Manganese Enhanced Multi-MRI for Murine HIV-1 Associated Neurocognitive Disorders

锰增强多重 MRI 治疗小鼠 HIV-1 相关神经认知障碍

基本信息

批准号：
8393064
负责人：
Yutong Liu
金额：
$ 14.86万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8393064
关键词：
AIDS Dementia Complex AIDS neuropathy Address Affect Algorithms Anatomy Animals Astrocytosis Atrophic Attenuated Award Axon Behavioral Biochemical Biological Markers Biomedical Research Brain Brain imaging Cells Characteristics Chronic Clinical Cognitive Cognitive deficits Data Analyses Dementia Detection Development Diagnosis Diffusion Magnetic Resonance Imaging Disease Disease Progression Disease model Doctor of Philosophy Dose Drops Edema Encephalitis Engineering Engraftment Event Faculty Fiber Focal Infection Foundations Functional disorder Generations Giant Cells Goals HIV-1 Highly Active Antiretroviral Therapy Histology Histopathology Human Image Imagery Imaging technology Impairment Incidence Infection International Laboratories Macrophage Activation Magnetic Resonance Magnetic Resonance Imaging Manganese Maps Mathematics Measures Medical Imaging Medical center Mentors Methods Metric Microglia Microscopic Microscopy Modeling Monitor Morphology Motor Mus Myelin Nebraska Nervous system structure Neuroanatomy Neurocognitive Neurodegenerative Disorders Neurologic Neurologic Dysfunctions Neurons Neurosciences Noise Operative Surgical Procedures Pallor Pathology Pathway interactions Patients Physiological Physiology Prevalence Procedures Process Radiology Specialty Relaxation Research Research Personnel Research Project Grants Resolution Scanning Severe Combined Immunodeficiency Signal Transduction Signs and Symptoms Slice Solid Staging Staining method Stains Stem cells Structure Synapses Techniques Testing Therapeutic Time Training Training and Education United States National Institutes of Health Universities Viral Viral Encephalitis Virus Virus Diseases Weight Western World Xenograft procedure antiretroviral therapy astrogliosis authority brain volume career density environmental change experience gray matter image processing in vivo irradiation macrophage manganese chloride member nervous system disorder neuroinflammation neuron loss neuropsychological neurotoxicity novel post-doctoral training public health relevance theories ultra high resolution uptake water diffusion white matter

项目摘要

DESCRIPTION (provided by applicant): The candidate, Yutong Liu PhD, is a junior faculty member in the Radiology Department with a strong background in engineering and mathematics, MRI theory, and medical image processing. Dr Liu has had extensive experience in the application of MRI and development of novel image processing methods both during his post-doctoral training and his first years as a junior faculty member. This provides him a solid foundation for biomedical research, but to develop as an independent investigator in neuroscience he requires training in basic neuroscience and practical aspects of performing animal studies. Dr. Liu has assembled a strong mentor and collaborator team with an excellent track record in MRI, neuroscience and image processing research. His primary mentor, Dr. Michael Boska is a leading expert in MRI and MRS. His co-mentor, Dr. Howard Gendelman is an international authority in neurodegenerative diseases. In addition, Dr. Liu will take graduate level courses in neuroscience provided in UNMC. The research project addresses an imperative need in NeuroAIDS research as detailed below. This project will provide training for Dr. Liu in 1) murine brain anatomy and physiology, 2) generation of disease models in mice including irradiation, human cell engraftment, cell acquisition, cultivation, infection and animal surgery, 3) immunohistochemical processing and analysis including, but not limited to slicing, staining and quantification of histopathological staining used for interpretation of results. Dr. Liu will submit a R01 to the NIH by the end of Year 3 of the award focused on the study of neurodegenerative diseases using advanced imaging technologies. His long term career goal is to become an independent investigator in neuroscience. HIV-1 associated neurocognitive disorders (HAND) occurs in the late stage HIV-1 infection and manifests with varying degrees of clinical cognitive, behavioral and motor abnormalities. These range from mild motor/cognitive deficits to overt dementia (HIV-1 associated dementia, HAD). With antiretroviral therapy the cumulative incidence is 25-38% and the prevalence is around 37%. Milder forms affect an additional 30-40% of patients. The chronic and fluctuating forms of HIV dementia are more common. The pathological correlate of HAD is HIV-1 encephalitis (HIVE). The presence of activated microglia and brain macrophages with lower levels of virus is a central pathological feature of disease. Tests that can clearly distinguish HAND from other diseases of the nervous system that occur during progressive HIV-1 infection are needed for definitive diagnosis, disease progression tracking and therapeutic monitoring. Murine models of HIVE and HAND have been developed at the University of Nebraska Medical Center. The objective of this proposal is to develop in-vivo manganese enhanced 3D multispectral magnetic resonance microscopy (MRM) that will serve as a biomarker for HAND. In vivo manganese enhanced multispectral MRM (MEmMRM) and MRM data analysis techniques will be developed to determine the time course of neuronal loss, macrophage/microglial activation and astrocytosis in the murine HIVE and HAND models. MEmMRM results in diseased mice will be confirmed with controls and histopathological analysis.

描述（由申请人提供）：候选人Yutong Liu PhD是放射学系的初级教职员工，具有工程和数学，MRI理论和医学图像处理方面的良好背景。 Liu博士在MRI的应用和新型图像处理方法的应用中都有丰富的经验，包括他的博士后培训和他作为初级教师的第一年。这为他提供了生物医学研究的坚实基础，但是要作为神经科学的独立研究者发展，他需要在基本神经科学和进行动物研究的实际方面进行培训。 Liu博士召集了一个强大的导师和合作团队，在MRI，神经科学和图像处理研究方面具有出色的往绩。他的主要导师迈克尔·博斯卡（Michael Boska）是MRI和MRS的主要专家。他的同事霍华德·盖德尔曼（Howard Gendelman）博士是神经退行性疾病的国际权威。此外，Liu博士将参加UNMC提供的神经科学的研究生水平课程。该研究项目解决了如下所述的神经辅助研究的必要性。该项目将在1）鼠脑解剖学和生理学中为Liu博士提供培训，2）在小鼠中产生疾病模型，包括辐射，人类细胞植入，习得，培养，感染和动物外科手术，3）免疫组织化学处理和分析，包括，包括，但不限于用于切片，染色和定量用于解释的组织病理学陈述。 Liu博士将在奖项的第3年底向NIH提交R01，重点是使用高级成像技术研究神经退行性疾病。他的长期职业目标是成为神经科学的独立研究者。 HIV-1相关的神经认知障碍（手）发生在晚期HIV-1感染中，并且表现出不同程度的临床认知，行为和运动异常。这些范围从轻度运动/认知缺陷到明显的痴呆（HIV-1相关痴呆，患有）。使用抗逆转录病毒疗法，累积发生率为25-38％，患病率约为37％。温和的形式影响了30-40％的患者。 HIV痴呆的慢性和波动形式更为普遍。 HAD的病理相关性是HIV-1脑炎（Hive）。病毒水平较低的活化的小胶质细胞和脑巨噬细胞的存在是疾病的中心病理特征。需要清楚地将手动与进行性HIV-1感染过程中发生的其他疾病区分开的测试需要确定性诊断，疾病进展跟踪和治疗性监测。内布拉斯加州大学医学中心已经开发了蜂巢和手的鼠模型。该提案的目的是开发体内锰增强的3D多光谱磁共振显微镜（MRM），该磁共振显微镜（MRM）将用作手动的生物标志物。将开发体内锰增强的多光谱MRM（MEMMRM）和MRM数据分析技术，以确定鼠蜂蜂和手部模型中神经元丧失，巨噬细胞/小胶质细胞激活和星形胶质细胞增多的时间过程。 MEMMRM结果将通过对照和组织病理学分析确认患病小鼠。