用于可视化超声诱导的温和热疗中三维药物释放的 Phantom。

A phantom for visualization of three-dimensional drug release by ultrasound-induced mild hyperthermia.

机构信息

Department of Biomedical Engineering, University of California at Davis, Davis, California 95616, USA.

出版信息

Med Phys. 2013 Aug;40(8):083301. doi: 10.1118/1.4813299.

DOI:10.1118/1.4813299

PMID:23927360

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3739833/

Abstract

PURPOSE

Ultrasound-induced mild hyperthermia has advantages for noninvasive, localized and controlled drug delivery. In this study, a tissue-mimicking agarose-based phantom with a thermally sensitive indicator was developed for studying the spatial drug delivery profile using ultrasound-induced mild hyperthermia.

METHODS

Agarose powder, regular evaporated milk, Dulbecco's phosphate-buffered saline (DPBS), n-propanol, and silicon carbide powder were homogeneously mixed with low temperature sensitive liposomes (LTSLs) loaded with a self-quenched near-infrared (NIR) fluorescent dye. A dual-mode linear array ultrasound transducer was used for insonation at 1.54 MHz with a total acoustic power and acoustic pressure of 2.0 W and 1.5 MPa, respectively. After insonation, the dye release pattern in the phantom was quantified based on optical images, and the three-dimensional release profile was reconstructed and analyzed. A finite-difference time-domain-based algorithm was developed to simulate both the temperature distribution and spatial dye diffusion as a function of time. Finally, the simulated dye diffusion patterns were compared to experimental measurements.

RESULTS

Self-quenching of the fluorescent dye in DPBS was substantial at a concentration of 6.25×10(-2) mM or greater. The transition temperature of LTSLs in the phantom was 35 °C, and the release reached 90% at 37 °C. The simulated temperature for hyperthermia correlated with the thermocouple measurements with a mean error between 0.03±0.01 and 0.06±0.02 °C. The R2 value between the experimental and simulated spatial extent of the dye diffusion, defined by the half-peak level in the elevation, lateral and depth directions, was 0.99 (slope=1.08), 0.95 (slope=0.99), and 0.80 (slope=1.04), respectively, indicating the experimental and simulated dye release profiles were similar.

CONCLUSIONS

The combination of LTSLs encapsulating a fluorescent dye and an optically transparent phantom is useful for visualizing and modeling drug release in vitro following ultrasound-induced mild hyperthermia. The coupled temperature simulation and dye-diffusion simulation tools were validated with the experimental system and can be used to optimize the thermal dose and spatial and temporal dye release pattern.

摘要

目的

超声诱导的轻度热疗具有非侵入性、局部性和可控性给药的优点。本研究开发了一种基于琼脂糖的组织模拟体，该模拟体含有热敏指示剂，用于研究超声诱导的轻度热疗下的空间药物输送分布。

方法

将琼脂糖粉末、普通炼乳、杜氏磷酸盐缓冲盐水（DPBS）、正丙醇和碳化硅粉末与装载自猝灭近红外（NIR）荧光染料的低温敏感脂质体（LTSL）均匀混合。使用双模线性阵列超声换能器在 1.54MHz 下进行超声，总声功率和声压分别为 2.0W 和 1.5MPa。超声后，根据光学图像定量测定体模中的染料释放模式，并对三维释放分布进行重建和分析。开发了一种基于有限差分时间域算法的方法，以模拟随时间变化的温度分布和空间染料扩散。最后，将模拟的染料扩散模式与实验测量结果进行比较。

结果

在浓度为 6.25×10(-2)mM 或更高时，DPBS 中荧光染料的自猝灭作用显著。体模中 LTSL 的相变温度为 35°C，在 37°C 时释放达到 90%。高温疗法的模拟温度与热电偶测量结果相关，平均误差在 0.03±0.01 至 0.06±0.02°C 之间。实验和模拟的空间扩展的染料扩散的 R2 值（通过垂直、水平和深度方向的半峰高水平定义）分别为 0.99（斜率=1.08）、0.95（斜率=0.99）和 0.80（斜率=1.04），表明实验和模拟的染料释放分布相似。