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      Diffusion Tensor-Derived Properties of Benign Oligemia, True “at Risk” Penumbra, and Infarct Core during the First Three Hours of Stroke Onset: A Rat Model

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          Abstract

          Objective

          The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true “at risk” penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset.

          Materials and Methods

          The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain.

          Results

          The mean volume of oligemia was 24.7 ± 14.1 mm 3, that of TP was 81.3 ± 62.6 mm 3, and that of IC was 123.0 ± 85.2 mm 3 at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from −24% to −36%) as compared with TP (from −7% to −13%). Significant differences ( p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was −33.90%. The metric values for oligemia and NT remained similar at all time points.

          Conclusion

          Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

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          Most cited references41

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          Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.

          To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved. Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile. For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.
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            High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis.

            The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modeling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution.
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              Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis.

              Stroke is a serious neurological disease, and constitutes a major cause of death and disability throughout the world. The pathophysiology of stroke is complex, and involves excitotoxicity mechanisms, inflammatory pathways, oxidative damage, ionic imbalances, apoptosis, angiogenesis and neuroprotection. The ultimate result of ischemic cascade initiated by acute stroke is neuronal death along with an irreversible loss of neuronal function. Therapeutic strategies in stroke have been developed with two main aims: restoration of cerebral flow and the minimization of the deleterious effects of ischemia on neurons. Intense research spanning over the last two decades has witnessed significant therapeutic advances in the form of carotid endarterectomy, thrombolytics, anticoagulant therapy, antiplatelet agents, neuroprotective agents, and treating associated risk factors such as hypertension and hyperlipidemia. However, the search for an effective neuroprotectant remains frustrating, and the current therapeutic protocols remain suboptimal. Till date only one FDA-approved drug is available for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA), utility of which is limited by short therapeutic window. The objective of this review is to critically evaluate the major mechanisms underlying stroke pathophysiology, with emphasis on potential novel targets for designing newer therapeutic modalities. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Korean J Radiol
                Korean J Radiol
                KJR
                Korean Journal of Radiology
                The Korean Society of Radiology
                1229-6929
                2005-8330
                Nov-Dec 2018
                18 October 2018
                : 19
                : 6
                : 1161-1171
                Affiliations
                [1 ]Department of Medical Imaging and Radiological Sciences, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.
                [2 ]Department of Radiology, Taoyuan Armed Forces General Hospital, Taoyuan 32551, Taiwan.
                [3 ]Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan.
                [4 ]Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
                [5 ]Graduate Institute of Biomedical Electrics and Bioinformatics, National Taiwan. University, Taipei 10617, Taiwan.
                [6 ]Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
                [7 ]Department of Radiology, Tri-Service General Hospital, Taipei 11490, Taiwan.
                [8 ]Department of Radiology, National Defense Medical Center, Taipei 11490, Taiwan.
                Author notes
                Corresponding author: Cheng-Yu Chen, MD, Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, No.252, Wu Xing street, SinYi Distric, Taipei 11031, Taiwan. Tel: (8862) 27372181, Fax: (8862) 2378-0943, sandy0932@ 123456gmail.com

                *These authors contributed equally to this work.

                Article
                10.3348/kjr.2018.19.6.1161
                6201972
                30386147
                14604ee7-9511-48ea-acfd-3feaf368b8b9
                Copyright © 2018 The Korean Society of Radiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 February 2018
                : 27 April 2018
                Funding
                Funded by: Ministry of Science and Technology, Taiwan, CrossRef https://doi.org/10.13039/501100004663;
                Award ID: 105-2221-E-038 -007 -MY3
                Categories
                Technology, Experiment, and Physics
                Original Article

                Radiology & Imaging
                diffusion tensor imaging,true penumbra,infarct core,benign oligemia,pure anisotropy,diffusion magnitude

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