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）：无创温度监测在诊断和治疗中有许多直接用途。这些包括帮助使用热疗（HT）治疗癌症，检测和定位肿瘤，诊断代谢异常，以及研究肌肉锻炼和恢复。温度的非侵入性监测对于恶性肿瘤的HT治疗特别有用，其中施加的热量取决于该区域及其周围环境的实际温度。使用从R21赠款（R21 CA 94040）的资金，我们已经开发了一种非侵入性MR温度计的基础上的超精细移动1H信号的顺磁性镧系元素配合物，TmDOTMA-的温度依赖性。TmDOTMA-的1H化学位移对温度的敏感性大约是水信号的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，开发的温度计，基于TmDOTMA-的质子化学位移，提供了灵敏和准确的方法监测温度。该R33提案的总体目标是将开发的MR测温方法与其他多核MR测量结合联合收割机，以研究治疗期间HT在实验肿瘤中的代谢和生理效应。该提案的中心假设是，在HT治疗时通过非侵入性MR波谱和成像（MRS/MRI）测量的肿瘤生物学反应比单独的HT温度提供了更准确和可靠的治疗结果信息，因为不同的肿瘤或肿瘤区域对温度具有不同的脆弱性。为了检验这一假设，将开发稳健的MR方法，以在磁体中输送受控射频（RF）HT，并通过体内31 P、23 Na和1H MRS/MRI同时监测/成像HT的代谢和生理效应。提出的MR技术将提供创新的方法来监测温度和代谢/生理反应HT治疗期间和之后。将所提出的技术应用于实验性肿瘤将增强我们对HT生物学的理解，这可能在设计使肿瘤对HT和其他疗法敏感的方法中证明是有价值的。动物实验将是将所提出的技术应用于人类患者进行MRI引导的HT治疗的一步。