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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

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.

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.

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.

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.

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.

Purpose: To evaluate multiple applicator implant configurations of interstitial ultrasound devices for large volume ablation of liver tumors. Methods: A 3D bioacoustic-thermal model using the finite element method was implemented to assess multiple applicator implant configurations for thermal ablation with interstitial ultrasound energy. Interstitial applicators consist of linear arrays of up to four 10 mm-long tubular ultrasound transducers, each under separate and dynamic power control, enclosed within a water-cooled delivery catheter (2.4 mm OD). The authors considered parallel implants with two and three applicators (clustered configuration), spaced 2–3 cm apart, to simulate open surgical placement. In addition, the authors considered two applicator implants with applicators converging and diverging at angles of ∼20°, 30°, and 45° to simulate percutaneous placement. Heating experiments (10–15 min) were performed and compared against simulations employing the same experimental parameters. To estimate the performance of parallel, multiple applicator configurations in an in vivo setting, simulations were performed taking into account a range of blood perfusion levels (0, 5, 12, and 15 kg m−3 s−1) that may occur in tumors of varying vascularity. The impact of tailoring the power supplied to individual transducer elements along the length of applicators is explored for applicators inserted in non-parallel (converging and diverging) configurations. Thermal dose (t43 > 240 min) and temperature thresholds (T > 52 °C) were used to define the ablation zones, with dynamic changes to tissue acoustic and thermal properties incorporated within the model. Results: Experiments in ex vivo bovine liver yielded ablation zones ranging between 4.0–5.6 cm × 3.2–4.9 cm, in cross section. Ablation zone dimensions predicted by simulations with similar parameters to the experiments were in close agreement (within 5 mm). Simulations of in vivo heating showed that 15 min heating and interapplicator spacing less than 3 cm are required to obtain contiguous, complete ablation zones. The ability to create complete ablation zone profiles for nonparallel implants was illustrated by tailoring applied power levels along the length of applicators. Conclusions: Parallel implants consisting of three interstitial ultrasound applicators in a triangular configuration yield complete ablation zones measuring up to 6.2 cm × 5.7 cm after 15 min heating. At larger interapplicator spacing, the level of blood perfusion in the tumor may yield indentations along the periphery of the ablation zone. Tailoring applied power along the length of the applicator can accommodate for nonparallel implants, without compromising safety.

Purpose: The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Methods: Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 deg.), bisectored (2x180 deg.), or trisectored (3x120 deg.) for control of energy deposition in angle and alongmore » the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. Results: The CTV in HDR brachytherapy plans extends 20.5{+-}5.0 mm from the endocervical tandem with the rectum and bladder typically 5EM{sub 43 Degree-Sign C} over 4-5 cm diameter with T{sub max}

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8-8.4 MHz, 3 mm OD, 6 mm length), with three 120 degrees independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min(-1)) within an expandable urethral balloon (35 mm long x 10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate approximately 90 degrees-100 degrees acoustic output patterns from each 120 degrees transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n = 3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 degrees C maximum temperature, t43 = 240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (approximately15 mm) during a short power application (approximately 8-16 W per active sector, 8-15 min), with approximately 200 degrees or 360 degrees sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within approximately 5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted.

Dynamic angular control of thermal ablation and hyperthermia therapy with current interstitial heating technology is limited in capability, and often relies upon nonadjustable angular power deposition patterns and/or mechanical manipulation of the heating device. The objective of this study was to investigate the potential of multisectored tubular interstitial ultrasound devices to provide control of the angular heating distribution without device manipulation. Multisectored tubular transducers with independent sector power control were incorporated into modified versions of internally cooled (1.9 mm OD) and catheter-cooled (2.4 mm OD) interstitial ultrasound applicators in this work. The heating capabilities of these multisectored devices were evaluated by measurements of acoustic output properties, measurements of thermal lesions produced in ex vivo tissue samples, biothermal simulations of thermal ablation and hyperthermia treatments, and MR temperature imaging of ex vivo and in vivo experiments. Acoustic beam measurements of each applicator type displayed a 35 degrees -40 degrees acoustic dead zone between each independent sector, with negligible mechanical or electrical coupling. Thermal lesions produced in ex vivo liver tissue with one, two, or three sectors activated ranged from 13-18 mm in radius with contiguous zones of coagulation between active sectors. The simulations demonstrated the degree of angular control possible by using variable power levels applied to each sector, variable duration of applied constant power to individual sectors, respectively, or a multipoint temperature controller to vary the power applied to each sector. Despite the acoustic dead zone between sectors, the simulations also showed that the variance from the maximum lesion radius with three elements activated is within 4%-13% for tissue perfusions from 1-10 kg m(-3) s(-1). Simulations of hyperthermia with maximum tissue temperatures of 45 degrees C and 48 degrees C displayed radial penetration up to 2 cm of the 40 degrees C steady-state contour. Thermal characterizations of trisectored applicators in ex vivo and in vivo muscle, using real-time MR thermal imaging, reinforced angular controllability and negligible radial variance of the heating pattern from the applicators, demonstrated effective heating penetration, and displayed MR compatibility. The multisectored interstitial ultrasound applicators developed in this study demonstrated a significant degree of dynamic angular control of a heating pattern without device manipulation, while maintaining heat penetration consistent with previously reported results from other interstitial ultrasound applicators.

Thermal therapy offers a minimally invasive option for treating benign prostatic hyperplasia (BPH) and localized prostate cancer. In this study we investigated a transurethral ultrasound applicator design utilizing curvilinear, or slightly focused, transducers to heat prostatic tissue rapidly and controllably. The applicator was constructed with two independently powered transducer segments operating at 6.5 MHz and measuring 3.5 mm x 10 mm with a 15 mm radius of curvature across the short axis. The curvilinear applicator was characterized by acoustic efficiency measurements, acoustic beam plots, biothermal simulations of human prostate, ex vivo heating trials in bovine liver, and in vivo heating trials in canine prostate (n=3). Each transducer segment was found to emit a narrow acoustic beam (max width

Purpose To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation. Materials and Methods Temperature distributions of two transurethral ultrasound applicators (90° sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two-dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal-to-noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames. Results When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12°C during rapid heating. Conclusion Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions. J. Magn. Reson. Imaging 2005;22:109–118. © 2005 Wiley-Liss, Inc.

High temperature ultrasound thermal therapy using interstitial and external approaches is becoming increasingly acceptable as a minimally invasive clinical treatment for cancerous and benign disease. The diameter of an interstitial applicator can influence its clinical practicality and effectiveness as well as application site. The purpose of this study was to determine whether the use of larger ultrasound transducers and the inherent increase in applicator size could be justified by potentially producing larger lesion diameters. Four applicator configurations and sizes were studied using ex vivo tissue experiments in liver and beef and using acoustic and biothermal simulations. Catheter-cooled and internally cooled applicators with outer diameters between 2.2 and 4.0 mm produced 3.5 to 5.0 cm diameter lesions in ex vivo liver and 3.0 to 3.5 cm lesions in ex vivo beef muscle with 20-40 W/cm applied for 10 min. Larger applicators produced lesions with radial penetration depths superior to their smaller counterparts at power levels in the 20-40 W/cm range. The higher cooling rates along the outer surface of the larger diameter applicators due to their greater surface area was a dominant factor in increasing lesion size. The higher cooling rates pushed the maximum temperature farther from the applicator surface and reduced the formation of high acoustic attenuation tissue zones. Applicator configuration and frequency (6.7-8.2 MHz) had less influence on lesion size than diameter in the ranges studied. Acoustic and biothermal simulations matched the experimental data well and were applied to model these applicators within sites of clinical interest such as prostate, uterine fibroid, brain, and normal liver. Lesions of 3.9 to 4.7 cm diameter were predicted for moderately perfused tissues such as prostate and fibroid and 2.8 to 3.2 cm for highly perfused tissues such as normal liver. In sites such as uterine fibroid where larger applicators placed using an endoscopic approach could be tolerated, treatment volume increases of 37% were predicted for an applicator diameter increase from 2.4 to 4.0 mm.

Catheter-cooled (CC) interstitial ultrasound applicators were evaluated for their use in high-temperature coagulative thermal therapy of tissue. Studies in ex vivo beef muscle were conducted to determine the influences of applied electrical power levels (5-20 W per element), catheter flow rate (20-60 ml min(-1)), circulating water temperature (7-40 degrees C), and frequency (7-9 MHz) on temperature distribution and thermal lesion geometry. The feasibility of using multiple interstitial applicators to thermally coagulate a predetermined volume of tissue was also investigated. Results of these studies revealed that the directional shape of the thermal lesions is maintained with increasing time and power. Radial depths of the thermal lesions ranged from 10.7 +/- 0.7 mm after heating for 4 min with an applied power level of 5 W, to 16.2 +/- 1.4 mm with 20 W. The axial length of the thermal lesions is controlled tightly by the number of active transducers. A catheter flow rate of 20 to 40 ml min(-1) (52.2 +/- 5.5 kPa at 40 ml min(-1)) with 22 degrees C water was determined to provide sufficient cooling of the transducers for power levels used in this study. In vivo temperatures measured in the center of a 3-cm-diam peripheral implant of four applicators in pig thigh muscle reached 89.3 degrees C after 4 min of heating, with boundaries of coagulation clearly defined by applicator position and directivity. Conformability of heating in a clinically relevant model was demonstrated by inserting two directional CC applicators with a 2 cm separation within an in vivo canine prostate, and generating a thermal lesion measuring 3.8 cm x 2.2 cm in cross section while directing energy away from, and protecting the rectum. Maximum measured temperatures at midgland exceeded 90 degrees C within 20 min of heating. The results of this study demonstrate the utility of single or multiple CC applicators for conformal thermal coagulation and high temperature thermal therapy, with potential for clinical applications in sites such as prostate, liver, breast, or uterus.

This study presents a comparative evaluation of the control of heating and thermal coagulation with microwave (MW) and ultrasound (US) interstitial applicators. Helical coil MW antennas (17 mm and 25 mm length radiating antennae) were tested using an external implant catheter (2.2 mm o.d.) with water-cooling. US applicators with tubular transducers (2.2 and 2.5 mm o.d., 10 mm length, single-element and 3-element) were utilized with a direct-coupled configuration and internal water-cooling. Measurements of E-field distributions (for MW) and acoustic beam distributions (for US) were used to characterize the applicator energy output. Thermal performance was evaluated through multiple heating trials in vitro (bovine liver) and in vivo (porcine thigh muscle and liver) at varied levels of applied power (20-40 W for microwave, 15-35 W for ultrasound) and heating times (0.5-5 min). Axial temperature distributions in the tissue were recorded during heating, and dimensions of the resulting lesions of thermal coagulation were measured. Both MW and US applicators produced large volumes of tissue coagulation ranging from 8 to 20 cm3 with singular heating times of 5 min. Radial depth of lesions for both MW and US applicators increased with heating duration and power levels, though US produced notably larger lesion diameters (30-42 mm for US vs 18-26 mm for MW, 5 min heating). Characteristic differences between the applicators were observed in axial energy distribution, tissue temperatures, and thermal lesion shapes. MW lesions increased significantly in axial dimensions (beyond the active applicator length) as applied power level and/or heating duration was increased, and lesion shapes were generally not uniform. US provided greater control and uniformity of heating, with energy deposition and axial extent of thermal lesions corresponding to the length of the active transducer(s). The improved ability to control the extent of thermal coagulation demonstrated by the US applicators provides greater potential to target a specific region of tissue.

Six aperture array dual concentric conductor (DCO) microwave hyperthermia applicators were studied using theoretical models to characterize power deposition (SAR) and steady state temperature distributions in perfused tissue. SAR patterns were calculated using the finite difference time domain (FDTD) numerical method, and were used as input to a finite difference thermal modeling program based on the Pennes Bio-Heat Equation in order to calculate corresponding temperature distributions. Numerous array configurations were investigated including the use of different size DCC apertures (2, 3, and 4 cm), different spacing between apertures (1.0-2.0 cm), and different water bolus thicknesses (5-15 mm). Thermal simulations were repeated using blood perfusion values ranging from 0.5 to 5 kg/m3 s. Results demonstrate the ability of DCC array applicators to effectively and uniformly heat tissue down to a depth of 7.5-10 mm below the skin surface for a large number of different combinations of DCC element size, spacing, and water bolus thickness. Results also reveal the close correlation between SAR patterns and corresponding temperature distributions, verifying that design studies of the applicator can be performed confidently by analysis of SAR, from which the thermal behavior can be estimated. These simulations are useful in the design optimization of large microwave DCC array applicators for superficial tissue heating and for identifying appropriate aperture spacing and bolus thickness parameters for different size DCC aperture arrays and tissue blood perfusion conditions.

The feasibility of using air-cooling to improve the thermal penetration of direct-coupled interstitial ultrasound(US) applicators was investigated using biothermal simulations, bench experiments, phantom testing, and in vivo thermal dosimetry. Two applicator configurations using tubular UStransducers were constructed and tested. The first design, intended for simultaneous thermobrachytherapy, utilizes a 2.5 mm OD transducer with a central lumen to accommodate a radiation source from remote afterloaders. The second applicator consists of a 2.2 mm OD transducer designed for coagulative thermal therapy. Both designs provide cooling of the inner transducer surface by the counterflow of chilled air or CO 2 gas through the annulus of the enclosed applicator. The average convective heat transfer (h a ) associated with each applicator was determined empirically from curve-fits of radial steady-state temperaturesmeasured in a tissue-mimicking phantom. High levels of convective heat transfer (h a >500 W m −2 °C −1 ) were demonstrated in both designs at relatively low flow rates ( L min −1 ). Transient and steady-state radial heating profiles were also measuredin vivo (pig thigh muscle) with and without cooling. The therapeutic radius for hyperthermia (41–45 °C) was extended from 5–6 mm (without cooling) to 11–19 mm with air-cooling (4.8 L min−1, airflow 10 °C), effectively doubling and tripling the thermal penetration in vivo. Similar improvements were demonstrated at higher temperatures with the thermal coagulation applicator. Biothermal simulations, which modeled the physical, thermal, and acoustic parameters of the air-cooled applicator and surrounding tissue, were also used to investigate potential improvements in heating patterns. The simulated radial heating profiles with transducer cooling demonstrated significantly enhanced thermal penetration over the experimental range of convective transfer, and also agreed with in vivo results. These theoretical and experimental results clearly show air-cooling controls the transducer surface temperature, significantly increases thermal penetration, and produces a greater treatment volume for direct-coupled US applicators in hyperthermia and thermal coagulation.

This study investigated the design concepts and development of a multielement intracavitary ultrasound applicator for use in hyperthermia. A necessary condition imposed on these applicators is that each transducer element be separately powered and produce collimated beams. This way, the power deposition within the target volume can be controlled by varying the power to each element. Theoretical computer simulations (acoustic and thermal) and bench experiments were used to determine the constraints on the transducer element size and the spacing between them. These have shown that the length of the cylindrical segments (or subsections of) must be greater than approximately 10 lambda for proper collimation and that the spacing between them must be less than approximately 1.5 mm for uniform heating. With these design principles in mind, applicators were constructed using sections of cylindrical transducers (wall-thickness resonance). These were surrounded by temperature-controlled circulating water which was enclosed by a latex membrane. This allowed for acoustic coupling and additional control over the depth of the maximum temperature from the cavity wall. This depth could be varied between the cavity surface and up to 1.5 cm for circulating water temperatures between 5 and 42 degrees C, respectively. These applicators were tested in vivo and were able to induce controlled transrectal heating, at depths of 2-3 cm, in the canine rectum and prostate gland.

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: 1. Learn background on devices and techniques for MR guided HIFU for cancer therapy 2. Understand issues and current status of clinical MRg HIFU 3. Understand strategies for compensating for organ movement during MRgHIFU 4. Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips

A simple modification is presented for two commercially available hyperthermia applicators which dramatically improves the regulation and dynamic control of the temperature at the bolus/tissue interface. This alteration requires the addition of a variable speed pump, bubble trap, simple heat exchanger, and a few minor changes to the existing system. With this modified design, the water within the bolus is directly circulated and temperature controlled. The convective nature of the circulating system ensures uniform temperature throughout the extended bolus and increases the thermal energy transfer at the bolus/tissue interface. This modification also provides significantly improved flexibility in controlling the treatment temperature distributions since the bolus/tissue interface temperature can now be dynamically varied during a treatment, in addition to adjusting the applicator power output and frequency.

Purpose: Feasibility 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. Methods: The 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 cm2, ∼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). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm2, in 4.5–5.8 cm3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm2, and in ∼6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. 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/cm2, 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. Conclusions: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20/20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice.

Introduction: In order to select appropriate candidates for treatment of uterine fibroids using MR guided focused ultrasound (MRgFUS), a careful review of the patients' history and imaging is required. Not infrequently, patients with uterine fibroids seeking MRgFUS have previously undergone uterine artery embolization (UAE). The most common embolic agent used during UAE is Embosphere microspheres (Merit Medical Systems, INC, South Jordan, UT). Following UAE, the microspheres remain in the capillary beds of the fibroid vessels indefinitely. However, little is known regarding the nature of Embosphere microspheres in the setting of elevated temperatures (65–85degrees C) generated by high intensity focused ultrasound (HIFU). Embosphere microspheres are made of an acrylic co‐polymer (trisacryl), which is cross‐linked with gelatin. The aim of the present study was to evaluate for changes in Embosphere microspheres that underwent HIFU. Purpose: To evaluate for changes in shape and nature of Embosphere microspheres following MRgFUS.Materials and Methods: 10cc of 500–700micron Embosphere microspheres were injected into chicken breast. HIFU thermal ablation was performed, reaching high enough temperature to coagulate the chicken breast surrounding the microspheres. Additionally a vial containing microspheres was placed in a bath of heating water and temperature monitoring was performed until a maximum temperature of 100 degrees C. Gross and microscopic evaluation of the microspheres following HIFU and waterbath heating was performed. Results: The microspheres maintained their normal structure without evidence of denaturing or melting when targeted directly with HIFU (Figure 1). Additionally, the microspheres in boiling water did not alter their shape and structural integrity (Figure 2). Conclusion: HIFU of Embosphere microspheres does not change the structural integrity of the particles. As such, in the setting of prior UAE with Embosphere microspheres, MRgFUS may be safe without inducing particle denaturing or melting.

The objective of this talk is to provide a contemporary review of ultrasound devices and techniques as applied to delivery of thermal therapy to the prostate. This technology allows focal treatment or direct destruction of tissue for treatment of cancer or benign prostatic hyperplasia (BPH), or as an adjunct in the delivery of radiation therapy or chemotherapy, including temperature targeted drug delivery. Two therapeutic regimens are explored ‐ hyperthermia in the 40–45°C range and high temperature (>50°C) at lethal thermal dose exposures for thermal ablation. Commercial and clinical systems in development are reviewed including: transrectal high‐intensity focused ultrasound (HIFU) systems integrated with ultrasoundimage guidance; transurethral and endorectal high‐intensity ultrasound devices under MR guidance and control; interstitial ultrasound for hyperthermia integrated with HDR brachytherapy; and multi‐sectored endorectal applicators for hyperthermia adjunct to external beam radiation therapy with potential for thermal sensitive drug delivery. These image guided ultrasound therapysystems have the promise to deliver selective and precise thermal therapy or larger volume hyperthermia as required for the specified strategy for treatment of prostate disease. Educational objectives include technical concepts and treatment strategies of ultrasound therapy technology applied to treating prostate disease.

Catheter‐based ultrasound applicators have been developed for delivering hyperthermia and thermal ablation for the treatment of cancer and benign diseases. This technology includes interstitial applicators for tumorablation and hyperthermia delivery during brachytherapy, transurethral devices for conformal prostate hyperthermia and ablation, and an endocavity applicator integrated with an HDR ring applicator for intrauterine hyperthermia. The common design incorporates arrays of multiple ultrasound transducers which provide dynamic axial and angular control of hyperthermia and thermal ablation. Performance was evaluated in phantom, excised tissue,in vivo experiments in canine prostate under MR temperature monitoring, clinical hyperthermia, and 3D‐biothermal simulations with patient specific anatomy. Interstitial and endocavity devices can tailor hyperthermia to large treatment volumes, with multi‐sectored and multi‐transducer power control useful to limit exposure to rectum and bladder. Transurethral applicators include curvilinear transducers with rotational sweeping of focused heating patterns, and multi‐sectored tubular devices capable of dynamic angular control without applicator movement. Curvilinear transurethral produce target conforming coagulation zones that can cover either the whole gland or defined focal regions. Multi‐sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the prostate without applicator manipulation. High‐power interstitial implants with directional devices can be used to effectively ablate defined target regions while avoiding sensitive tissues. MR temperature monitoring can effectively define the extent of thermal damage and provided a means for real‐time control of the applicators. Preliminary investigations have also demonstrated ultrasound strain imaging can be used to monitor the ablatedtissue. In summary, these catheter‐based ultrasound devices allow for dynamic control of heating profiles along the length and angular expanse of the applicator during therapy delivery, are amenable to MR monitoring, and provide a minimally‐invasive technique for true 3D control of hyperthermia and thermal ablation. (Support NIH R01CA122276, R01CA111981, & R41CA121740).