John R. Ballard

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.

In Vivo Ultrasound Thermography in Presence of Temperature Heterogeneity and Natural Motions

Real-time ultrasound thermography has been recently demonstrated on commercially available diagnostic imaging probes. In vitro experimental results demonstrate high sensitivity to small, localized temperature changes induced by subtherapeutic focused ultrasound. Most of the published results, however, are based on a thermally induced echo strain model that assumes infinitesimal change in temperature between imaging frames. Under this assumption, the echo strain is computed using a low-pass axial differentiator, which is implemented by a finite-impulse response digital filter. In this paper, we introduce a new model for temperature estimation, which employs a recursive axial filter that acts as a spatial differentiator-integrator of echo shifts. The filter is derived from first principles and it accounts for a nonuniform temperature baseline, when computing the spatial temperature change between two frames. This is a major difference from the previously proposed infinitesimal echo strain filter (δ-ESF) approach. We show that the new approach can be implemented by a first-order infinite-impulse response digital filter with depth-dependent spatial frequency response. Experimental results in vitro demonstrate the advantages over the δ-ESF approach in terms of suppressing the spatial variations in the estimated temperature without resorting to ad hoc low-pass filtering of echo strains. The performance of the new recursive echo strain filter (RESF) is also illustrated using echo data obtained during subtherapeutic localized heating in the hind limb of Copenhagen rat in vivo. In addition to the RESF, we have used an adaptive spatial filter to remove motion and deformation artifacts during real-time data collection. The adaptive filtering algorithm is described and comparisons with uncompensated estimated spatio-temporal temperature profiles are given. The results demonstrate the feasibility of in vivo ultrasound thermography with high sensitivity and specificity.

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.

Real-time monitoring of thermal and mechanical response to sub-therapeutic HIFU beams in vivo

We present first in vivo results of realtime 2D imaging of thermal and mechanical response to sub-therapeutic HIFU beams in a small-animal tumor model. A 2.5 MHz focused transducer with fnumber = 1.05 was used to generate short (≈ 1.5 sec) exposure in LNCap tumors implanted in the hindlimb of nude mice with power levels suitable to produce 4–6 °C rise in tissue (based on results in thermally-calibrated tissue mimicking phantoms). Beamformed RF data was collected at 99 frames per second to allow for capturing tissue displacements due to both temperature and breathing cycles. To ascertain the systems capability to cover an adequate range of periodic tissue motion, the sub-therapeutic HIFU beams were sinusoidally modulated at frequencies higher than the pulsatory frequency in the mouse model. Results from our previously published 2D temperature imaging algorithm demonstrate the capture of strains due to temperature change, pulsatory motions near arteries, and sinusoidal oscillations due to acoustic radiation force effects due to the HIFU-beam modulation. To reduce the effects of mechanical strains due to motion and ARF modulation, an iterative image reconstruction algorithm was used. The method employs alternating projections that employ the non-negativity constraints (TΔ(r, t) ≥ 0) and a multi-dimensional time-varying Gaussian filter derived from the spatio-temporal impulse response of the transient bioheat transfer equation (tBHTE) in each iteration. This method of projection onto convex sets (POCS) allows for the removal of artifacts inconsistent with the temperature evolution model in tissue media while preserving real temperature data until convergence is achieved. Our in vivo results show that the POCS algorithm achieves significant reduction in the temperature artifacts due to breathing and pulsations while preserving true temperature profiles with excellent spatial and temporal resolution. These results clearly demonstrate the sensitivity and specificity of ultrasound thermography to the spatially-confined sub-therapeutic HIFU beams. This performance is unmatched by other noninvasive methods for imaging temperature.

Adaptive motion compensation for in vivo ultrasound temperature estimation

Recent works have shown promising results in in vivo temperature estimation using diagnostic ultrasound. By applying speckle tracking algorithm on the M2D images taken by a diagnostic probe positioned in the fenestration of a Dual Mode Ultrasound Array (DMUA), localized temperature changes during sub-therapeutic High Intensity Focused Ultrasound (HIFU) operation can be detected. However, interference from natural motion and deformation of the tissue could result in severe errors in the estimated temperature profiles. Two-dimensional filtering inspired by the bio-heat equation was shown to partially mitigate these effects, but it is ineffective when the spatial frequencies of the deformations are within the same bandwidth of the temperature-induced strains. We present results of a new adaptive technique which is capable of largely suppressing the interference without sacrificing the dynamics of the temperature change. The method is based on finding points with strong deformation induced strains outside the targeted region before the therapy starts and training an adaptive filter with the signals from these points as it inputs. During the therapy, the strain data from selected points and trained coefficients are used to suppress the effect of natural motions using a spatial interference cancellation filter.

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.

Ultrasound thermography in vivo: A new model for calculation of temperature change in the presence of temperature heterogeneity

A new derivation of the temperature change estimation based on speckle-tracking estimation of axial echo shifts is presented which accounts for the nonuniform temperature baseline. The new method includes the spatial gradient of the temperature change in the thermal strain equation. In contrast to the previous method where thermal strain was calculated by accumulating the incremental displacement and differentiating along the axial direction, the solution to the new equation is shown to be found by using a differentiation-integration operator along the axial direction. Using a diagnostic probe and a High Intensity Focused Ultrasound (HIFU) transducer in Dual Mode Ultrasound Array (DMUA) setup the displacement data was collected from sub-therapeutic shots on the hind limb of a Copenhagen rat. The results of applying the new method showed a temperature change in a 2 mm axial extend which was consistent with the field scan pattern of the HIFU array.

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.

Dynamic imaging of tumor perfusion using contrast enhanced ultrasound: In vivo results

Despite almost 50 years of research on the use of microbubbles as ultrasound contrast agents (UCAs), the promise of high resolution dynamic perfusion imaging has not been fulfilled. This is due to the fact that the echogenicity enhancements from small clusters of bubbles in microvessels remain difficult to detect in the presence strong tissue echogenicity. A well-known pulse inversion (PI) method has been successful in exploiting the nonlinear behavior of UCAs and has led to enhanced myocardium and vascular imaging procedures. However, PI imaging has limited dynamic range due to noise amplification (fundamentally a subtraction method) We have recently proposed the use of the post-beamforming Volterra filter for separation of linear and non-linear echoes and maintaining very high dynamic range in addition to effective suppression of additive Gaussian noise. This method was shown to match or exceed the performance of PI imaging in static imaging of UCAs in flow phantoms. In this paper, we present in vivo results of UCA imaging using the cubic component of a third-order Volterra filter, together with a pixel-wise estimate of a temporal-perfusion index (TPI). We show that the TPI can be designed as a spatio-temporal estimator of the perfusion activity to provide separation between UCA activity and changes due to tissue motion due to breathing and/or pulsation. This is achieved using UCA injections with clinically-relevant concentrations and imaging at normal scanner setting, i.e. no sacrifice of bandwidth as may be necessary when using PI imaging. The results also demonstrate the high resolution nature of TPI imaging in both axial and lateral dimensions.