Quantitate and validate an endogenous ph magnetic resonance imaging technique

定量和验证内源 ph 磁共振成像技术

• 批准号: 8533776
• 负责人: Phillip Zhe Sun
• 金额: $ 17.52万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8533776
• 关键词: ASIC channel; Accounting; Acidosis; Acute; Algorithms; Amides; Animal Model; Animals; Chemicals; Complement; Diagnosis; Diagnostic; Diagnostic tests; Diffusion Magnetic Resonance Imaging; Disease; Drug Addiction; Drug Targeting; Edema; Energy Metabolism; Evolution; Goals; Histology; Image; Imaging Techniques; Infarction; Ischemia; Magnetic Resonance Imaging; Maps; Metabolic; Metabolic Diseases; Methods; Modeling; Monitor; Pathology; Perfusion; Pharmaceutical Preparations; Physiological; Predisposition; Principal Investigator; Proteins; Protons; Relaxation; Research; Resolution; Risk; Slice; Solutions; Spatial Distribution; Spectrum Analysis; Spreading Cortical Depression; Stroke; Surrogate Markers; Techniques; Testing; The Sun; Therapeutic; Thrombolytic Therapy; Time; Tissues; Translating; Variant; Weight; acute stroke; base; improved; in vivo; interest; irradiation; mathematical model; research study; spatiotemporal

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.

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，研究表明化学交换饱和转移 (CEST) MRI 可以监测微环境 pH 值，而酰胺质子转移 (APT) MRI（CEST 成像的一种变体）在急性缺血组织损伤的成像方面显示出良好的前景。然而，APT成像仅提供pH加权信息，其对比度随实验条件的不同而变化，并受水肿、蛋白质含量和组织松弛时间的影响而变化。另一方面，开发绝对组织 pH 成像以提供有关组织能量代谢的定量信息非常令人感兴趣。经过验证，绝对 pH MRI 技术可以补充传统的 基于光谱的技术（例如乳酸和^V）来提高其时空分辨率。此外，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性疾病。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) 使用整体和局灶性缺血卒中模型验证体内 pH MRI。 3）通过评估一种新的实验性治疗药物——酸传感离子通道（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，我们建议定量内源酰胺质子转移 MRI 以绘制绝对组织 pH 值。一旦得到验证，我们将评估其在急性中风等病理学中的诊断用途。