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Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

ABSTRACT: Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax > 10 sec/Tmax > 6 sec]); favorable TLC were regarded as HIR ≤ 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2).580 patients met inclusion criteria. Favorable TLC (β: 4.23, SE: 0.65; p < 0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31-4.21]; p < 0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70-0.79]; p < 0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status.We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.

SUBMITTER: Faizy TD

PROVIDER: S-EPMC8327120 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

Faizy Tobias D TD Kabiri Reza R Christensen Soren S Mlynash Michael M Kuraitis Gabriella G Broocks Gabriel G Hanning Uta U Nawabi Jawed J Lansberg Maarten G MG Marks Michael P MP Albers Gregory W GW Fiehler Jens J Wintermark Max M Heit Jeremy J JJ

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20210208 8

Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusi ...[more]

PMID: 33557694

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Project description:Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks were flipped along the brain midline to generate mirrored regions in the contralateral hemisphere of NCCT; NWU was calculated as one minus the ratio of densities between regions, removing voxels segmented as CSF and with HU outside thresholds of 20-80 (normal hemisphere and baseline CT) and 0-40 (infarct region on follow-up). Automated results were compared with those obtained using manually-drawn infarcts and an ASPECTS region-of-interest based method that samples densities within the infarct and normal hemisphere, using intraclass correlation coefficient (ρ). This was tested on serial CTs from 55 patients with anterior circulation LVO (including 66 follow-up CTs). Baseline NWU using automated core was 4.3% (IQR 2.6-7.3) and correlated with manual measurement (ρ = 0.80, p < 0.0001) and ASPECTS (r = -0.60, p = 0.0001). Automatically segmented infarct volumes (median 110-ml) correlated to manually-drawn volumes (ρ = 0.96, p < 0.0001) with median Dice similarity coefficient of 0.83 (IQR 0.72-0.90). Automated NWU was 24.6% (IQR 20-27) and highly correlated to NWU from manually-drawn infarcts (ρ = 0.98) and the sampling-based method (ρ = 0.68, both p < 0.0001). We conclude that this automated imaging pipeline is able to accurately quantify region of infarction and NWU from serial CTs and could be leveraged to study the evolution and impact of edema in large cohorts of stroke patients.

Project description:New treatments for cerebral small-vessel disease are needed to reduce the risk of small-vessel occlusion stroke and vascular cognitive impairment. We investigated an approach targeted to the signalling molecule cyclic guanosine monophosphate, using the phosphodiesterase 5 inhibitor tadalafil, to explore if it improves cerebral blood flow and endothelial function in patients with cerebral small-vessel disease and stroke. In a randomized, double-blinded, placebo-controlled, cross-over pilot trial (NCT02801032), we included patients who had a previous (>6 months) small-vessel occlusion stroke. They received a single dose of either 20 mg tadalafil or placebo on 2 separate days at least 1 week apart. We measured the following: baseline MRI for lesion load, repeated measurements of blood flow velocity in the middle cerebral artery by transcranial Doppler, blood oxygen saturation in the cortical microvasculature by near-infrared spectroscopy, peripheral endothelial response by EndoPAT and endothelial-specific blood biomarkers. Twenty patients with cerebral small-vessel disease stroke (3 women, 17 men), mean age 67.1 ± 9.6, were included. The baseline mean values ± standard deviations were as follows: blood flow velocity in the middle cerebral artery, 57.4 ± 10.8 cm/s; blood oxygen saturation in the cortical microvasculature, 67.0 ± 8.2%; systolic blood pressure, 145.8 ± 19.5 mmHg; and diastolic blood pressure, 81.3 ± 9.1 mmHg. We found that tadalafil significantly increased blood oxygen saturation in the cortical microvasculature at 180 min post-administration with a mean difference of 1.57 ± 3.02%. However, we saw no significant differences in transcranial Doppler measurements over time. Tadalafil had no effects on peripheral endothelial function assessed by EndoPAT and endothelial biomarker results conflicted. Our findings suggest that tadalafil may improve vascular parameters in patients with cerebral small-vessel disease stroke, although the effect size was small. Increased oxygenation of cerebral microvasculature during tadalafil treatment indicated improved perfusion in the cerebral microvasculature, theoretically presenting an attractive new therapeutic target in cerebral small-vessel disease. Future studies of the effect of long-term tadalafil treatment on cerebrovascular reactivity and endothelial function are needed to evaluate general microvascular changes and effects in cerebral small-vessel disease and stroke.

Project description:Background and Purpose- Accurate prediction of acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) that is amendable to mechanical thrombectomy remains a challenge. We developed and validated a prediction model for anterior circulation LVO stroke using past medical history elements present on admission and neurological examination. Methods- We retrospectively reviewed AIS patients admitted between 2009 and 2017 to 3 hospitals within a large healthcare system in the United States. Patients with occlusions of the internal carotid artery or M1 or M2 segments of the middle cerebral artery were randomly split into 2/3 derivation and 1/3 validation cohorts for development of an anterior circulation LVO prediction model and score that was further curtailed for potential use in the prehospital setting. Results- A total of 1654 AIS were reviewed, including 248 (15%) with proximal anterior circulation LVO AIS. In the derivation cohort, National Institutes of Health Stroke Scale score at the time of cerebrovascular imaging, current smoking status, type 2 diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis was significantly associated with anterior circulation LVO stroke. The prehospital score was curtailed to National Institutes of Health Stroke Scale score, current smoking status, and type 2 diabetes mellitus. The areas under the curve for the prediction model, prehospital score, and National Institutes of Health Stroke Scale score alone were 0.796, 0.757, and 0.725 for the derivation cohort and 0.770, 0.689, and 0.665 for the validation cohort, respectively. The Youden index J was 0.46 for a score of >6 with 84.7% sensitivity and 62.0% specificity for the prediction model. Conclusions- Previously reported LVO stroke prediction scores focus solely on elements of the neurological examination. In addition to stroke severity, smoking, diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis were associated with anterior circulation LVO AIS. Although atherosclerotic stenosis may not be known until imaging is obtained, smoking and diabetes mellitus history can be readily obtained in the field and represent important elements of the prehospital score supplementing National Institutes of Health Stroke Scale score.

Dataset Information

Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

Publications

Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

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