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Data science of stroke imaging and enlightenment of the penumbra.

ABSTRACT: Imaging protocols of acute ischemic stroke continue to hold significant uncertainties regarding patient selection for reperfusion therapy with thrombolysis and mechanical thrombectomy. Given that patient inclusion criteria can easily introduce biases that may be unaccounted for, the reproducibility and reliability of the patient screening method is of utmost importance in clinical trial design. The optimal imaging screening protocol for selection in targeted populations remains uncertain. Acute neuroimaging provides a snapshot in time of the brain parenchyma and vasculature. By identifying the at-risk but still viable penumbral tissue, imaging can help estimate the potential benefit of a reperfusion therapy in these patients. This paper provides a perspective about the assessment of the penumbral tissue in the context of acute stroke and reviews several neuroimaging models that have recently been developed to assess the penumbra in a more reliable fashion. The complexity and variability of imaging features and techniques used in stroke will ultimately require advanced data driven software tools to provide quantitative measures of risk/benefit of recanalization therapy and help aid in making the most favorable clinical decisions.

SUBMITTER: Scalzo F

PROVIDER: S-EPMC4350425 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Data science of stroke imaging and enlightenment of the penumbra.

Scalzo Fabien F Nour May M Liebeskind David S DS

Frontiers in neurology 20150305

Imaging protocols of acute ischemic stroke continue to hold significant uncertainties regarding patient selection for reperfusion therapy with thrombolysis and mechanical thrombectomy. Given that patient inclusion criteria can easily introduce biases that may be unaccounted for, the reproducibility and reliability of the patient screening method is of utmost importance in clinical trial design. The optimal imaging screening protocol for selection in targeted populations remains uncertain. Acute ...[more]

PMID: 25798125

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Project description:The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O2. Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions.

Project description:The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options.

Project description:Purpose: Automated postprocessing packages have been developed for managing acute ischemic stroke (AIS). These packages identify ischemic core and penumbra using either computed tomographic perfusion imaging (CTP) data or magnetic resonance imaging (MRI) data. Measurements of abnormal tissues and treatment decisions derived from different vendors can vary. The purpose of this study is to investigate the agreement of volumetric and decision-making outcomes derived from two software packages. Methods: A total of 594 AIS patients (174 underwent CTP and 420 underwent MRI) were included. Imaging data were accordingly postprocessed by two software packages: RAPID and RealNow. Volumetric outputs were compared between packages by performing intraclass correlation coefficient (ICC), Wilcoxon paired test and Bland–Altman analysis. Concordance of selecting patients eligible for mechanical thrombectomy (MT) was assessed based on neuroimaging criteria proposed in DEFUSE3. Results: In the group with CTP data, mean ischemic core volume (ICV)/penumbral volume (PV) was 14.9/81.1 mL via RAPID and 12.6/83.2 mL via RealNow. Meanwhile, in the MRI group, mean ICV/PV were 52.4/68.4 mL and 48.9/61.6 mL via RAPID and RealNow, respectively. Reliability, which was measured by ICC of ICV and PV in CTP and MRI groups, ranged from 0.87 to 0.99. The bias remained small between measurements (CTP ICV: 0.89 mL, CTP PV: −2 mL, MRI ICV: 3.5 mL and MRI PV: 6.8 mL). In comparison with CTP ICV with follow-up DWI, the ICC was 0.92 and 0.94 for RAPID and Realnow, respectively. The bias remained small between CTP ICV and follow-up DWI measurements (Rapid: −4.65 mL, RealNow: −3.65 mL). Wilcoxon paired test showed no significant difference between measurements. The results of patient triage were concordant in 159/174 cases (91%, ICC: 0.90) for CTP and 400/420 cases (95%, ICC: 0.93) for MRI. Conclusion: The CTP ICV derived from RealNow was more accurate than RAPID. The similarity in volumetric measurement between packages did not necessarily relate to equivalent patient triage. In this study, RealNow showed excellent agreement with RAPID in measuring ICV and PV as well as patient triage.

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Data science of stroke imaging and enlightenment of the penumbra.

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Data science of stroke imaging and enlightenment of the penumbra.

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