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

描述(由申请人提供)： 尽管进行了高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。一维(1D)磁共振波谱(MRS)通常只能研究6种大脑代谢物，即使使用3台特斯拉核磁共振扫描仪也是如此。最近，在围产期感染HIV的青少年和健康儿童的前额背外侧白质区域，使用自行开发的二维定域相关光谱(L-COSY)序列结合先验知识拟合(Proit)算法，对包括谷胱甘肽(GSH)、天冬氨酸(Asp)和肌醇等新代谢物在内的15种以上大脑代谢物进行了非侵入性定量。然而，要求更大的体素(27ml)和更长的采集时间是主要的限制。因此，本课题组最近实现了两种新的基于四维(4D)多体素的2D MRS序列，即回声平面J分辨光谱成像(EP-JRESI)和回波平面相关光谱成像(EP-COSI)。以前，由于空间和频谱维度之一所需的编码步骤数量，总持续时间约为30分钟。基于压缩感知(CS)重建的非均匀采样(NUS)或沿选定空间和光谱维度的稀疏采样提高MRI/MRSI和扩散张量成像(DTI)速度的可行性最近被证明。因此，本研究将检验以下假设：1)基于NUS的五维(5D)EP-JRESI数据采集和基于CS的重建将使总采集时间缩短至少8倍，提高临床适用性，AD将提供类似的光谱和空间分辨率。2)DTI将在多个脑区显示较高的径向和轴向弥散(反映神经炎症)和较低的分数各向异性(反映神经元损伤)，作为围产期感染HIV的年轻人(尚未用DTI研究的人群)脑微结构异常的标志。提出了三个具体目标：1)优化3T MRI扫描仪上的5D EP-JRESI序列，其中NUS将合并到2个空间维度和1个频谱维度，并使用自主开发的MATL AB代码进一步优化基于CS的5D MRSI数据重建；2)获取艾滋病毒感染患者和年龄/性别匹配的健康青年大脑代谢物的多体素2D J分辨率频谱和3D光谱图像；3)记录大脑的DTI，并将DTI措施与代谢物比率和其他艾滋病毒疾病变量相关联。正在进行的脑损伤将在围产期感染艾滋病毒的青年中进行评估，并与健康青年进行比较。这项新技术也可能扩展到成人艾滋病毒，还将允许改进对其他退行性神经疾病的大脑评估。 公共卫生相关性： 使用5D光谱成像和传统扩散张量成像的新型压缩传感重建，改进的、更全面的、非侵入性的脑成像将提供对围产期感染艾滋病毒幸存者的艾滋病毒神经发病机制的更多了解。我们的方法将缩短磁共振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(如更换抗逆转录病毒药物)，以改善神经功能，防止中枢神经系统恶化，并提高生活质量。

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.