High Intensity Focused Ultrasound (HIFU) is a minimally invasive surgical technique that has potential in interventional medicine, with applications that include tumor and fibroid ablation, vessel cauterization, and clot lyses. In the pre-clinical regulatory review of HIFU devices, characterization of devices involves multiple assessments, including prescription of the intensity field in a liquid me-dium, determination of temperature rise and lesion volume in a tissue-mimicking material or excised animal organ, and obtaining beam focus relative to the desired target. Characterization of HIFU beams is difficult at clinically relevant power levels due to the destructive potential of beams to expe-rimental sensors, as well as the possibility of interference of the sensors with the beam and the intro-duction of potential cavitation sites by these sensors. For higher intensities and powers, which are characteristics of HIFU devices, the acoustic pressure, measured in the liquid medium, can't be re-duced or ?derated? to estimate the pressure in a tissue medium. The gap in this research is that only a few HIFU devices are currently marketed in the US despite many technical advantages of HIFU. One obstacle impeding a faster path to market for HIFU devices is the lack of standardized and inex-pensive test methods for establishing the safety and efficacy of the devices. This, in turn, compli-cates the path to HIFU device commercialization, thereby limiting wider use of the devices clinically.
The long-term goal of this research is to improve characterization of HIFU transducers. The ob-jective is to test a nonlinear derating method that can evaluate the thermal effects of HIFU beams. The central hypothesis is that the derated pressure, obtained from measurements in water, can deter-mine temperatures and thermal doses for assessing bioeffects in tissues.
Intellectual Merit It is hypothesized that an algorithm for converting pressure mode amplitudes from water to amplitudes in tissue will be sufficiently accurate and that, when inserted into the expression for temperature modes, will enable accurate estimates of temperature rise in excised animal tissue or in a tissue phantom. To test the hypothesis, the specific aims are: SPECIFIC AIM 1: Evaluating the nonlinear derating method by measuring pressure using hydrophones embedded in a tissue phantom. SPECIFIC AIM 2: Comparing the temperature rise determined from the derating approach with Magnetic Resonance (MR) thermometry in a tissue phantom and obtain pressure field by applying finite-differencing of temperature data. To achieve the specific aim 1, following steps have been accomplished: During this project, pressure modal amplitudes in water were derived using HIFU_simulator_v1.2 to solve the nonlinear KZK equation for different powers. A derating algorithm, based on the Gaussian estimation of KZK equation, has been developed to assess the pressure harmonics in tissue using the known water modal amplitudes. The estimated tissue pressure harmonics by this algorithm were compared against the tissue pressure harmonics which have been derived by using HIFU_simulator_v1.2 to solve the KZK equation in tissue for Gaussian beams. The HIFU_simulator_v1.2 software has been revised through this collaborative effort. In addition, the estimated tissue pressure harmonics were used in the Green-function solution of the bioheat equation to derive the temperature at focal point. The focal point temperature by using estimated tissue modal amplitudes was compared against the finite difference solution of the bioheat equation using the direct solution of the KZK equation in tissue. Subsequently, HIFU induced pressure wave in water was recorded on beam axis as well as off axis using hydrophone. The acoustic power levels were considered high enough to make nonlinear pressure wave propagation in water. Fourier transforms of the acoustic pressure vs. time data were performed to obtain the modal amplitudes in water. The derived modal amplitudes in water were then multiplied by an appropriate scaling factor and derated, using Gaussian modal sums, to construct estimates of acoustic pressure in tissue phantom. In addition, a tissue phantom with acoustical and thermal properties similar to that of human tissue was made. The acoustic pressure wave at the transducer focus in tissue phantom was recorded using hydrophone. Derated pressure waveforms were compared with waveforms determined by hydrophone in tissue phantom. To achieve the specific aim 2, following steps have been accomplished: During this project period, 3 exposed porcine livers were ablated for obtaining temperature data for 3 sets of HIFU traducer powers in a MR bore. MR Thermometry was performed during the ablation process to measure the temperature rise using the proton resonance frequency (PRF) method. The temperature maps as well as the temperature rise during the sonication process were derived for different ablated locations. MR imaging of the ablated livers were performed to obtain lesion volume. Subsequently, the measured temperatures from these in vivo experiments were compared with numerical temperature derived by using HIFU_simulator_v1.2. In addition, histology study was performed on the porcine liver samples to evaluate the effect of increasing transducer acoustic power on lesion volume. Broader Impact Because of the knowledge gained in this interdisciplinary research, the PI has been instrumental in bridging the gap between engineers (from UC Mechanical Engineering Department), physicists (from FDA) and magnetic resonance technician (from CCHMC). This project has also enabled the physicists at FDA to utilize the CFD and heat transfer expertise of PI to perform synergistic research activities at FDA site. This helped in improving the HIFU device characterization effort that is underway at US FDA. Knowledge gained from acoustics-thermal-flow analysis allowed us to develop derating algorithm. The newly developed derating method, using HIFU_Simulator and KZK codes coupled with the in-vitro experiments at FDA, has been utilized to conduct the ex-vivo and the initial sets of in-vivo experiments at Cincinnati Children's Hospital Medical Center (CCHMC). Knowledge gained from this project has helped the PI revamp a graduate-level BioHeat Transfer course at the University of Cincinnati. The course was offered in winter 2010-2011, fall 2011- 2012 and fall 2012- 2013 academic year and was taught using the Problem Based Learning approach. The PI has also obtained workshop grant on Biotransport Education from NSF to disseminate findings in SBC.
