minor stroke (NIHSS < or = 3) who had brain MRI within 24 hours from symptom onset and at 30-day follow-up and had an acute lesion on baseline MRI were included. Using semiautomated software, 4 stroke fellows independently assessed ischemic lesions twice on acute diffusion-weighted imaging and follow-up fluid-attenuated inversion recovery. Eighty patients were included, with a median baseline NIHSS of 1. Mean baseline diffusion-weighted imaging lesion volume was 3.4+/-7.4 mL (87.5% had <5 mL). There was excellent inter-rater/intrarater reliability, with intraclass correlation coefficients of 0.94/0.96 for acute diffusion-weighted imaging, 0.74/0.92 for follow-up fluid-attenuated inversion recovery, and 0.81/0.93 for growth. We found excellent concordance between and within raters for acute diffusion-weighted imaging and 30-day follow-up fluid-attenuated inversion recovery lesion volume measurements in patients with transient ischemic attack and minor stroke.

Pretreatment Diffusion- and Perfusion-MR Lesion Volumes Have a Crucial Influence on Clinical Response to Stroke Thrombolysis

We hypothesized that pretreatment magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes may have influenced clinical response to thrombolysis in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). In 98 patients randomized to intravenous (IV) tissue plasminogen activator (tPA) or placebo 3 to 6 h after stroke onset, we examined increasing acute DWI and PWI lesion volumes (Tmax-with 2-sec delay increments), and increasing PWI/DWI mismatch ratios, on the odds of both excellent (modified Rankin Scale (mRS): 0 to 1) and poor (mRS: 5 to 6) clinical outcome. Patients with very large PWI lesions (most had internal carotid artery occlusion) had increased odds ratio (OR) of poor outcome with IV-tPA (58% versus 25% placebo; OR=4.13, P=0.032 for Tmax +2-sec volume >190 mL). Excellent outcome from tPA treatment was substantially increased in patients with DWI lesions <18 mL (77% versus 18% placebo, OR=15.0, P<0.001). Benefit from tPA was also seen with DWI lesions up to 25 mL (69% versus 29% placebo, OR=5.5, P=0.03), but not for DWI lesions >25 mL. In contrast, increasing mismatch ratios did not influence the odds of excellent outcome with tPA. Clinical responsiveness to IV-tPA, and stroke outcome, depends more on baseline DWI and PWI lesion volumes than the extent of perfusion-diffusion mismatch.