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

摘要

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 37-42°C. The system consists of a Siemens Antares 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 LabVIEW 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 8°C at the beam focus. We show that the system is able to maintain the temperature to within 0.1°C 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 39-42°C range, which is ideal for releasing drugs from thermally-sensitive liposomes.