Downfield MR spectroscopic imaging of the human brain

项目摘要 在人脑的质子磁共振波谱(MRS)中，信号同时出现在前场(UF)和 来自水的共振的前场(Df)。而UF MRS和MR光谱成像(MRSI)已经 在过去的30年里，在人类中进行了广泛的研究，很少有场外研究，所有的 他们使用单体素空间定位。最近，我们团队开发了第一个用于In的单层切片法 3T5的活体DF-MRSI。随后，我进一步实现了第一个三维(3D)DF-MRSI 方法在人脑全脑覆盖的基础上，对临床高场(3T)和超高场强进行研究。 现场(7T)磁共振系统。 目前，DF-MRSI存在两个重大的技术挑战，即：(A)缺乏脉冲序列 在最短的扫描时间内获得具有最佳灵敏度的3D DF-MRSI，以及(B)用于 对广泛且显著重叠的DF信号进行准确的量化和可视化。此外, DF-MRSI的临床和神经科学应用仍有待探索。为了解决这些问题，我 建议开发适用于3T和7T的优化的3D DF-MRSI脉冲序列，并开发一种开放的 用于改进DF共振的量化、分析和可视化的源软件包。DF谱 包含来自可交换质子和不可交换质子的信号，以及df-1的信息含量。 因此，MRSI可能是化学交换饱和转移(CEST)MRI的补充。特别是， 酰胺-质子转移(APT)CEST已被证明在评估人脑肿瘤方面相当成功； 本提案的R00阶段，在确定了规范性价值和再现性之后，对 3DDF-MRSI与APT-CEST在脑胶质瘤患者中的应用价值比较。我将特别关注 在接受高级别胶质瘤治疗的患者中区分复发肿瘤和放射性坏死的能力；这是一种 直接影响治疗选择的重要诊断问题，通常很难回答 使用常规核磁共振。 开发这些新技术需要在MRSI序列开发和 在数据分析方面。这项建议建立在我在生物医学成像方面的独特记录基础上，并接受了来自 由全球公认的核磁共振成像、临床多模式光谱成像、 并在约翰霍普金斯大学开发后处理和分析软件，表现出色 职业发展资源，成功地培训了我在这个独立之路奖。这 该项目将产生新的工具来研究神经和神经病理过程中的代谢过程 并利用它们的潜力来促进对脑瘤的理解，这可能预示着新的路线 朝着改进诊断和有效治疗策略的方向发展。

Project Summary In proton magnetic resonance spectroscopy (MRS) of the human brain, signals arise both upfield (UF) and downfield (DF) from the water resonance. While UF MRS and MR spectroscopic imaging (MRSI) have been extensively studied in humans over the last 30 years, there have been very few downfield studies, and all of them used single voxel spatial localization. Recently, our group developed the first single slice approach for in vivo DF-MRSI at 3T5. Subsequently, I have further implemented the first three-dimensional (3D) DF-MRSI methods in the human brain with whole brain coverage, on both clinical high-field (3T) and research ultra-high- field (7T) MR systems. Currently, there are two significant technical challenges for DF-MRSI, namely (a) the lack of pulse sequences to acquire 3D DF-MRSI with optimum sensitivity in the shortest possible scan time, and (b) specific software for the accurate quantification and visualization of the broad and significantly overlapping DF signals. In addition, the clinical and neuroscience applications of DF-MRSI have yet to be explored. To address these issues, I propose to develop optimized 3D DF-MRSI pulse sequences for both 3T and 7T, and also to develop an open- source software package for improved quantification, analysis, and visualization of DF resonances. DF spectra contain signals from both exchangeable and non-exchangeable protons, and the information content of DF- MRSI may therefore be complementary to chemical exchange saturation transfer (CEST) MRI. In particular, amide-proton transfer (APT) CEST has proven quite successful for the evaluation of human brain tumors; in the R00 phase of this proposal, after establishing normative values and reproducibility, a comparison of the value of 3D DF-MRSI vs. APT-CEST in patients with glioma will be performed. In particular, I will focus on the ability to distinguish recurrent tumor from radiation necrosis in patients treated for high grade glioma; this is an important diagnostic question that directly effects choice of treatment, and which is often difficult to answer using conventional MRI. Developing these novel techniques requires substantial expertise both in MRSI sequence development and in data analysis. This proposal builds upon my unique record in biomedical imaging with new training from a mentoring team of globally recognized experts in the fields of MRSI, clinical multimodal spectroscopic imaging, and development of post-processing and analysis software at the Johns Hopkins University with outstanding career development resources to successfully train me during this Pathway to Independence Award. This project will generate novel tools to study metabolic processes in neurological and neuropathological processes and leverage their potential to advance the understanding of brain tumors, potentially indicating new routes toward improved diagnosis and efficient therapy strategies.