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.

项目概要/摘要 HIV 诱导的中枢神经系统 (CNS) 免疫活动被认为可导致永久性大脑损伤 变化、神经认知功能障碍和功能障碍。磁共振波谱 (MRS) 是一种强大的非 用于评估 HIV+ 患者多个大脑部位的神经化学变化的侵入性工具。相比之下 使用扩散加权成像 (DWI)、扩散加权 (DW)-MR 光谱记录水的扩散率 可以检测细胞内代谢物的扩散性，例如 N-乙酰天冬氨酸、肌酸和胆碱，这些代谢物 完全位于细胞内空间，细胞内和细胞外之间的交换缓慢 隔间；因此，检测到的脑代谢物的表观扩散系数（ADC）只能 归因于细胞内空间的扩散。结果将提供更多信息（ 代谢物）比 DTI 的平均水扩散率。早期尝试研究了三个的 ADC 使用单体素局部 MRS 在大多数健康人类受试者中研究代谢物。使用径向 MR 成像 采样已被证明对运动和偏共振效应不太敏感。 DW 线扫描的早期工作 用于运动稳健性的回波平面光谱成像 (DW-LSEPSI) 因信噪比降低而受到影响。延伸 超极化碳 13 (13C) MRSI 的径向采样已得到证实；然而，实施 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)，用于评估细胞内代谢物的扩散，例如 NAA、Cr、 Cho和谷氨酰胺/谷氨酰胺(Glx)。代谢物 ADC 值的改变可能会产生有关以下方面的附加信息： 即使在抗逆转录病毒治疗（ART）之后，HIV 的潜在机制也是如此。通过利用收购策略 使用具有可变加速度重建的 FISTA 进行空间编码加速，径向 EPI 读数 DW-EPSI 序列将使多体素 DW 光谱的记录速度比以前快一个数量级 使用传统的相位编码。本研究的具体目标是：（1）利用 R-DW-EPSI 开发加速器 半激光定位，并在大脑模型和 10 名健康成年人中进行优化。 (2) 确定 Cr 的 ADC， 对 25 名 HIV+ 受试者进行 NAA、Cho、mI 和 Glx 分析，并评估其与 25 名年龄/性别匹配的受试者相比的差异 健康的成年人。结果将与 DTI 指标、神经心理学测试结果和其他相关 疾病变量。我们将测试以下假设： 1) 加速 3D r-DW-EPSI 采集将是 由于中心 k 空间中的过采样，对运动和化学位移偏共振效应不太敏感。 改变的非水分子 ADC 将在多个大脑区域进行测量，作为微结构的标记 异常以及相对代谢物浓度。 2) 代谢物 ADC 和相对浓度将 支持 DTI 结果与反映神经炎症的神经认知障碍相关 HIV感染者大脑中的神经元损伤。这是艾滋病毒研究中尚未探索的领域。成功的 r-DW-EPSI 的实施有可能扩展到以运动为主要因素的其他器官 忧虑。