Compressed Sensing 5D Spectroscopic Imaging of Perinatally HIV-Infected Youth

描述（由申请人提供）： 尽管接受了高度有效的抗逆转录病毒治疗，但艾滋病毒感染者（成人和儿童）仍会出现大脑异常。因此，非侵入性神经成像工具可以评估这些治疗在保护大脑健康方面的有效性，并可能导致治疗的改进。即使使用3特斯拉MRI扫描仪，由于频谱分散有限，一维（1D）MR波谱（MRS）通常也只能研究6种大脑代谢物。最近，超过15个脑代谢物已被量化非侵入性的前额叶背外侧白色物质区域的围产期HIV感染的青年和健康儿童，包括新的代谢物，如谷胱甘肽（GSH），天冬氨酸（Asp）和鲨肌醇使用自制的二维（2D）局部相关光谱（L-COSY）序列结合先验知识拟合（ProFit）算法。然而，需要更大的体素（27 ml）和更长的采集时间是主要的限制。因此，两个新的四维（4D）多体素为基础的2D MRS序列，即回波平面J-分辨光谱成像（EP-JRESI）和回波平面相关光谱成像（EP-COSI）最近被我们的小组实施，其中两个光谱维度与两个空间维度相结合。以前，由于空间和频谱维度之一所需的编码步骤的数量，大约30分钟的总持续时间是必要的。最近已经证明了使用非均匀采样（NUS）或稀疏采样（沿着所选择的空间和频谱维度，使用基于压缩感测（CS）的重建）来提高MRI/MRSI和扩散张量成像（DTI）的速度的可行性。因此，拟议研究将测试以下假设：1）基于NUS的五维（5D）EP-JRESI数据采集和基于CS的重建将使总采集持续时间缩短至少8倍，提高临床适用性，并将提供相似的光谱和空间分辨率。2)DTI将在多个脑区显示更高的径向和轴向扩散（反映神经炎症）和更低的各向异性分数（反映神经元损伤），作为围产期HIV感染青年（尚未使用DTI研究的人群）脑中微结构异常的标志。提出了三个具体目标：1）在3 T MRI扫描仪上优化5D EP-JRESI序列，其中NUS将被合并到2个空间和1个谱维中，并使用国内开发的MATLAB代码进一步优化5D MRSI数据的基于CS的重建; 2）获得HIV感染者和年龄/性别匹配的健康青年的脑代谢物的多体素2D J分辨光谱和3D光谱图像; 3）记录大脑的DTI，并将DTI测量与代谢物比率和其他HIV疾病变量相关联。将对围产期艾滋病毒感染青年与健康青年进行比较，以评估持续的脑损伤。这项新技术也可能扩展到成人艾滋病毒，也将允许改善其他退行性神经系统疾病的大脑评估。 公共卫生相关性： 改进的，更全面的，非侵入性成像的大脑使用一种新的压缩传感重建的5D光谱成像和传统的扩散张量成像将提供增强的知识艾滋病毒神经发病机制在围产期艾滋病毒感染的幸存者。我们的方法将缩短MR光谱成像所需的时间，并允许这些工具成为这些患者的标准评估。通过跟踪这些年轻人大脑的神经发病机制，可以使用和评估干预措施（如改变抗逆转录病毒药物），以改善神经功能，防止中枢神经系统恶化，提高生活质量。

DESCRIPTION (provided by applicant): Brain abnormalities occur in HIV-infected individuals (adults and children) despite highly active antiretroviral treatment. Hence, noninvasive neuroimaging tools could assess the effectiveness of these treatments in preserving brain health and possibly lead to improvements in therapy. One-dimensional (1D) MR Spectroscopy (MRS) usually enables study of only six cerebral metabolites due to limited spectral dispersion even with 3 Tesla MRI scanners. Recently, more than fifteen cerebral metabolites have been quantified non-invasively in the prefrontal dorsolateral white matter region of perinatally HIV-infected youth and healthy children including novel metabolites such as glutathione (GSH), aspartate (Asp) and scyllo-inositol using the home-developed two-dimensional (2D) localized correlated spectroscopy (L-COSY) sequence combined with the prior-knowledge fitting (ProFit) algorithm. However, the requirement of a bigger voxel (27ml) and longer acquisition times were major limitations. Hence, two novel four-dimensional (4D) multi-voxel based 2D MRS sequences, namely echo-planar J-resolved spectroscopic imaging (EP-JRESI) and echo-planar correlated spectroscopic imaging (EP-COSI) were recently implemented by our group where two spectroscopic dimensions were combined with two spatial dimensions. Previously, due to the required number of encoding steps for one of the spatial and the spectral dimensions, a total duration of approximately 30 minutes was necessary. The feasibility of enhancing the speed of MRI/MRSI and diffusion tensor imaging (DTI) using non uniform sampling (NUS) or sparse sampling along selected spatial and spectral dimensions using compressed sensing (CS) based reconstruction has recently been demonstrated. Hence, the proposed study will test the following hypotheses: 1) The NUS-based five-dimensional (5D) EP-JRESI data acquisition and CS-based reconstruction will shorten the total acquisition duration by at least 8 fold, improving clinical applicability, ad will offer similar spectral and spatial resolution. 2) DTI will show higher radial and axial diffuson (reflecting neuroinflammation) and lower fractional anisotropy (reflecting neuronal injury) in multiple brain regions as markers of microstructural abnormalities in the brains of perinatally HIV-infected youths (a population not yet studied using DTI). Three specific goals are proposed: 1) to optimize the 5D EP-JRESI sequence on a 3T MRI scanner in which NUS will be incorporated into 2 spatial and 1 spectral dimensions, and to further optimize the CS-based reconstruction of the 5D MRSI data using home developed MATLAB code; 2) to acquire multi-voxel 2D J-resolved spectra and 3D spectroscopic images of cerebral metabolites in HIV-infected and age/sex matched healthy youths; 3) to record DTI of the brain and to correlate DTI measures with metabolite ratios and other HIV disease variables. The ongoing brain injury will be assessed in perinatally HIV- infected youth compared to healthy youths. This novel technology may also be extended to adult HIV and will also permit improved brain assessments for other degenerative neurologic diseases. PUBLIC HEALTH RELEVANCE: Improved, more comprehensive, noninvasive imaging of the brain using a novel compressed sensing reconstruction of 5D spectroscopic imaging and conventional diffusion tensor imaging will provide enhanced knowledge of HIV neuropathogenesis in perinatally HIV-infected survivors. Our approach will shorten the time required for MR spectroscopic imaging and permit these tools to become standard assessments for these patients. By following the neuropathogenesis of the brain as these youth age, interventions can be used and assessed (such as change of antiretroviral medications) to improve neurologic function, prevent central nervous system deterioration, and improve quality of life.