NMR Monitoring of Temperature and Its Biological Effects

描述（由申请人提供）：无创体温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，研究肌肉运动和恢复。温度的非侵入性监测对于恶性肿瘤的高温治疗特别有用，在这种治疗中，所施加的热量取决于该区域及其周围环境的实际温度。利用R21基金（R21 CA94040）的资金，我们基于顺磁镧系化合物TmDOTMA-的超精细位移1H信号的温度依赖性开发了一种无创磁共振温度计。TmDOTMA-的1H化学位移对温度的敏感性约为水信号的60倍，对组织微环境的变化（如pH、其他离子的浓度和大分子的存在）不敏感。我们的初步数据表明，基于TmDOTMA-质子化学位移的温度计为温度监测提供了灵敏、准确的方法。本R33提案的总体目标是将开发的MR测温方法与其他多核MR测量相结合，研究HT在实验性肿瘤治疗期间的代谢和生理效应。该提案的中心假设是，肿瘤的生物反应，如在高温疗法治疗时通过无创磁共振光谱和成像（MRS/MRI）测量，提供了比单独高温疗法温度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的易变性不同。为了验证这一假设，将开发稳健的磁共振方法，在磁体中传递可控射频（RF）高温，同时通过体内31P， 23Na和1H MRS/MRI监测/成像高温的代谢和生理效应。提出的磁共振技术将提供创新的方法来监测治疗期间和治疗后的温度和代谢/生理反应。将所提出的技术应用于实验性肿瘤将增强我们对高温疗法生物学的理解，这可能在设计使肿瘤对高温疗法和其他疗法敏感的方法方面证明是有价值的。动物实验将是将提出的技术应用于mri引导下的人类HT治疗的一步。

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.