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      The ratio between cerebral blood flow and Tmax predicts the quality of collaterals in acute ischemic stroke

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          Abstract

          Background

          In acute ischemic stroke the status of collateral circulation is a critical factor in determining outcome. We propose a less invasive alternative to digital subtraction angiography for evaluating collaterals based on dynamic-susceptibility contrast magnetic resonance imaging.

          Methods

          Perfusion maps of Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF drop below 80% of healthy, contralateral tissue. For each patient a ratio between the volume of the CBF and the Tmax based perfusion deficit was calculated. Associations with collateral status and radiological outcome were assessed with the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as well as area under the receiver-operator-characteristic (ROC) curve.

          Results

          The CBF/Tmax volume ratios were significantly associated with bad collateral status in crude logistic regression analysis as well as with adjustment for NIHSS at admission and baseline infarct volume (OR = 2.5 95% CI[1.2–5.4] p = 0.020 for CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0–2.6] p = 0.031 for CBF/Tmax6s volume ratio). Moreover, the ratios were significantly correlated to final infarct size (Spearman’s rho = 0.711 and 0.619, respectively for the CBF/Tmax4s volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a high area under the ROC curve of 0.93 95%CI[0.86–1.00]) and 0.90 95%CI[0.80–1.00]respectively for predicting poor radiological outcome.

          Conclusions

          In the setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to differentiate between good and insufficient collateral circulation without the need for invasive procedures like conventional angiography.

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          Most cited references16

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          Failure of collateral blood flow is associated with infarct growth in ischemic stroke.

          Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P<0.001) and smaller baseline diffusion lesion volume (Rho -0.70, P<0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P=0.02) and relative (P<0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho -0.68, P<0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P=0.003) and relative (P=0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.
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            A digital map of middle cerebral artery infarcts associated with middle cerebral artery trunk and branch occlusion.

            Knowledge of the topographic distribution of infarcts of the middle cerebral artery (MCA) may give insight into the limits of the arterial territory and infarct mechanism and may influence the decision to use thrombolytic therapy. We describe the creation of a digital atlas of MCA (DA-MCA) infarction associated with MCA branch and trunk occlusion using magnetic resonance (MR) techniques. Hemispheric infarcts, with evidence of MCA trunk or branch occlusion, were manually segmented into binary images, linearly registered into a common stereotaxic coordinate space, and averaged to yield the probability of involvement by infarction at each voxel. Comparisons were made with existing maps of the MCA territory. Twenty-eight patients with median age of 74 years (range, 26 to 87 years) were studied. On the DA-MCA, the highest frequency of infarction was within the striatocapsular region, centrum semiovale, and the insula. The mean and maximal MCA infarct volumes were 195.5 cm3 and 366.3 cm3, respectively. Comparison with published maps showed that the most common difference from the DA-MCA was in the superomedial extent of the MCA territory. Some maps showed the MCA territory reaching the interhemispheric fissure, whereas in the DA-MCA it did not. There was a lower variability in the anterior boundary of the MCA territory compared with its posterior counterpart. We have created a digital atlas of MCA infarction using MR imaging techniques. This approach may be useful to establish the distribution of the MCA and other arterial territories and the border zones between them with greater certainty.
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              Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex.

              Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [C]iodoamphetamine technique, and 1/tau(c) values obtained using LSF, and used 1/tau(c) values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Investigation
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysis
                Role: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 January 2018
                2018
                : 13
                : 1
                : e0190811
                Affiliations
                [1 ] Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany
                [2 ] International Graduate Program Medical Neurosciences, Charité – University Medicine Berlin, Berlin, Germany
                [3 ] Berlin School of Mind and Brain, Humboldt-Universitaet zu Berlin, Berlin, Germany
                [4 ] Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
                [5 ] Institute of Medical Biometrics and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                Fraunhofer Research Institution of Marine Biotechnology, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4904-8251
                Article
                PONE-D-17-11579
                10.1371/journal.pone.0190811
                5790218
                29381701
                2d6dc80c-1b3e-445a-82a7-5f193d03fa79
                © 2018 Galinovic et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 March 2017
                : 20 December 2017
                Page count
                Figures: 3, Tables: 1, Pages: 9
                Funding
                The research leading to these results has received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801 and 01EO01301). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Data are from the 1000+ clinical patient study whose authors may be contacted through jochen.fiebach@ 123456charite.de . Due to legal and ethical reasons, the MR images and clinical information are not publicly available. Single images will be provided by the first author Ivana Galinovic ( ivana.galinovic@ 123456charite.de ) upon request. All other data used in this study has been made publicly available (DOI: 10.6084/m9.figshare.5271592).

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