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

健康和创伤昏迷中上行唤醒系统的体内图谱

• 批准号: 9278164
• 负责人: Marta Bianciardi
• 金额: $ 17.54万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278164
• 关键词: Address; Adult; Affect; Anatomy; Anesthesia procedures; Area; Arousal; Atlases; Autopsy; Brain; Brain Stem; Cell Nucleus; Clinical; Coma; Communities; Computing Methodologies; Conscious; Consciousness Disorders; Cytology; Data; Development; Diffusion; Disease; Dorsal; Echo-Planar Imaging; Educational workshop; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Gold; Grant; Health; Hemorrhage; Histology; Human; Image; Imaging Techniques; Impairment; Individual; Injury; Institutes; Investigation; Knowledge; Label; Location; Magnetic Resonance Imaging; Manuals; Maps; Mentored Research Scientist Development Award; Mentors; Methods; Neuroanatomy; Neurologic; Neurosciences; Pathway interactions; Patients; Pattern; Pharmacologic Substance; Physics; Play; Post-Head Injury Coma; Predisposition; Procedures; Property; Protocols documentation; Protons; Research; Research Personnel; Research Project Grants; Resolution; Role; Seeds; Sleep; Sleep Disorders; Specimen; Structure; System; Technology; Testing; Tissues; Training; Traumatic Brain Stem Hemorrhage; Weight; Work; Writing; advanced system; base; bioimaging; career; clinically relevant; cohort; connectome; contrast imaging; density; design; diffusion weighted; ex vivo imaging; gray matter; histological stains; image warping; imaging Segmentation; imaging modality; imaging study; improved; in vivo; injured; magnetic field; meetings; midbrain central gray substance; neuroimaging; novel; novel therapeutics; outcome prediction; predictive modeling; prognostic; public health relevance; research and development; skills; symposium; tool; tool development; translational neuroscience

 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.

 应聘者描述(申请人提供)：应聘者的职业目标是成为生物医学成像领域的一名独立研究人员，对大脑结构和功能的基本知识做出重大贡献，并开发有助于解决翻译神经科学中重要问题的新工具。候选人接受过物理学方面的培训；她的研究重点是低磁场和高磁场下的功能磁共振成像，为功能磁共振成像社区开发研究工具，以及调查健康中的大脑功能。K01奖励计划旨在允许候选人成为提升觉醒系统(AAS)的生物成像专家。候选人在本次K01获奖期间的目标是接受AAS的神经解剖学、神经科学和病理生理学方面的培训，这一领域与她之前的培训和研究重点不同。为了进行拟议的研究，她还将在神经解剖学的成像和计算方法方面获得新的研究技能。此外，候选人寻求加强她制定临床相关假设的能力，使用一套多样化的技能和工具来正确和迅速地测试这些假设，以及撰写拨款。这将通过定期与她的导师、她的研究和临床合作者会面、参加特定的教学课程/研讨会/会议，以及在拟议的研究项目开发期间进行实践培训来实现。AAS的灰质脑干核团(Bn)在调节觉醒方面起着至关重要的作用，觉醒是人类意识的一个关键组成部分。由于到目前为止，AAS的脑干Bn的活体识别一直难以通过现有的成像技术进行，因此健康(睡眠/清醒条件、麻醉)和疾病(意识障碍、睡眠障碍)中唤醒的神经解剖学和功能基础尚不清楚。候选人在本次K01获奖期间的主要研究目标是开发和验证一种新的程序，以描绘MNI空间中AAS的13个人Bn的体内概率结构图谱。该程序将使用一套新开发的方法来获取在7T下具有精确匹配的几何失真和分辨率的多对比回波平面图像，以及半自动分割过程。最后，本研究项目建议应用开发的工具在体内识别AAS中哪些Bn受到创伤性昏迷出血的影响，并评估AAS在健康和创伤性昏迷中的连通性。我们的初步结果表明，通过7T多对比成像生成AAS的四个Bn的概率模板，在3T时评估这些Bn在创伤性昏迷中受损组织的百分比，并绘制它们在健康环境中的功能连接性是可行的。我们与研究AAS在昏迷、睡眠和麻醉中的合作者有同样的热情，因为AAS Bn体内图谱的开发可能会极大地促进对觉醒机制的了解，提高昏迷早期预测的准确性，并促进针对觉醒状态改变的药物的开发。