Novel 10.5 T deuterium-based MRS/I method to measure brain metabolism

项目总结/摘要 人类代谢组的病理变化是所有脑疾病发病机制的普遍和基础。 疾病，包括癌症、痴呆和精神疾病。该项目旨在开发一种非侵入性的 磁共振成像工具，以前所未有的方式询问人脑代谢， 世界上第一台超高场10.5T全身人体MRI扫描仪和一种新型动态氘质子 交换（2 H至1H）MRS方法。两种互补策略，单体素光谱（SVS）和MR 光谱成像（MRSI）将平行开发。2 H到1H MRS将能够量化和成像 浓度和代谢通量在人脑中体内通过整个代谢途径，从一个 单扫描。在这个项目的第一部分，我们将利用最先进的MR兼容传感器和校准 扫描，以准确表征空间场不均匀性，并监测扫描仪和受试者依赖性 10.5T时的时间不稳定性在第二部分中，我们将开发并验证一种新型动态1H-SVS 技术，重点是通过靶向最大化可重复检测的代谢物范围 一个精确定义的大脑区域在第三部分中，我们将建立一个新的高度准确和强大的 用于10.5 T的动态1H-MRSI方法，其将权衡询问广泛代谢物的能力 因为我们有能力在整个大脑中对其中一些进行成像。在最后一部分，我们将证明的可行性， 在10.5 T和7 T下通过动态2 H-to-1H MRS无创地测量人脑代谢， 2 H标记的葡萄糖和估计实验和生理变异性。我们将比较 氘代谢成像的新工具。这个项目的成功完成将提供一个强大的工具 用于神经科学和代谢研究。

PROJECT SUMMARY/ABSTRACT Pathological changes in the human metabolome are ubiquitous and fundamental to the pathogenesis of all brain disorders including cancer, dementia, and psychiatric disorders. This project proposes to develop a non-invasive magnetic resonance imaging tool to interrogate human brain metabolism in an unprecedented way using the world’s first ultra-high field 10.5 T whole-body human MRI scanner and a novel dynamic deuterium to proton exchange (2H-to-1H) MRS approach. Two complimentary strategies, single-voxel spectroscopy (SVS) and MR spectroscopic imaging (MRSI) will be developed in parallel. 2H-to-1H MRS will be able to quantify and image concentrations and metabolic fluxes in the human brain in vivo through the entire metabolic pathway from a single scan. In the first part of this project, we will utilize state-of-the-art MR-compatible sensors and calibration scans to accurately characterize spatial field inhomogeneities and monitor scanner- and subject-dependent temporal instabilities at 10.5 T. In the second part, we will develop and validate a novel dynamic 1H-SVS technique at 10.5 T with the focus on maximizing the range of reproducibly detectable metabolites by targeting a single accurately defined brain region. In the third part, we will establish a new highly accurate and robust dynamic 1H-MRSI method for 10.5 T, which will trade-off the ability to interrogate a broad range of metabolites for the ability to image some of them over the entire brain. In the final part, we will proof the feasibility of measuring human brain metabolism in vivo non-invasively via dynamic 2H-to-1H MRS at 10.5 T and 7 T using 2H-labled glucose and estimate experimental and physiologic variability. We will compare the performance of our novel tool to deuterium metabolic imaging. Successful completion of this project will provide a powerful tool for neuroscience and metabolic research.