Computational Morphometry in Schizophrenia and Related Disorders

描述(由申请人提供)：本R01申请为期五年，旨在开发、评估和应用新的计算工具，以了解与精神分裂症相关的神经解剖结构的形态变化。形状测量对精神分裂症很感兴趣，因为这种疾病被一些人视为起源于神经发育，而且有证据表明，在大脑的形态发生过程中，异常的压力和/或组织形成可能会改变大脑结构的形状，特别是大脑中线的结构，以及影响新皮质的折叠模式。我们认为，计算形态测量工具对于准确地描述和量化形状变化是至关重要的。事实上，神经科学研究作为一个整体，已经显示出对许多情况下的计算机辅助形状研究的日益增长的兴趣，包括但不限于正常神经发育、阿尔茨海默病、精神分裂症和分裂型人格障碍(SPD)、双相情感障碍、精神病情感障碍和胎儿酒精暴露。因此，我们的主要目标是进一步开发新的图像分析技术，以便能够检测和定位种群之间的形状差异。我们将把这项新技术应用于首发精神分裂症受试者与首发情感性受试者(主要是躁狂症患者)和正常对照组的选定大脑结构。我们的次要目标是定量评估和比较当前最先进的形状分析工具，包括我们的工具，因为几乎没有算法得到验证。因此，将创建具有已知形状修改的合成数据集以在对照实验中使用。此外，我们将根据先前观察到的形状变化的真实数据来评估所有形状技术(例如，SPD患者的尾状核和精神分裂症患者的杏仁核-海马体)。最后，为了促进开放科学，我们将向科学界公开所有结果、数据、参数和算法。通过描述精神分裂症的形状异常，我们将进一步了解脑形态测量异常在精神分裂症中的作用，精神分裂症是一种主要的公共卫生问题，影响到近1%的总人口。公共卫生相关性：一个广为接受的假设是，一些大脑疾病的起源是神经发育，在大脑的形态形成过程中，异常的压力或组织形成可能会影响神经解剖结构的正常发育。这个项目的目标是设计计算工具来分析精神分裂症和相关障碍背景下的大脑结构的形态计量。我们相信，我们提出的设计和评估计算形态测量工具的研究，将为我们提供关于正常和异常神经发育及其与精神疾病的相关性的宝贵信息。

DESCRIPTION (provided by applicant): This R01 application is for five years of funding to develop, evaluate and apply novel computational tools for the purpose of understanding morphometric changes in neuroanatomical structures related to schizophrenia. Shape measures are of interest in schizophrenia because this disorder is viewed by some as a neurodevelopmental in origin and because there is evidence to suggest that during morphogenesis of the brain, abnormal pressures and/or tissue formations likely change the shape of brain structures, particularly those in the midline of the brain, as well as influencing folding patterns of the neocortex. We believe that computational morphometry tools are critical to characterize and to quantify shape changes accurately. In fact, neuroscience research as a whole has shown a growing interest in computer assisted shape studies for numerous conditions including, but not limited to, normal neurodevelopment, Alzheimer's disease, schizophrenia and schizotypal personality disorder (SPD), bipolar disorder, psychotic affective disorder, and fetal alcohol exposure. Our primary objective is thus to develop further new image analysis techniques to enable the detection and localization of shape differences between populations. We will apply this new technology to selected brain structures in first episode schizophrenic subjects compared to first episode affective subjects (mainly manic), and normal controls. Our secondary objective is to quantitatively evaluate and compare current state-of-the-art shape analysis tools, including ours, as few algorithms have been validated. Accordingly, a synthetic data set with known shape modifications will be created to use in a control experiment. In addition, we will evaluate all shape techniques on real data with previously observed shape changes (i.e., caudate nucleus in SPDs and amygdala-hippocampus in patients with schizophrenia). Finally, in an effort to promote open science, we will make all results, data, parameters and algorithms publicly available to the scientific community. By characterizing and delineating shape abnormalities in schizophrenia, we will understand further the role of brain morphometry abnormalities in schizophrenia, a disorder that is a major public health problem, affecting close to 1% of the general population. PUBLIC HEALTH RELEVANCE: A well accepted hypothesis is that some brain disorders are neurodevelopmental in origin and that during morphogenesis of the brain, abnormal pressures or tissue formations likely impact the proper development of neuroanatomical structures. The goal of this project is to design computational tools to analyze the morphometry of brain structures in the context of schizophrenia and related disorders. We believe that our proposed study, to design and to evaluate computational morphometric tools, will provide us with invaluable information about normal and abnormal neurodevelopment and its correlation with mental illnesses.