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

项目总结/摘要 嗅觉缺陷是许多脑部疾病（包括精神分裂症）的核心特征和临床前体征。 嗅觉系统提供了直接进入与疾病相关的眶额边缘神经回路的途径， 这是一个独特的条件，并为理解异常的神经发育过程提供了独特的承诺。然而一个主要 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学 嗅觉丧失的基质。迄今为止，嗅觉的临床评价仅限于心理物理学方面， 评估，对于潜在的异常情况是主观的且没有信息。在大脑中，小的- 直径高达100-150微米的小泡是局部组织灌注的主要调节剂。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生物学意义的信息，并将大大加强对嗅觉丧失的研究。 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， 用以下方法定量测量人嗅觉皮层中的小血管和淋巴管 目的：目的1：建立和优化MRI测量动、静脉心肌血容量的方法。 在嗅皮层中分别有微血管。众所周知，嗅觉皮层很难进行MRI，因为 由组织和鼻腔之间的边界处的磁化率效应引起的众所周知的信号损失。我们 将为嗅觉区域开发和优化新的MRI序列，以恢复靠近鼻腔的信号丢失 腔目的2：建立和优化MRI测量小淋巴管动态信号变化的方法 大脑中的血管最近在硬脑膜和筛状周围发现了淋巴管 在大脑的嗅觉区。脑淋巴管的非侵入性成像方法是 非常罕见，大多数仅限于大淋巴管。此外，现有的方法不能 由于需要长的扫描时间，因此可以以足够的时间分辨率检测动态淋巴信号变化。 本文在前人工作的基础上，提出了基于造影剂的MRI动态信号测量方法 脑内小淋巴管的变化，从中可以推断出血管体积信息。目标3： 为了描述精神分裂症患者嗅觉系统的小血管和淋巴管异常， 以及它们与嗅觉缺陷的关系，通过行为测试进行评估。综合考虑， 研究将促进我们对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靶点的发展。 此外，该研究将提供MRI方法，可用于探测类似的生理 其他脑区和疾病的变化。

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.