Heating Protocol Design Affected by Nanoparticle Redistribution and Thermal Damage Model in Magnetic Nanoparticle Hyperthermia for Cancer Treatment
Heating Protocol Design Affected by Nanoparticle Redistribution and Thermal Damage Model in Magnetic Nanoparticle Hyperthermia for Cancer Treatment
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DOI：
10.1115/1.4046967
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发表时间：
2020-07-01
影响因子：
--
通讯作者：
Zhu, Liang
中科院分区：
文献类型：
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作者：
Singh, Manpreet;Gu, Qimei;Zhu, Liang
最近的micro-CT扫描显示，局部加热后肿瘤中的磁性纳米颗粒分布体积比不加热的大得多，这表明可能是加热诱导的纳米颗粒迁移。在这项研究中，对注射了磁性纳米颗粒的肿瘤进行了理论模拟，以评估纳米颗粒重新分布对PC 3肿瘤造成永久性热损伤所需的温度升高和热剂量的影响程度。将0.1cc含有磁性纳米颗粒的市售铁磁流体直接注射到PC 3肿瘤的中心。对照组为瘤内注射后切除的4个PC 3肿瘤，而实验组为注射铁磁流体并在局部加热25 min后切除的另外4个PC 3肿瘤。将微CT扫描产生的肿瘤模型附着于小鼠身体模型。首先，基于使用红外相机的平均小鼠表面温度的实验数据，提取小鼠体内和PC 3肿瘤中的血液灌注率。将先前确定的纳米颗粒浓度与纳米颗粒诱导的体积产热速率之间的关系实施到理论模拟中。模拟结果显示，对照组肿瘤的平均稳态温升高于实验组，纳米颗粒从肿瘤中心向肿瘤周边扩散更多（对照组：70.6 ± 4.7摄氏度与实验组：69.2 ± 2.6摄氏度）。此外，我们根据每个肿瘤中的纳米颗粒分布，评估了对整个肿瘤造成永久性热损伤所需的加热时间。实验组中纳米颗粒向肿瘤周围扩散的更多导致加热时间比对照组长得多。由John皮尔斯博士改进的热损伤模型导致了几乎相同的温升分布;然而，所需的加热时间比使用传统的Arrhenius积分至少短24%，尽管初始时间延迟。从这项研究的结果表明，在未来的模拟，加热过程中考虑动态纳米粒子迁移时所需的加热时间可能是19和29分钟之间的基础上皮尔斯模型。总之，该研究表明了在加热过程中包括动态纳米颗粒扩散和准确的热损伤模型到肿瘤温度升高的理论模拟中以确定磁性纳米颗粒热疗设计中所需的热剂量的重要性。
Recent micro-CT scans have demonstrated a much larger magnetic nanoparticle distribution volume in tumors after localized heating than those without heating, suggesting possible heating-induced nanoparticle migration. In this study, a theoretical simulation was performed on tumors injected with magnetic nanoparticles to evaluate the extent to which the nanoparticle redistribution affects the temperature elevation and thermal dosage required to cause permanent thermal damage to PC3 tumors. 0.1cc of a commercially available ferrofluid containing magnetic nanoparticles was injected directly to the center of PC3 tumors. The control group consisted of four PC3 tumors resected after the intratumoral injection, while the experimental group consisted of another four PC3 tumors injected with ferrofluid and resected after 25min of local heating. The micro-CT scan generated tumor model was attached to a mouse body model. The blood perfusion rates in the mouse body and PC3 tumor were first extracted based on the experimental data of average mouse surface temperatures using an infrared camera. A previously determined relationship between nanoparticle concentration and nanoparticle-induced volumetric heat generation rate was implemented into the theoretical simulation. Simulation results showed that the average steady-state temperature elevation in the tumors of the control group is higher than that in the experimental group where the nanoparticles are more spreading from the tumor center to the tumor periphery (control group: 70.6 +/- 4.7 degrees C versus experimental group: 69.2 +/- 2.6 degrees C). Further, we assessed heating time needed to cause permanent thermal damage to the entire tumor, based on the nanoparticle distribution in each tumor. The more spreading of nanoparticles to tumor periphery in the experimental group resulted in a much longer heating time than that in the control group. The modified thermal damage model by Dr. John Pearce led to almost the same temperature elevation distribution; however, the required heating time was at least 24% shorter than that using the traditional Arrhenius integral, despite the initial time delay. The results from this study suggest that in future simulation, the heating time needed when considering dynamic nanoparticle migration during heating is probably between 19 and 29min based on the Pearce model. In conclusion, the study demonstrates the importance of including dynamic nanoparticle spreading during heating and accurate thermal damage model into theoretical simulation of temperature elevations in tumors to determine thermal dosage needed in magnetic nanoparticle hyperthermia design.