Dual-mode Ultrasound Array Research Articles

Dual-Mode 1-D Linear Ultrasound Array for Image-Guided Drug Delivery Enhancement Without Ultrasound Contrast Agents.

Pulsed high-intensity focused ultrasound (pHIFU) uses nonlinearly distorted millisecond-long ultrasound pulses of moderate intensity to induce inertial cavitation in tissue without administration of contrast agents. The resulting mechanical disruption permeabilizes the tissue and enhances the diffusion of systemically administered drugs. This is especially beneficial for tissues with poor perfusion such as pancreatic tumors. Here, we characterize the performance of a dual-mode ultrasound array designed for image-guided pHIFU therapies in producing inertial cavitation and ultrasound imaging. The 64-element linear array (1.071 MHz, an aperture of 14.8×51.2 mm, and a pitch of 0.8 mm) with an elevational focal length of 50 mm was driven by the Verasonics V-1 ultrasound system with extended burst option. The attainable focal pressures and electronic steering range in linear and nonlinear operating regimes (relevant to pHIFU treatments) were characterized through hydrophone measurements, acoustic holography, and numerical simulations. The steering range at ±10% from the nominal focal pressure was found to be ±6 mm axially and ±11 mm azimuthally. Focal waveforms with shock fronts of up to 45 MPa and peak negative pressures up to 9 MPa were achieved at focusing distances of 38-75 mm from the array. Cavitation behaviors induced by isolated 1-ms pHIFU pulses in optically transparent agarose gel phantoms were observed by high-speed photography across a range of excitation amplitudes and focal distances. For all focusing configurations, the appearance of sparse, stationary cavitation bubbles occurred at the same P- threshold of 2 MPa. As the output level increased, a qualitative change in cavitation behavior occurred, to pairs and sets of proliferating bubbles. The pressure P- at which this transition was observed corresponded to substantial nonlinear distortion and shock formation in the focal region and was thus dependent on the focal distance of the beam ranging within 3-4 MPa for azimuthal F -numbers of 0.74-1.5. The array was capable of B-mode imaging at 1.5 MHz of centimeter-sized targets in phantoms and in vivo pig tissues at depths of 3-7 cm, relevant to pHIFU applications in abdominal targets.

Image-Guided Measurement of Radiation Force Induced by Focused Ultrasound Beams.

The radiation force balance (RFB) is a widely used method for measuring acoustic power output of ultrasonic transducers. The reflecting cone target is attractive due to its simplicity and long-term stability, at a reasonable cost. However, accurate measurements using this method depend on the alignment between the ultrasound beam and cone axes, especially for highly focused beams utilized in therapeutic applications. With the advent of dual-mode ultrasound arrays (DMUAs) for imaging and therapy, image-guided measurements of acoustic output using the RFB method can be used to improve measurement accuracy. In this article, we describe an image-guided RFB measurement of focused DMUA beams using a widely used commercial instrument. DMUA imaging is used to optimize the alignment between the acoustic beam and reflecting cone axes. In addition to image-guided alignment, DMUA echo data is used to track the displacement of the cone, which provides an auxiliary measurement of acoustic power. Experimental results using a DMUA prototype with [Formula: see text] shows that 1-2 mm of misalignment can result in 5%-14% error in the measured acoustic power. In addition to the use of B-mode image guidance for improving measurement accuracy, we present preliminary results demonstrating the benefit of displacement tracking using real-time DMUA imaging during the application of (sub)therapeutic focused beams. Displacement tracking provides a direct measurement of the radiation force with high sensitivity and follows the expected dependence on changes in amplitude and duty cycle (DC) of the focused ultrasound (FUS) beam. This could lead to simpler, more reliable methods for measuring acoustic power based on the radiation force principle. Combined with appropriate computational modeling, the direct measurement of acoustic radiation force could lead to reliable dosimetry in situ in emerging applications such as transcranial FUS (tFUS) therapies.

Safety and feasibility study of non-invasive robot-assisted high-intensity focused ultrasound therapy for the treatment of atherosclerotic plaques in the femoral artery: protocol for a pilot study

IntroductionPeripheral arterial disease (PAD) is an atherosclerotic disease leading to stenosis and/or occlusion of the arterial circulation of the lower extremities. The currently available revascularisation methods have an acceptable initial...

A Dual-Mode 2D Matrix Array for Ultrasound Image-Guided Noninvasive Therapy.

Focused ultrasound (FUS) lacks reliable real-time image guidance, which hinders the development of non-invasive ultrasound treatment in many important clinical applications. A dual-mode ultrasound array, capable of both imaging and therapy offers a new and reliable strategy for image-guided ultrasound therapy applications. The strategy has the advantages of real-time use, low cost, portability and inherent registration between imaging and therapeutic coordinate systems. In this work, a dual-mode two-dimensional (2D) matrix array with 1 MHz center frequency and 256 elements for ultrasound image-guided non-invasive therapy is reported. The array can provide three-dimensional (3D) volumetric ultrasound imaging and 3D focus control. Ultrasound imaging and therapeutic applications for the brain of small animals demonstrated the multi-functional capability of the dual-mode 2D matrix array. A method of rat brain positioning based on ultrasound imaging was proposed and verified. Transcranial ultrasound image-guided blood-brain barrier (BBB) opening of multiple-targets was achieved in vivo, using the proposed dual-mode 2D array. The obtained results indicate that the dual-mode 2D matrix array is a promising method for practical use in ultrasound image-guided non-invasive therapy applications.

Precision Targeted Ablation of Fine Neurovascular Structures In Vivo Using Dual-mode Ultrasound Arrays

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.

Safety and feasibility of arterial wall targeting with robot-assisted high intensity focused ultrasound: a preclinical study

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.

Design and Implementation of a Transmit/Receive Ultrasound Phased Array for Brain Applications

Focused ultrasound phased array systems have attracted increased attention for brain therapy applications. However, such systems currently lack a direct and real-time method to intraoperatively monitor ultrasound pressure distribution for securing treatment. This study proposes a dual-mode ultrasound phased array system design to support transmit/receive operations for concurrent ultrasound exposure and backscattered focal beam reconstruction through a spherically focused ultrasound array. A 256-channel ultrasound transmission system was used to transmit focused ultrasonic energy (full 256 channels), with an extended implementation of multiple-channel receiving function (up to 64 channels) using the same 256-channel ultrasound array. A coherent backscatter-received beam formation algorithm was implemented to map the point spread function (PSF) and focal beam distribution under a free-field/transcranial environment setup, with the backscattering generated from a strong scatterer (a point reflector or a microbubble-perfused tube) or a weakly scattered tissue-mimicking graphite phantom. Our results showed that PSF and focal beam can be successfully reconstructed and visualized in free-field conditions and can also be transcranially reconstructed following skull-induced aberration correction. In vivo experiments were conducted to demonstrate its capability to preoperatively and semiquantitatively map a focal beam to guide blood-brain barrier opening. The proposed system may have potential for real-time guidance of ultrasound brain intervention, and may facilitate the design of a dual-mode ultrasound phased array for brain therapeutic applications.

Real-time monitoring of transcranial focused ultrasound in vivo

Transcranial focused ultrasound (tFUS) is being investigated in a variety of medical applications. Both thermal and mechanical bioeffects of tFUS are of interest, but localization of the tFUS therapeutic beam remains a major concern in the presence of beam distortion through the skull. We have developed a system for monitoring and delivery of tFUS using dual-mode ultrasound array (DMUA) transducers. The system is capable of delivering therapeutic tFUS in pulsed mode with imaging pulses interleaved at frame rates up to 500 fps utilizing the same array elements. In this way, the DMUA provides inherent registration between the imaging and therapy system thus providing feedback from the target region as well as tissue structures in the path of the beam. The beamformed DMUA echo data was used to image the thermal and mechanical tissue response to the tFUS beam with high spatial specificity. In vivo data from small-animal experiments have shown a temperature sensitivity of 0.2°C with high spatial specificity. Speckle tracking at up to 500 fps also allowed for tracking mechanical deformation produced by the tFUS beam in the presence of pulsations and other brain tissue motions. These results demonstrate the feasibility of characterizing both mechanical and thermal effects of subtherapeutic tFUS beams in vivo. The results are significant in burgeoning applications where the neuromodulatory response is induced by a combination of thermal and mechanical interactions.Transcranial focused ultrasound (tFUS) is being investigated in a variety of medical applications. Both thermal and mechanical bioeffects of tFUS are of interest, but localization of the tFUS therapeutic beam remains a major concern in the presence of beam distortion through the skull. We have developed a system for monitoring and delivery of tFUS using dual-mode ultrasound array (DMUA) transducers. The system is capable of delivering therapeutic tFUS in pulsed mode with imaging pulses interleaved at frame rates up to 500 fps utilizing the same array elements. In this way, the DMUA provides inherent registration between the imaging and therapy system thus providing feedback from the target region as well as tissue structures in the path of the beam. The beamformed DMUA echo data was used to image the thermal and mechanical tissue response to the tFUS beam with high spatial specificity. In vivo data from small-animal experiments have shown a temperature sensitivity of 0.2°C with high spatial specificity. S...

Wideband transskull refocusing of ultrasound beams using dual-mode ultrasound arrays: Ex vivo results

Transcranial focused ultrasound (tFUS) is capable of providing subtherapeutic and therapeutic ablative treatments for a variety of brain disorders. A major challenge towards widespread use of tFUS-based therapies stems from the complexity of the skull that could result in severe loss of focusing gain. Using extensive hydrophone scan measurements in plain water as well as transskull, we have documented a range of tFUS beam distortions for a variety of target points and access angles. In this paper, we present quantitative measurements of tFUS distortions due to skull aberrations at different operating frequencies. In addition, refocusing results for a variety of target points at different frequencies within the transducer bandwidth are presented in terms of improvement in focusing gain. Dual-mode ultrasound array (DMUA) prototype (64 elements, concave with 40-mm radius of curvature) was used. Skull samples were extracted from animal subjects that have undergone tFUS treatments using the DMUA prototype were utilized. Experiments were performed at a set of 31 discrete frequencies in the range 2.0 MHz–5.0 MHz. A needle hydrophone was used to measure the pressure waveforms at the target locations. The element transmission efficiency varied as a function of frequency in a nonmonotonic manner with a range of 5–15 dB variation for the different target points. The array focusing gain also varied nonmonotonically suggesting the need for broadband refocusing.Transcranial focused ultrasound (tFUS) is capable of providing subtherapeutic and therapeutic ablative treatments for a variety of brain disorders. A major challenge towards widespread use of tFUS-based therapies stems from the complexity of the skull that could result in severe loss of focusing gain. Using extensive hydrophone scan measurements in plain water as well as transskull, we have documented a range of tFUS beam distortions for a variety of target points and access angles. In this paper, we present quantitative measurements of tFUS distortions due to skull aberrations at different operating frequencies. In addition, refocusing results for a variety of target points at different frequencies within the transducer bandwidth are presented in terms of improvement in focusing gain. Dual-mode ultrasound array (DMUA) prototype (64 elements, concave with 40-mm radius of curvature) was used. Skull samples were extracted from animal subjects that have undergone tFUS treatments using the DMUA prototype were...

Excitation of leaky lamb waves in cranial bone using a phased array transducer in a concave therapeutic configuration

Ultrasonic therapeutic transducers that consist of large numbers of unfocused, low power elements have begun to replace single, focused, high power elements. This allows the operator to use phased array techniques to change the focal position in the tissue during therapy. In transcranial therapy, this phased array configuration is essential to reduce local heating at the highly attenuating bone. Recently, Dual Mode Ultrasound Arrays (DMUAs) have been developed which leverage existing elements for imaging during therapy. DMUAs have the benefit of both the therapeutic and imaging systems being co-registered. This improves upon the existing approach of using a separate ultrasound system for guidance, as the acoustic beam path is the same for both. Unfortunately, the highly reflective nature of bone means that DMUAs have not been applied to transcranial therapy. However the recent near-field observation of lamb waves in cranial bone opens the possibility for DMUAs to be applied to a guided wave scan of the skull. This would allow co-registration of the bone’s ultrasonic properties with the therapeutic axis which would facilitate adaptive beamforming. In this work, a beamforming scheme for the excitation of guided waves in cranial bone using a therapeutic phased array is described and demonstrated experimentally.

Anatomical-based model for simulation of HIFU-induced lesions in atherosclerotic plaques

Purpose: The aim of this study was to simulate the effect of high intensity focused ultrasound (HIFU) in non-homogenous medium for targeting atherosclerotic plaques in vivo. Materials and methods: A finite-difference time-domain heterogeneous model for acoustic and thermal tissue response in the treatment region was derived from ultrasound images of the treatment region. A 3.5 MHz dual mode ultrasound array suitable for targeting peripheral vessels was used. The array has a lateral and elevation focus at 40 mm with fenestration in its centre through which a 7.5 MHz diagnostic transducer can be placed. Two cases were simulated where seven adjacent HIFU shots (∼5000 W/cm2, 2-s exposure time) were targeted on the plaque tissue within the femoral artery. The transient bioheat equation with a convective term to account for blood flow was used to predict the thermal dose. The results of the simulation model were then validated against the histology data. Results: The simulation model predicted the HIFU-induced damage for both cases, and correlated well with the histology data. For the first case thermal damage was detected within the targeted plaque, while for the second case thermal damage was detected in the pre-focal region. Conclusion: The results suggest that a realistic, image-based acoustic and thermal model of the treatment region is capable of predicting the extent of thermal damage to target plaque tissue. The model considered the effect of the wall thickness of large arteries and the heat-sink effect of flowing blood. The model is used for predicting the size and pattern of HIFU damage in vivo.

4:24 PM; Abstract No. 61 - Dual mode ultrasound array imaging interpretation for high intensity focused ultrasound therapy in ex vivo models

4:24 PM; Abstract No. 61 - Dual mode ultrasound array imaging interpretation for high intensity focused ultrasound therapy in ex vivo models

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

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. Laboratory feasibility study. University-based laboratory. Ex vivo canine and bovine ovaries. DMUA-guided HIFU. Detection of ovarian damage by ultrasound imaging, gross pathology, and histology. 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. 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.

Feasibility of Targeting Atherosclerotic Plaques by High-Intensity–focused Ultrasound: An In Vivo Study

To investigate the feasibility and acute safety of targeting atherosclerotic plaques by high-intensity-focused ultrasound (US) in vivo through a noninvasive extracorporeal approach. 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. 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. 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.

TU‐C‐144‐01: Image Guidance and Assessment of Therapeutic Ultrasound

Despite significant advances made over the past decade in ultrasound (US) and magnetic resonance imaging (MRI) for guidance and assessment of high intensity focused ultrasound (HIFU) treatments many challenges remain. Recent developments address clinically relevant barriers to image guidance of therapeutic ultrasound. This session will feature invited presentations on (1) the use of MRI temperature mapping in presence of fat, within bone, and moving tissues, (2) dual mode ultrasound array (DMUA) systems for imaging and therapy with the advantage of inherent registration between the image‐guidance and therapeutic coordinate systems, (3) echo decorrelation imaging, providing real‐time feedback about cumulative heat‐induced tissue changes, (4) laparoscopic US imaging and HIFU treatments with special emphasis on the use of US to assess temperature change as well as tissue characteristics; and (5) opportunities for medical physicists to participate in the development, treatment planning, and quality control aspects of image‐guided HIFU therapy.Learning Objectives:1. To understand the role of various MRI and US technologies in guidance and monitoring of HIFU therapy, including MR temperature mapping, dual mode ultrasound array systems, echo decorrelation imaging for ablation assessment, and laparoscopic US‐guided HIFU2. To identify opportunities for medical physicists in assessment and deployment of technologies in image‐guided therapeutic ultrasoundDr. Carol is the Chief Development Officer for US HIFU, LLC

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.

Feasibility of high-intensity–focused ultrasound (HIFU) for treatment of polycystic ovarian syndrome: potential for noninvasive treatment

Purpose Polycystic ovarian syndrome (PCOS) affects 5-10 % of females in the child bearing period and is a common cause of infertility in this population. Surgical treatment is indicated for patients resistant to medical management. We investigate the feasibility of using HIFU as a non-invasive treatment of PCOS. Materials and Methods Ex-vivo canine ovaries fixed in gelatin were held in degassed water in front of an integrated 3.5 MHz dual mode ultrasound array (DMUA) system fenestrated to allow simultaneous use of a diagnostic transducer. DMUAs are transducers capable of imaging and treating with HIFU simultaneously using the same elements. Synthetic aperture (SA) and single transmit focus (STF) imaging were used to guide the treatment and HIFU shots (about 9-11 kW/cm 2 , 2 sec exposure time) were done at 6-7 mm depth. Ovaries were then sectioned and photographed to inspect the resultant damage. Results Echogenic changes were observed on imaging at the focal spot. Localized damage (~8×5 mm) was detected at the cortico-medullary interface; corresponding to the site of the echogenic changes. The ovarian surface was smooth and intact. SA imaging clearly showed the anatomical details of the ovaries. Conclusion We report the first use of DMUAs for potential treatment of PCOS by HIFU. Results demonstrate the feasibility of inducing thermal damage in ovaries without significant damage to the ovarian surface. This could potentially reduce the incidence of post-operative pelvic adhesions. Further, it should be possible to apply HIFU through a transvaginal probe, thus eliminating the risk associated with laparoscopy. SA imaging provided high resolution imaging that can guide the treatment. Further research is still needed to refine the exposure parameters and provide histological characterization of the HIFU induced damage.

Abstract No. 382: Dynamic dual mode ultrasound arrays for high intensity focused ultrasound therapy in an ex vivo model

Abstract No. 382: Dynamic dual mode ultrasound arrays for high intensity focused ultrasound therapy in an ex vivo model

Abstract No. 139: Feasibility of targeting atheromatous plaques by high intensity focused ultrasound using dual-mode ultrasound array systems: an early experience

Abstract No. 139: Feasibility of targeting atheromatous plaques by high intensity focused ultrasound using dual-mode ultrasound array systems: an early experience

Adaptive transthoracic focusing using dual‐mode ultrasound arrays.

Dual‐mode ultrasound array (DMUA) systems have been recently shown to be capable of refocusing high‐intensity focused ultrasound beams in the presence of strongly scattering objects, e.g., the ribs. A refocusing approach based on a modified forward/inverse propagation operator accounting for the ribs was experimentally demonstrated. The propagation operator is obtained from DMUA‐based images of the target region, including the ribs. This image‐based approach to refocusing implicitly accounts for the heterogeneity by defining a propagation operator to the proximal rib surface using DMUA directivity vectors assuming a homogeneous medium. In this paper, we address the consequences of this simplification on the quality of the refocused beam. We also present an adaptive refocusing approach that identifies the inhomogeneous directivity vectors to the target location(s) in the presence of the ribs. Example experimental results will be presented using a true real time DMUA system where the adaptive refocusing is achieved within milliseconds. Implications on real time adaptive refocusing in the context of scanning multiple target points and motion compensation will also be discussed with illustrative experimental data.