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Carotid bodies (CBs) are chemoreceptors that monitor and register changes in the blood, including the levels of oxygen, carbon dioxide, and pH, and regulate breathing. Enhanced activity of CBs was shown to correlate with a significant elevation in the blood pressure of patients with hypertension. CB removal or denervation were previously shown to reduce hypertension. Here we demonstrate the feasibility of a dual-mode ultrasound array (DMUA) system to safely ablate the CB in vivo in a spontaneously hypertensive rat (SHR) model of hypertension. DMUA imaging was used for guiding and monitoring focused ultrasound (FUS) energy delivered to the target region. In particular, 3D imaging was used to identify the carotid bifurcation for targeting the CBs. Intermittent, high frame rate imaging during image-guided FUS (IgFUS) delivery was used for monitoring the lesion formation. DMUA imaging provided feedback for closed-loop control (CLC) of the lesion formation process to avoid overexposure. The procedure was tolerated well in over 100 SHR and normotensive rats that received unilateral and bilateral treatments. The measured mean arterial pressure (MAP) exhibited measurable deviation from baseline 2–4 weeks post IgFUS treatment. The results suggest that the direct unilateral FUS treatment of the CB might be sufficient to reduce the blood pressure in hypertensive rats and justify further investigation in large animals and eventually in human patients.

Purpose High-intensity focused ultrasound (HIFU) is a potential noninvasive thermal ablation method for the treatment of peripheral artery disease. Dual-mode ultrasound arrays (DMUA) offer the possibility of simultaneous imaging and treatment. In this study, safety and feasibility of femoral artery robot-assisted HIFU/DMUA therapy was assessed. Methods In 18 pigs (∼50kg), angiography and diagnostic ultrasound were used to visualize diameter and blood flow of the external femoral arteries (EFA). HIFU/DMUA-therapy was unilaterally applied to the EFA dorsal wall using a 3.5 MHz, 64-element transducer, closed-loop-control was used to automatically adjust energy delivery to control thermal lesion formation. A continuous lesion of at least 25 mm was created by delivering 6–8 HIFU shots per imaging plane perpendicular to the artery spaced 1 mm apart. Directly after HIFU/DMUA-therapy and after 0, 3 or 14 days follow up, diameter and blood flow were measured and the skin was macroscopically examined for thermal damage. The tissue was removed for histological analysis. Results No complications were observed. The most frequently observed treatment effect was formation of scar tissue, predominantly in the adventitia and the surrounding tissue. No damage to the endothelium or excessive damage of the surrounding tissue was observed. There was no significant decrease in the mean arterial diameter after HIFU/DMUA-therapy. Conclusion HIFU/DMUA therapy successfully targeted the vessel walls of healthy porcine arteries, without causing endothelial damage or other vascular complications. Therefore, this therapy can be safely applied to healthy arterial walls in animals. Future studies should focus on safety and dose-finding in atherosclerotic diseased arteries.

Background Transcranial focused ultrasound (tFUS) at low intensities has been reported to directly evoke responses and reversibly inhibit function in the central nervous system. While some doubt has been cast on the ability of ultrasound to directly evoke neuronal responses, spatially-restricted transcranial ultrasound has demonstrated consistent, inhibitory effects, but the underlying mechanism of reversible suppression in the central nervous system is not well understood. Objective/hypothesis In this study, we sought to characterize the effect of transcranial, low-intensity, focused ultrasound on the thalamus during somatosensory evoked potentials (SSEP) and investigate the mechanism by modulating the parameters of ultrasound. Methods TFUS was applied to the ventral posterolateral nucleus of the thalamus of a rodent while electrically stimulating the tibial nerve to induce an SSEP. Thermal changes were also induced through an optical fiber that was image-guided to the same target. Results Focused ultrasound reversibly suppressed SSEPs in a spatially and intensity-dependent manner while remaining independent of duty cycle, peak pressure, or modulation frequency. Suppression was highly correlated and temporally consistent with in vivo temperature changes while producing no pathological changes on histology. Furthermore, stereotactically-guided delivery of thermal energy through an optical fiber produced similar thermal effects and suppression. Conclusion We confirm that tFUS predominantly causes neuroinhibition and conclude that the most primary biophysical mechanism is the thermal effect of focused ultrasound.

Tumors in organs partially obscured by the rib cage represent a challenge for high-intensity focused ultrasound (HIFU) therapy. The ribs distort the HIFU beams in a manner that reduces the focusing gain at the target, which could result in treatment-limiting collateral damage. In fact, skin burns are a common complication during the ablation of hepatic tumors. This problem can be addressed by employing optimal refocusing algorithms that are designed to achieve a specified focusing gain at the target while controlling the exposure to the ribs in the path of the HIFU beam. However, previously proposed optimal refocusing algorithms did not allow for the controlled transmission through the ribs. In this article, we introduce a new approach for refocusing that can more efficiently steer power toward the target while limiting the power deposition on the ribs. The approach utilizes the semidefinite relaxation (SDR) technique to approximate the original (nonconvex) optimization problem. An important advantage of the SDR-based method over previously proposed optimization methods is the control of the side lobes in the focal plane. The method also allows for specifying an acceptable level of exposure to the ribs. Simulation results using a 1-MHz spherical concave phased array focused on an inhomogeneous medium are presented to demonstrate the performance of the SDR refocusing approach. A finite-difference time-domain propagation model was used to model the propagation in the inhomogeneous tissues, including the ribs. Temperature simulations based on the inhomogeneous transient bioheat transfer equation (tBHTE) demonstrate the significance of the improvements in the focusing gain when using the limited power deposition (LPD) method. The results also demonstrate that the LPD method yields well-behaved array excitation vectors, realizable by currently existing drivers.

Focused ultrasound (FUS) has been proposed for a variety of transcranial applications, including neuromodulation, tumor ablation, and blood–brain barrier opening. A flurry of activity in recent years has generated encouraging results demonstrating its feasibility in these and other applications. To date, monitoring of FUS beams has been primarily accomplished using MR guidance, where both MR thermography and elastography have been used. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm in transcranial focusing. In this paper, we present first experimental results of ultrasound-guided transcranial FUS (tFUS) application in a rodent brain, both ex vivo and in vivo. DMUA imaging is used for visualization of the treatment region for placement of the focal spot within the brain. This includes the detection and localization of pulsating blood vessels at or near the target point(s). In addition, DMUA imaging is used to monitor and localize the FUS-tissue interactions in real time. In particular, a concave (40 mm radius of curvature), 32-element, 3.5-MHz DMUA prototype was used for imaging and tFUS application in ex vivo and in vivo rat models. The ex vivo experiments were used to evaluate the point spread function of the transcranial DMUA imaging at various points within the brain. In addition, DMUA-based transcranial ultrasound thermography measurements were compared with thermocouple measurements of subtherapeutic tFUS heating in rat brain ex vivo. The ex vivo setting was also used to demonstrate the capability of DMUA to produce localized thermal lesions. The in vivo experiments were designed to demonstrate the ability of the DMUA to apply, monitor, and localize subtherapeutic tFUS patterns that could be beneficial in transient blood–brain barrier opening. The results show that although the DMUA focus is degraded due to the propagation through the skull, it still produces localized heating effects within a sub-millimeter volume. In addition, DMUA transcranial echo data from brain tissue allow for reliable estimation of temperature change.

We have previously introduced methods for noninvasive estimation of temperature change using diagnostic ultrasound. The basic principle was validated both in vitro and in vivo by several groups worldwide. Some limitations remain, however, that have prevented these methods from being adopted in monitoring and guidance of minimally invasive thermal therapies, e.g., RF ablation and high-intensity-focused ultrasound (HIFU). In this letter, we present first results from a real-time system for 2-D imaging of temperature change using pulse-echo ultrasound. The front end of the system is a commercially available scanner equipped with a research interface, which allows the control of imaging sequence and access to the RF data in real time. A high-frame-rate 2-D RF acquisition mode, M2D, is used to capture the transients of tissue motion/deformations in response to pulsed HIFU. The M2D RF data is streamlined to the back end of the system, where a 2-D temperature imaging algorithm based on speckle tracking is implemented on a graphics processing unit. The real-time images of temperature change are computed on the same spatial and temporal grid of the M2D RF data, i.e., no decimation. Verification of the algorithm was performed by monitoring localized HIFU-induced heating of a tissue-mimicking elastography phantom. These results clearly demonstrate the repeatability and sensitivity of the algorithm. Furthermore, we present in vitro results demonstrating the possible use of this algorithm for imaging changes in tissue parameters due to HIFU-induced lesions. These results clearly demonstrate the value of the real-time data streaming and processing in monitoring, and guidance of minimally invasive thermotherapy.

We present a dual-element concave ultrasound transducer system for generating and tracking of localized tissue displacements in thin tissue constructs on rigid substrates. The system is comprised of a highly focused PZT-4 5-MHz acoustic radiation force (ARF) transducer and a confocal 25-MHz polyvinylidene fluoride imaging transducer. This allows for the generation of measurable displacements in tissue samples on rigid substrates with thickness values down to 500 microm. Impulse-like and longer duration sine-modulated ARF pulses are possible with intermittent M-mode data acquisition for displacement tracking. The operations of the ARF and imaging transducers are strictly synchronized using an integrated system for arbitrary waveform generation and data capture with a shared timebase. This allows for virtually jitter-free pulse-echo data well suited for correlation-based speckle tracking. With this technique we could faithfully capture the entire dynamics of the tissue axial deformation at pulse-repetition frequency values up to 10 kHz. Spatio-temporal maps of tissue displacements in response to a variety of modulated ARF beams were produced in tissue-mimicking elastography phantoms on rigid substrates. The frequency response was measured for phantoms with different modulus and thickness values. The frequency response exhibited resonant behavior with the resonance frequency being inversely proportional to the sample thickness. This resonant behavior can be used in obtaining high-contrast imaging using magnitude and phase response to sinusoidally modulated ARF beams. Furthermore, a second order forced harmonic oscillator (FHO) model was shown to capture this resonant behavior. Based on the FHO model, we used the extended Kalman filter (EKF) for tracking the apparent modulus and viscosity of samples subjected to dc and sinusoidally modulated ARF. The results show that the stiffness (apparent modulus) term in the FHO is largely time-invariant and can be estimated robustly using the EKF. On the other hand, the damping (apparent viscosity) is time varying. These findings were confirmed by comparing the magnitude response of the FHO (with parameters obtained using the EKF) with the measured ones for different thin tissue constructs.

The authors have recently presented a new algorithm for high-speed parallel processing of ultrasound pulse-echo data for real-time three-dimensional (3-D) imaging. The approach utilizes a discretized linear model of the echo data received from the region of interest (ROI) using a conventional beam former. The transmitter array elements are fed with binary codes designed to produce distinct impulse responses from different directions in ROI. Image reconstruction in ROI is achieved with a regularized pseudoinverse operator derived from the linear receive signal model. The reconstruction operator can be implemented using a transversal filter bank with every filter in the bank designed to extract echoes from a specific direction in the ROI. The number of filters in the bank determines the number of image lines acquired simultaneously. In this paper, the authors present images of a cyst phantom reconstructed based on their formulation. A number of issues of practical significance in image reconstruction are addressed. Specifically, an augmented model is introduced to account for imperfect blocking of echoes from outside the ROI. The authors have also introduced a column-weighting algorithm for minimizing the number of filter coefficients. In addition, a detailed illustration of a full image reconstruction using subimage acquisition and compounding is given. Experimental results have shown that the new approach is valid for phased-array pulse-echo imaging of speckle-generating phantoms typically used in characterizing medical imaging systems. Such coded-excitation-based image reconstruction from speckle-generating phantoms, to the best of the authors' knowledge, have not been reported previously.

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