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

项目摘要/摘要 嗅觉缺陷是包括精神分裂症在内的许多大脑疾病的核心特征和临床前迹象。 嗅觉系统提供了直接进入眼眶前额-边缘神经回路的途径，这些神经回路与疾病相关。 它为理解异常的神经发育过程提供了独特的希望。然而，一个主要的 嗅觉研究的障碍是缺乏非侵入性的方法来捕捉潜在的神经生理 嗅觉丧失的底物。到目前为止，嗅觉的临床评估仅限于心理物理方面-- 评估，这是关于潜在异常的主观性和非信息性。在大脑里，小阿尔- 直径可达100-150微米的Terioles是局部组织灌流的主要调节剂。淋巴 在大脑中也发现了血管，这些血管被认为在清除废物方面起着关键作用。 产品。对嗅觉系统中的小血管和淋巴管进行定量测量将 提供有关嗅觉丧失的具有生物学意义的信息，并将大大加强对 脑部疾病的预测和分期。在这里，我们建议开发和优化磁共振成像技术，用于 人嗅觉皮质内小血管和淋巴管的定量测量 目的：目的1：建立和优化微动静脉血容量的MRI测量方法。 嗅皮层中的小血管是分开的。众所周知，嗅觉皮质对MRI来说是很困难的，因为 众所周知，由于组织和鼻腔交界处的敏感性效应造成的信号损失。我们 将为嗅觉区域开发和优化新的MRI序列，以恢复鼻部附近的信号丢失 空洞。目的2：建立和优化测量小淋巴管动态信号变化的MRI方法 大脑中的血管。最近在硬脑膜和筛骨周围发现了淋巴管。 大脑中嗅觉区的一块平板。脑淋巴管的非侵入性成像方法有 极其稀少，大多仅限于大淋巴管。此外，现有的方法不能 由于需要较长的扫描时间，因此能够以足够的时间分辨率检测动态淋巴信号的变化。 在前人工作的基础上，我们提出了使用基于造影剂的磁共振成像方法来测量动态信号 大脑中小淋巴管的变化，由此可以推断血管的体积信息。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。总而言之，拟议的 研究将促进我们对与嗅觉缺陷相关的潜在生理变化的理解 这可能有助于疾病生物标记物和潜在治疗靶点的开发。 此外，这项研究将提供可用于探测类似生理问题的MRI方法 其他大脑区域和疾病的变化。

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.