Ultra-Resolution Imaging of Brain Circuitry and its Development in Mental Health

脑回路超分辨率成像及其在心理健康领域的发展

• 批准号: 8506266
• 负责人: CHUNLEI LIU
• 金额: $ 39.25万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-03 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506266
• 关键词: 22q11.2; Adult; American; Atlases; Axon; Behavioral Symptoms; Brain; Brain Diseases; Brain Mapping; Brain imaging; Clinical; Corpus striatum structure; Demyelinations; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Fiber; Functional disorder; Genes; Genetic; Glutamates; Hippocampus (Brain); Human; Image; Imaging Techniques; Life; Lipids; MRI Scans; Magnetic Resonance Imaging; Magnetism; Mental Health; Mental disorders; Methodology; Methods; Modeling; Molecular; Molecular Abnormality; Myelin; Neurobehavioral Manifestations; Neurons; Pathogenesis; Patients; Phase; Predisposition; Proteins; Research; Resolution; Risk Assessment; Schizophrenia; Sensitivity and Specificity; Specificity; Symptoms; Synapses; Synaptic plasticity; Techniques; Testing; Transgenic Mice; Translations; Traumatic Brain Injury; base; clinical Diagnosis; developmental genetics; effective intervention; emerging adult; experience; imaging modality; improved; in vivo; innovation; knowledge of results; mouse model; multidisciplinary; myelination; neurodevelopment; novel; preclinical study; prevent; public health relevance; relating to nervous system; treatment strategy; ultra high resolution; white matter; young adult

DESCRIPTION (provided by applicant): One in four adult Americans experiences a mental health disorder in a given year. About 2.4 million Americans live with schizophrenia. There are considerable and growing evidences suggesting schizophrenia may originate from early neurodevelopment involving abnormal neuronal circuits. However, schizophrenia still cannot be diagnosed until young adulthood at the earliest when the most rapid phase of neurodevelopment has already completed. The lack of earlier risk assessment has severely limited our understanding of the developmental trajectory of the disease thus preventing more effective intervention before symptom onset. This project will develop a novel non-invasive MRI technique that will provide the necessary sensitivity and resolution (10 micron) to detect potential developmental abnormalities associated with neuronal circuits. Our preliminary studies have demonstrated a markedly improved sensitivity and resolution compared to state-of- the-art MRI techniques. We will further develop this novel technique and determine its molecular basis of the improved sensitivity. We will test the technique on transgenic mouse models of schizophrenia and investigate its ability to detect abnormalities in neuronal circuits before symptoms occur. In particular, we will determine the relationship between the new image contrast and abnormalities of myelination and synapses associated with corticostriatal and corticohippocampal connectivity. The rationale of the research is that the proposed multidisciplinary imaging-genetics study would help us to better understand the genetic and developmental components of the disease, to detect circuit abnormalities before behavioral symptoms, and to eventually guide treatment strategies.

描述（由申请人提供）：四分之一的成年美国人在给定的一年中患有精神健康障碍。大约有240万美国人患有精神分裂症。有很大的证据表明，精神分裂症可能起源于涉及异常神经元回路的早期神经发育。但是，直到最早的神经发育阶段已经完成后，精神分裂症仍无法诊断为成年。缺乏较早的风险评估严重限制了我们对疾病发育轨迹的理解，从而阻止了症状发作前的有效干预。该项目将开发一种新型的非侵入性MRI技术，该技术将提供必要的灵敏度和分辨率（10微米），以检测与神经元回路相关的潜在发育异常。我们的初步研究表明，与最先进的MRI技术相比，灵敏度和分辨率明显提高。我们将进一步开发这种新颖的技术，并确定其提高灵敏度的分子基础。我们将在精神分裂症的转基因小鼠模型上测试技术，并研究其在症状发生之前检测神经元回路异常的能力。特别是，我们将确定新图像对比度与髓鞘形式异常与与皮质纹状体和皮质层状连通性相关的突触之间的关系。该研究的理由是，拟议的多学科成像基因研究将帮助我们更好地了解疾病的遗传和发育成分，以在行为症状前检测电路异常，并最终指导治疗策略。