Image-Guided High Intensity Focused Ultrasound System for Large Animal Nerve Ablation Studies.

High intensity focused ultrasound (HIFU) is a form of thermal ablation technique, which can treat a variety of medical afflictions. One promising therapeutic use is the permanent destruction of nerves non-invasively in patients with severe spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU requires ultrasound guidance, which allows the non-invasive, target-specific deposition of thermal energy to the targeted nerve, thereby blocking axonal conduction. In this paper, a composite system comprising both ultrasound-imaging and HIFU therapy was developed and used to induce localized non-invasive nerve blockage in an in vivo large animal study. Five pigs were used with the femoral nerve as the target. Calibrated needle thermocouples inserted at the target site were employed to monitor the target tissue temperature. The degree of nerve blockage was assessed by measuring compound action potential (CAP) signal with a clinical nerve electrophysiology system before and after HIFU exposures. An average CAP signal amplitude reduction of 49% of baseline with a standard deviation of 9% was observed after 20-30 min post exposure. These results demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a potential non-invasive nerve ablation method.

Frequency-domain photoacoustic phased array probe for biomedical imaging applications.

We report the development of a frequency-domain biomedical photoacoustic imaging system that utilizes a continuous-wave laser source with a custom intensity modulation pattern, ultrasonic phased array for signal detection, and processing coupled with a beam-forming algorithm for reconstruction of photoacoustic correlation images. Sensitivity to optical contrast was demonstrated using tissue-mimicking phantoms and in-vivo tissue samples.

Characterization of changes in therapeutic ultrasound transducer performance over time using the angular spectrum method.

Strongly focused large aperture transducers used in high-intensity focused ultrasound treatments are prone to manufacturing defects and degradation. Current methods for evaluating transducer quality measure only bulk physical changes of transducers. We have determined the pressure distribution at the transducer surface, using the angular spectrum method, to detect defects of the transducer. Three therapeutic transducers were investigated. The pressure distribution at the focal plane of each transducer was measured and input into a back-projection algorithm to calculate the pressure distribution at the transducer surface. A number of scan window sizes were used for the pressure distribution measurement at the focal plane to determine the effect on the resolution of the calculated pressure distribution at the transducer surface. Results showed that one transducer might have suffered manufacturing defects. The second transducer degraded over 1 year of use with one half of the transducer suffering a partial loss of efficiency. The third transducer remained unchanged over 1 year. The scan window of 40 mm X 40 mm at the focal plane was required to identify defects 6 mm in diameter on the transducer surface. The results demonstrate that the angular spectrum method could be a useful tool for evaluating transducer quality.

Determination of the optical properties of turbid media using relative interstitial radiance measurements: Monte Carlo study, experimental validation, and sensitivity analysis.

Interstitial quantification of the optical properties of tissue is important in biomedicine for both treatment planning of minimally invasive laser therapies and optical spectroscopic characterization of tissues, for example, prostate cancer. In a previous study, we analyzed a method first demonstrated by Dickey et al., [Phys. Med. Biol. 46, 2359 (2001)] to utilize relative interstitial steady-state radiance measurements for recovering the optical properties of turbid media. The uniqueness of point radiance measurements were demonstrated in a forward sense, and strategies were suggested for improving performance under noisy experimental conditions. In this work, we test our previous conclusions by fitting the P3 approximation for radiance to Monte Carlo predictions and experimental data in tissue-simulating phantoms. Fits are performed at: 1. a single sensor position (0.5 or 1 cm), 2. two sensor positions (0.5 and 1 cm), and 3. a single sensor position (0.5 or 1 cm) with input knowledge of the sample's effective attenuation coefficient. The results demonstrate that single sensor radiance measurements can be used to retrieve optical properties to within approximately 20%, provided the transport albedo is greater than approximately 0.9. Furthermore, compared to the single sensor fits, employing radiance data at two sensor positions did not significantly improve the accuracy of recovered optical properties. However, with knowledge of the effective attenuation coefficient of the medium, optical properties can be retrieved experimentally to within approximately 10% for an albedo greater or equal to 0.5.

A model based upon pseudo regular spacing of cells combined with the randomisation of the nuclei can explain the significant changes in high-frequency ultrasound signals during apoptosis.

Recent ultrasound (US) experiments on packed myeloid leukaemia cells have shown that, at frequencies from 32 to 40 MHz, significant increases of signal amplitude were observed during apoptosis. This paper is an attempt to explain these signal increases based upon a simulation of the backscattered signals from the cells nuclei. The simulation is an expansion of work in which a condensed sample of cells, with fairly regular sizes, could be considered as an imperfect crystal. Thus, destructive interference could occur and this would be observed as a large reduced value of backscattered signals compared with the values obtained from a similar, but random, scattering source. This current paper explores the possibility that simple changes in the nuclei, such as their observed condensation or the small loss of nuclei scatterers from cells, could cause a significant increase in the observed backscattered signals. This model indicates that the greater backscattered signals can be explained by further randomisation of the average positions of the scattering sources in each cell. When these "microechoes" are added together, so that the destructive interference is reduced, a large increase in the signal is predicted. The simplified model strongly suggests that much of observed large increases of the backscattered signals could be simply explained by the randomisation of the position of the condensed nuclei during apoptosis, and the destruction of the nuclei could produce further signal amplitude changes due to disruption of the cloud of backscattered waves.