Continuous Detection of Cerebral Vasodilatation and Vasoconstriction Using Intracranial Pulse Morphological Template Matching Shadnaz Asgari 1,2 , Nestor Gonzalez 2 , Andrew W. Subudhi 4,5 , Robert Hamilton 2,3 , Paul Vespa 2 , Marvin Bergsneider 2,3 , Robert C. Roach 5 , Xiao Hu 2,3 * 1 Department of Computer Engineering and Computer Science, California State University, Long Beach, California, United States of America, 2 Department of Neurosurgery, University of California Los Angeles, Los Angeles, California, United States of America, 3 Department of Bioengineering, University of California Los Angeles, Los Angeles, California, United States of America, 4 Department of Biology, University of Colorado, Colorado Springs, Colorado, United States of America, 5 Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Denver, Colorado, United States of America Abstract Although accurate and continuous assessment of cerebral vasculature status is highly desirable for managing cerebral vascular diseases, no such method exists for current clinical practice. The present work introduces a novel method for real- time detection of cerebral vasodilatation and vasoconstriction using pulse morphological template matching. Templates consisting of morphological metrics of cerebral blood flow velocity (CBFV) pulse, measured at middle cerebral artery using Transcranial Doppler, are obtained by applying a morphological clustering and analysis of intracranial pulse algorithm to the data collected during induced vasodilatation and vasoconstriction in a controlled setting. These templates were then employed to define a vasodilatation index (VDI) and a vasoconstriction index (VCI) for any inquiry data segment as the percentage of the metrics demonstrating a trend consistent with those obtained from the training dataset. The validation of the proposed method on a dataset of CBFV signals of 27 healthy subjects, collected with a similar protocol as that of training dataset, during hyperventilation (and CO 2 rebreathing tests) shows a sensitivity of 92% (and 82%) for detection of vasodilatation (and vasoconstriction) and the specificity of 90% (and 92%), respectively. Moreover, the proposed method of detection of vasodilatation (vasoconstriction) is capable of rejecting all the cases associated with vasoconstriction (vasodilatation) and outperforms other two conventional techniques by at least 7% for vasodilatation and 19% for vasoconstriction. Citation: Asgari S, Gonzalez N, Subudhi AW, Hamilton R, Vespa P, et al. (2012) Continuous Detection of Cerebral Vasodilatation and Vasoconstriction Using Intracranial Pulse Morphological Template Matching. PLoS ONE 7(11): e50795. doi:10.1371/journal.pone.0050795 Editor: Alice Y. W. Chang, Kaohsiung Chang Gung Memorial Hospital, Taiwan Received June 14, 2012; Accepted October 23, 2012; Published November 30, 2012 Copyright: ß 2012 Asgari 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. Funding: The present work is partially supported by NS059797 and R01 awards NS066008 and National Heart, Lung, and Blood Institute grant HL-070362. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: xhu@mednet.ucla.edu Introduction Modern strategies for managing patients in neurocritical care units utilize a set of monitoring techniques to evaluate various fluctuating physiological markers to inform intervention decisions on an individual basis [1]. Various monitoring modalities [2,3] have been introduced in neurocritical units to provide the assessment of cerebral hemodynamics [e.g. cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV)], intracranial hydraulics [e.g. intracranial pressure (ICP)], electrophysiology [e.g. electroencephalography (EEG)], cerebral oxygenation [e.g., partial pressure of oxygen], and brain metabolism [e.g. microdialysis (MD)]. However, the methods currently available to evaluate the pathophysiological changes of the cerebral circulation have significant time resolution limitations and do not allow continuous evaluations of the fluctuations in cerebral perfusion. A modality capable of providing real time information on the changes occurring in the cerebral vasculature could potentially increase the time effectiveness of therapeutic interventions and prevent secondary cerebral damage due to ischemia or hyperperfusion. Such a modality could play a fundamental role in the management of conditions such as cerebral vasospasm after subarachnoid hemorrhage, evaluation of the collateral flow in patients with acute and chronic unstable ischemic stroke and monitoring of cerebro- vascular changes associated with traumatic brain injury [4,5]. Methodologies to assess the cerebral vasculature like Transcra- nial Doppler (TCD) are limited due to the skull density that only allows insonation of large vessels of the circle of Willis in individuals with favorable windows by trained technicians. While digital subtraction, CT, or MRI angiographic methods provide accurate images of the cerebral vasculature and in some cases functional information of the cerebral blood flow [6], they can only be preformed intermittently and carry risks associated with the use of contrast media, radiation or the endovascular intervention. A few indirect metrics also exist that can be used to assess the cerebral vasculature using hemodynamic concepts such as resistance and vascular tone, e.g. Gosling pulsatility index (PI) [7], Pourcelot resistance index (RI) [8], and critical closing pressure (CCP) and resistance area product (RAP) [9]. Although there is some success of applying them in detecting cerebrovas- PLOS ONE | www.plosone.org 1 November 2012 | Volume 7 | Issue 11 | e50795