Andrew J. Casper

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.

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 DMUAs 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 fnumber 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.

Realtime Control of Multiple-focus Phased Array Heating Patterns Based on Noninvasive Ultrasound Thermography

A system for the realtime generation and control of multiple-focus ultrasound phased-array heating patterns is presented. The system employs a 1-MHz, 64-element array and driving electronics capable of fine spatial and temporal control of the heating pattern. The driver is integrated with a realtime 2-D temperature imaging system implemented on a commercial scanner. The coordinates of the temperature control points are defined on B-mode guidance images from the scanner, together with the temperature set points and controller parameters. The temperature at each point is controlled by an independent proportional, integral, and derivative controller that determines the focal intensity at that point. Optimal multiple-focus synthesis is applied to generate the desired heating pattern at the control points. The controller dynamically reallocates the power available among the foci from the shared power supply upon reaching the desired temperature at each control point. Furthermore, anti-windup compensation is implemented at each control point to improve the system dynamics. In vitro experiments in tissue-mimicking phantom demonstrate the robustness of the controllers for short (2-5 s) and longer multiple-focus high-intensity focused ultrasound exposures. Thermocouple measurements in the vicinity of the control points confirm the dynamics of the temperature variations obtained through noninvasive feedback.

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.

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.

Robust detection and control of bubble activity during high intensity focused ultrasound ablation

We present results from a real-time ultrasound-guided focused ultrasound platform designed to monitor and control bubble activity. A single element transducer is used in a dual-mode fashion to interleave HIFU therapy with imaging pulses. Use of the same element for both therapy and monitoring creates an inherent alignment between the imaging focus and the therapy focus. Field programmable gate arrays (FPGA) control the signal generation and echo reception enabling real-time data processing to detect and control bubble activity with microsecond latency. Results are presented from in vitro experiments in swine liver and bovine cardiac tissue demonstrating the ability to detect bubble activity and control lesion growth at intensities up to 15 kW/cm2.

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-20...

Multiple-frequency phased array pattern synthesis for HIFU surgery

We present a simulation/experimental study to evaluate and optimize the focusing capabilities of a phased array prototype when excited by multiple-frequency components. A multiple-focus multiple-frequency pattern synthesis algorithm for phased arrays has been developed and tested using linear simulations in Matlab. The algorithm maintains the precise phase relationship between the frequency components at each focal spot to achieve a desirable therapeutic outcome. Preliminary simulations indicate that the focal region can be shaped based on the alignment and phase of multiple-frequency components. The pattern synthesis algorithm is experimentally validated with a 3.5 MHz, 64-element prototype designed for small-animal and superficial therapeutic HIFU applications (Imasonic, Inc) which has a 52% fractional bandwidth, allowing for therapeutic output in the frequency range of 2.7-4.6 MHz. Validation with hydrophone measurements at the focal locations showed that there is in increase in harmonic generation at the focal point with the frequency mixed patterns when compared to a conventional single frequency excitation pattern. This increased non-linearity, will allow for increased thermal absorption at the focal point, thus allowing for larger treatment volumes with the same total power or reduced treatment time per shot when compared to the single frequency case. Ex vivo experiments with fresh porcine liver were conducted to study the effect of multiple-frequency patterns when compared with conventional single frequency patterns during lesion formation. The lesion size was increased for the multiple-frequency patterns when compared the single frequency pattern at normalized power with respect to each other. In conclusion, wideband piezocomposite array transducers, together with multi-channel arbitrary waveform generators are enabling technologies which allow for complex, multiple-focus, multiple-frequency HIFU patterns. These patterns can enhanced the focal gain with proper phase alignment. Furthermore, multiple frequency patterns have been shown to be able to increase the harmonic generation at the focal spot, thus improving local absorption. Our early results with ex vivo porcine liver indicate that multiple frequency excitation can enhance the therapeutic gain at the focal points.

Realtime control of multiple-focus phased array heating patterns based on noninvasive ultrasound thermography

We present results from realtime feedback control of single- and multiple-focus phased array heating patterns based on ultrasound thermography. The results illustrate several important aspects of realtime control of phased array heating patterns as they are envisioned to be used in noninvasive, image-guided thermal therapy applications. First, complex, multiple-focus heating patterns require multi-point, noninvasive temperature feedback that may not be easily available using thermocouple or other invasive proibes. Second, multiple-focus pattern synthesis must be optimized to maintain the highest efficiency of the phased array driver in order to achieve the control objectives. This has led to the development of a dynamic power reallocation algorithm for realtime management of the power share of each focus accoring to maximize its heating rate. Third, realtime integration between the feedback thermography and array driver control with high spatial and temporal resolution is necessary, especially for short exposures used in ablative treatments. These aspects are well illustrated by the results shown: 1) realtime thermography at frame rates up to 100 fps, 2) realtime multiple-focus pattern resynthesis with update rates up to 1000 patterns per second, and 3) an intelligent dynamic power reallocation scheme to distribute the available driving power according to the collective needs of the individual foci in the multiple-focus heating patterns. Without this dynamic power reallocation, the standard multiple-focus pattern synthesis may produce low-efficiency driving patterns that may fail to achieve the control objective at the some or all control points in the heating pattern.