Perfusion-weighted Imaging Lesion Volumes Research Articles

Abstract TP63: Detection of Perfusion Deficits Using FLAIR and GRE Based Vessel Signs

Background: The presence of a perfusion deficit in an acute stroke patient can play an important role in their clinical management. However, many patients are unable to have perfusion-weighted imaging (PWI) due to renal disease. Perfusion deficits are often accompanied by FLAIR hyperintense vessels (FHV), presumably due to slow arterial blood flow, and GRE hypointense vessels (GHV), presumably due to venous congestion. Purpose: To determine how well FHV and GHV perform at identifying PWI lesions. Methods: One rater, blinded to the PWI MR sequences, retrospectively reviewed the DWI, FLAIR and GRE scans of acute stroke patients enrolled in the NIH Natural History of Stroke study during 2013-2014 who had an MRI with PWI prior to being treated with IV tPA. DWI images were used to guide evaluation of the FLAIR and GRE images for FHV and GHV and in each case were classified as definitively present, possibly present or absent. PWI lesion volumes were calculated by thresholding the time-to-peak (TTP) maps at 4 seconds beyond normal tissue. ROC analysis was used to assess the performance of FHV and GHV at various PWI lesion volume thresholds. Results: 102 patients were included in the analysis; their mean PWI lesion volume was 52 mL with a standard deviation of +/- 66 mL. 22% of patients had no perfusion deficit. The ROC analysis found the presence of any FHV performed the best with an area under the curve (AUC) of 0.925 displayed in the figure. Any GHV performed modestly with an AUC of 0.776. Combining FHV with GHV did not improve the performance over FHV alone (AUC=0.876). The sensitivity and specificity for identifying any perfusion deficit with FHV was 95% and 67% respectively with 87% being correctly classified. For detecting a PWI lesion greater than 10 mL, FHV had an 80% sensitivity and 93% specificity classifying 83% correctly. Conclusions: FHV is highly sensitive for identifying a perfusion deficit in stroke patients, and for patients with a lesion volume greater than 10 mL it is highly specific.

Magnetic Resonance Imaging in Acute Ischemic Stroke Patients with Mild Symptoms: An Opportunity to Standardize Intravenous Thrombolysis

Patients presenting with mild stroke symptoms are excluded inconsistently from intravenous (IV) thrombolysis. We aimed to compare acute magnetic resonance imaging findings in patients with mild symptoms to those with more severe deficits to identify clinically mild patients who might benefit from IV thrombolysis. We retrospectively studied consecutive stroke patients presenting with perfusion deficit who underwent time-of-flight magnetic resonance angiography within 24 hours of time last seen normal. Two raters measured the lesion volumes on diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) with mismatch (MM) calculated as PWI minus DWI. Occlusion site was categorized as "proximal," "distal," or "magnetic resonance angiography-negative" by consensus review. Stroke with mild symptoms was defined as admit National Institutes of Health Stroke Scale score of 4 or less. Values were reported as n (%). Ninety-one patients were included; 56 (61.5%) with nonmild and 35 (38.5%) with mild symptoms. After stratifying for occlusion site, there were no differences in PWI and MM lesion volumes for the nonmild versus mild patients (P = .34-.98 and P = .54-1, respectively). Furthermore, there was a trend for thrombolyzed mild stroke patients (88%, n = 7 of 8) to more likely have a favorable clinical outcome (discharge modified Rankin score ≤ 2) versus untreated patients (70%, n = 16 of 23). When present, conspicuous vessel occlusions in clinically mild stroke patients are concomitant with similar perfusion deficit and MM volumes in more clinically severe stroke patients. Coupled with a trend toward better outcomes in mild stroke patients who were treated with IV tissue plasminogen activator (t-PA), this could indicate that advanced imaging may be used in standardizing the way these patients are selected for IV t-PA therapy.

Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort

We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2). Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days. Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014. HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

Abstract 35: Early Diffusion Weighted Imaging and Perfusion Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2

Background: It is hypothesized that early DWI lesions accurately estimate the size of the irreversibly injured ischemic core and that appropriately thresholded PWI lesions (Tmax &gt; 6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and post-treatment PWI is hypothesized to predict infarct volume. Methods: This is a substudy of DEFUSE 2; all patients who had technically adequate MRI scans at 3 time points were included: just prior to endovascular therapy, within 12 hours post-therapy, and at 5 days. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program and manually adjusted by the DEFUSE 2 core lab if needed. Final infarct volumes were assessed on the Day 5 FLAIR and corrected for edema. Reperfusion was defined based on the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes. Results: Seventy-eight patients were eligible; the 28 patients with &gt;90% reperfusion show a high correlation between early DWI volume and final infarct volume (r = 0.81, p &lt; 0.001) with a slope of 0.95. Twelve patients with &lt;10% reperfusion have a high correlation between baseline PWI (Tmax &gt;6 sec) volume and final infarct volume with a slope of 1.17 (r = 0.93, p &lt; 0.001). Using all 78 patients, the union of baseline DWI with early follow-up PWI is highly correlated with final volume (r = 0.86, p &lt; 0.001) with a slope of 1.01. The median absolute difference between observed and predicted final volume is 15 ml (IQR, 4.8-32.8). Conclusions: Early DWI and PWI (Tmax &gt; 6 sec) volumes provide a reasonable approximation of final infarct volume following endovascular therapy.

Moving Beyond a Single Perfusion Threshold to Define Penumbra

The mismatch lesion volumes defined by perfusion-weighted imaging exceeding diffusion-weighted imaging have been used as a marker of ischemic penumbral tissue. Defining the perfusion lesion by thresholding has shown promise as a practical tool; several positron emission tomography studies have indicated a more probabilistic relationship between perfusion and infarction. Here, we used a randomized controlled trial dataset of tissue-type plasminogen activator 3 to 6 hours after stroke to: (1) quantify the relationship between severity of hypoperfusion (measured by Tmax) and risk of infarction; (2) exploit this relationship to present a novel definition of mismatch based on infarct probabilities rather than dichotomies; and (3) examine the treatment response in the subgroup of patients with mismatch by the new definition. Patients from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) were included. Baseline perfusion-weighted imaging and 90-day T2-weighted imaging were coregistered. Perfusion-weighted imaging lesion volumes were divided into 10 Tmax delay strata, and infarct risk was defined as the fraction of the tissue at a given Tmax strata that progressed to infarction by day 90. Sixty-two patients were studied. Infarct risk was an increasing function of Tmax for all subgroups, including the whole cohort. The probabilistic approach outperformed all Tmax thresholds, with exception of the Tmax ≥ 10 threshold, for which it was only favored by a trend. Infarct risk and treatment effect increased with severity of perfusion abnormalities. This suggests that a severity-weighted mismatch definition may define penumbral tissue more accurately.

RAPID Automated Patient Selection for Reperfusion Therapy

Background and Purpose— The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome. Methods— Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥8-point improvement on the National Institutes of Health Stroke Scale score at Day 90. Results— In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10±23 mL with reperfusion versus 40±44 mL without reperfusion; P &lt;0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85±74 mL with reperfusion versus 95±79 mL without reperfusion; P =0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10±15 mL with reperfusion versus 17±30 mL without reperfusion; P =0.9) in No Mismatch patients. Conclusions— MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

Pretreatment Diffusion-Weighted Imaging Lesion Volume Predicts Favorable Outcome After Intravenous Thrombolysis With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke

Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging-selected, acute stroke patients treated with IV-tPA. We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging-based IV-tPA treatment initiated ≤6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome. Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years; P=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15; P<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL; P=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (P=0.017), National Institutes of Health Stroke Scale score on admission (P<0.001), and diffusion-weighted imaging lesion volume (P=0.047) were identified as independent predictors of favorable outcome. A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.

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.

Impact of Baseline Tissue Status (Diffusion-Weighted Imaging Lesion) Versus Perfusion Status (Severity of Hypoperfusion) on Hemorrhagic Transformation

The frequency of hemorrhagic transformation (HT) on gradient echo imaging and its impact on stroke outcomes continues to be debated. We investigated the factors associated with HTs and the influence of the HTs observed on gradient echo imaging on the early course after a stroke. We analyzed the data from a prospectively maintained registry of patients who were eligible for recanalization therapy. Serial diffusion-weighted imaging and perfusion-weighted imaging were performed, and HTs were assessed on follow-up gradient echo imaging. Tmax perfusion lesion maps were generated and hypoperfused regions were divided into severe (Tmax >or=8 seconds) delay and mild (Tmax >or=2 seconds but Tmax <8 seconds) delay. The factors associated with HTs, including the mode of recanalization therapy, pretreatment diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, and reperfusion indices, were evaluated. The early clinical outcome was assessed during the first 7 days of admission. A total of 184 patients were included in this study. HTs were noted in 73 (39.7%) patients. Multiple logistic regression analysis identified aggressive treatment (OR, 5.12; 95% CI, 1.73 to 15.18) and a large area of severe perfusion delay (OR for highest quartile of Tmax >8 seconds, 12.91; 95% CI, 3.69 to 45.17) as independent predictors of HTs. Neither risk factor profiles nor diffusion-weighted imaging lesion volumes were associated with HTs. There was a poor correlation between the radiological (HT types) and clinical (asymptomatic or symptomatic) categories of HTs. Even a parenchymal hematoma was not always associated with symptomatic worsening or affected the early clinical outcomes. The results of this study indicate that the perfusion status (severe perfusion delay) rather than the tissue status (diffusion-weighted imaging lesions) and aggressive treatment were independently associated with HTs. HT on gradient echo imaging was common but usually associated with severe hypoperfusion and not always associated with clinical deterioration.

Assessing the outcome of stroke: a comparison between MRI and clinical stroke scales

To assess the correlation of diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) findings with the severity of acute neurologic deficit and their ability to predict short and long-term clinical outcomes of stroke. The ability of DWI and PWI to predict the outcome was compared with the ability of clinical stroke scales to predict the outcome. Forty-eight patients with acute stroke underwent diffusion DWI and PWI on the first and eighth day after the ictus. Clinical and functional scales were carried out before each scan and 3 months after the stroke. The volumes of both the DWI and the PWI lesions correlated well with the acute neurologic deficit and the final outcome. The first day PWI (r = 0.64) and the National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.70) correlated well with the final outcome. However, in logistic regression analysis, only the NIHSS score at the acute stage was the only independent predictor of the long-term clinical outcome. While the PWI and DWI lesion volumes correlated well with the outcome of the stroke, the imaging measurements did not improve the prognostic power over plain clinical stroke scale scores.

Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome ( p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion ( p=0.009), and in patients with larger pretreatment PWI ( p=0.001) and DWI ( p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion ( p=0.02) and a delayed time to peak (TTP) on pretreatment PWI ( p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume ( p=0.025). Recanalization was associated with a lower final infarct size ( p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.

Clinical and Radiological Correlates of Reduced Cerebral Blood Flow Measured Using Magnetic Resonance Imaging

Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models. To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke. Case series. Referral center. We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score. Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02). Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.