Diffusion tensor MR spectroscopic imaging in human brain

描述（由申请人提供）：自闭症谱系障碍（ASD）白质微观结构异常的扩散张量成像（DTI）表征通常显示额叶皮层和胼胝体的水扩散各向异性减少，与自闭症的额叶失联理论一致。然而，DTI在ASD中的发现显示出相当大的异质性，并且对细胞内和细胞外区室的差异参与或水扩散变化的机制知之甚少，这限制了DTI用于表征ASD发育过程的程度。扩散张量1H MRSI （DTSI）可以提供关于细胞内特性的独特信息，如黏度、细胞肿胀、亚细胞结构限制和细胞质流动，这可能有助于表征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年和2006年，Upadhyay等人2007年），因为传统的磁共振成像技术（Posse等人1993b）对运动非常敏感，不允许绘制代谢物在被假设与自闭症有关的扩展脑区域的扩散图。本提案的目的是开发单次扩散敏感的MRSI，以显着降低运动敏感性，并证明使用临床3特斯拉全身扫描仪对健康成人和儿童ASD代谢物扩散进行体积测绘的可行性。本建议的具体目的是：1。通过(a)压缩感知结合并行成像和(b) SURE-SENSE重建，进一步提高空间分辨率，开发单镜头二维空间光谱编码和宏观运动校正的DTSI。探索利用二维压缩感知结合并行成像技术实现单镜头三维空间光谱编码的可行性。2. 工作假设是，单次DTSI可以绘制组织水、胆碱、肌酸和NAA的扩散张量，单位时间和单位体积的灵敏度与单体素扩散张量光谱相当。3. 为了证明3岁ASD儿童3岁时DTSI的可行性，工作假设是DTSI可以检测到ASD中NAA扩散各向异性的区域减少。探索性目的是确定与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，从而暗示细胞内炎症过程。这种DTSI方法通过描述细胞内区室的参与以及与疾病进展的时间进程的关系，有助于阐明ASD中大脑异常发育的机制，从而有可能扩大ASD成像研究的范围。在其他器官和肌肉上的应用也可以预见。

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.