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

项目摘要/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大脑 改变、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 评估HIV+患者多个脑部位神经化学变化的侵入性工具。与之形成鲜明对比的是 用扩散加权成像(DWI)、扩散加权(DW)-磁共振波谱记录水的扩散率 可以检测细胞内代谢产物的扩散率，如N-乙酰天冬氨酸、肌酸和胆碱，这些物质 仅位于细胞内空间，细胞内和细胞外交换缓慢 因此，检测到的大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(扩散性 代谢物)高于DTI的平均水扩散系数。早先的尝试已经调查了三个ADC 在大多数健康受试者中使用单体素定位MRS的代谢物。使用径向的磁共振成像 采样已被证明对运动和非共振效应不那么敏感。DW行扫描的早期工作 回波平面光谱成像(DW-LSEPSI)的运动稳健性因信噪比降低而受到影响。扩展 已经演示了对超极化碳-13(13C)MRSI的径向采样；然而，在 1H MRSI尚未得到证实。我们建议发展基于体积径向的回波平面扩散-- 加权光谱成像(r-DW-EPSI)，以评估细胞内代谢物的扩散，如NAA，Cr， Cho和谷氨酰胺/谷氨酰胺(Glu/Glu/Glx)。代谢物ADC值的改变可能会产生关于 艾滋病毒的潜在机制，即使在抗逆转录病毒治疗(ART)之后也是如此。通过利用收购战略 使用Fista进行空间编码的可变加速重建的加速，径向EPI读出在 DW-EPSI序列将使多体素DW谱的记录速度比在以下情况下快数量级 使用传统的相位编码。本研究的具体目标是：(1)开发加速的r-DW-EPSI 半激光定位，并在脑模体和10名健康成年人中进行优化。(2)测定铬的ADC， 25例HIV+患者的NAA、CHO、MI和GLX，并与25例年龄/性别匹配的患者进行比较 健康的成年人。结果将与DTI指标、神经心理测试结果和其他指标相关联 疾病变量。我们将检验以下假设：1)加速的3D r-DW-EPSI采集将是 由于中心k空间中的过采样，对运动和化学位移不太敏感的非共振效应。 将在多个脑区测量非水分子的改变的ADC，作为微结构的标志 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发现与反映神经炎症和神经炎症的神经认知损害相关 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 R-DW-EPSI的实施有可能扩展到运动是质数的其他器官 担忧。

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.