建立适用于活体生物组织高分辨磁共振定域谱的新方法

In vivo magnetic resonance spectroscopy (MRS) as a non-invasive tool can provide spectral information about metabolism and biochemical composition of tissues and has already been used for pathogenesis investigation and clinical diagnostics. However, the field homogeneity is degraded due to the magnetic susceptibility inhomogeneity in living organisms, such as blood vessels, air, fat, and lesions, etc., resulting in poor spectral resolution. The application of the MRS method is to some extent limited. It has been found that high-resolution spectra can be obtained by the intermolecular Single-Quantum Coherence (iSQC)-based NMR method in inhomogeneous magnetic field. In this project, based on a series of intermolecular Multiple-Quantum Coherence (iMQC)-based high-resolution NMR methods developed by our group, a novel method for in vivo high-resolution 1H MRS of biological tissue will be proposed. Through theoretical formulation and computer simulation of the characteristics of the magnetic field inhomogeneity caused by inhomogeneous magnetic susceptibility between different biological tissues, the physical models for the evolution of iSQC signal of biological tissue can be established. The spin-locking technology will be proposed to reduce the rapid attenuation of the NMR signal due to spin exchange and magnetic susceptibility inhomogeneity. Three possible implementations of localized iSQC spectroscopy and the feasibility of the iSQC-based MRS comparing with the traditional MRS method will be discussed. Through optimizing the experimental parameters to further improve the signal to noise ratio and resolution of iSQC, the method for in vivo high-resolution 1H MRS of biological tissue will be developed. In addition, the new developed MRS method will be used for the in vivo breast cancer research of rat, the results will be expected to provide a new 1H MRS method for the characterization of biological tissue and helpful fundamental and experimental support for the early diagnosis of breast cancer.

磁共振定域谱（MRS）能够无创地提供活体组织指定区域的代谢和生化信息，成为临床医学中具有广泛应用前景的诊断方法。然而，血管、空气、脂肪和坏死区域等组织磁化率的不均匀会影响代谢物的检出，在一定程度上局限了MRS方法的临床应用。研究发现基于分子间单量子相干（iSQC）技术的NMR方法能够在不均匀磁场中获得高分辨谱。本课题拟以本研究组开发的一系列不均匀磁场下iMQC高分辨NMR方法为基础，通过理论表述和计算机模拟研究由磁化率不均匀引起的磁场不均匀性的特点，针对活体组织由于自旋交换和磁化率不均匀等导致NMR信号快速衰减的问题，拟采用自旋锁定技术加以克服；对比定域模块的不同执行方式，与传统MRS方法进行比较，进一步优化实验、脉冲序列参数提高iSQC信号的信噪比和分辨率，建立适用于活体组织高分辨磁共振定域谱的新方法。并将该方法应用于活体大鼠乳腺癌研究，为乳腺癌的早期诊断临床应用提供理论依据和技术支持。

在本项目的支持下，我们以一系列不均匀磁场下分子间多量子相干(iMQC)高分辨NMR方法为基础，通过理论和模拟系统定量地研究了生物组织磁化率不均匀对iMQC信号的影响，获得了生物组织信号演化的物理模型；通过调整相位循环方式、缩短信号演化时间以及优化脉冲序列参数等方式进一步提高iMQC信号的信噪比和分辨率；对比定域模块的不同执行方式，与传统MRS方法进行比较；利用iMQC技术与快速采样方法的有机结合，建立和发展了适用于不均匀的活体生物组织高分辨磁共振定域谱方法以及快速实验方法，并将其应用到了一系列的离体和活体生物组织以及不均匀的食品体系。研究结果表明iMQC技术可作为萃取法和魔角旋转法的有效补充方法，而不必经过组织萃取和特殊的魔角旋转技术直接获得生物组织和不均匀食品体系的高分辨谱，推动了iMQC等NMR新技术在实际体系中的应用。