基于CEST机制的pH成像方法、原理和应用

化学交换饱和转移（Chemical Exchange Saturation Transfer，CEST）技术作为一种新型的磁共振成像（Magnetic Resonance Imaging，MRI）技术.它的原理为溶质池中被激发饱和的质子与游离水中未被饱和的质子间的化学交换，能够引起水质子磁共振信号的下降，从而获得组织内生物分子的相关信息.由于质子间的交换速率k_ex与组织微环境的pH值之间存在直接联系，因而可以通过溶质质子的CEST信号对活体组织进行pH成像.目前用于pH成像的溶质分子既包括内源性游离的蛋白质、多肽分子，还包括一系列的外源性小分子和金属螯合物.通过不同类型的比率法、内源性胺和酰胺浓度-独立检测（Amine and Amide Concentration-independent Detection，AACID）等成像方法，能够获得肾脏、中风脑组织以及肿瘤组织的pH图谱.本文详细总结了2000年以来利用CEST技术进行pH成像方面的研究进展，包括对比剂、成像方法和相关应用，展望了活体组织pH成像的发展趋势和应用前景.

pH Imaging Based on Chemical Exchange Saturation Transfer: Principles,Methods, Applications and Recent Progresses

Chemical exchange saturation transfer (CEST) is a novel molecular magnetic resonance imaging (MRI) method that makes full use of the chemical exchange between water protons and exchangeable protons from solute molecules. Through chemical exchanges, the MRI signal of bulk water decreases when saturating at specific frequency of solute protons. Important biological information related to the chemical exchange processes could be extracted from the amplitude of water signal decrease. For example, the CEST signals have been used for in vivo pH imaging since the proton exchange rate is often pH-dependent. CEST signals originated from endogenous proteins/peptides and exogenous small molecule/metal chelate probes have been used for in vivo pH imaging. Using the ratiometric methods or the amine and amide concentration-independent detection (AACID) methods, in vivo pH maps have been acquired from kidneys, ischemic brain and tumors. In this paper, we thoroughly reviewed the progresses during the past twenty years in the field of in vivo pH imaging with CEST contrast. Principles, methods and applications were discussed, as well as development trends and future directions.