Non-invasive MR thermometry using a paramagnetic complex

使用顺磁复合体进行非侵入式 MR 测温

• 批准号: 6420017
• 负责人: NAVIN BANSAL
• 金额: $ 14.84万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6420017
• 关键词: bioimaging /biomedical imaging; contrast media; image enhancement; laboratory mouse; magnetic resonance imaging; neoplasm /cancer thermotherapy; rare earth element; technology /technique development; thermometry

DESCRIPTION (Provided by Applicant): Noninvasive thermometry is pivotal to the future advances of regional hyperthermia as a treatment modality. Current magnetic resonance (MR) thermometry methods suffer from poor resolution due to relatively weak dependence of chemical shift of the 1H water signal on temperature. The main objective of this research is to develop noninvasive MR thermometry methods for reliable and accurate monitoring and imaging of temperature in tumors using a paramagnetic lanthanide complex. Our preliminary data show that 1H chemical shifts of a prototype lanthanide complex, thulium- 1,4,7,10-tetraazacyclododecane-1 ,4,7,10- tetraacetate (TmDOTA), are about two orders of magnitudes more sensitive to temperature than the water and thus, provide excellent accuracy and resolution. In addition, TmDOTA proton shifts are insensitive to the paramagnetic complex concentration, ph, [Ca2+] or presence of plasma macromolecules and ions. This will greatly simplify the procedures for using the lanthanide complex for MR thermometry because hyperthermia is known to produce changes in tissue pH and other parameters. The main goals of this project are: 1) to investigate the use of methyl substituted analogs of TmDOTK, thulium 1,4,7,1 0-Tetraazacyclodoecane-a,a ,a,"a"-tetramethyl-1 ,4,7, 1 0-tetraacetate (TmDOTMA) for MR thermometry, 2) to develop MR thermometry techniques for reliable, accurate and rapid imaging of temperature using a TmDOTMk complex, 3) to demonstrate feasibility of in vivo monitoring and imaging of temperature during hyperthermia in a mouse tumor model, and 4) to perform a preliminary study on acute effects of hyperthermia on tumor lactate and perfusion. The major advantage of the TmDOTMA is that the proton signals from methyl groups are more intense and sharper compared to the proton signals from TmDOTA. This will greatly help in improving the spatial, temporal and thermal resolution in temperature imaging. TmDOTk and TmDOTMK are expected to be non-toxic because similar complexes of gadolinium are clinically used as MR contrast agents.

描述（由申请人提供）：无创测温对于 区域热疗作为治疗方式的未来进展。当前的 磁共振 (MR) 测温方法由于以下原因而分辨率较差 1H水信号的化学位移的依赖性相对较弱 温度。本研究的主要目标是开发无创 MR 用于可靠、准确监测和成像的测温方法 使用顺磁性镧系元素络合物调节肿瘤温度。 我们的初步数据表明原型镧系元素的 1H 化学位移 配合物，铥- 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸酯 (TmDOTA)，对温度的敏感度比 水，从而提供出色的精度和分辨率。此外， TmDOTA 质子位移对顺磁络合物浓度不敏感， ph、[Ca2+] 或血浆大分子和离子的存在。这将大大 简化使用稀土配合物进行 MR 测温的程序 因为已知高温会导致组织 pH 值和其他因素发生变化 参数。 该项目的主要目标是：1）调查甲基的用途 TmDOTK 的取代类似物，铥 1,4,7,1 0-四氮杂环十二烷-a,a ,a,“a”-四甲基-1 ,4,7,1 0-四乙酸酯 (TmDOTMA) 用于 MR 测温，2) 至 开发 MR 测温技术，以实现可靠、准确和快速的成像 使用 TmDOTMk 复合物的温度，3) 证明体内的可行性 小鼠肿瘤热疗期间的温度监测和成像 模型，4) 对高热的急性影响进行初步研究 对肿瘤乳酸和灌注的影响。 TmDOTMA 的主要优点是 与来自甲基的质子信号相比，来自甲基的质子信号更强烈、更尖锐。 来自 TmDOTA 的质子信号。这对于改善空间、 温度成像中的时间和热分辨率。 TmDOTk 和 TmDOTMK 是 预计是无毒的，因为临床上有类似的钆复合物 用作MR造影剂。