Late lesion growth following endovascular therapy: is 24 hours too early to assess acute infarct size including the effects of secondary injury?

Introduction Stroke lesion volume on MRI or CT provides objective evidence of tissue injury as a consequence of ischemic stroke. Measurement of "final" lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome. The goals of this study were to quantify lesion growth during the first week after treatment, identify early predictors, and explore the association with clinical outcome. Methods This is a prospective study of stroke patients at two centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, and iii) had 3T MRI post-EVT at 24hr and 5-day. We defined "Early" and "Late" lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively. Complete reperfusion was defined as >90% reduction of the volume of tissue with perfusion delay (Tmax>6sec) between pre-EVT and 24hr post-EVT. Favorable clinical outcome was defined as modified Rankin scale (mRS) of 0-2 at 30 or 90 days. Results One hundred twelve patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 66% with M1 occlusion, and median baseline DWI volume 21.2mL. Successful recanalization was achieved in 87% and 68% had complete reperfusion, with an overall favorable clinical outcome rate of 53%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.3mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (64%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (87%: 46% mTICI 2b/ 41% mTICI 3). Late lesion growth patients had a 27.4mL change in Late lesion volume and 30.1mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome. Conclusion Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Most patients with no Early lesion growth had no Late lesion growth. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally, it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.

Good outcome associated with blood-brain barrier disruption and lower blood pressure after endovascular therapy.

OBJECTIVES: To evaluate the association between post-endovascular thrombectomy (EVT) blood-brain barrier (BBB) disruption on MRI or CT and average systolic blood pressure (SBP) with favorable 90-day functional outcome. Observational studies have found elevated SBP associated with worse outcomes post-EVT, while recent randomized trials found no difference in targeted BP reduction. There may be a subgroup of patients who benefit from targeted BP reduction post-EVT. METHODS: This is a single-center study of 1) anterior large vessel occlusion stroke patients treated with EVT from 2015 to 2021, 2) achieved mTICI grade 2b or 3. Hyperintense acute reperfusion marker (HARM), hemorrhagic transformation (HT), and midline shift at 3 h post-EVT and 24 h imaging were assessed independently by multiple raters. Binary logistic regression models were used to determine the association of post-EVT SBP with outcomes. BBB disruption was defined as HT or HARM on 3h post-EVT imaging. RESULTS: Of 103 patients, those with SBP 100-129 versus SBP 130-160 found no significant difference in favorable 90-day outcome (64% vs. 46%, OR 2.11, 95% CI 0.78-5.76, p=0.143). However, among 71 patients with BBB disruption, a significant difference in favorable outcome of 64% in SBP 100-129 vs. 39% in SBP 130-160 group (OR 5.93, 95% CI 1.50-23.45, p=0.011) was found. There was no difference in symptomatic ICH, 90-day mortality, midline shift (≥5 mm), and hemicraniectomy, between BP or BBB groups. CONCLUSIONS: BBB disruption on 3h post-EVT imaging and lower SBP was associated with favorable outcome. This imaging finding may guide targeted BP therapy and suggests need for a randomized control trial.

Estimating Perfusion Deficits in Acute Stroke Patients Without Perfusion Imaging.

BACKGROUND: Perfusion weighted imaging (PWI) is critical for determining whether stroke patients presenting in an extended time window are candidates for mechanical thrombectomy. However, PWI is not always available. Fluid-attenuated inversion recovery hyperintense vessels (FHVs) are seen in patients with a PWI lesion. We investigated whether a scale measuring the extent FHV could serve as a surrogate for PWI to determine eligibility for thrombectomy. METHODS: The National Institutes of Health (NIH) FHV score was developed to quantify the burden of FHV and applied to magnetic resonance imaging scans of stroke patients with fluid-attenuated inversion recovery and perfusion imaging. The NIH-FHV was combined with the diffusion weighted image volume to estimate the diffusion-perfusion mismatch ratio. Linear regression was used to compare PWI volumes and mismatch ratios with estimates from the NIH-FHV score. Receiver operating characteristic analysis was used to test the ability of the NIH-FHV score to identify a significant mismatch. RESULTS: There were 101 patients included in the analysis, of whom 78% had a perfusion deficit detected on PWI with a mean lesion volume of 47 (±59) mL. The NIH-FHV score was strongly associated with the PWI lesion volume (P<0.001; R2=0.32; ß-coefficient, 0.57). When combined with diffusion weighted image lesion volume, receiver operating characteristic analysis testing the ability to detect a mismatch ratio ≥1.8 using the NIH-FHV score resulted in an area under the curve of 0.94. CONCLUSIONS: The NIH-FHV score provides an estimate of the PWI lesion volume and, when combined with diffusion weighted imaging, may be helpful when trying to determine whether there is a clinically relevant diffusion-perfusion mismatch in situations where perfusion imaging is not available. Further studies are needed to validate this approach.

Association of Multiple Passes during Mechanical Thrombectomy with Incomplete Reperfusion and Lesion Growth.

INTRODUCTION: Despite complete recanalization by mechanical thrombectomy, abnormal perfusion can be detected on MRI obtained post-endovascular therapy (EVT). The presence of residual perfusion abnormalities post-EVT may be associated with blood-brain barrier breakdown in response to mechanical disruption of the endothelium from multiple-pass thrombectomy. We hypothesize that multiple-pass versus single-pass thrombectomy is associated with a higher rate of residual hypoperfusion and increased lesion growth at 24 h. MATERIALS AND METHODS: For this analysis, we included patients presenting to one of two stroke centers between January 2015 and February 2018 with an acute ischemic stroke within 12 h from symptom onset if they had a large vessel occlusion of the anterior circulation documented on magnetic resonance angiography or CTA, baseline MRI pre-EVT with imaging evidence of hypoperfusion, underwent EVT, and had a post-EVT MRI with qualitatively interpretable perfusion-weighted imaging data at 24 h. MRI Tmax maps using a time delay threshold of >6 s were used to quantitate hypoperfusion volumes. Residual hypoperfusion at 24 h was solely defined as Tmax volume >10 mL with >6 s delay. Complete recanalization was defined as modified treatment in cerebral infarction visualized on angiography at EVT completion. Hyperintense acute reperfusion injury marker was assessed on post-EVT pre-contrast fluid-attenuated inversion recovery at 24 h. Major early neurological improvement was defined as a reduction of the admission National Institutes of Health Stroke Scale by ≥8 points or a score of 0-1 at 24 h. Good functional outcome was defined as 0-2 on the modified Rankin Scale on day 30 or 90. RESULTS: Fifty-five patients were included with median age 67 years, 58% female, 45% Black/African American, 36% White/Caucasian, median admission National Institutes of Health Stroke Scale 19, large vessel occlusion locations: 71% M1, 14.5% iICA, 14.5% M2, 69% treated with intravenous recombinant tissue plasminogen activator. Of these, 58% had multiple-pass thrombectomy, 39% had residual perfusion abnormalities at 24 h, and 64% had severe hyperintense acute reperfusion injury marker at 24 h. After adjusting for complete recanalization, only multiple-pass thrombectomy (odds ratio, 4.3 95% CI, 1.07-17.2; p = 0.04) was an independent predictor of residual hypoperfusion at 24 h. Patients with residual hypoperfusion had larger lesion growth on diffusion-weighted imaging (59 mL vs. 8 mL, p < 0.001), lower rate of major early neurological improvement (24% vs. 70%, p = 0.002) at 24 h, and worse long-term outcome based on the modified Rankin Scale at 30 or 90 days, 5 versus 2 (p < 0.001). CONCLUSIONS: Our findings suggest that incomplete reperfusion on post-EVT MRI is present even in some patients with successful recanalization at the time of EVT and is associated with multiple-pass thrombectomy, lesion growth, and worse outcome. Future studies are needed to investigate whether patients with residual hypoperfusion may benefit from immediate adjunctive therapy to limit lesion growth and improve clinical outcome.

Fluid-Attenuated Inversion Recovery Hyperintense Ischemic Stroke Predicts Less Favorable 90-Day Outcome after Intravenous Thrombolysis.

INTRODUCTION: The absence of an ischemic lesion on MRI fluid-attenuated inversion recovery (FLAIR) is helpful in predicting stroke onset within 4.5 h. However, some ischemic strokes become visible on FLAIR within 4.5 h. We hypothesized that the early lesion visibility on FLAIR may predict stroke outcome 90 days after intravenous (IV) thrombolysis, independent of time. MATERIALS AND METHODS: We analyzed data from acute ischemic stroke patients presenting over the last 10 years who were screened with MRI and treated with IV thrombolysis within 4.5 h from onset. Three independent readers assessed whether ischemic lesions seen on diffusion-weighted imaging were also FLAIR positive based on visual inspection. Multivariable regression analyses were used to obtain an adjusted odds ratio of favorable clinical and radiological outcomes based on FLAIR positivity. RESULTS: Of 297 ischemic stroke patients, 25% had lesion visibility on initial FLAIR. The interrater agreement for the FLAIR positivity assessment was 84% (κ = 0.604, 95% CI: 0.557-0.652). Patients with FLAIR-positive lesions had more right hemispheric strokes (57 vs. 41%, p = 0.045), were imaged later (129 vs. 104 min, p = 0.036), and had less frequent favorable 90-day functional outcome (49 vs. 63%, p = 0.028), less frequent early neurologic improvement (30 vs. 58%, p = 0.001), and more frequent contrast extravasation to the cerebrospinal fluid space (44 vs. 26%, p = 0.008). CONCLUSIONS: Early development of stroke lesion on FLAIR within 4.5 h of onset is associated with reduced likelihood of favorable 90-day outcome after IV thrombolysis.

Blood-brain barrier integrity of stroke patients presenting in an extended time window.

BACKGROUND: Current guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications. Risk of hemorrhage increases with increasing blood-brain barrier (BBB) disruption. This study aimed to determine, in a cohort of patients presenting outside of an IV-tPA treatment window, whether disruption of the BBB is time dependent, and what proportion of patients could be safely treated. METHODS: We analyzed untreated stroke patients, seen between 2011 and 2015, who had MRI studies in the time window of 4 to 24 h from symptoms onset. Permeability of the BBB was measured within the ischemic tissue using an application of dynamic susceptibility contrast imaging. Patients were dichotomized into two groups based on a 20% threshold of BBB disruption and compared using logistic regression. RESULTS: Of the 222 patients included in the final analysis, over half, 129 (58%), had preserved BBB integrity below the 20% threshold. There was no relationship between time imaged after symptom onset and the amount of BBB disruption (p = 0.138) across the population; BBB disruption varied widely. CONCLUSIONS: Estimating BBB integrity may help to expand the treatment window for stroke patients by identifying those individuals for whom thrombolytic therapy can be considered.

Routine use of FLAIR-negative MRI in the treatment of unknown onset stroke.

BACKGROUND: Treatment of FLAIR-negative stroke in patients presenting in an unknown time window has been shown to be safe and effective. However, implementation can be challenging due to the need for hyper-acute MRI screening. The purpose of this study was to review the routine application of this practice outside of a clinical trial. METHODS: Patients presenting from 3/1/16 to 8/22/18 in a time window <4.5 h from symptom discovery but >4.5 h from last known normal were included if they had a hyper-acute MRI performed. Quantitative assessment based on the MR WITNESS trial and qualitative assessment based on the WAKE-UP trial were used to grade the FLAIR images. The MR WITNESS trial used a quantitative assessment of FLAIR change where the fractional increase in signal change had to be <1.15, whereas the WAKE-UP trial used a visual assessment requiring the absence of marked FLAIR signal changes. RESULTS: During the study period, 136 stroke patients presented and were imaged in the specified time window. Of these, 17 (12.5%) received IV tPA. Three patients had hemorrhage on 24-h MRI follow up; none had an increase in NIHSS ≥4. Of the 119 patients who were screened but not treated, 18 (15%) were eligible based on FLAIR quantitative assessment and 55 (46%) were eligible based on qualitative assessment. In all cases where patients were not treated, there was an identifiable exclusion based on trial criteria. During the study period, IV tPA utilization was increased by 5.6% due to screening and treating patients with unknown onset stroke. CONCLUSIONS: Screening stroke patients in an unknown time window with MRI is practical in a real-world setting and increases IV tPA utilization.

Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients.

Background and Purpose- The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization. Methods- Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0-2 using the latest available modified Rankin Scale score. Results- Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%; P=0.001), any hemorrhagic transformation (60% versus 36%; P=0.04) and poor clinical outcome (67% versus 36%; P=0.008). Only age (odds ratio, 1.1; 95% CI, 1.01-1.12; P=0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93-26.92; P=0.003). Conclusions- In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Rapid Apparent Diffusion Coefficient Evolution After Early Revascularization.

Background and Purpose- In this era of endovascular therapy (EVT) with early, complete recanalization and reperfusion, we have observed an even more rapid apparent diffusion coefficient (ADC) normalization within the acute ischemic lesion compared with the natural history or IV-tPA-treated patient. In this study, we aimed to evaluate the effect of revascularization on ADC evolution within the core lesion in the first 24 hours in acute ischemic stroke patients. Methods- This retrospective study included anterior circulation acute ischemic stroke patients treated with EVT with or without intravenous tPA (IVT) from 2015 to 2017 compared with a consecutive cohort of IVT-only patients treated before 2015. Diffusion-weighted imaging and ADC maps were used to quantify baseline core lesions. Median ADC value change and core reversal were determined at 24 hours. Diffusion-weighted imaging lesion growth was measured at 24 hours and 5 days. Good clinical outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Results- Twenty-five patients (50%) received IVT while the other 25 patients received EVT (50%) with or without IVT. Between these patient groups, there were no differences in age, sex, baseline National Institutes of Health Stroke Scale, interhospital transfer, or IVT rates. Thirty-two patients (64%) revascularized with 69% receiving EVT. There was a significant increase in median ADC value of the core lesion at 24 hours in patients who revascularized compared with further ADC reduction in nonrevascularization patients. Revascularization patients had a significantly higher rate of good clinical outcome at 90 days, 63% versus 9% (P=0.003). Core reversal at 24 hours was significantly higher in revascularization patients, 69% versus 22% (P=0.002). Conclusions- ADC evolution in acute ischemic stroke patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding. The early ADC normalization we have observed in this setting may include a component of secondary injury and serve as a potential imaging biomarker for the development of future adjunctive therapies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Identifying perfusion deficits on CT perfusion images using temporal similarity perfusion (TSP) mapping.

OBJECTIVES: Deconvolution-derived maps of CT perfusion (CTP) data may be confounded by transit delays. We propose temporal similarity perfusion (TSP) analysis to decrease CTP maps' dependence on transit times and investigate its sensitivity to detect perfusion deficits. METHODS: CTP data of acute stroke patients obtained within 9 h of symptom onset was analyzed using a delay-insensitive singular value decomposition method and with TSP. The TSP method applies an iterative process whereby a pixel's highest Pearson's R value is obtained through comparison of a pixel's time-shifted signal density time-series curve and the average whole brain signal density time-series curve. Our evaluation included a qualitative and quantitative rating of deconvolution maps (MTT, CBV, and TTP), of TSP maps, and of follow-up CT. RESULTS: Sixty-five patients (mean 68 (SD 13) years, 34 male) were included. A perfusion deficit was identified in 90%, 86%, 65%, and 84% of MTT, TTP, CBV, and TSP maps. The agreement of MTT, TTP, and TSP with CT follow-up was comparable but noticeably lower for CBV. CBV had the best relationship with final infarct volume (R2 = 0.77, p < 0.001), followed by TSP (R2 = 0.63, p < 0.001). Intra-rater agreement of an inexperienced reader was higher for TSP than for CBV/MTT maps (kappa's of 0.79-0.84 and 0.63-0.7). Inter-rater agreement for experienced readers was comparable across maps. CONCLUSIONS: TSP maps are easier to interpret for inexperienced readers. Perfusion deficits detected by TSP are smaller which may suggest less dependence on transit delays although more investigation is required. KEY POINTS: • Temporal similarity perfusion mapping assesses CTP data based on similarities in signal time-curves. • TSP maps are comparable in perfusion deficit detection to deconvolution maps. • TSP maps are easier to interpret for inexperienced readers.

Perfusion Deficits and Association with Clinical Outcome in Patients with Anterior Choroidal Artery Stroke.

BACKGROUND AND PURPOSE: Anterior choroidal artery (AChA) strokes have a varied pattern of tissue injury, prognosis, and clinical outcome. It is unclear whether perfusion deficit in AChA stroke is associated with the clinical outcome. This study aims to determine the frequency of perfusion abnormalities in AChA stroke and association with clinical outcome. METHODS: The study cohort was derived from ischemic stroke patients admitted to 2 stroke centers between July 2001 and July 2014. All patients received an acute magnetic resonance imaging (MRI) scan. Patients with ischemic stroke restricted to the AChA territory were included in the study. Lesion size was measured as the largest diameter on diffusion-weighted imaging (DWI) or apparent diffusion coefficient and divided into 2 groups (<20 mm or ≥20 mm). Group comparisons were performed among patients with and without perfusion abnormalities and based on diffusion diameter. Favorable clinical outcome was defined as discharge to home. RESULTS: A total of 120 patients were included in the study. Perfusion deficits were identified in 67% of patients. The admission National Institutes of Health Stroke Scale (NIHSS) was higher in patients with perfusion abnormalities (P = .027). Diameter lesion size on DWI was larger among patients with a perfusion deficit median [interquartile range], 1.63 [1.3-2.0], as compared with those without, 1.18 [1.0-1.7], P < .0001. Patients with a perfusion deficit were less likely to be discharged to home than those without (36% versus 60%, P = .013). CONCLUSIONS: Two thirds of patients with an AChA stroke have a perfusion deficit on MRI, higher admission NIHSS, and larger DWI lesion size at presentation.

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

BACKGROUND AND PURPOSE: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. METHODS: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. RESULTS: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. CONCLUSIONS: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

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

BACKGROUND: 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. METHODS: 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 (%). RESULTS: 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). CONCLUSIONS: 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.

Immediate changes in stroke lesion volumes post thrombolysis predict clinical outcome.

BACKGROUND AND PURPOSE: We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome. METHODS: Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1. RESULTS: Seventy-one patients met the study criteria with mean (±SD) age of 71.6 (±16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4-18), median onset to triage 45 minutes (30-65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39-59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165; P=0.014; 95% confidence interval [CI], 1.031-1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221; P=0.012; 95% confidence interval, 1.045-1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021; P=0.031; 95% confidence interval, 1.002-1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173; P=0.027; 95% confidence interval, 1.018-1.351) were significant predictors of favorable clinical outcome. CONCLUSIONS: Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.

Assessing reperfusion with whole-brain arterial spin labeling: a noninvasive alternative to gadolinium.

BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a perfusion imaging technique that does not require gadolinium. The study aimed to assess the reliability of ASL for evaluating reperfusion in acute ischemic stroke in comparison with dynamic susceptibility contrast (DSC) imaging. METHODS: The study included 24 patients with acute ischemic stroke on admission and 24-hour follow-up ASL and DSC scans. Two readers rated images for interpretability and evidence of reperfusion. Cohen unweighted κ was used to assess (1) inter-rater reliability between readers for determining interpretability and the presence of reperfusion, (2) agreement between ASL and DSC for determining reperfusion for individual raters, and (3) agreement between ASL and DSC for determining reperfusion after consensus. RESULTS: Inter-rater reliability for both ASL and DSC was moderate to good (κ of 0.67 versus 0.55, respectively). Reader 1 rated 16 patients as having interpretable ASL and DSC when compared with 15 patients for reader 2. The κ between ASL and DSC for determining reperfusion was 0.50 for reader 1 and 0.595 for reader 2. After consensus, 18 ASL and 17 DSC image sets were rated interpretable for reperfusion and 13 had both interpretable ASL and DSC scans, yielding a κ for assessment of reperfusion of 0.8. CONCLUSIONS: Inter-rater reliability of ASL and DSC was moderate to good. Agreement between ASL and DSC for determining reperfusion was moderate for each individual rater and increased substantially after consensus. ASL is a noninvasive and practical alternative to DSC for reperfusion assessments in patients with confirmed acute ischemic stroke.

Validity of acute stroke lesion volume estimation by diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomographic Score depends on lesion location in 496 patients with middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL. METHODS: We analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume. RESULTS: A total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (r=-0.78; P<0.0001). With regards to lesion localization, correlation was weaker in deep MCA region (r=-0.19; P=0.038) when compared with superficial (r=-0.72; P<0.001) or combined superficial and deep MCA lesions (r=-0.72; P<0.001). Receiver-operating characteristics analysis revealed ASPECTS≤6 as best cutoff to identify ≥100-mL DWI lesion volume; however, positive predictive value was low (0.35). CONCLUSIONS: ASPECTS has limitations when lesion location is not considered. Identification of patients with malignant profile by DWI-ASPECTS may be unreliable. ASPECTS may be a useful tool for the evaluation of noncontrast computed tomography. However, if MRI is used, ASPECTS seems dispensable because lesion volume can easily be quantified on DWI maps.

Edema progression in proximity to traumatic microbleeds: evolution of cytotoxic and vasogenic edema on serial MRI.

Introduction: Although cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. Methods: This study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 hours, ~1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. Results: Our results indicated the presence of ADC+ lesions ≤48 hours and ~1 week were associated with FLAIR+ lesions at ~1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR+ lesions at 30 days (67%) were ADC+ ≤48 hours. However, ADC+ lesions ≤48 hours were not associated with FLAIR+ lesions at 30 days; 10 out of 25 (40%) ADC+ lesions ≤48 hours were FLAIR+ at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC+ to FLAIR+. FLAIR SIRs at ~1 week were significantly higher when lesions were ADC+ ≤48 hours (1.22 [1.08-1.32] vs 1.03 [0.97-1.11], p=0.002). Conclusion: Awareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.

We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8 ml and 45.2 ml (WMHs/no WMHs), p = 0.139, and 24.6 ml and 25.9 ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (ß = - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (ß = - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.