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Background: In acute ischemic stroke (AIS) with large vessel occlusion (LVO), core/perfusion mismatch modifies the effect of mechanical thrombectomy (MT) on clinical outcome, MT appears to have greater benefit in patients with significant mismatch. We aimed to study the prevalence of core/perfusion mismatch according to ASPECT score in a large population of LVO-related AIS imaged either with MRI or CT. Methods: Retrospective study including AIS patients with ICA/M1 occlusion and baseline perfusion imaging (MRI or CT) performed within 24hrs from last seen well. To avoid selection bias, patients were selected from (1) the registries of 3 comprehensive centers with systematic use of MRI- or CT-perfusion imaging and including both MT-treated and untreated patients, and (2) one thrombectomy trial where MT decisions were performed blinded to the results of MRI perfusion imaging. Core/perfusion mismatch was defined as mismatch ratio (Tmax>6s volume/ core volume) >1.8 and volume (Tmax>6s - core volume) >15 mL. ASPECT score was rated on diffusion weighted imaging (DWI) or non-contrast CT blinded from the perfusion imaging. Results: Overall, 580 and 350 patients were included in the MRI and CT cohorts. Last-seen-well to imaging time was 4.8hrs (IQR 3.0-8.7) and 3.2hrs (1.3-8.0) in the MRI and CT cohorts, respectively, median ASPECT score was 7 (5-8) and 8 (7-9), and core/perfusion mismatch was present in 393/580 (68%) and 315/350 (90%) patients. In both cohorts, 75% of patients were treated with MT following imaging. In the MRI cohort, mismatch prevalence was 44% (75/170) and 92% (378/410) for DWI-ASPECTS 0-5 and 6-10, respectively. In the CT cohort, mismatch prevalence was 47% (15/32) and 94% (300/318) for ASPECTS 0-5 and 6-10, respectively. Conclusion: About 90% of patients with ASPECTS 6-10 have a core/perfusion mismatch regardless of imaging type. However, patients with ASPECTS ≤5 are heterogeneous in terms of mismatch status. Therefore, perfusion imaging may be particularly useful to select appropriate MT candidates with low ASPECT scores, regardless of imaging type, which has implications for large core trials.

Background: One potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there is a paucity of data regarding the occurrence of pre-interventional reperfusion in patients randomized to IVT or no-IVT before MT. Methods: SWIFT DIRECT was a randomized controlled trial including acute ischemic stroke IVT-eligible patients being directly admitted to a comprehensive stroke center, with allocation to either MT alone or IVT + MT. Primary endpoint of this analysis was the occurrence of pre-interventional reperfusion defined as pre-interventional expanded Thrombolysis in Cerebral Infarction score ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results: Out of the 396 patients analyzed, pre-interventional reperfusion occurred in 20 (10.0%) of patients randomized to IVT+MT, and 7 (3.6%) of patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (aOR 2.91 [95% CI 1.23 - 6.87]). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture (p for interaction=0.33), although the effect tended to be stronger in patients with Randomization-to-Groin-Puncture >28 minutes (aOR 4.65 [95% CI 1.16 - 18.68]). There were no significant difference in rates of functional outcomes between patients with and without pre-interventional reperfusion. Conclusion: Even for patients with proximal large vessel occlusions and direct access to MT, IVT leads towards an absolute increase of 6.9% (95% CI 1.7-12.2%) in the rates of pre-interventional reperfusion. The effect of IVT tended to be more pronounced when Randomization-to-Groin-Puncture intervals were longer, but this heterogeneity did not reach statistical significance.

Background: Predicting infarct growth rate (IGR) in acute stroke with large vessel occlusion (LVO) is important for treatment decision-making. IGR has typically been studied in patients treated with thrombectomy, which likely has underestimated the prevalence of ‘fast progressors’, as large core patients are less frequently treated. We aimed to study IGR in an unselected LVO population and study the association between Hypoperfusion Intensity Ratio (HIR, a surrogate marker of collaterals) and IGR as assessed by both CT and MRI. Methods: Retrospective study including ICA/M1 stroke patients with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24hrs from symptoms onset. To avoid selection bias, patients were selected from (1) the registries of 3 centers with systematic use of MRI- or CT-perfusion and including both MT-treated and untreated patients, and (2) one trial where thrombectomy decisions were performed blinded from perfusion MRI results. IGR was defined as core volume/onset-to-imaging time, and fast progressors as IGR≥10mL/hr. HIR was defined as the proportion of Tmax>6s volume with Tmax>10s. Results: Overall, 423 and 215 patients were included in the MRI and CT cohorts. Median IGR was 6.4mL/hr (IQR 2.2-21.3) and 5.2mL/hr (0-25.2) in the MRI and CT cohorts, and median HIR was 0.44 (0.27-0.59) and 0.45 (0.25-0.60). 174 (41%) MRI patients and 86 (40%) CT patients were fast progressors. IGR was increasing with increase of HIR quartiles in both cohorts ( P P P Conclusion: In this unselected LVO population, 40% of patients were fast progressors regardless of imaging modality. HIR was a strong predictor of IGR in both CT and MRI-assessed patients, and may help for patient triage, e.g . for transfer decision from an outside hospital for thrombectomy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations.METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy.FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard.INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations.FUNDING: US National Institutes of Health (R01 AG26484).