In vivo atlas of the ascending arousal system in health and traumatic coma

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 DESCRIPTION (provided by applicant): The candidate's career goals are to become an independent researcher in the field of biomedical imaging, to make significant contributions to the basic knowledge of brain structure and function, and to develop novel tools that will be useful to address important issues in translational neuroscience. The candidate has received training in Physics; her research has focused on fMRI at low and high magnetic fields, on the development of research tools for the fMRI community, and on the investigation of brain function in health. The K01 award proposal was designed to allow the candidate to become an expert bio-imager of the ascending arousal system (AAS). The candidate's objective for this K01 award period is to receive training in the neuroanatomy, neuroscience and patho-physiology of the AAS, an area different from her previous training and research focus. To conduct the proposed research, she will also gain new research skills in imaging and computational methods for neuro-anatomy. Further, the candidate seeks to strengthen her ability of formulating clinically relevant hypotheses, of using a diversified set of skills and tools to test these hypotheses properly and promptly, and of grant writing. This will be achieved by regular meetings with her mentors, her research and clinical collaborators, by attending to specific didactic courses / workshops / conferences, and by hands-on training during the development of the proposed research project. Gray matter brainstem nuclei (Bn) of the AAS play a crucial role in regulating arousal, a key component of human consciousness. Because an in vivo identification of brainstem Bn of the AAS has been elusive so far by current imaging techniques, the neuro-anatomic and functional basis of arousal in health (sleep/wake conditions, anesthesia) and in disease (disorders of consciousness, sleep disorders) is poorly understood. The candidate's main research objective for this K01 award period is to develop and validate a novel procedure to delineate an in vivo probabilistic structural atlas of 13 human Bn of the AAS in MNI space. The procedure will use a newly developed set of methods to acquire multi-contrast echo-planar-images with exactly matched geometric distortion and resolution at 7 T, and semi-automatic segmentation procedures. Finally, this research project proposes to apply the developed tool to identify in vivo which Bn of the AAS are affected by hemorrhages in traumatic coma, and to evaluate the AAS connectivity in health and traumatic coma. Our preliminary results show the feasibility of generating a probabilistic template of four Bn of the AAS by 7 T multi- contrast imaging, of evaluating at 3 T the percent of injured tissue of these Bn in traumatic coma, and of mapping their functional connectivity in health. We share our enthusiasm with our collaborators that study the AAS in coma, sleep and anesthesia because the development of an in vivo atlas of Bn of the AAS might greatly advance the knowledge of the mechanism of arousal, improve the accuracy of prognostication in the early stage of coma, and facilitate the development of pharmaceuticals for altered states of arousal.