Evaluating HIFU‐mediated local drug release using thermal strain imaging: Phantom and preliminary in‐vivo studies

Abstract

Purpose High‐intensity focused ultrasound (HIFU)‐mediated drug release becomes a promising therapeutic technique for treatment of cancer, which has merits of deep penetration, noninvasive approach and nonionizing radiation. However, conventional thermocouple‐based approach for treatment monitoring would encounter big challenges such as the viscous heating artifact and difficulty in monitoring in the deep region. In this study, we develop an effective method based on thermal strain imaging (TSI) for the evaluation of HIFU‐mediated drug release. Methods Both phantom experiments and preliminary animal experiments were performed to investigate the feasibility of the proposed approach. Doxorubicin (DOX)‐loaded cerasomes (HIFU and temperature‐sensitive cerasomes, HTSCs) were prepared. In the phantom experiments, the HTSC solution is contained inside a cylindrical chamber within a tissue‐mimicking phantom. In the animal experiments, the HTSCs are intravenously injected into tumor‐bearing mice. An HIFU transducer is used to trigger DOX release from the HTSCs within the phantom or mice, and TSI is performed during HIFU heating. In the phantom experiments, the accuracy of temperature estimation using TSI is validated by measuring with a thermocouple. In animal experiments, the spatial consistency between the distribution of DOX released within the tumor and the location of the heating region estimated by TSI is validated using a spectrofluorophotometer. Results In the phantom experiments, the HTSCs show a burst release of DOX when the temperature of the HTSC solution estimated by TSI reaches about 42°C, which is in agreement with the condition for drug release from the HTSCs. The temperature estimation using TSI has high accuracy with error below 2.5%. In animal experiments, fluorescence imaging of the tumor validates that the heating region of HIFU could be localized by the low‐strain region of TSI. Conclusion The present framework demonstrates a reliable and effective solution to the evaluation of HIFU‐mediated local drug delivery.

Quantitative analysis of heat-source estimation of high-intensity focused ultrasound using thermal strain imaging

“…´to 1.3 10 K 3 / ´for water bearing tissue around body temperature, and is at least an order of magnitude larger than the coefficient of thermal expansion. [20][21][22] All experiments used a tissue mimicking material (TMM) phantom produced based on the IEC60601-2-37, whose mass fractions and acoustic parameters are shown in Tables I and II. As for the TMM phantom, the coefficient z ( ) b is assumed to be 1.3 10 K 3 / ´in the temperature range of 23 °C-37 °C, calculated from the temperature coefficient of 2.1 m s −1 K −1 as reported on the acoustic properties of an IEC agar-based TMM phantom.…”

External Basic Hyperthermia Devices for Preclinical Studies in Small Animals

“…In order to minimize interference between the FUS beams and the ultrasound imaging, both transducers should not be operated simultaneously. US imaging is performed during the “OFF” period of the FUS pulse with an interval of ~100 μs every 100 ms ( Figure 5 C) [ 122 ].…”

“…Ultrasound imaging is performed during the “OFF” period of the therapeutic transducer with an interval of ~100 μs. Image B and C are adapted from Wu et al, Seip et al, Lee et al, and Farr et al [ 117 , 121 , 122 , 134 ].…”

Comparison between thermal strain and acoustic radiation force imaging methods for estimation of heat source distribution of high-intensity focused ultrasound

“…27) The value of the thermal expansion coefficient a z ( ) can be ignored because a z ( ) is at least an order of magnitude smaller than the coefficient of thermal dependence of sound speed b z ( ) in water bearing tissue at a temperature below around 50 °C. [27][28][29] 2.3. Experimental setup Figure 1 shows the experimental setup.…”