Real-Time Control of Nanoparticle-Mediated Thermal Therapy Using Photoacoustic Imaging.

OBJECTIVE: This work aims to determine whether photoacoustic (PA) thermometry from a commercially available PA imaging system can be used to control the temperature in nanoparticle-mediated thermal therapies. METHODS: The PA imaging system was interfaced to obtain PA images while scanning ex-vivo tissue. These images were then used to obtain temperature maps in real-time during heating. Validation and calibration of the PA thermometry were done using a fluoroptic thermometer. This thermometer was also used to develop and tune a software-based proportional integral derivative (PID) controller. Finally, a PA-based PID closed-loop controller was used to control gold nanorod (GNR) mediated laser therapy. RESULTS: The use of GNRs substantially enhanced laser heating; the temperature rise increased 7-fold by injecting a GNR solution with a concentration of 0.029 mg/mL. The control experiments showed that the desired temperature could be achieved and maintained at a targeted location in the ex-vivo tissue. The steady-state mean absolute deviations (MAD) from the targeted temperature during control were between 0.16 [Formula: see text] and 0.5 [Formula: see text], depending on the experiment. CONCLUSION: It was possible to control hyperthermia treatments using a software-based PID controller and a commercial PA imaging system. SIGNIFICANCE: The monitoring and control of the temperature in thermal-based therapies are important for assuring a prescribed temperature to the target tissue while minimizing the temperature of the surrounding healthy tissue. This easily implemented non-invasive control system will facilitate the realization of a broad range of hyperthermia treatments.

Enhancing laser thermal-therapy using ultrasound-microbubbles and gold nanorods of in vitro cells.

Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal therapy. However, a key challenge is delivering sufficient concentration of GNRs to induce a therapeutic effect. In this study, ultrasound and microbubbles (USMBs) were used to enhance intracellular uptake of GNRs. AML-5 cells in suspension (0.6 mL) were exposed to ultrasound (1.3 and 1.7 MPa peak negative pressure) and definity microbubbles (1.7% v/v) for 1 min at varying GNR concentrations (0-2.5×10(11) per mL). Following ultrasound-microbubble treatment, cells were centrifuged twice and treated with an 810 nm laser at an average fluence rate of 3.6 W/cm(2) for 5 min. In addition, cells were incubated with GNRs for 12 h prior to laser treatment. Following the treatment, cell viability (V(PI)) was assessed using propidium iodide (PI) and flow cytometry. Cell viability decreased by ∼4-folds with the combined treatment of USMB+GNR+Laser (V(PI)=17%) compared to cells incubated with GNR+Laser (V(PI)=68%). This effect depended on ultrasound pressure and GNR concentration. Higher cell death was achieved at higher GNR concentration and 1.3 MPa peak negative pressure. Cell viability decreased from 92% to 29% with increasing GNR concentration from 1×10(11) to 1.5×10(11) GNR/mL. In addition, higher temperatures were observed using a thermal camera with the combined treatment (USMB+GNR+Laser) of 59±1°C compared to 54±0.9°C for cells incubated with GNRs. The combined treatment of ultrasound-microbubble and gold nanorod laser induced thermal-therapy improved treatment response of in vitro cells.