NMR Monitoring of Temperature and Its Biological Effects

温度及其生物效应的核磁共振监测

• 批准号: 7149251
• 负责人: NAVIN BANSAL
• 金额: $ 26.71万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-10 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149251
• 关键词: neoplasm /cancer; temperature

DESCRIPTION (provided by applicant): Noninvasive temperature monitoring has many direct uses in diagnosis and therapy. These include aiding in the use of hyperthermia (HT) for treatment of cancer, detection and localization of tumors, diagnosing metabolic abnormalities, and studying muscle exercise and recovery. Noninvasive monitoring of temperature is particularly useful for HT treatment of malignant tumors, where the amount of heat applied depends on the actual temperature in the region and its surroundings. Using the funding from a R21 grant (R21 CA94040) we have developed a noninvasive MR thermometer based on the temperature dependence of hyperfine shifted 1H signal of the paramagnetic lanthanide complex, TmDOTMA-. 1H chemical shifts of TmDOTMA- are approximately 60 times more sensitive to temperature than the water signal and are insensitive to changes in tissue microenvironment such as pH and concentration of other ions and presence of macromolecules. Our preliminary data show that the developed thermometer, based on the proton chemical shift of TmDOTMA-, provides sensitive and accurate methods for monitoring temperature. The overall goal of this R33 proposal is to combine the developed MR thermometry method with other multinuclear MR measurements to investigate the metabolic and physiologic effects HT in experimental tumors during the treatment. The central hypothesis of the proposal is that biological response of tumors, as measured by noninvasive MR spectroscopy and imaging (MRS/MRI) at the time of HT treatment, provides more accurate and reliable information about therapy outcome than HT temperature alone because different tumors or tumor regions have different vulnerability to temperature. To test this hypothesis, robust MR methods will be developed to deliver controlled radiofrequency (RF) HT in the magnet and simultaneously monitor/image the metabolic and physiological effects of HT by in vivo 31P, 23Na, and 1H MRS/MRI. The proposed MR techniques will provide innovative methods to monitor temperature and metabolic/physiologic response to HT treatment during and after the therapy. Application of the proposed techniques to experimental tumors will enhance our understanding of HT biology, which may prove valuable in designing methods to sensitize tumors to HT and other therapies. The animal experiments will be a step toward the application of the proposed techniques to human patients for MRI-guided HT treatment.

描述（由申请人提供）：非侵入性温度监测在诊断和治疗中有许多直接用途。这些包括有助于使用高温（HT）治疗癌症的治疗，肿瘤的检测和定位，诊断代谢异常以及研究肌肉运动和康复。对温度的无创监测对于HT治疗恶性肿瘤特别有用，其中施加的热量取决于该地区及其周围环境的实际温度。使用R21 Grant（R21 CA94040）的资金，我们基于超精细的温度依赖性而开发了一种非侵入性MR温度计，这使磁磁性灯笼型复合物的1H信号TMDOTMA-信号TMDOTMA-。 TMDOTMA-的1H化学位移对温度的敏感性比水信号高60倍，并且对组织微环境的变化不敏感，例如pH和其他离子的浓度以及大分子的存在。我们的初步数据表明，根据TMDOTMA-的质子化学移位，开发的温度计为监测温度提供了敏感而准确的方法。该R33提案的总体目标是将开发的MR温度计方法与其他多核MR测量相结合，以研究治疗过程中实验性肿瘤中的代谢和生理效应HT。该提案的核心假设是，通过非侵入性MR光谱和成像（MRS/MRI）在HT治疗时通过单独使用HT温度来衡量的肿瘤的生物学反应（MRS/MRI）提供了更准确，更可靠的治疗信息信息，因为不同的肿瘤或肿瘤区域具有不同的温度。为了检验该假设，将开发出鲁棒的MR方法，以在磁铁中提供受控的射频（RF）HT，并同时监视/图像HT通过体内31p，23NA和1H MRS/MRS/MRI对HT的代谢和生理效应。提出的MR技术将提供创新的方法，以监测治疗期间和之后HT治疗的温度和代谢/生理反应。提出的技术在实验性肿瘤中的应用将增强我们对HT生物学的理解，这可能证明在设计将肿瘤敏感到HT和其他疗法的方法中很有价值。动物实验将是将提出的技术应用于人类患者进行MRI引导的HT治疗的一步。