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Open Access Publications from the University of California

Scholarly Works (29 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2017)

The goals of this work are to investigate the feasibility of endoluminal ultrasound for delivering thermal ablation and hyperthermia to pancreatic tumors, and to perform a comprehensive design analysis of both practical and more intricate ultrasound applicator configurations suitable for endoluminal thermal therapy.

A platform for modeling the 3D acoustic, temperature, and thermal dose distributions generated from endoluminal ultrasound applicators and applied to pancreatic tumors and surrounding anatomy was developed. Performance ranges of practical endoluminal applicator designs were determined through comprehensive parametric analyses of applicator design and expected tissue parameters. Modeling studies in patient specific anatomies highlighted the capability of endoluminal ultrasound applicators positioned in the duodenum or stomach to deliver conformal and volumetric ablation or hyperthermia of pancreatic tumors with boundaries within 3-4 cm of the luminal wall while mitigating thermal damage to surrounding sensitive tissues.

A family of MR-compatible endoluminal ultrasound applicators, with distinct transducer configurations (~3 MHz, planar or curvilinear-focused) were designed, fabricated, and acoustically-characterized using bench-top methods. The capability of these applicators to be endogastrically delivered within the GI tract and to generate ablative temperature distributions in pancreatic tissue was evaluated in ex vivo and in vivo porcine studies, performed under MR navigation guidance and real-time treatment monitoring using MR temperature imaging. Preliminary acute studies in four in vivo pigs demonstrated the capabilities of the applicators to generate ablative temperature elevations of ~20-30 °C in pancreatic tissue at ~2-3 cm depths from the applicator, resulting in histologically-verified localized thermal lesions.

Novel endoluminal ultrasound applicator configurations that integrate deployable balloon-based acoustic reflector and fluid lens components were introduced and analyzed using theoretical modeling analysis and preliminary experimental validation. These applicators would be endoluminally delivered in a small profile, then expanded at the target luminal site to enhance the effective therapeutic aperture. A modeling framework, incorporating wave refraction and reflection at material interfaces was developed and used to perform comprehensive parametric studies for “end-firing” and “side-firing” design alternatives. Simulation studies illustrated the capability of these designs to achieve more localized thermal lesion formation and deeper penetration (up to 8-10 cm) as compared to conventional endoluminal ultrasound applicator designs.

    Cover page: Endoluminal Ultrasound Applicators for Thermal Therapy of Pancreatic Tumors
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2015)
    Catheter-based ultrasound (CBUS) is applied to deliver minimally invasive thermal therapy to solid cancer tumours, benign tissue growth, vascular disease, and tissue remodelling. Compared to other energy modalities used in catheter-based surgical interventions, unique features of ultrasound result in conformable and precise energy delivery with high selectivity, fast treatment times, and larger treatment volumes. We present a concise review of CBUS technology being currently utilized in animal and clinical studies or being developed for future applications. CBUS devices have been categorised into interstitial, endoluminal and endovascular/cardiac applications. Basic applicator designs, site-specific evaluations and possible treatment applications have been discussed in brief. Particular emphasis has been given to ablation studies that incorporate image guidance for applicator placement, therapy monitoring, feedback control, and post-procedure assessment. Examples of devices included here span the entire spectrum of the development cycle from preliminary simulation-based design studies to implementation in clinical investigations. The use of CBUS under image guidance has the potential for significantly improving precision and applicability of thermal therapy delivery.
      Cover page: Catheter-based ultrasound technology for image-guided thermal therapy: Current technology and applications
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)
      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.
        Cover page: Deployable cylindrical phased-array applicator mimicking a concentric-ring configuration for minimally-invasive delivery of therapeutic ultrasound
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2013)
        Endoluminal and catheter-based ultrasound applicators are currently under development and are in clinical use for minimally invasive hyperthermia and thermal ablation of various tissue targets. Computational models play a critical role in device design and optimisation, assessment of therapeutic feasibility and safety, devising treatment monitoring and feedback control strategies, and performing patient-specific treatment planning with this technology. The critical aspects of theoretical modelling, applied specifically to endoluminal and interstitial ultrasound thermotherapy, are reviewed. Principles and practical techniques for modeling acoustic energy deposition, bioheat transfer, thermal tissue damage, and dynamic changes in the physical and physiological state of tissue are reviewed. The integration of these models and applications of simulation techniques in identification of device design parameters, development of real time feedback-control platforms, assessing the quality and safety of treatment delivery strategies, and optimisation of inverse treatment plans are presented.
          Cover page: Modelling of endoluminal and interstitial ultrasound hyperthermia and thermal ablation: Applications for device design, feedback control and treatment planning
          • Thesis
          • Peer Reviewed
          UC San Francisco Electronic Theses and Dissertations (2014)

          The goals of this work are to investigate the feasibility of interstitial ultrasound ablation of tumors in and near the spine and to develop treatment guidelines. Interstitial ultrasound ablation, which allows for directional control of heat deposition, could potentially take advantage of the preferential acoustic absorption and heating that occurs along sonicated bone surfaces in order to ablate targets adjacent to vertebrae without damaging nearby critical anatomy such as the spinal cord.

          A platform for modeling patient-specific temperature and thermal dose distributions during catheter-cooled interstitial ultrasound ablation involving bone was developed in Comsol. The 3D, transient, finite element models developed herein considered various approximations of the complex interactions between ultrasound and bone. Experiments in phantoms, ex vivo tissues, and in vivo tissues were used to validate the numerical models and to characterize the impact of bone on ablation performance. Temperature distributions were measured using both invasive thermometry and MR-based techniques. Comprehensive parametric and patient-specific simulation studies were performed to investigate the feasibility of interstitial ultrasound ablation of paraspinal tumors and osteolytic vertebral tumors and to develop treatment guidelines.

          High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated and/or reduced the necessary treatment times. Models using simplified approximations produced temperature and thermal dose profiles closely matching both experimental measurements and more comprehensive models. Patient-specific and parametric simulations indicated that tumors up to 44 mm in diameter and insulated from the spinal canal by at least 4-5 mm of bone could be completely ablated within 15 min. Critical anatomy closer to the tumor could be preserved by reducing the acoustic energy aimed towards these structures and/or through gaseous insulation. Preferential bone heating and the insulating quality of bone resulted in thermal lesions closely conforming to the shapes of osteolytic targets and fast treatment times.

          This work demonstrates that interstitial ultrasound ablation appears feasible for treatment of paraspinal and vertebral tumors. Models and experiments indicate that preferential bone heating may provide improved localization, faster treatment times, and larger treatment zones in unossified tumors bordering bone as compared to other heating modalities.

            Cover page: Theoretical and Experimental Investigation of Interstitial Ultrasound for Ablation of Tumors in and Near the Vertebrae and Other Bones
            • Thesis
            • Peer Reviewed
            UC San Francisco Electronic Theses and Dissertations (2010)

            Catheter-based ultrasound technology has demonstrated locally targeted heating for ablation or hyperthermia treatment of cancerous tissue with minimal heating of organs at risk. Site-specific selection of device parameters and treatment strategies is necessary for achieving thermal goals. This dissertation investigates the influences of applicator parameters and treatment strategies on heating patterns in the prostate and cervix using biothermal simulation, which translates into the design of an intrauterine ultrasound applicator that is experimentally characterized and implemented in clinical treatment. Thermal therapy offers potential for prostate cancer/BPH treatment with reduced morbidity. Ultrasound absorption by pelvic bones can cause pain and damage to adjacent nerves. Guidelines for device properties and treatment regimens in relation to prostate size and pelvic bone distance are developed by analyzing their impact on bone heating and treatment time during transurethral prostate ablation. A sectored tubular design is superior to planar and curvilinear designs in reducing bone heating and treatment time with bone <3 cm from the gland. The feasibility of the endocavity ultrasound device, consisting of an array of multi-sectored tubular transducers, to heat tumor targets in the cervix is explored with extensive theoretical analysis. Coverage of 4-5cm targets with therapeutic temperature (>41°C) is possible, using sector orientation for preferential avoidance of rectum and bladder. Hyperthermia delivery in conjunction with interstitial devices is investigated using treatment planning software for 14 patient cases. Temperatures >41°C throughout targets are achieved in most cases using sectoring and aiming to limit Tmax <47°C and rectum and bladder <41.5-42.5°C. Devices were characterized for acoustic emission, imaging compatibility, radiation attenuation, and thermal output using implanted thermometry and MR temperature imaging. Collimated acoustic output with independent power control to sectors and transducers is demonstrated and used to produce tailored heating along the device length and in angle with temperatures of 41°C >2cm in tissue. Thermal delivery is more penetrating than implantable RF devices and more controllable than deep heating technology. The applicator was implemented in two clinical treatments, demonstrating facile integration with HDR brachytherapy, delivery of temperatures >41°C throughout the target, and resulting in disease remission without adverse side effects in one patient.

              Cover page: Endocavity Ultrasound Thermal Therapy of Pelvic Malignancies: Modeling and Device Development
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2020)
              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 (3.5 mm outer diameter (OD), 14 mm length, 6.5 MHz, 8.8-10.2 W/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 1.8 cm3 over 60 EM43 °C, with at least 10 mm radial penetration depth, 1.2 mm urethral sparing, and no lethal damage to the vagina and adjacent bone (< 60 EM43 °C). Endovaginal cooling can be applied to further reduce the vaginal wall exposure (< 15 EM43 °C). Simulations on 3D anatomical models indicate that dual-sectored transurethral ultrasound applicators can selectively heat pelvic floor tissue lateral to the mid-urethra in short treatment durations, without damaging adjacent vaginal and bone tissues, as a potential alternative treatment option for stress urinary incontinence. Graphical abstract Schema for in silico investigation of transurethral ultrasound thermal therapy applicator for minimally invasive treatment of SUI.
                Cover page: Dual-sectored transurethral ultrasound for thermal treatment of stress urinary incontinence: in silico studies in 3D anatomical models
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2018)

                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 remodeling 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 × 10 mm, 28 mm ROC) with single 90 s sonication can create heated zones with 11 mm penetration (>50 °C) while sparing the inner 1.8 mm (<45 °C) radial depth of the urethral mucosa. Sequential and discrete applicator rotations can sweep out bilateral coagulation volumes (1.4 W power, 15° rotations, 600 s total time), produce large volumetric (1124 mm³ above 60 EM43 °C) and wide angular (∼50.5° per lateral sweep) coverage, with up to 15.6 mm thermal penetration and at least 1.6 mm radial urethral protection (<5 EM43 °C).

                Conclusion

                Transurethral applicators with curvilinear ultrasound transducers can deliver spatially selective temperature elevations to lateral mid-urethral targets as a possible means to tighten the endopelvic fascia and adjacent tissues.
                  Cover page: Transurethral high-intensity ultrasound for treatment of stress urinary incontinence (SUI): simulation studies with patient-specific models
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2012)

                  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 (t(43) > 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.
                    Cover page: Multiple applicator hepatic ablation with interstitial ultrasound devices: Theoretical and experimental investigation
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2018)

                    Background

                    Hyperthermia 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 30-60 min, 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).

                    Methods

                    The 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 3 T 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.

                    Results

                    Five various shapes of the region of treatment, defined on a 5 × 5 grid (35 × 35 mm, 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 (2:58-7:44 min) 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.

                    Conclusions

                    We 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.
                      Cover page: MR thermometry-guided ultrasound hyperthermia of user-defined regions using the ExAblate prostate ablation array
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