缺血缺氧脑损伤的磁共振pH定量成像研究

Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and neonatal neurodevelopmental abnormalities. Intracellular pH alters earlier than cell death, which therefore could serve as a sensitive index for early detection of metabolic abnormalities. Magnetic resonance amide proton transfer (APT) imaging is a state-of-the-art way for intracellular pH measurement, but the technique is challenged with imperfect imaging methodology, inferior quantification accuracy and long scan time. Herein, we propose a novel APT ratiometric imaging method with integrating double-power RF saturation pulses to remove the confounding influences of labile proton concentration, chemical exchange rate as well as imaging parameters. The quantification accuracy would be improved by decoupling direct water saturation and magnetization transfer which are estimated from tissue relaxation characteristics. In addition, partial sampling schedule of Z spectra is designed to accelerate APT imaging. Temporal-spatial progression of pH as well as its applicability in detecting and evaluating hypoxic-ischemic brain injury is assessed by comparing to conventional imaging techniques with histological analysis as reference. The study will not only provide a new method for quantitative intracellular pH imaging, but also shed light on the evolution of hypoxic-ischemic brain injury from the molecular metabolic level, which is of great research and clinical importance.

缺血缺氧脑病（HIE）是目前围生期死亡和新生儿神经发育异常的主要原因。细胞内pH值的变化早于细胞坏死，是超早期发现代谢异常的敏感参量。磁共振氨基质子转移（APT）成像为pH测量提供全新途径，但现有技术在成像方法、定量精度和成像速度方面均面临巨大挑战。针对上述问题，本项目提出双饱和射频脉冲能量的APT效应比率方法，消除氨基质子浓度、化学交换速率以及成像条件等因素的影响；基于组织弛豫特征，建立直接水饱和效应和磁化转移的估计算法，解决多化学池之间的耦合干扰问题，提高pH量化的准确性；发展部分Z谱数据采集方法，降低频谱采集数目，实质性提高成像速度；综合常规成像技术，对照组织病理学结果，明确HIE pH时空动态变化特征及其在损伤检测和预后评估中的价值。该项目的实施，不仅为细胞内pH定量成像提供有效方法，同时从分子代谢层面揭示缺血缺氧脑损伤的进展规律，具有重要的研究价值和临床意义。

缺血缺氧脑病（HIE）是目前围生期死亡和新生儿神经发育异常的主要原因。细胞内pH值的变化早于细胞坏死，是超早期发现代谢异常的敏感参量。磁共振化学交换饱和转移（CEST）成像为pH测量提供全新途径，但现有技术在成像方法、定量精度和成像速度方面均面临巨大挑战。针对上述问题，本项目开展以下研究工作：（1）构建基于克拉美罗界的成像参数测度函数，建立CEST pH关键成像参数全局优化方法，为成像策略的智能优化提供理论依据；（2）提出类稳态成像（QUASS）新理论，在保证pH定量精度的同时，成像时间缩短5倍以上；（3）建立了直接水饱和校正（DISC）成像新方法，可同步解决主磁场偏移、直接水饱和效应以及磁化转移等因素对CEST信号量化的严重干扰；（4）建立了组织弛豫特征和组织磁化转移效应异质性校正的MRAPT pH成像技术，有效解决弛豫特征和磁化转移等组织异质性对pH定量的影响，pH定量准确性比传统方法提高56%，定量误差小于0.1 pH单位；（5）提出双饱和射频脉冲比率法ratiometric pH成像技术，可有效解决可交换质子浓度、纵向弛豫率差异等影响对pH定量的影响，pH定量误差小于0.1 pH单位；（6）开展了急性脑缺血动物模型实验研究，结合弥散成像、灌注成像等常规磁共振成像技术，实现了缺血核心区、缺血半暗带、良性缺血区等重要区域的识别和定位，为脑组织损伤精细分区和精准评价提供全新手段。该项目的实施，不仅为细胞内pH定量成像提供有效方法，同时从分子代谢层面揭示缺血缺氧脑损伤的变化规律，具有重要的研究价值和临床意义。