A phantom for visualization of three‐dimensional drug release by ultrasound‐induced mild hyperthermia. Issue 8 (26th July 2013)

• Record Type: Journal Article
• Authors: Lai, Chun‐Yen; Kruse, Dustin; Seo, Jai Woong; Kheirolomoom, Azadeh; Ferrara, Katherine W.
• Is Part Of: Medical physics. Volume 40:Issue 8(2013)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2013-07-26
• Subjects: Therapeutic applications -- Reconstruction -- Biomedical instrumentation and transducers, including micro‐electro‐mechanical systems (MEMS) -- Biomedical imaging -- Biothermics and thermal processes in biology; biodiffusion -- biological tissues -- biomedical optical imaging -- biomedical transducers -- drug delivery systems -- dyes -- evaporation -- finite difference time‐domain analysis -- fluorescence -- hyperthermia -- image reconstruction -- medical image processing -- phantoms -- radiation quenching -- temperature distribution -- thermocouples -- ultrasonic therapy -- ultrasonic transducers; ultrasound -- mild hyperthermia -- tissue‐mimicking phantom -- low temperature sensitive liposome -- FDTD; Devices for introducing media into, or onto, the body; Devices for transducing body media or for taking media from the body; Devices for producing or ending sleep or stupor -- Ultrasound therapy -- Evaporating -- Processes or apparatus for generating mechanical vibrations of infrasonic, sonic or ultrasonic frequency -- Organic dyes or closely‐related compounds for producing dyes; Mordants; Lakes -- Using thermo‐electric elements, e.g. thermo‐couples -- Digital computing or data processing equipment or methods, specially adapted for specific applications -- Image data processing or generation, in general; Fluorescence -- Diffusion -- Drug delivery -- Ultrasonography -- Near infrared imaging -- Solid solutions -- Phase transitions -- Finite difference time domain calculations -- Lipids -- Liposomes; Medical physics -- Periodicals; Medical physics; Geneeskunde; Natuurkunde; Toepassingen; Biophysics; Periodicals; Periodicals; Electronic journals; 610.153
• DOI: 10.1118/1.4813299
• Languages: English
• ISSNs: 0094-2405

Abstract

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 R 2 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.