Clinical validation of real-time tissue change monitoring during prostate tissue ablation with high intensity focused ultrasound.

BACKGROUND: The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. METHODS: Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients' data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. RESULTS: In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C. CONCLUSIONS: The TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications.

This paper discusses the design, fabrication, and testing of sensitive broadband lithium niobate (LiNbO3) single-element ultrasonic transducers in the 20-80 MHz frequency range. Transducers of varying dimensions were built for an f# range of 2.0-3.1. The desired focal depths were achieved by either casting an acoustic lens on the transducer face or press-focusing the piezoelectric into a spherical curvature. For designs that required electrical impedance matching, a low impedance transmission line coaxial cable was used. All transducers were tested in a pulse-echo arrangement, whereby the center frequency, bandwidth, insertion loss, and focal depth were measured. Several transducers were fabricated with center frequencies in the 20-80 MHz range with the measured -6 dB bandwidths and two-way insertion loss values ranging from 57 to 74% and 9.6 to 21.3 dB, respectively. Both transducer focusing techniques proved successful in producing highly sensitive, high-frequency, single-element, ultrasonic-imaging transducers. In vivo and in vitro ultrasonic backscatter microscope (UBM) images of human eyes were obtained with the 50 MHz transducers. The high sensitivity of these devices could possibly allow for an increase in depth of penetration, higher image signal-to-noise ratio (SNR), and improved image contrast at high frequencies when compared to previously reported results.

Design, fabrication, and evaluation of high frequency, single-element transducers incorporating different materials.

The performance of high frequency, single-element transducers depends greatly on the mechanical and electrical properties of the piezoelectric materials used. This study compares the design and performance of transducers incorporating different materials. The materials investigated include 1-3 lead zirconate titanate (PZT) fiber composite, lead titanate (PbTiO3) ceramic, poly(vinylidene fluoride) (PVDF) film, and lithium niobate (LiNbO3) single crystal. All transducers were constructed with a 3-mm aperture size and an f-number between 2 and 3. Backing and matching materials were selected based on design goals and fabrication limitations. A simplified coaxial cable tuning method was employed to match the transducer impedance to 50 ohms for the PZT fiber composite and PbTiO3 ceramic transducers. Transducers were tested for two-way loss and -6 dB bandwidth using the pulse/echo response from a flat quartz target. Two-way loss varied from 21 to 46 dB, and bandwidths measured were in the range from 47 to 118%. In vitro ultrasonic backscatter microscope (UBM) images of an excised human eye were obtained for each device and used to compare imaging performance. Both press-focusing and application of a lens proved to be useful beam focusing methods for high frequency. Under equal gain schemes, the LiNbO3 and PbTiO3 transducers provided better image contrast than the other materials.