Diffusion tensor MR spectroscopic imaging in human brain

描述(申请人提供)：自闭症谱系障碍(ASD)患者脑白质微结构异常的扩散张量成像(DTI)特征通常显示额叶皮质和穹隆体水扩散各向异性降低，这与自闭症的额叶断连理论一致。然而，DTI在ASD中的发现显示出相当大的异质性，对细胞内和细胞外的不同参与或水扩散变化的潜在机制知之甚少，这些机制限制了DTI在ASD中描述发育过程的程度。弥散张量1HMRSI(DTSI)可以提供有关细胞内特性的独特信息，如粘度、细胞肿胀、亚细胞结构限制和细胞质流动，这些信息可能有助于描述自闭症可能的炎症过程。到目前为止，所有的人类研究都使用了单体素定位方法(例如，Posse等人1993a，ElleGood等人2005和2006，Upadhyay等人2007)，这是由于传统MRSI技术的压倒性运动敏感性(Posse等人)。(1993b)，这不允许绘制代谢物在假设与自闭症有关的扩展脑区之间的扩散图。这项建议的目的是开发单次激发扩散敏感磁共振成像，以显著降低运动敏感性，并显示使用临床3Tesla全身扫描仪对健康成人和患有ASD的儿童代谢物扩散进行体积映射的可行性。这一建议的具体目标是：1.开发单次激发2D空间频谱编码的DTSI，并使用(A)压缩传感与并行成像相结合的宏观运动校正和(B)确定性重建以进一步提高空间分辨率。探索性的目的是研究使用2D压缩传感和并行成像相结合的单次激发3D空间光谱编码的可行性。2.为了验证3T体模和健康成人脑的DTSI，工作假设是单次激发DTSI能够以单位时间和单位体积的灵敏度映射组织水、胆碱、肌酸和NAA的扩散张量，与单体素扩散张量谱相当。3.为了证明DTSI在3岁ASD儿童脑中的可行性，工作假设是DTSI将检测到ASD患者NAA扩散各向异性的区域性降低。一个探索性的目的是确定与DTSI和DTI测量的组织水的扩散各向异性相比，这些区域的NAA扩散各向异性是否会更强烈地降低，这意味着细胞内的炎症过程。这种DTSI方法有可能扩大ASD的成像研究范围，通过表征细胞内间隔的参与以及与疾病进展的时间进程的关系，帮助阐明ASD脑发育异常的潜在机制。其他器官和肌肉的应用也是可以预见的。 与公众健康相关：这项研究的目标是开发一种新的超高速磁共振光谱成像技术，用于使用3特斯拉全身核磁共振扫描仪绘制大脑代谢物的扩散张量。这项研究的目的是通过测量细胞内代谢物的迁移率来提高广泛使用的扩散张量成像(DTI)方法在神经系统疾病临床研究中的特异性，并将这种测量与疾病进展的时间进程联系起来。这项应用的具体目标是(A)结合3T压缩传感和并行成像重建技术开发单激发扩散敏感的1HMR波谱成像，(B)在3T条件下在人脑中验证这一方法，以及(C)在3T条件下在3岁自闭症谱系障碍儿童的大脑中证明DTSI的可行性。其他器官和肌肉的应用也是可以预见的。

DESCRIPTION (provided by applicant): Diffusion tensor imaging (DTI) characterization of white matter microstructure abnormalities in autism spectrum disorder (ASD) generally demonstrate decreased water diffusion anisotropy in frontal cortex and corpus callosum, consistent with frontal disconnectivity theories of autism. However, DTI findings in ASD show considerable heterogeneity and little is known about differential involvement of the intracellular and extracellular compartments or mechanisms underlying changes in water diffusion that limit the extent to which DTI can be used to characterize developmental processes in ASD. Diffusion tensor 1H MRSI (DTSI) can provide unique information on intracellular properties, such as viscosity, cell swelling, restriction in subcellular structures and cytoplasmic streaming, that may help to characterize possible inflammatory processes in autism. All human studies so far have used single voxel localization method (e.g. Posse et al 1993a, Ellegood et al 2005 and 2006, Upadhyay et al 2007) due to overwhelming motion sensitivity of conventional MRSI techniques (Posse et al. 1993b), which do not allow mapping of metabolite diffusion across extended brain areas hypothesized to be involved in autism. The objective of this proposal is to develop single-shot diffusion sensitive MRSI to dramatically reduce motion sensitivity, and to show feasibility of volumetric mapping of metabolite diffusion in healthy adults and children with ASD using a clinical 3 Tesla whole body scanner. The specific aims of this proposal are: 1. to develop DTSI with single-shot 2D spatial-spectral encoding and correction for macroscopic movement using (a) compressed sensing combined with parallel imaging and (b) SURE-SENSE reconstruction to further increase spatial resolution. An exploratory aim is to investigate feasibility of single-shot 3D spatial- spectral encoding using 2D compressed sensing combined with parallel imaging. 2. To validate DTSI in phantoms and healthy adult brain at 3 T The working hypothesis is that single-shot DTSI can map the diffusion tensors of tissue water, Choline, Creatine and NAA with sensitivity per unit time and unit volume that is comparable to single-voxel diffusion tensor spectroscopy. 3. To demonstrate feasibility of DTSI in the brains of 3 year old children with ASD at 3 T The working hypothesis is that DTSI will detect regional decreases in diffusion anisotropy of NAA in ASD. An exploratory aim is to determine whether NAA diffusion anisotropy in these regions will be more strongly decreased in comparison to diffusion anisotropy of tissue water measured with DTSI and DTI, implicating intracellular inflammatory processes. This DTSI methodology has the potential to enhance the scope of imaging studies of ASD by helping to clarify mechanisms underlying abnormal brain development in ASD through characterizing the involvement of intracellular compartments and in relationship to the time course of disease progression. Applications to other organs and muscle are also foreseeable. PUBLIC HEALTH RELEVANCE: The objective of this research is to develop a novel ultra high-speed MR spectroscopic imaging technique for mapping the diffusion tensors of brain metabolites using a 3 Tesla whole body MRI scanner. The goal of this research is to enhance the specificity of the widely used diffusion tensor imaging (DTI) method for clinical studies of neurological diseases by measuring metabolite mobility in the intracellular compartments and to relate this measure to the time course of disease progression. The specific aims of this application are (a) Develop single-shot diffusion sensitive 1H MR spectroscopic imaging using a combination of compressed sensing and parallel imaging reconstruction at 3 T, (b) validate this methodology in human brain at 3 T, and (c) demonstrate the feasibility of DTSI in the brains of 3 year old children with Autism Spectrum Disorder at 3 T. This DTSI methodology has the potential to enhance the scope of imaging studies of ASD by helping to clarify mechanisms underlying abnormal brain development in ASD through characterizing the involvement of intracellular compartments and in relationship to the time course of disease progression. Applications to other organs and muscle are also foreseeable.