Lorenzato Cyril, Oerlemans Chris, Cernicanu Alexandru, Ries Mario, Denis de Senneville Baudouin, Moonen Chrit, Bos Clemens
University Medical Center Utrecht, Department of Radiology, Imaging Division, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.
NMR Biomed. 2014 Nov;27(11):1267-74. doi: 10.1002/nbm.3182. Epub 2014 Sep 10.
Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, on heating. Here, the mathematical method used to extract both R2 * and R1 from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R2 * was obtained from a fit to the ME-SPGR data. Absolute R1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R1 map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R2 *, R1 and temperature maps were measured with a 5-s temporal resolution. Both R2 *and R1 measured were found to change with temperature. The dynamic R1 measurements after heating agreed with the Look-Locker R1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R1 increase near the phase transition temperature, as well as a shallow R2 * increase. Simultaneous temperature, R2 * and R1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies.
通过热敏感脂质体(TSLs)热诱导药物释放进行局部给药,可能会降低化疗的全身毒性,同时维持或提高其疗效。弛豫性造影剂可与药物共同包封,以便通过R2 *可视化脂质体的存在,并通过R1在加热时实现造影剂和药物的共同释放。在此,介绍并分析了用于从快速动态多回波扰相梯度回波(ME-SPGR)中提取R2 *和R1的数学方法。最后,该方法用于监测此类释放事件。R2 *通过拟合ME-SPGR数据获得。绝对R1是根据针对表观质子密度变化校正后的信号幅度变化和基线Look-Locker R1图计算得出的。该方法用于监测肌肉组织的近乎均匀的水浴加热和局部聚焦超声加热,并在体外可视化钆螯合物从TSLs中的释放。以5秒的时间分辨率测量R2 *、R1和温度图。发现测量的R2 *和R1均随温度变化。如果考虑平衡磁化强度随温度的变化,加热后的动态R1测量结果与Look-Locker R1值一致。在相变温度附近,通过R1升高以及R2 *的轻微升高检测到钆从TSLs中的释放。同时进行温度、R2 *和R1映射是可行的,并且有潜力用于图像引导的药物递送研究。