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效用。最近，它已被证明，化学交换饱和转移（CEST）MRI可以监测微环境pH值，酰胺质子转移（APT）MRI，CEST成像的一种变体，已被证明有希望在成像急性缺血性组织损伤。然而，APT成像仅提供pH加权信息，其对比度随实验条件变化，并受水肿、蛋白质含量和组织弛豫时间变化的影响。而另一方面，它是巨大的兴趣，开发一个绝对的组织pH成像，提供定量信息的组织能量代谢。经验证，绝对pH MRI技术可以补充传统的 基于光谱的技术（例如，乳酸盐和μ V）以提高其时空分辨率。此外，经验证的非侵入性pH MRI技术可作为改变的组织代谢状态的替代标志物，因此，最终可增强常用的灌注和扩散MRI，以更准确地表征病理组织状态。事实上，非侵入性pH MRI技术可以帮助诊断急性中风以外的许多代谢紊乱。在拟议的研究中，我们将1）开发，定量和校准CEST MRI的绝对pH值。2）验证在体内pH MRI使用全局和局灶性缺血aninrial中风模型。3)通过评价一种新的实验性治疗药物酸敏感离子通道（ASIC）阻断剂来测试pH MRI的诊断价值。 相关性：非侵入性pH成像通常是一个未满足的需求，我们建议定量内源性酰胺质子转移MRI映射绝对组织pH值。一旦验证，我们将评估其在病理学，如急性中风的诊断用途。

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.