Quantitate and validate an endogenous ph magnetic resonance imaging technique

描述(由申请人提供)：我们的研究旨在开发和验证定量pH成像技术，并评估其在急性缺血等病理学中的诊断价值。近年来，化学交换饱和转移(CEST)MRI被证明可以监测微环境的pH值，而酰胺质子转移(APT)MRI是CEST成像的一种变体，在急性缺血性组织损伤的成像中具有广阔的应用前景。然而，APT成像只提供了pH加权信息，其对比度随实验条件而变化，并受水肿、蛋白质含量和组织弛豫时间的影响而变化。另一方面，发展一种能够提供组织能量代谢定量信息的绝对组织pH成像技术也引起了人们极大的兴趣。在经过验证的情况下，绝对pH磁共振技术可以补充传统的 基于光谱学的技术(例如乳酸和^V)，以提高其时空分辨率。此外，一种经过验证的非侵入性pH MRI技术可以作为组织代谢状态改变的替代标记，因此，最终可能会增强常用的灌注和扩散MRI，以更准确地表征组织的病理状态。事实上，一种非侵入性的pH磁共振技术可以帮助诊断急性中风以外的一系列代谢紊乱。在拟议的研究中，我们将1)开发、定量和校准CEST MRI的绝对pH。2)用全脑和局灶性脑缺血模型验证在体pH磁共振成像。3)通过对一种新的实验性治疗药物--酸敏离子通道(ASIC)阻滞剂的评价，检验pH MRI的诊断价值。 相关性：无创pH成像通常是一种未得到满足的需求，我们建议对内源性酰胺质子转移磁共振成像进行定量，以绘制组织的绝对pH图。一旦得到证实，我们将评估其在急性中风等病理诊断中的应用。

DESCRIPTION (provided by applicant): Our research aims to develop and validate quantitative pH imaging technique, and evaluate its diagnostic utility in pathologies such as acute ischemia. Recently, it has been shown that chemical exchange saturation transfer (CEST) MRI can monitor microenvironment pH, and amide proton transfer (APT) MRI, a variant of CEST imaging, has been shown promising in imaging acute ischemic tissue damage. However, APT imaging provides only pH-weighted information, and its contrast varies with experimental conditions, and under the influence of edema, protein content and tissue relaxation time change. While on the other hand, it is of tremendous interest to develop an absolute tissue pH imaging that provide quantitative information about tissue energy metabolism. In validated, an absolute pH MRI technique may complement conventional spectroscopy-based techniques (e.g., lactate and ^V) to improve its spatiotemporal resolution. In addition, a validated non-invasive pH MRI technique may serve as a surrogate marker for altered tissue metabolic status, and hence, may eventually augment commonly used perfusion and diffusion MRI for more acute characterization of pathological tissue status. In fact, a non-invasive pH MRI technique can aid the diagnosis of a host of metabolic disorders beyond acute stroke. In the proposed research, we will 1) develop, quantitate and calibrate CEST MRI for absolute pH. 2) validate in vivo pH MRI using both global and focal ischemia aninrial stroke model. 3) test the diagnostic value of pH MRI by evaluating a new experimental therapeutic drug, acid sensing ion channel (ASIC) blockade. RELEVANCE: Non invasive pH imaging is generally an unmet need, and we propose to quantitate endogenous amide proton transfer MRI for mapping absolute tissue pH. Once verified, we will evaluate its diagnostic use in pathologies such as acute stroke.