Feasibility of targeting atherosclerotic plaques by high-intensity-focused ultrasound: an in vivo study.

PURPOSE: To investigate the feasibility and acute safety of targeting atherosclerotic plaques by high-intensity-focused ultrasound (US) in vivo through a noninvasive extracorporeal approach. MATERIALS AND METHODS: Four swine were included in this prospective study, three of which were familial hypercholesterolemic swine. The procedure was done under general anesthesia. After US identification of atherosclerotic plaques within the femoral arteries, plaques were targeted by high-intensity focused US with an integrated dual-mode US array system. Different ablation protocols were used to meet the study objectives, and animals were then euthanized at different time points. Targeted arterial segments were stained by hematoxylin and eosin for histopathologic examination. Numeric values are presented as means ± standard deviation. RESULTS: All swine tolerated the procedure well, with no arterial dissection, perforation, or rupture. Discrete lesions were detected in the first two swine, measuring 0.54 mm ± 0.10 and 0.25 mm ± 0.03 in cross-sectional dimensions in the first and 0.50 mm ± 0.12 and 0.24 mm ± 0.15 in the second. Confluent ablation zones were identified in the last two swine, measuring 6.92 mm and 0.93 mm in the third and 2.97 mm and 2.52 mm in the fourth. Lesions showed necrotic cores and peripheral reactive inflammatory infiltration. The endothelium overlying targeted arterial segments remained intact. CONCLUSIONS: The results demonstrate the feasibility and acute safety of targeting atherosclerotic plaques by high-intensity-focused US in vivo. Further long-term studies are needed to assess how induction of these lesions can modify the progression of atherosclerotic plaques.

High-intensity focused ultrasound for potential treatment of polycystic ovary syndrome: toward a noninvasive surgery.

OBJECTIVE: To investigate the feasibility of using high-intensity focused ultrasound (HIFU), under dual-mode ultrasound arrays (DMUAs) guidance, to induce localized thermal damage inside ovaries without damage to the ovarian surface. DESIGN: Laboratory feasibility study. SETTING: University-based laboratory. ANIMAL(S): Ex vivo canine and bovine ovaries. INTERVENTION(S): DMUA-guided HIFU. MAIN OUTCOME MEASURE(S): Detection of ovarian damage by ultrasound imaging, gross pathology, and histology. RESULT(S): It is feasible to induce localized thermal damage inside ovaries without damage to the ovarian surface. DMUA provided sensitive imaging feedback regarding the anatomy of the treated ovaries and the ablation process. Different ablation protocols were tested, and thermal damage within the treated ovaries was histologically characterized. CONCLUSION(S): The absence of damage to the ovarian surface may eliminate many of the complications linked to current laparoscopic ovarian drilling (LOD) techniques. HIFU may be used as a less traumatic tool to perform LOD.

Real-time implementation of a dual-mode ultrasound array system: in vivo results.

A real-time dual-mode ultrasound array (DMUA) system for imaging and therapy is described. The system utilizes a concave (40-mm radius of curvature) 3.5 MHz, 32 element array, and modular multichannel transmitter/receiver. The system is capable of operating in a variety of imaging and therapy modes (on transmit) and continuous receive on all array elements even during high-power operation. A signal chain consisting of field-programmable gate arrays and graphical processing units is used to enable real time, software-defined beamforming and image formation. Imaging data, from quality assurance phantoms as well as in vivo small- and large-animal models, are presented and discussed. Corresponding images obtained using a temporally-synchronized and spatially-aligned diagnostic probe confirm the DMUA's ability to form anatomically-correct images with sufficient contrast in an extended field of view around its geometric center. In addition, high-frame rate DMUA data also demonstrate the feasibility of detection and localization of echo changes indicative of cavitation and/or tissue boiling during high-intensity focused ultrasound exposures with 45-50 dB dynamic range. The results also show that the axial and lateral resolution of the DMUA are consistent with its f(number) and bandwidth with well-behaved speckle cell characteristics. These results point the way to a theranostic DMUA system capable of quantitative imaging of tissue property changes with high specificity to lesion formation using focused ultrasound.

Adaptive transthoracic refocusing of dual-mode ultrasound arrays.

We present experimental validation results of an adaptive, image-based refocusing algorithm of dual-mode ultrasound arrays (DMUAs) in the presence of strongly scattering objects. This study is motivated by the need to develop noninvasive techniques for therapeutic targeting of tumors seated in organs where the therapeutic beam is partially obstructed by the ribcage, e.g., liver and kidney. We have developed an algorithm that takes advantage of the imaging capabilities of DMUAs to identify the ribs and the intercostals within the path of the therapeutic beam to produce a specified power deposition at the target while minimizing the exposure at the rib locations. This image-based refocusing algorithm takes advantage of the inherent registration between the imaging and therapeutic coordinate systems of DMUAs in the estimation of array directivity vectors at the target and rib locations. These directivity vectors are then used in solving a constrained optimization problem allowing for adaptive refocusing, directing the acoustical energy through the intercostals, and avoiding the rib locations. The experimental validation study utilized a 1-MHz, 64-element DMUA in focusing through a block of tissue-mimicking phantom [0.5 dB/(cm .MHz)] with embedded Plexiglas ribs. Single transmit focus (STF) images obtained with the DMUA were used for image-guided selection of the critical and target points to be used for adaptive refocusing. Experimental results show that the echogenicity of the ribs in STF images provide feedback on the reduction of power deposition at rib locations. This was confirmed by direct comparison of measured temperature rise and integrated backscatter at the rib locations. Direct temperature measurements also confirm the improved power deposition at the target and the reduction in power deposition at the rib locations. Finally, we have compared the quality of the image-based adaptive refocusing algorithm with a phase-conjugation solution obtained by direct measurement of the complex pressures at the target location. It is shown that our adaptive refocusing algorithm achieves similar improvements in power deposition at the target while achieving larger reduction of power deposition at the rib locations.

Monitoring and guidance of HIFU beams with dual-mode ultrasound arrays.

We present experimental results illustrating the unique advantages of dual-mode array (DMUA) systems in monitoring and guidance of high intensity focused ultrasound (HIFU) lesion formation. DMUAs offer a unique paradigm in image-guided surgery; one in which images obtained using the same therapeutic transducer provide feedback for: 1) refocusing the array in the presence of strongly scattering objects, e.g. the ribs, 2) temperature change at the intended location of the HIFU focus, and 3) changes in the echogenicity of the tissue in response to therapeutic HIFU. These forms of feedback have been demonstrated in vitro in preparation for the design and implementation of a real-time system for imaging and therapy with DMUAs. The results clearly demonstrate that DMUA image feedback is spatially accurate and provide sufficient spatial and contrast resolution for identification of high contrast objects like the ribs and significant blood vessels in the path of the HIFU beam.