Imaging small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia

精神分裂症嗅觉系统小血管和淋巴管异常的成像

• 批准号: 9767303
• 负责人: Jun Hua
• 金额: $ 54.57万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767303
• 关键词: Affect; Air; Area; Arteries; Biological; Biological Markers; Blood; Blood Vessels; Blood Volume; Blood flow; Brain; Brain Diseases; Brain region; Caliber; Cells; Cerebrum; Contrast Media; Data; Deltastab; Detection; Development; Disease; Dura Mater; Human; Image; Imaging Techniques; Imaging technology; Investigation; Link; Lymph; Lymphatic; Lymphatic System; Lymphatic vessel; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Methodology; Methods; Morphologic artifacts; Nasal cavity; Nerve Degeneration; Neurons; Nose; Nutrient; Olfactory Cortex; Olfactory Pathways; Onset of illness; Oxygen; Parkinson Disease; Pathology; Patients; Perfusion; Physiologic pulse; Physiological; Physiology; Play; Predisposition; Process; Psychophysics; Research; Research Personnel; Role; Scanning; Schizophrenia; Severities; Signal Transduction; Smell Perception; Staging; Structure; Sum; Techniques; Time; Tissues; Tracer; Venous; Waste Products; Work; arteriole; base; behavior test; biomarker development; brain tissue; cerebral blood volume; cerebrovascular; cribriform plate; imaging approach; imaging modality; lymph flow; lymphatic duct; neurodevelopment; neuropathology; neurophysiology; neuropsychiatry; non-invasive imaging; piriform cortex; pre-clinical; research clinical testing; response; temporal measurement; theories

PROJECT SUMMARY/ABSTRACT Olfactory deficits are a core feature and pre-clinical sign of numerous brain diseases, including schizophrenia. The olfactory system provides direct access to orbitofrontal-limbic neurocircuitry implicated in the disease con- ditions and holds a unique promise for understanding aberrant neurodevelopment processes. However, a major hurdle for studies of olfaction is the lack of non-invasive methods to capture the underlying neurophysiological substrates of olfactory loss. To date, clinical evaluation of olfaction has been limited to psychophysical as- sessment, which is subjective and uninformative regarding the underlying abnormalities. In the brain, small ar- terioles with diameters up to 100-150 microns are the primary regulator of local tissue perfusion. Lymphatic vessels have also been identified in the brain, which are believed to play a crucial role in the clearance of waste products. Quantitative measurement of the small blood and lymphatic vessels in the olfactory system would provide biologically meaningful information on olfactory loss, and would significantly enhance efforts for the prediction and staging of brain diseases. Here, we propose to develop and optimize MRI techniques for the quantitative measurement of small blood and lymphatic vessels in the human olfactory cortex with the following aims: Aim 1: To develop and optimize MRI methods for measuring blood volume in arteriolar and venous mi- crovessels separately in the olfactory cortex. The olfactory cortex is notoriously difficult for MRI due to the well-known signal loss caused by the susceptibility effects at the boundary between tissue and nasal cavity. We will develop and optimize new MRI sequences for the olfactory regions to recover signal loss close to the nasal cavity. Aim 2: To develop and optimize MRI methods for measuring dynamic signal changes in small lymphatic vessels in the brain. Lymphatic vessels have recently been found in the dura mater and around the cribriform plate in the olfactory area in the brain. Non-invasive imaging methods for the cerebral lymphatic vessels are extremely scarce and are mostly limited to large lymphatic ducts only. In addition, the existing methods cannot detect dynamic lymphatic signal changes with sufficient temporal resolution due the long scan time needed. Based on previous work, we propose to use contrast agent-based MRI methods to measure dynamic signal changes in small lymphatic vessels in the brain, from which vessel volume information can be deduced. Aim 3: To characterize small blood and lymphatic vessel abnormalities of the olfactory system in schizophrenia patients, and their association with the olfactory deficits assessed by behavioral tests. Taken together, the proposed studies will advance our understanding of the underlying physiological changes associated with olfactory deficits in schizophrenia, which may facilitate the development of disease biomarkers and potential treatment targets. Furthermore, the research will provide MRI methodologies that can be used to probe similar physiological changes in other brain regions and diseases.

项目概要/摘要 嗅觉缺陷是包括精神分裂症在内的许多脑部疾病的核心特征和临床前症状。 嗅觉系统提供了直接进入与疾病有关的眶额边缘神经回路的通道。 并为理解异常的神经发育过程提供了独特的前景。然而，一个主要的 嗅觉研究的障碍是缺乏非侵入性方法来捕获潜在的神经生理学信息 嗅觉丧失的底物。迄今为止，嗅觉的临床评估仅限于心理物理学方面的评估： 评估，这是主观的并且对于潜在的异常缺乏信息。在大脑中，小 直径达100-150微米的teriole是局部组织灌注的主要调节器。淋巴管 大脑中也发现了血管，据信这些血管在清除废物方面发挥着至关重要的作用 产品。嗅觉系统中小血管和淋巴管的定量测量将 提供有关嗅觉丧失的具有生物学意义的信息，并将显着加强针对嗅觉丧失的努力 脑部疾病的预测和分期。在这里，我们建议开发和优化 MRI 技术 通过以下方法定量测量人类嗅觉皮层中的小血管和淋巴管 目标： 目标 1：开发和优化用于测量动脉和静脉血容量的 MRI 方法 嗅觉皮层中的小血管分开。众所周知，嗅觉皮层很难进行 MRI 检查，因为 众所周知，由于组织和鼻腔之间的边界处的磁敏感效应而导致信号丢失。我们 将为嗅觉区域开发和优化新的 MRI 序列，以恢复靠近鼻腔的信号丢失 空腔。目标 2：开发和优化测量小淋巴动态信号变化的 MRI 方法 大脑中的血管。最近在硬脑膜和筛状周围发现了淋巴管 大脑嗅觉区的板块。脑淋巴管的非侵入性成像方法有 极其稀少，且大多仅限于大淋巴管。另外，现有方法无法 由于需要较长的扫描时间，以足够的时间分辨率检测动态淋巴信号变化。 基于之前的工作，我们建议使用基于造影剂的 MRI 方法来测量动态信号 大脑中小淋巴管的变化，从中可以推断出血管体积信息。目标 3： 为了表征精神分裂症患者嗅觉系统的小血管和淋巴管异常， 以及它们与通过行为测试评估的嗅觉缺陷的关联。综合起来，建议 研究将增进我们对与嗅觉缺陷相关的潜在生理变化的理解 在精神分裂症中，这可能有助于疾病生物标志物和潜在治疗目标的开发。 此外，该研究还将提供 MRI 方法，可用于探测类似的生理功能。 其他大脑区域的变化和疾病。