Garrard, James

Background: Identifying optimal candidates for endovascular treatment (EVT) remains an ongoing priority to maximize treatment efficacy. The recent large core trials have called into question the use of infarct volume alone for selecting patients. This study aimed at exploring the feasibility of using routinely acquired Computed Tomography Perfusion (CTP) to capture how lesion location impacts brain connectivity and how this in turn affects the ability to benefit from EVT. Methods: Consecutive patients from a multi-centric stroke imaging registry were included in this study if they had a proven anterior circulation large vessel occlusion (LVO) and available baseline CTP data. Hypoperfusion (Tmax >6 seconds) and ischemic core (relative cerebral blood flow <30%) maps were automatically generated using e-CTP (Brainomix, UK) and used to derive disconnection maps via a DTI template. A voxel-based, multivariate method (Sparse Canonical-Correlation-Analysis – LESYMAPS) was used to explore associations between disconnection maps and NIHSS subitems in recanalized patients. The mismatch between Tmax and core disconnection volumes (disconnection mismatch volume) (Figure 1) was used to predict modified Rankin Scale (mRS) at 3-months using an ordinal shift regression adjusted for age, recanalization status and infarct volume. Results: One-hundred and seventy-one patients were included. The median NIHSS was 16 (11.5 to 22). The total NIHSS was associated with disconnection predominantly within the left basal ganglia, brainstem and corpus callosum. Upper and lower limb deficits (NIHSS 5a, 5b, 6a, 6b) were associated with corticospinal tract disconnection, with negative correlations within the contralateral tracts (Figure 2). Language deficits were associated with left hemisphere tract disconnection, also showing negative correlations within the contralateral tracts. The disconnection mismatch volume was an independent predictor of functional outcome at 3-months (Table 1). Conclusion: The results from this study showed that it is possible to use routinely acquired CTP to capture the effects of stroke lesion on brain connectivity and its impact on functional outcome following recanalization treatment. Such an approach could enable more nuanced treatment selection for patients based on specific neurological deficits.

Background: There is an unmet need to better understand the likelihood of a good functional outcome in older and frailer populations undergoing endovascular therapy (EVT) following large-vessel occlusion (LVO) ischemic stroke. One approach is to improve the understanding of pre-morbid brain health (“brain frailty”) as a predictor of functional outcome. This study explored the relationship between the spatial pattern of brain atrophy and functional outcome to determine whether this is a predictor of outcomes following EVT. Methods: Patients with LVO from four hospitals in Europe and the USA were included. Three cohorts were used as a derivation cohort, and the fourth served for validation. Presenting CT imaging was processed using Brainomix in-house software to automatically localize and quantify atrophy (frailty-index). Masks from the derivation cohort were used to localize regions of atrophy significantly associated with poorer functional outcome (modified Ranking Scale 3-6) using a voxel-based, multivariate method (Sparse Canonical-Correlation-Analysis) (see Figure 1). For both derivation and validation cohorts, the degrees of overlap between each patient’s atrophy mask and the regions associated at a group level with poor outcome were calculated. This was used as an independent predictor of functional outcome in multivariate analysis adjusting for overall brain frailty-index, recanalization status, and ASPECT score Results: The derivation cohort consisted of 658 patients (mean age 69.6±15.0, median ASPECTS 9 [7-10]), while the validation cohort consisted of 447 patients (mean age 64.7 ±15.5, median ASPECTS 8 [5-10] ). Atrophy localized to the lateral ventricles and sylvian fissure was significantly associated with poorer outcomes (Figure 1). In both derivation and validation cohort, the presence of this spatial pattern of brain frailty (quantified using the degree of overlap) was an independent predictor of poor functional outcome (Table 1). Conclusion: A better understanding of pre-stroke brain health, such as the distribution of atrophy, may provide additional information to inform the prediction of outcome following LVO. This could improve patient selection for treatment following ischemic stroke through better prognostication and a more personalized approach to decision making.

Background Identifying eloquent regions associated with poor outcomes based on CT perfusion (CTP) may help inform personalized decisions on selection for endovascular therapy (EVT) in patients with large vessel occlusion (LVO) ischemic stroke. This study aimed to characterize the relationship between CTP-defined hypoperfusion and National Institutes of Health Stroke Scale (NIHSS) subitem deficits. Methods Patients with anterior circulation LVO, baseline CTP, itemized NIHSS at presentation and 24 hours were included. CTP was analyzed using e-CTP (Brainomix, UK). Time to maximal contrast (Tmax) prolongation was defined as >6 s, and penumbra as the difference between Tmax and ischemic core (relative cerebral blood flow<30%). Voxel-lesion-symptom mapping was performed using sparse canonical correlation analysis. For each NIHSS subitem, and total NIHSS, the associations were plotted between Tmax voxels with baseline NIHSS, and penumbra voxels with delta NIHSS (24 hours minus baseline). Results This study included 171 patients. Total NIHSS was predicted by hypoperfusion in left frontal cortex and subcortical white matter tracts. Voxels associated with neurological recovery were symmetrical and subcortical. Limb deficits were associated with respective motor cortex regions and descending motor tracts, with negative correlation within the contralateral hemispheres. A similar but smaller cluster of voxels within the penumbra was associated with NIHSS improvement. Language impairment correlated with left frontal cortex and superior temporal gyrus voxels. With the exception of dysarthria, significant associations were observed and more diffusely distributed in all other NIHSS subitems. Conclusions These results demonstrate the feasibility of hypoperfusion-to-symptom mapping in LVO. Symptom-based mapping from presenting imaging could refine treatment decisions targeting specific neurological deficits.