Novel Radial Diffusion-Weighted MR Spectroscopic Imaging of HIV: Biomarker Detection Using Functional Imaging and Neurocognitive Correlates

HIV 的新型径向扩散加权 MR 光谱成像：使用功能成像和神经认知相关性进行生物标志物检测

• 批准号: 10256718
• 负责人: MICHAEL Albert THOMAS
• 金额: $ 21.9万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256718
• 关键词: 3-Dimensional; AIDS dementia; Acceleration; Acquired Immunodeficiency Syndrome; Acute; Adult; Age; American; Anatomy; Anisotropy; Basal Ganglia; Biological Markers; Brain; Brain Neoplasms; Brain region; Carbon; Centers for Disease Control and Prevention (U.S.); Cerebral Ischemia; Cerebrum; Characteristics; Chemicals; Choline; Cognitive; Complex; Creatine; Dementia; Detection; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Environment; Evaluation; Frequencies; Functional Imaging; Functional disorder; Glutamates; Glutamine; HIV; HIV Infections; HIV-associated neurocognitive disorder; Health; Human; Image; Imaging Device; Imaging Techniques; Immune; Impaired cognition; Individual; Inflammatory; Inositol; Intracellular Space; Lead; Life; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolic; Metabolism; Methods; Morphologic artifacts; Motion; N-acetylaspartate; Neuraxis; Neurocognitive; Neurologic Symptoms; Neuronal Injury; Neurons; Neuropsychological Tests; Neuropsychology; Noise; Organ; Outcome; Pathologic; Patients; Phase; Prevalence; Protocols documentation; Radial; Reporting; Reproducibility; Research; Research Personnel; Sampling; Scanning; Speed; Structure; Techniques; Technology; Test Result; Testing; United States; Variant; Water; Work; antiretroviral therapy; base; cohort; diffusion weighted; excitotoxicity; functional disability; gray matter; human subject; improved; innovation; magnetic resonance spectroscopic imaging; neurochemistry; neuroimaging; neuroinflammation; non-invasive imaging; novel; reconstruction; sex; spectroscopic imaging; tool; water diffusion; white matter

Project Summary/Abstract HIV-induced immune activity in the central nervous system (CNS) is believed to lead to permanent brain changes, neurocognitive dysfunction and functional impairment. MR Spectroscopy (MRS) is a powerful non- invasive tool for assessing neurochemical changes in multiple brain locations of HIV+ patients. In contrast to diffusivity of water recorded using diffusion weighted imaging (DWI), diffusion-weighted (DW)-MR spectroscopy can detect the diffusivity of intracellular metabolites such as, N-acetylaspartate, creatine, and choline, which are exclusively located in the intracellular space, with a slow exchange between intra- and extra-cellular compartments; therefore, the detected apparent diffusion coefficients (ADCs) of cerebral metabolites can only be attributed to diffusion in the intracellular space. The outcome would provide more information (diffusivity of metabolites) than averaged water diffusivity from DTI. Earlier attempts have investigated the ADCs of three metabolites using single-voxel localized MRS in mostly healthy human subjects. MR imaging using radial sampling has been shown to be less sensitive to motion and off-resonance effects. Earlier work on DW line scan echo planar spectroscopic imaging (DW-LSEPSI) for motion robustness suffered from reduced SNR. Extending radial sampling to hyperpolarized carbon-13 (13C) MRSI has been demonstrated; however, implementation in 1H MRSI has not been demonstrated. We propose to develop volumetric radial-based echo-planar diffusion- weighted spectroscopic imaging (r-DW-EPSI), to evaluate diffusion of intracellular metabolites such as NAA, Cr, Cho, and Glu/glutamine (Glx). Alterations in metabolite ADC values may generate additional information about mechanisms underlying HIV, even after anti-retroviral therapy (ART). By exploiting strategies of acquisition acceleration of spatial encoding using FISTA with variable acceleration reconstruction, the radial EPI readout in the DW-EPSI sequence will enable recording of multi-voxel DW-spectra an order of magnitude faster than when using conventional phase-encoding. Specific aims of this study are: (1) Develop accelerated r-DW-EPSI using semi-LASER localization, and optimize it in brain phantoms and 10 healthy adults. (2) Determine ADCs of Cr, NAA, Cho, mI and Glx in 25 HIV+ subjects, and assess their differences compared to 25 age-/sex-matched healthy adults. The outcome will be correlated with DTI metrics, neuropsychological test results, and other disease variables. We will test the following hypotheses: 1) The accelerated 3D r-DW-EPSI acquisition will be less sensitive to motion and chemical shift off-resonance effects due to oversampling in the central k-space. Altered ADCs of non-water molecules will be measured in multiple brain regions as markers of microstructural abnormalities as well as relative metabolite concentrations. 2) Metabolite ADCs and relative concentrations will support DTI findings correlating with neurocognitive cognitive impairments reflecting neuroinflammation and neuronal injury in the brains of HIV-infected subjects. This is unexplored territory in HIV research. Successful implementation of the r-DW-EPSI has the potential to be extended to other organs where motion is a prime concern.

项目总结/摘要 HIV在中枢神经系统（CNS）中诱导的免疫活动被认为会导致永久性的脑损伤。 变化、神经认知功能障碍和功能损害。磁共振波谱（MRS）是一种强大的非 用于评估HIV+患者多个大脑位置的神经化学变化的侵入性工具。相比 使用扩散加权成像（DWI）、扩散加权（DW）-MR波谱记录水的扩散率 可以检测细胞内代谢物如N-乙酰天冬氨酸、肌酸和胆碱的扩散率， 仅位于细胞内空间，细胞内和细胞外之间的缓慢交换 因此，检测到的脑代谢物的表观扩散系数（ADC）只能 可能是由于细胞内空间的扩散。结果将提供更多的信息（ 代谢物）比来自DTI的平均水扩散率。早期的尝试研究了三种ADC 在大多数健康的人类受试者中使用单体素局部MRS检测代谢物。MR成像使用径向 已经证明采样对运动和非共振效应不太敏感。DW行扫描的早期工作 回波平面光谱成像（DW-LSEPSI）的运动鲁棒性遭受降低的SNR。延伸 已经证明了对超极化碳-13（13 C）MRSI的径向采样;然而， 1H MRSI尚未得到证实。我们建议开发基于体积径向的回波平面扩散- 加权光谱成像（r-DW-EPSI），以评价细胞内代谢物如NAA，Cr， Cho和Glu/谷氨酰胺（Glx）。代谢物ADC值的变化可能产生关于以下方面的额外信息： 即使在抗逆转录病毒治疗（ART）后，也可以了解艾滋病毒的潜在机制。通过利用收购策略 使用具有可变加速重建的FISTA的空间编码加速， DW-EPSI序列将使得能够记录多体素DW-光谱 使用传统的相位编码。本研究的具体目的是：（1）开发加速r-DW-EPSI使用 半激光定位，并优化它在脑幻影和10名健康成人。(2)确定Cr的ADC， 25例HIV阳性受试者的NAA、Cho、mI和Glx，并评估其与25例年龄/性别匹配受试者相比的差异 健康成人结果将与DTI指标，神经心理学测试结果和其他相关因素相关。 疾病变量我们将测试以下假设：1）加速的3D r-DW-EPSI采集将 对由于中心k空间中的过采样而引起的运动和化学位移非共振效应不太敏感。 将在多个脑区域中测量非水分子的改变的ADC，作为微结构的标志物。 异常以及相对代谢物浓度。2)代谢物ADC和相对浓度将 支持与反映神经炎症的神经认知障碍相关的DTI结果， HIV感染者大脑中的神经元损伤。这是艾滋病研究中尚未探索的领域。成功 r-DW-EPSI的实施有可能扩展到运动是主要因素的其他器官 关心