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The size of catheter-based ultrasound devices for delivering ultrasound energy to deep-seated tumors is constrained by the access pathway which limits their therapeutic capabilities.To devise and investigate a deployable applicator suitable for minimally-invasive delivery of therapeutic ultrasound, consisting of a 2D cylindrical sectored-ring ultrasound phased array, integrated within an expandable paraboloid-shaped balloon-based reflector. The balloon can be collapsed for compact delivery and expanded close to the target position to mimic a larger-diameter concentric-ring sector-vortex array for enhanced dynamic control of focal depth and volume.Acoustic and biothermal simulations were employed in 3D generalized homogeneous and patient-specific heterogeneous models, for three-phased array transducers with 32, 64, and 128 elements, composed of sectored 4, 8, and 16 tubular ring transducers, respectively. The applicator performance was characterized as a function of array configuration, focal depth, phasing modes, and balloon reflector geometry. A 16-element proof-of-concept phased array applicator assembly, consisting of four tubular transducers each divided into four sectors, was fabricated, and characterized with hydrophone measurements along and across the axis, and ablations in ex vivo tissue.Simulation results indicated that transducer arrays (1.5 MHz, 9 mm OD × 20 mm long), balloon sizes (41-50 mm expanded diameter, 20-60 mm focal depth), phasing mode (0-4) and sonication duration (30 s) can produce spatially localized acoustic intensity focal patterns (focal length: 3-22 mm, focal width: 0.7-8.7 mm) and ablative thermal lesions (width: 2.7-16 mm, length: 6-46 mm) in pancreatic tissue across a 10-90 mm focal depth range. Patient-specific studies indicated that 0.1, 0.46, and 1.2 cmThe results of this study demonstrated the feasibility of a novel compact ultrasound applicator design capable of focusing, deep penetration, electronic steering, and volumetric thermal ablation. The proposed applicator can be used for compact endoluminal or laparoscopic delivery of localized ultrasound energy to deep-seated targets.

ObjectiveChanges in ultrasound backscatter energy (CBE) imaging can monitor thermal therapy. Catheter-based ultrasound (CBUS) can treat deep tumors with precise spatial control of energy deposition and ablation zones, of which CBE estimation can be limited by low contrast and robustness due to small or inconsistent changes in ultrasound data. This study develops a multi-spatiotemporal compounding CBE (MST-CBE) imaging approach for monitoring specific to CBUS thermal therapy.MethodsEx vivo thermal ablations were performed with stereotactic positioning of a 180° directional CBUS applicator, temperature monitoring probes, endorectal US probe, and subsequent lesion sectioning and measurement. Five frames of raw radiofrequency data were acquired throughout in 15s intervals. Using window-by-window estimation methods, absolute and positive components of MST-CBE images at each point were obtained by the compounding ratio of squared envelope data within an increasing spatial size in each short-time window.ResultsCompared with conventional US, Nakagami, and CBE imaging, the detection contrast and robustness quantified by tissue-modification-ratio improved by 37.2 ± 4.7 (p < 0.001), 37.5 ± 5.2 (p < 0.001), and 6.4 ± 4.0 dB (p < 0.05) in the MST-CBE imaging, respectively. Correlation coefficient and bias between cross-sectional dimensions of the ablation zones measured in tissue sections and estimated from MST-CBE were up to 0.91 (p < 0.001) and -0.02 mm2, respectively.ConclusionThe MST-CBE approach can monitor the detailed changes within target tissues and effectively characterize the dimensions of the ablation zone during CBUS energy deposition.SignificanceThe MST-CBE approach could be practical for improved accuracy and contrast of monitoring and evaluation for CBUS thermal therapy.

PURPOSE: To investigate the design of an endoluminal deployable ultrasound applicator for delivering volumetric hyperthermia to deep tissue sites as a possible adjunct to radiation and chemotherapy. METHOD: This study considers an ultrasound applicator consisting of two tubular transducers situated at the end of a catheter assembly, encased within a distensible conical shaped balloon-based reflector that redirects acoustic energy distally into the tissue. The applicator assembly can be inserted endoluminally or laparoscopically in a compact form and expanded after delivery to the target site. Comprehensive acoustic and biothermal simulations and parametric studies were employed in generalized 3D and patient-specific pancreatic head and body tumor models to characterize the acoustic performance and evaluate heating capabilities of the applicator by investigating the device at a range of operating frequencies, tissue acoustic and thermal properties, transducer configurations, power modulation, applicator positioning, and by analyzing the resultant 40, 41 and 43 °C isothermal volumes and penetration depth of the heating volume. Intensity distributions and volumetric temperature contours were calculated to define moderate hyperthermia boundaries. RESULTS: Parametric studies demonstrated the frequency selection to control volume and depth of therapeutic heating from 62 to 22 cm(3) and 4 to 2.6 cm as frequency ranges from 1 MHz to 4.7 MHz, respectively. Width of the heating profile tracks closely with the aperture. Water cooling within the reflector balloon was effective in controlling temperature to 37 °C maximum within the luminal wall. Patient-specific studies indicated that applicators with extended OD in the range of 3.6 – 6.2 cm with 0.5 – 1 cm long and 1 cm OD transducers can heat volumes of 1.1 – 7 cm(3), 3 – 26 cm(3) and 3.3 – 37.4 cm(3) of pancreatic body and head tumors above 43 °C, 41 °C and 40°C, respectively. CONCLUSION: In silico studies demonstrated the feasibility of combining endoluminal ultrasound with an integrated expandable balloon reflector for delivering volumetric hyperthermia in regions adjacent to body lumens and cavities.

Objective To develop a thermochromic tissue-mimicking phantom (TTMP) with an embedded 3D-printed bone mimic of the lumbar spine to evaluate MRgFUS ablation of the facet joint and medial branch nerve. Materials and methods Multiple 3D-printed materials were selected and characterized by measurements of speed of sound and linear acoustic attenuation coefficient using a through-transmission technique. A 3D model of the lumbar spine was segmented from a de-identified CT scan, and 3D printed. The 3D-printed spine was embedded within a TTMP with thermochromic ink color change setpoint at 60 °C. Multiple high energy sonications were targeted to the facet joints and medial branch nerve anatomical location using an ExAblate MRgFUS system connected to a 3T MR scanner. The phantom was dissected to assess sonication targets and the surrounding structures for color change as compared to the expected region of ablation on MR-thermometry. Results The measured sound attenuation coefficient and speed of sound of gypsum was 240 Np/m-MHz and 2471 m/s, which is the closest to published values for cortical bone. Following sonication, dissection of the TTMP revealed good concordance between the regions of color change within the phantom and expected areas of ablation on MR-thermometry. No heat deposition was observed in critical areas, including the spinal canal and nerve roots from either color change or MRI. Conclusion Ablated regions in the TTMP correlated well with expected ablations based on MR-thermometry. These findings demonstrate the utility of an anatomic spine phantom in evaluating MRgFUS sonication for facet joint and medial branch nerve ablations.

PURPOSE Application of the Nakagami statistical model and associated m parameter has the potential to suppress artifacts from adjustable system parameters and operator selections typical in echo amplitude-coded microbubble-enhanced ultrasound (MEUS). However, the feasibility of applying m estimation and determination of the associated Nakagami distribution features for in vivo MEUS remain to be investigated. Sensitivity and discriminability of m-coded MEUS are often limited since raw envelopes are regulated by complex radiofrequency (RF) and video-frequency (VF) processing. This study aims to develop an improved imaging approach for the m parameter estimation which can overcome the above limitations in in vivo condition. METHOD The regulation effects of RF processing of pulse-inversion (PI) harmonic detection techniques and VF processing of logarithmic compression in Nakagami distributions were investigated in MEUS. A window-modulated compounding moment estimator was developed to estimate the MEUS m values. The sensitivity and discriminability of m-coded MEUS were quantified with contrast-to-tissue ratio (CTR), contrast-to-noise ratio (CNR), and axial and lateral resolutions, which were validated through in vivo perfusion experiments on rabbit kidneys. RESULTS Regulated by RF and VF processing, the distributions of MEUS obeyed the Nakagami statistical model. The Nakagami-fitted correlation coefficient was 0.996 ± 0.003 (P

An endoscopic ultrasound phased array applicator is introduced, consisting of a phased array transducer enclosed in a distensible reflector balloon that is filled with water. The applicator can be collapsed for delivery and expanded close to the target position to enhance its therapeutic capabilities. Acoustic and biothermal simulations were performed for a 64-element cylindrical phased array transducer composed of 8 tubular transducers, each divided into 8 sectors, in water medium and 3D generalized tissue medium. The transducer-reflector design mimics the focal quality of a large diameter combined concentric-ring sector-vortex phased array. Simulation results indicated that transducer arrays (1.5 MHz, 9 mm OD x 20 mm length, 8 rings, 8 sectors), balloon sizes (42 – 50 mm expanded diameter, 20 – 60 mm focal depth), phasing mode (0 – 4) and sonication durations (120 s) can produce spatially-localized focal intensity patterns (Axial FWHM: 3 – 19 mm, Transverse FWHM: 2 – 8 mm) and ablative thermal lesions (width: 3.6 – 27 mm, length: 5 – 22.5 mm) in generalized pancreatic tissue across a 20 – 70 mm depth range. The results of this study demonstrated the feasibility of a novel ultrasound applicator design that can be collapsed for compact endoluminal or laparoscopic delivery and deployed close to the target to emulate a large concentric-ring sector-vortex phased array capable of focusing, deep penetration, electronic steering and volumetric thermal ablation.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a completely non-invasive technology that has been approved by FDA to treat several diseases. This report, prepared by the American Association of Physicist in Medicine (AAPM) Task Group 241, provides background on MRgFUS technology with a focus on clinical body MRgFUS systems. The report addresses the issues of interest to the medical physics community, specific to the body MRgFUS system configuration, and provides recommendations on how to successfully implement and maintain a clinical MRgFUS program. The following sections describe the key features of typical MRgFUS systems and clinical workflow and provide key points and best practices for the medical physicist. Commonly used terms, metrics and physics are defined and sources of uncertainty that affect MRgFUS procedures are described. Finally, safety and quality assurance procedures are explained, the recommended role of the medical physicist in MRgFUS procedures is described, and regulatory requirements for planning clinical trials are detailed. Although this report is limited in scope to clinical body MRgFUS systems that are approved or currently undergoing clinical trials in the United States, much of the material presented is also applicable to systems designed for other applications.

Therapeutic Low-intensity Pulsed Ultrasound (LIPUS) has been applied clinically for bone fracture healing and has been shown to stimulate extracellular matrix (ECM) metabolism in numerous soft tissues including intervertebral disc (IVD). In-vitro LIPUS testing systems have been developed and typically include polystyrene cell culture plates (CCP) placed directly on top of the ultrasound transducer in the acoustic near-field (NF). This configuration introduces several undesirable acoustic artifacts, making the establishment of dose-response relationships difficult, and is not relevant for targeting deep tissues such as the IVD, which may require far-field (FF) exposure from low frequency sources. The objective of this study was to design and validate an in-vitro LIPUS system for stimulating ECM synthesis in IVD-cells while mimicking attributes of a deep delivery system by delivering uniform, FF acoustic energy while minimizing reflections and standing waves within target wells, and unwanted temperature elevation within target samples. Acoustic field simulations and hydrophone measurements demonstrated that by directing LIPUS energy at 0.5, 1.0, or 1.5 MHz operating frequency, with an acoustic standoff in the FF (125–350 mm), at 6-well CCP targets including an alginate ring spacer, uniform intensity distributions can be delivered. A custom FF LIPUS system was fabricated and demonstrated reduced acoustic intensity field heterogeneity within CCP-wells by up to 93% compared to common NF configurations. When bovine IVD cells were exposed to LIPUS (1.5 MHz, 200 μs pulse, 1 kHz pulse frequency, and ISPTA = 120 mW cm−2) using the FF system, sample heating was minimal (+0.81 °C) and collagen content was increased by 2.6-fold compared to the control and was equivalent to BMP-7 growth factor treatment. The results of this study demonstrate that FF LIPUS exposure increases collagen content in IVD cells and suggest that LIPUS is a potential noninvasive therapeutic for stimulating repair of tissues deep within the body such as the IVD.

Background, Motivation and Objectives: Intraluminal and percutaneous catheter-based ultrasound (CBUS) technology can achieve precise energy control and delivery, and thus treat deep tumors with conforming ablation volumes. However, methods of real-time ultrasound monitoring of CBUS typically have low sensitivity and contrast, with limited ability of temperature estimation. Thus, this study aimed to propose a multi spatial scale change in backscatter energy (MS-CBE) monitoring approach of temperature to improve the detection sensitivity and contrast of energy changes by CBUS. Statement of Contribution/Methods: A directional CBUS applicator with 3 elements (180° active sector, 1.5 mm OD x 10 mm transducers, catheter OD = 2.4 mm, fc ≈ 7.6 MHz) was used for thermal ablation within ex vivo muscle (burst = 10 s, duration = 10 min, duty = 97%, power = 10 W). Raw radiofrequency data were recorded real-time by Ultrasonix MDP system equipped with a stereotactically aligned BCL9-5 endorectal probe at 11 Hz within a short-time window of 270 ms, in which CBUS power was paused. Multijunction thermocouple probes were used to detect the temperature changes to correlate MS-CBE with temperature. Each point value in MS-CBE is quantified by the average power ratio of the scale parameter of the statistical analysis within 4 increasing volumes from 3×3 to 12×12 wavelengths. MS-CBE maps of positive and absolute components and the corresponding spatial fitting maps were finally reconstructed. Results, Discussion and Conclusions: Detection sensitivity and contrast of the proposed MS-CBE were quantified by the tissue-modification-ratio (TMR). The detailed changes in tissue coagulation during energy delivery from the directional CBUS were clearly monitored by the MS-CBE. The corresponding regional ablation size was also effectively characterized by the fitting MS-CBE. Compared with B mode and conventional CBE, the proposed MS-CBE has the highest TMR with 30 dB improvement. Moreover, the proposed MS-CBE has a high correlation coefficient of 0.99 (p < 0.001, a norm of residuals = 0.9) with temperature elevation. These results suggest that the proposed CBUS-based MS-CBE method with temperature component could be useful to provide accurate monitoring and evaluation with a high TMR for the CBUS precise thermal therapy.

Background, Motivation and Objectives: The distribution of echoes from simulated and in vitro nonlinear scattering microbubbles obeys the Nakagami (NK) model, of which shape parameter ( $m$ ) has the potential to suppress the artifacts from systems and operators in echo amplitude-coding contrast-enhanced ultrasound (CEUS) (Med. Phys. 2019, 46: 5467–5477). However, the feasibility of $m$ estimation in in vivo CEUS is still controversial and its sensitivity and discriminability are limited, since raw envelopes are regulated by complex radiofrequency (RF) and video-frequency (VF) processing. This study aimed to illustrate this regulation mechanism and overcome these limitations. Statement of Contribution/Methods: The regulation mechanism of eight harmonic detection techniques and logarithmic compression on NK distributions was investigated in both B and pulse-inversion (PI) modes. A window-modulated compounding moment estimator (WMCME) was developed to estimate the CEUS $m$ values. Sensitivity and discriminability of $m$ -coding CEUS were respectively quantified by m-contrast-to-tissue ratio (mCTR), m-contrast-to-noise ratio (mCNR), and −2 dB half-lengths of axial and lateral autocorrelation functions, which were validated via in vivo perfusion experiments of rabbit kidneys. Results, Discussion and Conclusions: Regulated by the RF&VF processing, the distributions of CEUS also obeyed the NK model, of which NK-fitted correlation coefficient was $.99\pm 0.01\ (p in t-test and $p in Kolmogorov-Smirnov test). In all m-coding CEUS methods, logarithmic m-coding PI scheme well-characterized the ring-like perfusion features and details within the renal cortex. The $m$ CTR, $m$ CNR, −2 dB axial and lateral half-lengths were up to $7.9\pm 1.5\ \mathrm{dB},\ 34.4\pm 1.7\ \mathrm{dB},\ 1.02\pm 0.02$ and $.91\pm 0.02\ \mathrm{mm}$ , respectively, which were higher than or comparable with amplitude-coding CEUS. The NK model can characterize CEUS even if the envelope distributions were regulated by the RF & VF processing. The logarithmic $m$ -coding PI scheme significantly improved the sensitivity, discriminability, and robustness of $m$ estimation in CEUS. This scheme provided an option to remove those artifacts in echo amplitude-coding CEUS and more distinctly characterize the inherent microvasculature marked by microbubbles, which could provide a valuable technique to improve precise diagnoses and therapy.

Low intensity pulsed ultrasound (LIPUS) may have utility for non-invasive treatment of discogenic lower back pain through stimulating, remodeling and accelerating healing of injured or degenerated intervertebral disc (IVD) tissues. This study investigates the feasibility of delivering LIPUS to lumbar IVDs between L2 and S1 spine vertebra using a planar extracorporeal phased array (8 × 8 cm, 1024 elements, 500 kHz). Three 3D anatomical models with heterogenous tissues were generated from patient CT image sets and used in the simulation-based analysis. Time-reversal acoustic modeling techniques were applied to optimize posterior-lateral placement of the array with respect to the body to facilitate energy deposition in discrete target regions spanning the annulus fibrosus and central nucleus of each IVD. Forward acoustic and biothermal simulations were performed with time-reversal optimized array placements and driving amplitude/phase settings to predict LIPUS intensity distributions at target sites and to investigate off-target energy deposition and heating potential. Simulation results demonstrate focal intensity gain of 5-168 across all IVD targets and anatomical models, with greater average intensity gain (>50) and energy localization in posterior, posterolateral, and lateral target sites of IVDs. Localized LIPUS delivery was enhanced in thinner patient anatomies and in the high lumbar levels (L2-L3 and L3-L4). Multiple amplitude/phasing illumination patterns could be sequenced at a fixed array position for larger regional energy coverage in the IVD. Biothermal simulations demonstrated that LIPUS-appropriate exposures of 100 mW cm-2 ISPTA to the target disc region would result in

High-intensity ultrasound (US) ablation produces deeper myocardial lesions than radiofrequency ablation. The presence of intravascular microbubble (MB) contrast agents enhances pulsed-wave US ablation via cavitation-related histotripsy, potentially facilitating ablation in persistently perfused/conducting myocardium. US ablation catheters were developed and tested in the presence of MBs using ex vivo and in vivo models. High-frame-rate videomicroscopy and US imaging of gel phantom models confirmed MB destruction by inertial cavitation. MB-facilitated US ablation in an ex vivo perfused myocardium model generated shallow (2 mm) lesions and, in an in vivo murine hindlimb model, reduced perfusion by 42% with perivascular hemorrhage and inflammation, but no myonecrosis.

Purpose Catheter-based ultrasound applicators can generate thermal ablation of tissues adjacent to body lumens, but have limited focusing and penetration capabilities due to the small profile of integrated transducers required for the applicator to traverse anatomical passages. This study investigates a design for an endoluminal or laparoscopic ultrasound applicator with deployable acoustic reflector and fluid lens components, which can be expanded after device delivery to increase the effective acoustic aperture and allow for deeper and dynamically adjustable target depths. Acoustic and biothermal theoretical studies, along with benchtop proof-of-concept measurements, were performed to investigate the proposed design. Methods The design schema consists of an array of tubular transducer(s) situated at the end of a catheter assembly, surrounded by an expandable water-filled conical balloon with a secondary reflective compartment that redirects acoustic energy distally through a plano-convex fluid lens. By controlling the lens fluid volume, the convex surface can be altered to adjust the focal length or collapsed for device insertion or removal. Acoustic output of the expanded applicator assembly was modeled using the rectangular radiator method and secondary sources, accounting for reflection and refraction at interfaces. Parametric studies of transducer radius (1-5 mm), height (3-25 mm), frequency (1.5-3 MHz), expanded balloon diameter (10-50 mm), lens focal length (10-100 mm), lens fluid (silicone oil, perfluorocarbon), and tissue attenuation (0-10 Np/m/MHz) on beam distributions and focal gain were performed. A proof-of-concept applicator assembly was fabricated and characterized using hydrophone-based intensity profile measurements. Biothermal simulations of endoluminal ablation in liver and pancreatic tissue were performed for target depths between 2-10 cm. Results Simulations indicate that focal gain and penetration depth scale with the expanded reflector-lens balloon diameter, with greater achievable performance using perfluorocarbon lens fluid. Simulations of a 50 mm balloon OD, 10 mm transducer outer diameter (OD), 1.5 MHz assembly in water resulted in maximum intensity gain of ~170 (focal dimensions: ~12 mm length x 1.4 mm width) at ~5 cm focal depth and focal gains above 100 between 24-84 mm depths. A smaller (10 mm balloon OD, 4 mm transducer OD, 1.5 MHz) configuration produced a maximum gain of 6 at 9 mm depth. Compared to a conventional applicator with a fixed spherically-focused transducer of 12 mm diameter, focal gain was enhanced at depths beyond 20 mm for assembly configurations with balloon diameters ≥ 20 mm. Hydrophone characterizations of the experimental assembly (31 mm reflector/lens diameter, 4.75 mm transducer radius, 1.7 MHz) illustrated focusing at variable depths between 10-70 mm with a maximum gain of ~60 and demonstrated agreement with theoretical simulations. Biothermal simulations (30 s sonication, 75°C maximum) indicate that investigated applicator assembly configurations, at 30 mm and 50 mm balloon diameters, could create localized ellipsoidal thermal lesions increasing in size from 10-55 mm length x 3-6 mm width in liver tissue as target depth increased from 2-10 cm. Conclusions Preliminary theoretical and experimental analysis demonstrates that combining endoluminal ultrasound with an expandable acoustic reflector and fluid lens assembly can significantly enhance acoustic focal gain and penetration from inherently smaller diameter catheter-based applicators. This article is protected by copyright. All rights reserved.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

A novel design for a deployable catheter-based ultrasound applicator for endoluminal and laparoscopic intervention is introduced. By combining a 1D cylindrical ring phased array with an expandable paraboloid or conical-shaped balloon-based reflector, the applicator can be controllably collapsed for compact delivery and deployed to mimic a forward-firing larger diameter concentric ring array with tight focusing and electronic steering capabilities in depth. Comprehensive acoustic and biothermal parametric studies were employed to characterize the capabilities of the applicator design as a function of transducer dimensions, phased array configuration, and balloon reflector geometry. Modeling results indicate that practical balloon sizes (43-57 mm expanded diameter), transducer array configurations (e.g. 1.5 MHz, 10 mm OD × 20 mm length, 8 or 16 array elements), and sonication durations (30 s) are capable of producing spatially-localized acoustic intensity focal patterns and ablative thermal lesions (width: 2.8-4.8 mm; length: 5.3-40.1 mm) in generalized soft tissue across a 5-100 mm depth range. Larger focal intensity gain magnitudes and narrower focal dimensions are attainable using paraboloid-shaped balloon reflectors with natural geometric focal depths of 25-55 mm, whereas conical-shaped reflectors (angled 45-55°) produce broader foci and extend electronic steering range in depth. A proof-of-concept phased array applicator assembly was fabricated and characterized using hydrophone and radiation force balance measurements and demonstrated good agreement with simulation. The results of this study suggest that combining small diameter cylindrical phased arrays with expandable balloon reflectors can enhance minimally invasive ultrasound-based intervention by augmenting achievable focal gains and penetration depths with dynamic adjustment of treatment depth.

Purpose: Endoluminal ultrasound may serve as a minimally invasive option for delivering thermal ablation to pancreatic tumors adjacent to the stomach or duodenum. The objective of this study was to explore the basic feasibility of this treatment strategy through the design, characterization, and evaluation of proof-of-concept endoluminal ultrasound applicators capable of placement in the gastrointestinal (GI) lumen for volumetric pancreas ablation under MR guidance. Methods: Two variants of the endoluminal applicator, each containing a distinct array of two independently powered transducers (10 × 10 mm 3.2 MHz planar; or 8 × 10 × 20 mm radius of curvature 3.3 MHz curvilinear geometries) at the distal end of a meter long flexible catheter assembly, were designed and fabricated. Transducers and circulatory water flow for acoustic coupling and luminal cooling were contained by a low-profile polyester balloon covering the transducer assembly fixture. Each applicator incorporated miniature spiral MR coils and mechanical features (guiding tips and hinges) to facilitate tracking and insertion through the GI tract under MRI guidance. Acoustic characterization of each device was performed using radiation force balance and hydrophone measurements. Device delivery into the upper GI tract, adjacent to the pancreas, and heating characteristics for treatment of pancreatic tissue were evaluated in MR-guided ex vivo and in vivo porcine experiments. MR guidance was utilized for anatomical target identification, tracking/positioning of the applicator, and MR temperature imaging (MRTI) for PRF-based multislice thermometry, implemented in the real-time RTHawk software environment. Results: Force balance and hydrophone measurements indicated efficiencies of 48.8% and 47.8% and −3 dB intensity beam-widths of 3.2 and 1.2 mm for the planar and curvilinear transducers, respectively. Ex vivo studies on whole-porcine carcasses revealed capabilities of producing ablative temperature rise (ΔT > 15 °C) contours in pancreatic tissue 4–40 mm long and 4–28 mm wide for the planar transducer applicator (1–13 min sonication duration, ∼4 W/cm2 applied acoustic intensity). Curvilinear transducers produced more selective heating, with a narrower ΔT > 15 °C contour length and width of up to 1–24 mm and 2–7 mm, respectively (1–7 min sonication duration, ∼4 W/cm2 applied acoustic intensity). Active tracking of the miniature spiral coils was achieved using a Hadamard encoding tracking sequence, enabling real-time determination of each coil's coordinates and automated prescription of imaging planes for thermometry. In vivo MRTI-guided heating trials in three pigs demonstrated capability of ∼20 °C temperature elevation in pancreatic tissue at 2 cm depths from the applicator, with 5–7 W/cm2 applied intensity and 6–16 min sonication duration. Dimensions of thermal lesions in the pancreas ranged from 12 to 28 mm, 3 to 10 mm, and 5 to 10 mm in length, width, and depth, respectively, as verified through histological analysis of tissue sections. Multiple-baseline reconstruction and respiratory-gated acquisition were demonstrated to be effective strategies in suppressing motion artifacts for clear evolution of temperature profiles during MRTI in the in vivo studies. Conclusions: This study demonstrates the technical feasibility of generating volumetric ablation in pancreatic tissue using endoluminal ultrasound applicators positioned in the stomach lumen. MR guidance facilitates target identification, device tracking/positioning, and treatment monitoring through real-time multislice PRF-based thermometry.

Neuromyelitis optica spectrum disorders (herein called NMO) is an autoimmune disease of the CNS characterized by astrocyte injury, inflammation, and demyelination. In seropositive NMO, immunoglobulin G autoantibodies against aquaporin-4 (AQP4-IgG) cause primary astrocyte injury. A passive transfer model of NMO was developed in which spatially targeted access of AQP4-IgG into the CNS of seropositive rats was accomplished by pulsed focused ultrasound through intact skin. Following intravenous administration of microbubbles, pulsed ultrasound at 0.5 MPa peak acoustic pressure was applied using a 1 MHz transducer with 6-cm focal length. In brain, the transient opening of the blood-brain barrier (BBB) in an approximately prolate ellipsoidal volume of diameter ∼3.5 mm and length ∼44 mm allowed entry of IgG-size molecules for up to 3–6 hours. The ultrasound treatment did not cause erythrocyte extravasation or inflammation. Ultrasound treatment in AQP4-IgG seropositive rats produced localized NMO pathology in brain, with characteristic astrocyte injury, inflammation, and demyelination after 5 days. Pathology was not seen when complement was inhibited, when non-NMO human IgG was administered instead of AQP4-IgG, or in AQP4-IgG seropositive AQP4 knockout rats. NMO pathology was similarly created in cervical spinal cord in seropositive rats. These results establish a noninvasive, spatially targeted model of NMO in rats, and demonstrate that BBB permeabilization, without underlying injury or inflammation, is sufficient to create NMO pathology in AQP4-IgG seropositive rats.

The purpose of this study is to investigate the feasibility and performance of a stationary, non-focused dual-sectored tubular transurethral ultrasound applicator for thermal exposure of tissue regions adjacent to the urethra for treatment of stress urinary incontinence (SUI) through acoustic and biothermal simulations on 3D anatomical models. Parametric studies in a generalized tissue model over dual-sectored ultrasound applicator configurations (acoustic surface intensities, lateral active acoustic output sector angles, and durations) were performed. Selected configurations and delivery strategies were applied on 3D pelvic anatomical models. Temperature and thermal dose distributions on the target region and surrounding tissues were calculated. Endovaginal cooling was explored as a strategy to mitigate vaginal heating. The 75-90° dual-sectored transurethral tubular transducer (3.5mm outer diameter (OD), 14mm length, 6.5MHz, 8.8-10.2W/cm2) and 2-3-min sonication duration were selected from the parametric study for acoustic and biothermal simulations on anatomical models. The transurethral applicator with two opposing 75-90° active lateral tubular sectors can create two heated volumes for a total of up to 1.8cm3 over 60 EM43°C, with at least 10mm radial penetration depth, 1.2mm urethral sparing, and no lethal damage to the vagina and adjacent bone (

BACKGROUND: Stress Urinary Incontinence (SUI) is prevalent in adult women, attributed to weakened endopelvic supporting tissues, and typically treated using drugs and invasive surgical procedures. The objective of this in silico study is to explore transurethral high intensity ultrasound for delivery of precise thermal therapy to the endopelvic tissues adjacent to the mid-urethra, to induce thermal remodelling as a potential minimally invasive treatment alternative. METHODS: 3D acoustic (Rayleigh-Sommerfeld) and biothermal (Pennes Bioheat) models of the ultrasound applicator and surrounding tissues were devised. Parametric studies over transducer configuration (frequency, radius-of-curvature (ROC)) and treatment settings (power, duration) were performed, and select cases on patient specific models were used for further evaluation. Transient temperature and thermal dose distributions were calculated, and temperature and dose metrics reported. RESULTS: Configurations using a 5 MHz curvilinear transducer (3.5 mm x 10 mm, 28 mm ROC) with single 90s sonication can create heated zones with 11 mm penetration (>50°C) while sparing the inner 1.8mm (

BackgroundHyperthermia therapy (HT) has shown to be an effective adjuvant to radiation, chemotherapy, and immunotherapy. In order to be safe and effective, delivery of HT requires maintenance of target tissue temperature within a narrow range (40-44°C) for 30-60min, which necessitates conformal heat delivery and accurate temperature monitoring. The goal of this project was to develop an MR thermometry-guided hyperthermia delivery platform based upon the ExAblate prostate array that would achieve uniform stable heating over large volumes within the prostate, while allowing the user to precisely control the power deposition patterns and shape of the region of treatment (ROT).MethodsThe HT platform incorporates an accelerated multi-slice real time MR thermometry pulse sequence and reconstruction pipeline. Temperature uniformity over a large contiguous area was achieved by multi-point temperature sampling with multi-focal feedback power control. The hyperthermia delivery system was based on an InSightec ExAblate 2100 prostate focused ultrasound ablation system, and HeartVista's RTHawk real-time MRI system integrated with a 3T MRI scanner. The integrated system was evaluated in experiments with a tissue-mimicking phantom for prolonged exposures with a target temperature increase of 7°C from baseline.ResultsFive various shapes of the region of treatment, defined on a 5 × 5 grid (35 × 35mm, 11-25 focal spots per shape), were implemented to evaluate the performance of the system. MR temperature images, acquired after steady state was reached, showed different patterns of heating that closely matched the prescribed regions. Temperature uncertainty of the thermometry acquisition was 0.5°C. The time to reach the target temperature (2:58-7:44min) depended on the chosen ROT shape and on the distance from transducer to focal plane. Pre-cooling with circulating water helped to reduce near-field heating.ConclusionsWe have implemented a real-time MR thermometry-guided system for hyperthermia delivery within user-defined regions with the ExAblate prostate array and evaluated it in phantom experiments for different shapes and focal depths. Our results demonstrate the feasibility of using a commercially available endorectal FUS transducer to perform spatially-conformal hyperthermia therapy and could lead to a new set of exciting applications for these devices.

The goal of the study was to establish early hyperpolarized (HP) 13 C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual-agent (13 C pyruvate and 13 C urea) 13 C MRI/multiparametric 1 H MRI approach was used to measure prostate cancer metabolism and perfusion 3-4 h, 1 d, and 5 d after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin. In ablated regions, the intensity of HP 13 C lactate or HP 13 C urea and dynamic contrast-enhanced (DCE) MRI area under the curve images were reduced to the level of background noise by 3-4 h after treatment with no recovery by the 5 d time point in either case. In the tissues that received sub-lethal heat dose, there was a significant 60% ± 12.4% drop in HP 13 C lactate production and a significant 30 ± 13.7% drop in urea perfusion 3-4 h after treatment, followed by recovery to baseline by 5 d after treatment. DCE MRI Ktrans showed a similar trend to HP 13 C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region, while having a 40%-50% decrease 3-4 h after treatment followed by recovery to baseline values by 5 d in the margin region. The utility of the HP 13 C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies.

Low intensity pulsed ultrasound (LIPUS)can induce cellular and bulk tissue effects that can be exploited for therapeutic purposes. In contrast to HIFU ablation, these acoustic exposures are minimal, and at most generate low temperature elevation. In order to facilitate clinical studies of image-guided therapeutic ultrasound for intervertebral disc regeneration and treatment of back pain, we plan to: (i) implement studies in proven animal models in vivo to demonstrate potential of ultrasound to increase cellularity, reduce inflammation, and improve remodeling to acute or degenerative disc-related back injury; and (ii) to demonstrate through experiments that a MRg-HIFU system is one possible vehicle for therapeutic delivery.

Clinical management of many chronic ophthalmological disorders requires direct delivery of drugs into the vitreous. There is an important need to investigate novel needle-less alternatives to deliver drugs to the vitreous. The purpose of this study is to assess the effects of a needle-less system using ultrasound to enhance vitreal delivery of small molecules through the sclera in an ex vivo model and to evaluate whether changes in permeability are mainly due to the heat generated by sonication. An eye cup containing 1 mL of sodium fluorescein 0.1% was placed on top of the sclera of cadaveric rabbit eyes. Treated eyes were sonicated for 10 minutes, and left in contact with the fluorescein solution for an additional 50 minutes. Control eyes received the same exposure to fluorescein solution (60 minutes) in the eye cup without ultrasound treatment. Vitreous humor was collected and analyzed using a fluorescence spectrophotometer to calculate the concentration of fluorescein that diffused into the vitreous humor. An additional set of eyes was treated using a heating probe to evaluate whether changes in permeability were mainly due to heat. Vitreous samples from ultrasound-treated eyes showed a 44.6% higher concentration of fluorescein compared to control eyes. The concentration of fluorescein in the vitreous of heat-treated eyes did not show a significant difference when compared to control eyes. Thus, phonophoresis is a promising needle-less method for vitreal drug delivery, and local heating conducted to the surface of the sclera should be mitigated because it does not enhance the efficacy of the method.

The goal of the study was to establish early hyperpolarized (13)C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined hyperpolarized (HP) dual agent ((13)C-pyruvate and (13)C-urea) (13)C MRI/mp-(1)H MRI approach was used to measure prostate cancer metabolism and perfusion 3–4 hours, 1 day and 5 days after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate (TRAMP) tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin. In ablated regions, the intensity of HP (13)C lactate or HP (13)C urea and DCE MRI AUC images were reduced to the level of background noise by 3 to 4 hours after treatment with no recovery by the 5-day time point in either case. In the tissues that received sub-lethal heat dose, there was a significant 60% ± 12.4% drop in HP (13)C lactate production and a significant 30 ± 13.7% drop in urea perfusion 3–4 hours after treatment, followed by recovery back to baseline by 5 days after treatment. DCE MRI K(trans) showed a similar trend as HP (13)C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region while having a 40%–50% decrease 3–4 hours after treatment followed by recovery to baseline values by 5 days. The utility of the HP (13)C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies.

OBJECTIVEMinimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.METHODSUsing an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.RESULTSThermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.CONCLUSIONSThe authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

PurposeThe aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models.Materials and methodsParametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1-5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (> 240 EM(43 °C)) and moderate hyperthermia (40-45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70-80 °C for ablation and 45 °C for hyperthermia in target regions.ResultsParametric studies indicated that 1-3 MHz planar transducers are the most suitable for volumetric ablation, producing 5-8 cm(3) lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20-45 mm depth from the GI tract and enhance thermal sparing (T(max)

Purpose To demonstrate the feasibility of using ultrashort echo-time MRI to quantify T1 changes in cortical bone due to heating. Methods Variable flip-angle T1 mapping combined with 3D ultrashort echo-time imaging was used to measure T1 in cortical bone. A calibration experiment was performed to detect T1 changes with temperature in ex vivo cortical bone samples from a bovine femur. Ultrasound heating experiments were performed using an interstitial applicator in ex vivo bovine femur specimens, and heat-induced T1 changes were quantified. Results The calibration experiment demonstrated that T1 increases with temperature in cortical bone. We observed a linear relationship between temperature and T1 with a linear coefficient between 0.67 and 0.84 ms/°C over a range of 25–70°C. The ultrasound heating experiments showed increased T1 changes in the heated regions, and the relationship between the temperature changes and T1 changes was similar to that of the calibration. Conclusion We demonstrated a temperature dependence of T1 in ex vivo cortical bone using a variable flip-angle ultrashort echo-time T1 mapping method. Magn Reson Med 74:1548–1555, 2015. © 2015 Wiley Periodicals, Inc.

The speed of sound (SOS) for ultrasound devices used for imaging soft tissue is often calibrated to water, 1540 m/s1 , despite in-vivo soft tissue SOS varying from 1450 to 1613 m/s2 . Images acquired with 1540 m/s and used in conjunction with stereotactic external coordinate systems can thus result in displacement errors of several millimeters. Ultrasound imaging systems are routinely used to guide interventional thermal ablation and cryoablation devices, or radiation sources for brachytherapy3 . Brachytherapy uses small radioactive pellets, inserted interstitially with needles under ultrasound guidance, to eradicate cancerous tissue4 . Since the radiation dose diminishes with distance from the pellet as 1/r2 , imaging uncertainty of a few millimeters can result in significant erroneous dose delivery5,6. Likewise, modeling of power deposition and thermal dose accumulations from ablative sources are also prone to errors due to placement offsets from SOS errors7 . This work presents a method of mitigating needle placement error due to SOS variances without the need of ionizing radiation2,8. We demonstrate the effects of changes in dosimetry in a prostate brachytherapy environment due to patientspecific SOS variances and the ability to mitigate dose delivery uncertainty. Electromagnetic (EM) sensors embedded in the brachytherapy ultrasound system provide information regarding 3D position and orientation of the ultrasound array. Algorithms using data from these two modalities are used to correct bmode images to account for SOS errors. While ultrasound localization resulted in >3 mm displacements, EM resolution was verified to

Endoluminal high-intensity ultrasound offers spatially-precise thermal ablation of tissues adjacent to body lumens, but is constrained in treatment volume and penetration depth by the effective aperture of integrated transducers, which are limited in size to enable delivery through anatomical passages, endoscopic instrumentation, or laparoscopic ports. This study introduced and investigated three distinct endoluminal ultrasound applicator designs that can be delivered in a compact state then deployed or expanded at the target luminal site to increase the effective therapeutic aperture. The first design incorporated an array of planar transducers which could be unfolded at specific angles of convergence between the transducers. Two alternative designs consisted of fixed transducer sources surrounded by an expandable multicompartment balloon that contained acoustic reflector and dynamically-adjustable fluid lenses compartments. Parametric studies of acoustic output were performed across device design parameters via the rectangular radiator and secondary sources methods. Biothermal models were used to simulate resulting temperature distributions in three-dimensional heterogeneous tissue models. Simulations indicate that a deployable transducer array can increase volumetric coverage and penetration depth by ~80% and ~20%, respectively, while permitting more conformal thermal lesion shapes based on the degree of convergence between the transducers. The applicator designs incorporating reflector and fluid lenses demonstrated enhanced focal gain and penetration depth that increased with the diameter of the expanded reflector-lens balloon. Thermal simulations of assemblies with ~12 mm compact profiles and ~50 mm expanded balloon diameters demonstrated generation of localized thermal lesions at depths up to ~10 cm in liver tissue.

Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor – α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

MR-guided high-intensity focused ultrasound ablation is a promising, noninvasive method for treatment of bone tumors and palliation of pain. During thermal therapy, temperature mapping is necessary to ensure proper heat deposition in targeted tumors as well as to prevent unnecessary heating in surrounding tissues. Conventional MR thermometry exploits the proton resonant frequency shift of water protons, which normally requires a long echo time; therefore, this method is not appropriate for cortical bone due to its short T2* relaxation time. This work demonstrates that ultrashort echo-time MRI can characterize T1 changes in cortical bone caused by temperature changes. Ex vivo experiments were performed to heat diaphysis segments of bovine femurs with an interstitial ultrasound applicator. The T1 increase in the heated parts of cortical bone was observed. The temerature dependence of T1 in cortical born was also assessed by heating bovine bone samples in a temperature-controlled water bath. T1 mapping of co...

BackgroundThe goal of this study was to theoretically investigate the feasibility of intraductal and transgastric approaches to ultrasound-based thermal therapy of pancreatic tumors, and to evaluate possible treatment strategies.MethodsThis study considered ultrasound applicators with 1.2mm outer diameter tubular transducers, which are inserted into the tissue to be treated by an endoscopic approach, either via insertion through the gastric wall (transgastric) or within the pancreatic duct lumen (intraductal). 8 patient-specific, 3D, transient, biothermal and acoustic finite element models were generated to model hyperthermia (n = 2) and ablation (n = 6), using sectored (210°-270°, n = 4) and 360° (n = 4) transducers for treatment of 3.3-17.0cm3 tumors in the head (n = 5), body (n = 2), and tail (n = 1) of the pancreas. A parametric study was performed to determine appropriate treatment parameters as a function of tissue attenuation, blood perfusion rates, and distance to sensitive anatomy.ResultsParametric studies indicated that pancreatic tumors up to 2.5 or 2.7cm diameter can be ablated within 10min with the transgastric and intraductal approaches, respectively. Patient-specific simulations demonstrated that 67.1-83.3% of the volumes of four sample 3.3-11.4cm3 tumors could be ablated within 3-10 min using transgastric or intraductal approaches. 55.3-60.0% of the volume of a large 17.0cm3 tumor could be ablated using multiple applicator positions within 20-30 min with either transgastric or intraductal approaches. 89.9-94.7% of the volume of two 4.4-11.4cm3 tumors could be treated with intraductal hyperthermia. Sectored applicators are effective in directing acoustic output away from and preserving sensitive structures. When acoustic energy is directed towards sensitive structures, applicators should be placed at least 13.9-14.8mm from major vessels like the aorta, 9.4-12.0mm from other vessels, depending on the vessel size and flow rate, and 14mm from the duodenum.ConclusionsThis study demonstrated the feasibility of generating shaped or conformal ablative or hyperthermic temperature distributions within pancreatic tumors using transgastric or intraductal ultrasound.

PurposeFeasibility of targeted and volumetric hyperthermia (40-45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy.MethodsThe simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm(2), ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W).ResultsAcoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm(2)). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13-23 cm(3) volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm(2), in 4.5-5.8 cm(3) volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm(2), and in ∼6.0 cm(3) for curvilinear (cylindrical) beam patterns at 0.75 W/cm(2). Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm(2), 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations.ConclusionsThe ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 – 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, ...

Preferential acoustic absorption and heating of bone can significantly impact interstitial ultrasound ablation of tumors within or bordering the spine. Furthermore, intervening cortical bone may provide acoustic and thermal insulation that can protect sensitive structures nearby, such as the spinal cord. The objectives of this study are firstly, to apply parametric and patient-specific models to theoretically assess the feasibility of interstitial ultrasound ablation of tumors within and near the spine, and secondly, to identify potential energy delivery strategies, safety criteria, advantages, and disadvantages of interstitial ultrasound in this setting. Transient biothermal models using previously validated approximations for power deposition within bone from interstitial sources were employed. Multilayered axisymmetric models were used to perform a parametric assessment of the impact of tumor dimensions, attenuation (dependent on residual bone content), perfusion, and maximum temperature thresholds on ...

This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (∼7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 – 3 W/cm2 and lasted for 60 – 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 – 12 thermocouple sensors ...

An image-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. By considering a directional transducer array of planar, tubular, or curvilinear transducers, this design offers the potential for fast volumetric therapy and 3D spatial control over the energy deposition profile. Treatment of pancreatic tumor tissue would be performed in a minimally invasive fashion with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal wall would be achieved with a water-cooled balloon surrounding the transducers. A theoretical evaluation of this design was performed by developing a 3D acoustic and bioheat transfer model, with temperature and thermal dose solutions obtained using a FEM solver (COMSOL Multiphysics). Parametric studies were performed on a generalized anatomical model of the pancreas, tumor, and adjacent luminal wall to determine preferred transducer configurations and frequencies for maximizi...

An MR-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. Minimally invasive ablation or hyperthermia treatment of pancreatic tumor tissue would be performed with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal tissue would be achieved with a water-cooled balloon surrounding the ultrasound transducers. This approach offers the capability of conformal volumetric therapy for fast treatment times, with control over the 3D spatial deposition of energy. Prototype endoluminal ultrasound applicators have been fabricated using 3D printed fixtures that seat two 3.2 or 5.6 MHz planar or curvilinear transducers and contain channels for wiring and water flow. Spiral surface coils have been integrated onto the applicator body to allow for device localization and tracking for therapies performed under MR guidance. Heating experiments with a tissue-mimicking phantom in a 3T MR scanner were performe...