5A-3 Spatial and Temporal Controlled Tissue Heating on a Modified Clinical Ultrasound Scanner for Generating Mild Hyperthermia in Tumors

We present a new system for generating controlled tissue heating with a clinical ultrasound scanner and initial in vitro and in vivo results that demonstrate both transient and sustained heating in the mild- hyperthermia range of 37-42degC. The system consists of a Siemens Antarestrade ultrasound scanner, a custom dual-frequency 3-row transducer array, and an external temperature feedback control system. The transducer has 2 outer rows that operate at 1.5 MHz for tissue heating and a center row that operates at 5 MHz for B-mode imaging. Temperature measurement is accomplished using a thermocouple encased within a 29 gauge stainless steel needle. The temperature measurements are fed into a modified proportional-differential-integral (PID) control loop programmed in LabVIEWtrade running on an external PC. Modifications to the PID loop include a limited bandwidth differential section and integrator anti-windup. The PID loop controls duty cycle by varying the PRF on a SIEMENS Antares ultrasound scanner, and the resulting PRF update rate is approximately 3 Hz. The heating beam is directed using the pulsed-Doppler cursor with reference to a 5 MHz B-mode image. B-mode updates also occur at approximately 3 Hz. In vitro results show differential heating of chicken breast of 8degC at the beam focus. We show that the system is able to maintain the temperature to within 0.1degC of the desired temperature both in vitro and in vivo. In vivo tests of the system were performed on a mouse bearing Met-1 tumors, which is a model of aggressive, metastatic and highly vascular breast cancer. In superficially implanted tumors, we demonstrate controlled heating to temperatures in the 39-42degC range, which is ideal for releasing drugs from thermally-sensitive liposomes.