Hypoperfused Tissue Research Articles

Pial collaterals limit stroke progression and metabolic stress in hypoperfused tissue: An MRI perfusion and mq-BOLD study.

In acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), the relationship between cerebral oxygen extraction fraction (OEF) as the hallmark of the ischemic penumbra and leptomeningeal collateral supply is not well established. We aimed to investigate the relationship between pial collateralization and tissue oxygen extraction in patients with LVO using magnetic resonance imaging (MRI). Data from 14 patients with anterior circulation LVO who underwent MRI before acute stroke treatment were analyzed. In addition to diffusion-weighted imaging and perfusion-weighted imaging (PWI), the protocol comprised sequences for multiparametric quantitative blood-oxygen-level-dependent imaging for the calculation of relative OEF (rOEF). Pial collateral supply was quantitatively assessed by analyzing the signal variance in T2*-weighted PWI time series. Relationships between collateral supply, infarct volume, rOEF in peri-infarct hypoperfused tissue, and clinical stroke severity were assessed. The PWI-based parameter quantifying collateral supply was negatively correlated with baseline ischemic core volume and rOEF in the hypoperfused peri-infarct area (p<.01). Both reduced collateral supply and increased rOEF correlated significantly with higher scores on the National Institutes of Health Stroke Scale (p<.05). Increased rOEF within hypoperfused tissue was associated with higher baseline (p=.043) and follow-up infarct volume (p=.009). Signal variance-based mapping of collaterals with PWI depicts pial collateral supply, which is closely tied to tissue pathophysiology and clinical and imaging outcomes. Magnetic-resonance-derived mapping of cerebral rOEF reveals penumbral characteristics of hypoperfused tissue and might provide a promising imaging biomarker in AIS.

Abstract TMP85: Endovascular Thrombectomy for Large Ischemic Strokes With Tandem Lesions: A SELECT2 Subanalysis

Introduction: Trials evaluating thrombectomy (EVT) efficacy and safety in large vessel occlusion (LVO) excluded patients with cervical tandem lesions (TL). We aimed to evaluate EVT efficacy and safety in large stroke patients with TL from the SELECT2 trial. Methods: SELECT2 was a randomized controlled trial evaluating EVT vs. medical management (MM) in patients with LVO ischemic strokes (ASPECTS 3-5 on computed tomography (CT) or ischemic core ≥50 ml on CT Perfusion/MR diffusion-perfusion). TL were defined as internal carotid artery occlusion with a concomitant LVO as determined by the core lab. Functional, safety, and imaging outcomes were compared between patients in EVT vs. MM. Results: Of 352 enrolled, 100 (28%) had tandem occlusions, with 56 receiving EVT. ASPECTS (EVT: 4 [3-5] vs. MM: 4 [4-5]), ischemic core estimates (EVT: 86 [58-133] ml vs. MM: 81 [61-121] ml) and critically hypoperfused tissue volume (EVT: 185 [131-266] ml vs. MM: 192 [142-252] ml) were similar between groups. TL Patients receiving EVT demonstrated significantly better functional outcomes (mRS at 90d: EVT 4[3-6] vs MM 5[4-6]; aGenOR: 2.22; 95%CI, 1.47-3.34; p&lt;0.001), similar to those without TL (aGenOR: 1.59, 95% CI: 1.23-2.05, p&lt;0.001; P-int-0.29) and a higher proportion of patients achieving functional independence (EVT: 20% vs. MM: 2%; aRR: 9.53; 95%CI, 1.71-53.21; p=0.010) and independent ambulation (EVT: 38% vs MM: 11%; aRR: 3.60; 95%CI, 1.68-7.67; p=0.001), with significantly reduced complete dependence or death (mRS 5-6) (aRR: 0.66 (0.48-0.90), p=0.009). There was no difference in symptomatic ICH (EVT: 2% vs MM: 0%) or parenchymal hemorrhage (EVT: 2% vs MM: 0%). Complications occurred in 10 (18%) patients receiving EVT. In the EVT group, successful reperfusion (mTICI 2b-3) was associated with better functional outcome (aGenOR: 2.30; 95%CI, 1.14-4.65; p=0.021). Conclusion: In patients with tandem lesions, EVT and successful reperfusion were associated with better functional outcomes. Frequency of vascular complications was similar to those without tandem lesions and no patients receiving immediate stenting demonstrated parenchymal hemorrhage. Our findings support consideration of EVT in patients with tandem lesions with large ischemic strokes. NCT03876457

The role of neurophysiological tools in the evaluation of ischemic stroke evolution: a narrative review.

Ischemic stroke is characterized by a complex cascade of events starting from vessel occlusion. The term "penumbra" denotes the area of severely hypo-perfused brain tissue surrounding the ischemic core that can be potentially recovered if blood flow is reestablished. From the neurophysiological perspective, there are local alterations-reflecting the loss of function of the core and the penumbra-and widespread changes in neural networks functioning, since structural and functional connectivity is disrupted. These dynamic changes are closely related to blood flow in the affected area. However, the pathological process of stroke does not end after the acute phase, but it determines a long-term cascade of events, including changes of cortical excitability, that are quite precocious and might precede clinical evolution. Neurophysiological tools-such as Transcranial Magnetic Stimulation (TMS) or Electroencephalography (EEG)-have enough time resolution to efficiently reflect the pathological changes occurring after stroke. Even if they do not have a role in acute stroke management, EEG and TMS might be helpful for monitoring ischemia evolution-also in the sub-acute and chronic stages. The present review aims to describe the changes occurring in the infarcted area after stroke from the neurophysiological perspective, starting from the acute to the chronic phase.

Computed Tomography Perfusion Imaging in Acute Ischemic Stroke: Accurate Interpretation Matters.

Computed Tomography Perfusion Imaging in Acute Ischemic Stroke: Accurate Interpretation Matters.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines,cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale=0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6seconds) volumes (median [IQR]: 64 [26-96]ml vs MMpri : 40 [14-76]ml, p< 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p< 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR]= 1.29, 95% confidence interval [CI]= 0.82-2.03, p= 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p< 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p< 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR=1.68, 95% CI=1.01-2.81, p= 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR=0.39, 95% CI=0.12-1.34, p= 0.13) without target mismatch (pinteraction = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Abstract WP99: One-stop Stroke Mangement: Core And Hypoperfusion Maps From Multiphase Flat-panel Ct

Introduction: Acute ischemic stroke (AIS) patients transferred directly to the interventional suite can undergo flat-panel CT (FPCT) to bypass multidetector CT (MDCT) and eliminate delays to reperfusion therapy. However, the diagnostic adequacy of FPCT needs to be corroborated prior to eliminating MDCT from stroke care pathways. CT perfusion (CTP) maps played an important role in assessing infarcted vs. hypoperfused cerebral tissue in the 6-24 hour time window in the DAWN and DEFUSE-3 trials. We evaluated the diagnostic accuracy of FPCTP to identify infarcted vs. hypoperfused tissue using MDCTP as a reference. Materials and Methods: Between Oct. 19 and Nov. 21, 16 AIS patients at a tertiary urban hospital underwent FPCT and FPCTP. IRB approval and informed written consent was obtained. Ten patients underwent CTP in the ED. FPCTP was obtained using a Siemens Artis Q Biplane system. Data was post-processed on a separate prototype workstation, allowing visualization of ten 3D volumes in different phases of contrast enhancement (colored), and perfusion maps (CBF, CBV, MTT, TTP, T max , and TTD) (Figure 1). The CBF and T max , volumes have been further processed to generate color-coded hypoperfusion and core maps. Results: Eight FPCTP acquisitions were excluded due to technical problems, no available CTP, or severe motion artifacts. The infarcted and hypoperfused regions identified on FPCTP qualitatively agree with the regions identified on MDCTP. The time between CTP and FPCTP scans was a mean of 1h 2min (± 34min, 40- 2h30min). Three patients were under GA, the remaining 5 patients were scanned under moderate sedation. Three patients received IV-rtPA. Conclusion: FPCTP can be acquired to generate CBF, CBV, MTT, TTP, T max , and TTD maps in the interventional suite, potentially bypassing MDCTP and eliminating delays to reperfusion therapy. Quantitative results require advanced post-processing, particularly for artifact mitigation. The study is limited by the small sample size.

Abstract P325: Validation of Deep Learning Based Critical Hypoperfusion and Ischemic Core Prediction in a Multicenter External Randomized Controlled Trial

Objective: We previously developed two separate deep learning (DL) models to segment the ischemic core and critically hypoperfused tissue on baseline imaging of acute ischemic stroke patients. We aimed to validate the models in an external, multi-center randomized clinical trial (DEFUSE3) and compare with the current clinical standard. Methods: The DL models were previously trained in a separate dataset in which follow-up MRI, obtained at 3-7 days, was used as the reference for critically hypoperfused tissue in patients who did not reperfuse and as the reference for the ischemic core in patients who did reperfuse. For validation, we included DEFUSE3 patients with adequate quality baseline MR perfusion and a 24-hour follow-up DWI scan. The 24-hour DWI lesion served as the reference for ischemic core in patients in the thrombectomy arm and for critically hypoperfused tissue for patients in the medical arm. RAPID was used to generate perfusion maps (Tmax, cerebral blood flow, cerebral blood volume, and mean transient time). The accuracy of segmenting the ischemic core and critically hypoperfused tissue on baseline imaging was compared between the DL approach and the traditional thresholding approach implemented in RAPID. Results: In the 46 patients included for analysis, 24 were in the medical arm and 22 in the thrombectomy arm. Compared to a traditional thresholding method, the DL model segmented the ischemic core more accurately (AUC of 0.92 vs 0.72, p=0.0001 and volume difference of -8ml vs -21ml, p=0.001). Similarly, the DL model segmented critically hypoperfused tissue more accurately (AUC of 0.93 vs 0.80, p&lt;0.0001; volume difference 14ml vs. 55ml, p=0.0005). However, great heterogeneity in final infarct was noticed in medical arm. See tables and figures. Conclusions: The DL-based critical hypoperfusion and ischemic core prediction provides more accurate prediction on final infarct than a commonly used thresholding method in this external validation.

Objective evaluation of improved image quality with application of novel noise reduction filter in dynamic myocardial CT perfusion

Abstract Funding Acknowledgements Type of funding sources: None. Background Dynamic myocardial CT perfusion (CTP) is a non-invasive imaging technique able to depict cardiac ischemia. It is expected that the application of a new dynamic perfusion image noise reducing filter, the similarity filter (4DSF) would improve the image quality of CTP, resulting in clear visualization of perfusion deficits and hypo-perfused tissue and allowing for a substantial reduction in the radiation dose in dynamic myocardial CTP. Purpose To evaluate image quality before and after the application of a novel noise reducing filter on dynamic myocardial CT perfusion images reconstructed with deep learning-based algorithm. Methods The image datasets of patients with stable chest pain at intermediate risk of cardiovascular disease, who underwent stress dynamic CTP scanning as clinically indicated were retrospectively collected. The images were acquired with a 320-slice CT system, reconstructed using a deep learning-based algorithm (8 mm slice thickness) and filtered with the 4DSF. For each case, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) in six regions-of-interest (ROIs, 33-38 mm2) were computed, before and after filtering. The signal ROIs were located midventricular, in both four-chamber and short-axis views in the left ventricle blood pool, and the background ROIs in the cardiac septum and lateral wall. Differences in the SNR and CNR values were compared using paired t-tests. Results As a part of an ongoing study, twenty five cases were analysed to date. The following results (means for AiCE and AiCE + 4DSF, and corresponding p-values) were obtained in short axis view: septum SNR: 3.46 vs 6.25 (p = 0.007), lateral wall SNR: 3.66 vs 6.52 (p = 0.000), septum CNR: 13.35 vs 23.85 (p = 0.005), lateral wall CNR: 13.16 vs 23.57 (p = 0.010); and in four-chamber view: septum SNR: 3.67 vs 7.44 (p = 0.003), lateral wall SNR: 3.97 vs 7.65 (p = 0.001) and septum CNR: 13.92 vs 29.97 (p = 0.016), lateral wall CNR: 13.63 vs 29.75 (p = 0.018). All results are statistically significant. Conclusions We confirmed that the similarity filter decreases noise and therefore improves the objective image quality in both short axis and four chamber views. Therefore, the improved tissue texture depiction and improved visualization of perfusion defects may facilitate detection of ischemia and lead to reduction in radiation dose necessary for dynamic CTP, maintaining image quality. Abstract Figure. Region-of-interests (ROIs) location

Combining unsupervised and supervised learning for predicting the final stroke lesion.

Predicting the final ischaemic stroke lesion provides crucial information regarding the volume of salvageable hypoperfused tissue, which helps physicians in the difficult decision-making process of treatment planning and intervention. Treatment selection is influenced by clinical diagnosis, which requires delineating the stroke lesion, as well as characterising cerebral blood flow dynamics using neuroimaging acquisitions. Nonetheless, predicting the final stroke lesion is an intricate task, due to the variability in lesion size, shape, location and the underlying cerebral haemodynamic processes that occur after the ischaemic stroke takes place. Moreover, since elapsed time between stroke and treatment is related to the loss of brain tissue, assessing and predicting the final stroke lesion needs to be performed in a short period of time, which makes the task even more complex. Therefore, there is a need for automatic methods that predict the final stroke lesion and support physicians in the treatment decision process. We propose a fully automatic deep learning method based on unsupervised and supervised learning to predict the final stroke lesion after 90 days. Our aim is to predict the final stroke lesion location and extent, taking into account the underlying cerebral blood flow dynamics that can influence the prediction. To achieve this, we propose a two-branch Restricted Boltzmann Machine, which provides specialized data-driven features from different sets of standard parametric Magnetic Resonance Imaging maps. These data-driven feature maps are then combined with the parametric Magnetic Resonance Imaging maps, and fed to a Convolutional and Recurrent Neural Network architecture. We evaluated our proposal on the publicly available ISLES 2017 testing dataset, reaching a Dice score of 0.38, Hausdorff Distance of 29.21 mm, and Average Symmetric Surface Distance of 5.52 mm.

Computational methods for visualizing and measuring verapamil efficacy for cerebral vasospasm

Cerebral vasospasm is a dreaded sequelae of aneurysmal subarachnoid hemorrhage (aSAH), requiring timely intervention with therapeutic goals of improving brain perfusion. There are currently no standardized real-time, objective assessments of the interventional procedures performed to treat vasospasm. Here we describe real-time techniques to quantify cerebral perfusion during interventional cerebral angiography. We retrospectively analyzed 39 consecutive cases performed to treat clinical vasospasm and quantified the changes in perfusion metrics between pre- and post- verapamil administrations. With Digital Subtraction Angiography (DSA) perfusion analysis, we are able to identify hypoperfused territories and quantify the exact changes in cerebral perfusion for each individual case and vascular territory. We demonstrate that perfusion analysis for DSA can be performed in real time. This provides clinicians with a colorized map which directly visualizes hypoperfused tissue, combined with associated perfusion statistics. Quantitative thresholds and analysis based on DSA perfusion may assist with real-time dosage estimation and help predict response to treatment, however future prospective analysis is required for validation.

Automated MRI perfusion-diffusion mismatch estimation may be significantly different in individual patients when using different software packages

ObjectiveTo compare two established software applications in terms of apparent diffusion coefficient (ADC) lesion volumes, volume of critically hypoperfused brain tissue, and calculated volumes of perfusion-diffusion mismatch in brain MRI of patients with acute ischemic stroke.MethodsBrain MRI examinations of 81 patients with acute stroke due to large vessel occlusion of the anterior circulation were analyzed. The volume of hypoperfused brain tissue, ADC volume, and the volume of perfusion-diffusion mismatch were calculated automatically with two different software packages. The calculated parameters were compared quantitatively using formal statistics.ResultsSignificant difference was found for the volume of hypoperfused tissue (median 91.0 ml vs. 102.2 ml; p < 0.05) and the ADC volume (median 30.0 ml vs. 23.9 ml; p < 0.05) between different software packages. The volume of the perfusion-diffusion mismatch differed significantly (median 47.0 ml vs. 67.2 ml; p < 0.05). Evaluation of the results on a single-subject basis revealed a mean absolute difference of 20.5 ml for hypoperfused tissue, 10.8 ml for ADC volumes, and 27.6 ml for mismatch volumes, respectively. Application of the DEFUSE 3 threshold of 70 ml infarction core would have resulted in dissenting treatment decisions in 6/81 (7.4%) patients.ConclusionVolume segmentation in different software products may lead to significantly different results in the individual patient and may thus seriously influence the decision for or against mechanical thrombectomy.Key Points• Automated calculation of MRI perfusion-diffusion mismatch helps clinicians to apply inclusion and exclusion criteria derived from randomized trials.• Infarct volume segmentation plays a crucial role and lead to significantly different result for different computer programs.• Perfusion-diffusion mismatch estimation from different computer programs may influence the decision for or against mechanical thrombectomy.

Perfusion Imaging to Select Patients with Large Ischemic Core for Mechanical Thrombectomy.

Background and PurposePatients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.MethodsThis was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0–3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).ResultsA total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.ConclusionsIn patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.

In ischemic stroke with viable hypoperfused tissue, alteplase &gt; 4.5 h after last seen well improves function

Tsivgoulis G, Katsanos AH, Malhotra K, et al. Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window. Neurology. 2020;94:e1241-8. 31892636.

Twenty Years of Cerebral Ultrasound Perfusion Imaging-Is the Best yet to Come?

Over the past 20 years, ultrasonic cerebral perfusion imaging (UPI) has been introduced and validated applying different data acquisition and processing approaches. Clinical data were collected mainly in acute stroke patients. Some efforts were undertaken in order to compare different technical settings and validate results to gold standard perfusion imaging. This review illustrates the evolution of the method, explicating different technical aspects and milestones achieved over time. Up to date, advancements of ultrasound technology as well as data processing approaches enable semi-quantitative, gold standard proven identification of critically hypo-perfused tissue in acute stroke patients. The rapid distribution of CT perfusion over the past 10 years has limited the clinical need for UPI. However, the unexcelled advantage of mobile application raises reasonable expectations for future applications. Since the identification of intracerebral hematoma and large vessel occlusion can also be revealed by ultrasound exams, UPI is a supplementary multi-modal imaging technique with the potential of pre-hospital application. Some further applications are outlined to highlight the future potential of this underrated bedside method of microcirculatory perfusion assessment.

Retrograde blood flow in the internal jugular veins of humans with hypertension may have implications for cerebral arterial blood flow.

To use multi-parametric magnetic resonance imaging (MRI) to test the hypothesis that hypertensives would have higher retrograde venous blood flow (RVBF) in the internal jugular veins (IJV) vs. normotensives, and that this would inversely correlate with arterial inflow and gray matter, white matter, and cerebrospinal fluid volumes. Following local institutional review board approval and written consent, a prospective observational 3-T MRI study of 42 hypertensive patients (53 ± 2years, BMI 28.2 ± 0.6kg/m2, ambulatory daytime systolic BP 148 ± 2mmHg, ambulatory daytime diastolic BP 101 ± 2mmHg) and 35 normotensive patients (48 ± 2years, BMI 25.2 ± 0.8kg/m2, ambulatory daytime systolic BP 119 ± 3mmHg, ambulatory daytime diastolic BP 90 ± 2mmHg) was performed. Phase contrast imaging calculated percentage retrograde venous blood flow (%RVBF), brain segmentation estimated regional brain volumes from 3D T1-weighted images, and pseudo-continuous arterial spin labeling measured regional cerebral blood perfusion. Statistical analysis included two-sample equal variance Student's T tests, two-way analysis of variance with Tukey's post hoc correction, and permutation-based two-group general linear modeling (p < 0.05). In the left IJV, %RVBF was higher in hypertensives (6.1 ± 1.5%) vs. normotensives (1.1 ± 0.3%, p = 0.003). In hypertensives, there was an inverse relationship of %RVBF (permutation-based general linear modeling) to cerebral blood flow in several brain regions, including the left occipital pole and the cerebellar vermis (p < 0.01). Percentage retrograde flow in the left IJV correlated inversely with the total matter volume (gray plus white matter volume) in hypertensives (r = - 0.49, p = 0.004). RVBF in the left IJV is greater in hypertensives vs. normotensives and is linked to regional hypoperfusion and brain total matter volume. • Hypertensive humans have higher retrograde cerebral venous blood flow, associated with regional brain hypoperfusion and lower tissue volume, compared with controls. • Cerebral retrograde venous blood flow may add further stress to already hypoperfused tissue in hypertensive patients. • The amount of retrograde venous blood flow in hypertensive patients may predict which patients might be at higher risk of developing cerebral pathologies.

Abstract WP61: Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3

Background and Purpose: Accurate prediction of 24-hour infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial, we evaluated the accuracy of early ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy vs. medical management. We also assessed if the volume of persistent hypoperfusion at 24 hours predicts infarct volume. Methods: Patients in DEFUSE 3 with CT or MRI DWI/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax&gt;6s hypoperfusion volumes at baseline and 24 hours were calculated using RAPID software and compared with the 24-hour infarct volumes. Patients were stratified by reperfusion status for analyses. Results: Of 125 eligible patients, 59 patients with &gt;90% reperfusion had a strong correlation between baseline ischemic core volumes and 24-hour infarct volume (r = 0.83; p &lt; 0.0001), and 14 patients with &lt;10% reperfusion had a strong correlation between baseline Tmax&gt;6s volume and 24-hour infarct volume (r = 0.77; p &lt; 0.001). In the 52 patients with 10-90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the Tmax&gt;6s perfusion volume at 24 hours was highly correlated with 24-hour infarct volume (for N=125, r = 0.83; p &lt; 0.0001), with a median absolute difference of 21.3 ml between observed and predicted infarct volumes. Conclusions: The union of the irreversibly injured ischemic core and critically hypoperfused tissue volumes, as identified by CT perfusion or MR DWI/perfusion, predicted infarct volume at 24 hours in DEFUSE 3 patients. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415

Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome. In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered. We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low. Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Medtronic.

Complete Restitution of the Ischemic Penumbra after Successful Thrombectomy : APilot Study Using Quantitative MRI.

Endovascular thrombectomy is highly effective in patients with proximal large artery occlusion but the relevance of reperfusion injury after recanalization is amatter of debate. The aim of this study was to investigate potential residual metabolic distress and microstructural tissue damage or edema after reperfusion using quantitative oxygen-sensitive T2' and T2-mapping in patients successfully treated by thrombectomy. Included in this study were 11patients (mean age 70 ± 11.4 years) with acute ischemic stroke due to internal carotid artery and/or middle cerebral artery occlusion. Quantitative T2 and T2' (1/T2' = 1/T2* - 1/T2) were determined within the ischemic core and hypoperfused but salvaged tissue with delayed time-to-peak (TTP) in patients before and after successful thrombectomy and compared to acontrol region within the unaffected hemisphere. Decreased T2' values within hypoperfused tissue before thrombectomy showed anormalization after recanalization (p < 0.01). In formerly hypoperfused but salvaged tissue, T2 values increased significantly after thrombectomy (p < 0.05) but did not differ from reference values in the control region. In salvaged tissue, increases of quantitative T2' and T2 to follow-up were more pronounced in areas with severe TTP delay. After successful recanalization, T2' re-increased back to normal in formerly hypoperfused areas as asign of prompt normalization of oxygen metabolism. Furthermore, quantitative T2 in the formerly hypoperfused tissue did not differ from reference values in unaffected tissue. These results indicate complete restitution of salvaged tissue after reperfusion and support the overall safety of endovascular thrombectomy with respect to microstructural tissue integrity.

Abstract TP62: Computed Tomography Perfusion Infarct Measurement Compared to Diffusion-Weighted Magnetic Resonance Imaging in Patients Without Revascularization of Anterior Circulation, Large Artery Occlusions

Introduction: The CT Perfusion (CTP) parameter Time-Maximum greater than 6 seconds (Tm &gt; 6s) represents delayed blood flow in critically hypoperfused brain tissue. Though Tm &gt; 6s is expected to accurately represent infarct size in stroke patients who do not undergo revascularization, some brain tissue at risk may not progress to infarction and recover spontaneously (“benign oligemia”). We sought to investigate the relationship between Tm &gt; 6s and the gold standard of final infarct volume on DWI MRI in patients with anterior circulation, large artery occlusion (LAO) acute ischemic stroke (AIS) who do not achieve reperfusion. Hypothesis: Critically hypoperfused brain tissue, as represented by CTP Tm &gt; 6s, overestimates final infarct volume on DWI MRI in at least 50% of patients with ICA or proximal MCA occlusions without angiographic revascularization. Methods: From a large healthcare system’s stroke network database, we conducted a retrospective analysis comparing delayed perfusion volume (Tm &gt; 6s; RAPID iSchemaView) on CTP and DWI MRI volume (ADC &lt; 620cc; RAPID iSchemaView) in patients with ICA, M1, or M2 occlusions between November 2016 and June 2017 not treated with acute reperfusion therapy, or without angiographic revascularization (TICI 0). Results: Over an 8-month period, 19 cases were identified with baseline CTP, follow-up MRI, and no reperfusion of an ICA, M1, or M2 occlusion. Mean age was 65.8 years old and median NIHSS was 8. Mean duration from last known well time to CTP and MRI was 4.4 and 22.8 hours, respectively. Three patients were treated with IV TPA and endovascular therapy, 4 received only endovascular therapy, and 12 did not receive IV TPA nor endovascular intervention. The Tm &gt;6s volume was greater than follow-up DWI MRI volume in 13/19 (68%) cases by an average of 37.4cc. Conclusions: Critically hypoperfused brain tissue on CTP, represented by Tm &gt; 6s, may spontaneously recover in patients with proximal, LAO AIS. Establishing CTP parameters that delineate ischemic penumbra from benign oligemia will aid in identifying the volume of ischemic tissue truly at risk for infarction in LAO patients.