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      Iterative analysis of cerebrovascular reactivity dynamic response by temporal decomposition

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          Abstract

          Objective

          To improve quantitative cerebrovascular reactivity ( CVR) measurements and CO 2 arrival times, we present an iterative analysis capable of decomposing different temporal components of the dynamic carbon dioxide‐ Blood Oxygen‐Level Dependent ( CO 2BOLD) relationship.

          Experimental Design

          Decomposition of the dynamic parameters included a redefinition of the voxel‐wise CO 2 arrival time, and a separation from the vascular response to a stepwise increase in CO 2 (Delay to signal Plateau – DTP) and a decrease in CO 2 (Delay to signal Baseline – DTB). Twenty‐five (normal) datasets, obtained from BOLD MRI combined with a standardized pseudo‐square wave CO 2 change, were co‐registered to generate reference atlases for the aforementioned dynamic processes to score the voxel‐by‐voxel deviation probability from normal range. This analysis is further illustrated in two subjects with unilateral carotid artery occlusion using these reference atlases.

          Principal Observations

          We have found that our redefined CO 2 arrival time resulted in the best data fit. Additionally, excluding both dynamic BOLD phases ( DTP and DTB) resulted in a static CVR, that is maximal response, defined as CVR calculated only over a normocapnic and hypercapnic calibrated plateau.

          Conclusion

          Decomposition and novel iterative modeling of different temporal components of the dynamic CO 2BOLD relationship improves quantitative CVR measurements.

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          Most cited references28

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          Measuring cerebrovascular reactivity: what stimulus to use?

          Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasodilatory or vasoconstrictive stimulus. Measuring variations of cerebrovascular reactivity between different regions of the brain has the potential to not only advance understanding of how the cerebral vasculature controls the distribution of blood flow but also to detect cerebrovascular pathophysiology. While there are standardized and repeatable methods for estimating the changes in cerebral blood flow in response to a vasoactive stimulus, the same cannot be said for the stimulus itself. Indeed, the wide variety of vasoactive challenges currently employed in these studies impedes comparisons between them. This review therefore critically examines the vasoactive stimuli in current use for their ability to provide a standard repeatable challenge and for the practicality of their implementation. Such challenges include induced reductions in systemic blood pressure, and the administration of vasoactive substances such as acetazolamide and carbon dioxide. We conclude that many of the stimuli in current use do not provide a standard stimulus comparable between individuals and in the same individual over time. We suggest that carbon dioxide is the most suitable vasoactive stimulus. We describe recently developed computer-controlled MRI compatible gas delivery systems which are capable of administering reliable and repeatable vasoactive CO2 stimuli.
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            The cerebrovascular response to carbon dioxide in humans.

            Carbon dioxide (CO2) increases cerebral blood flow and arterial blood pressure. Cerebral blood flow increases not only due to the vasodilating effect of CO2 but also because of the increased perfusion pressure after autoregulation is exhausted. Our objective was to measure the responses of both middle cerebral artery velocity (MCAv) and mean arterial blood pressure (MAP) to CO2 in human subjects using Duffin-type isoxic rebreathing tests. Comparisons of isoxic hyperoxic with isoxic hypoxic tests enabled the effect of oxygen tension to be determined. During rebreathing the MCAv response to CO2 was sigmoidal below a discernible threshold CO2 tension, increasing from a hypocapnic minimum to a hypercapnic maximum. In most subjects this threshold corresponded with the CO2 tension at which MAP began to increase. Above this threshold both MCAv and MAP increased linearly with CO2 tension. The sigmoidal MCAv response was centred at a CO2 tension close to normal resting values (overall mean 36 mmHg). While hypoxia increased the hypercapnic maximum percentage increase in MCAv with CO2 (overall means from76.5 to 108%) it did not affect other sigmoid parameters. Hypoxia also did not alter the supra-threshold MCAv and MAP responses to CO2 (overall mean slopes 5.5% mmHg⁻¹ and 2.1 mmHg mmHg⁻¹, respectively), but did reduce the threshold (overall means from 51.5 to 46.8 mmHg). We concluded that in the MCAv response range below the threshold for the increase of MAP with CO2, the MCAv measurement reflects vascular reactivity to CO2 alone at a constant MAP.
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              Prospective targeting and control of end-tidal CO2 and O2 concentrations.

              Current methods of forcing end-tidal PCO2 (PETCO2) and PO2 (PETO2) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control PETCO2 and PETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change PETCO2 from control (40 mmHg for PETCO2 and 100 mmHg for PETO2) to two target PETCO2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), PETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and PETCO2 with PETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, PETCO2 and PETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for PETCO2 was +/-1 mmHg, and for PETO2 was +/-4 mmHg. PETCO2 varied by +/-1 mmHg and PETO2 by +/-5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (+/-7.6 l min(-1)). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.
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                Author and article information

                Contributors
                jorn.fierstra@usz.ch
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                26 July 2017
                September 2017
                : 7
                : 9 ( doiID: 10.1002/brb3.2017.7.issue-9 )
                : e00705
                Affiliations
                [ 1 ] Department of Neurosurgery University Hospital Zurich University of Zurich Zurich Switzerland
                [ 2 ] Clinical Neuroscience Center University Hospital Zurich Zurich Switzerland
                [ 3 ] Department of Neuroradiology University Hospital Zurich University of Zurich Zurich Switzerland
                [ 4 ] Department of Anesthesiology University Health Network University of Toronto Toronto ON Canada
                [ 5 ] Department of Neurology University Hospital Zurich University of Zurich Zurich Switzerland
                [ 6 ] Cereneo Center for Neurology and Rehabilitation Vitznau Switzerland
                Author notes
                [*] [* ] Correspondence

                Jorn Fierstra, Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.

                Email: jorn.fierstra@ 123456usz.ch

                [†]

                Equal first author contribution.

                Article
                BRB3705
                10.1002/brb3.705
                5607533
                28948064
                85654f60-d28a-4416-9a14-39c9cbab3c96
                © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 October 2016
                : 28 February 2017
                : 01 March 2017
                Page count
                Figures: 4, Tables: 0, Pages: 12, Words: 7546
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb3705
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.0 mode:remove_FC converted:21.09.2017

                Neurosciences
                blood‐oxygen‐level‐dependent,carbon dioxide,cerebrovascular reactivity,functional magnetic resonance imaging,humans

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