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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 Low-dose-rate brachytherapy is a highly effective treatment modality for prostate carcinoma, but postimplant dosimetry quality is essential and correlated with likelihood of treatment success. Registered ultrasound and fluoroscopy (iRUF) can facilitate real-time intraoperative monitoring and plan adaptation, with the aim of attaining superior dosimetric outcomes. The purpose of this research was to compare clinical postimplant dosimetric results of iRUF-guided brachytherapy against brachytherapy using standard ultrasound-guided intraoperative dosimetry methods. Methods and Materials We analyzed postimplant dosimetry in 292 patients treated with Pd-103 between January 2007 and December 2018. All patients had postimplant dosimetry measured on day 0 to 1 using fused magnetic resonance/computed tomography assessment. Fifty-two patients were treated in 2 prospective clinical trials using iRUF intraoperative dosimetry, including 6 patients in a pilot study and 46 treated in a phase 2 study. Postimplant dosimetry in iRUF-treated patients was compared with dosimetry from 240 patients treated using standard (real-time ultrasound) intraoperative seed tracking. Results For every parameter measuring dose coverage to the prostate, iRUF patients had significantly higher values, irrespective of adjustment for year of treatment. In adjusted analyses, parameters of dose to urethra and rectum were not significantly higher among iRUF-treated patients. Conclusions Use of iRUF intraoperative dosimetry was associated with improved postimplant dose coverage in prostate, without associated increases in doses to urethra or rectum.

The primary objective of cancer intervention is the selective removal of malignant cells while conserving surrounding healthy tissues. However, the accessibility, size and shape of the cancer can make achieving appropriate margins a challenge. One minimally invasive treatment option for these clinical cases is interstitial needle based therapeutic ultrasound (NBTU). In this work, we develop a finite element model (FEM) capable of simulating continuous rotation of a directional NBTU applicator. The developed model was used to simulate the thermal deposition for different rotation trajectories. The actual thermal deposition patterns for the simulated trajectories were then evaluated using magnetic resonance thermal imaging (MRTI) in a porcine skin gelatin phantom. An MRI-compatible robot was used to control the rotation motion profile of the physical NBTU applicator to match the simulated trajectory. The model showed agreement when compared to experimental measurements with Pearson correlation coefficients greater than 0.839 when comparing temperature fields within an area of 12.6 mm radius from the ultrasound applicator. The average temperature error along a 6.3 mm radius profile from the applicator was $1.27\;^\circ\mathrm{C}$ . The model was able to compute 1 s of thermal deposition by the applicator in 0.2 s on average with a 0.1 mm spatial resolution and 0.5 s time steps. The developed simulation demonstrates performance suitable for real-time control which may enable robotically-actuated closed-loop conformal tumor ablation.

Purpose To develop and test in animal studies ex vivo and in vivo, an intravascular (IV) MRI-guided high-intensity focused ultrasound (HIFU) ablation method for targeting perivascular pathology with minimal injury to the vessel wall. Methods IV-MRI antennas were combined with 2- to 4-mm diameter water-cooled IV-ultrasound ablation catheters for IV-MRI on a 3T clinical MRI scanner. A software interface was developed for monitoring thermal dose with real-time MRI thermometry, and an MRI-guided ablation protocol developed by repeat testing on muscle and liver tissue ex vivo. MRI thermal dose was measured as cumulative equivalent minutes at 43°C (CEM43 ). The IV-MRI IV-HIFU protocol was then tested by targeting perivascular ablations from the inferior vena cava of 2 pigs in vivo. Thermal dose and lesions were compared by gross and histological examination. Results Ex vivo experiments yielded a 6-min ablation protocol with the IV-ultrasound catheter coolant at 3-4°C, a 30 mL/min flow rate, and 7 W ablation power. In 8 experiments, 5- to 10-mm thick thermal lesions of area 0.5-2 cm2 were produced that spared 1- to 2-mm margins of tissue abutting the catheters. The radial depths, areas, and preserved margins of ablation lesions measured from gross histology were highly correlated (r ≥ 0.79) with those measured from the CEM43 = 340 necrosis threshold determined by MRI thermometry. The psoas muscle was successfully targeted in the 2 live pigs, with the resulting ablations controlled under IV-MRI guidance. Conclusion IV-MRI-guided, IV-HIFU has potential as a precision treatment option that could preserve critical blood vessel wall during ablation of nonresectable perivascular tumors or other pathologies.

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 (

procedures. Methods: Beveled prostate brachytherapy needles were inserted through all holes of a grid template under real-time transrectal ultrasound (TRUS) guidance. The needle tip position as indicated by the TRUS image was compared to their observed physical location. A new device was developed to measure the ultrasound elevation beamwidth. Results: Imaging parameters of the TRUS scanner have direct impact on the localization error ranging from 0.5 up to 4 mm. The smallest localization error was observed laterally close to the center of the grid template and axially within the beam’s focal zone. Largest localization error occurs laterally around both sides of the grid template and axially within the beam’s far field. The authors also found that the localization errors vary with both lateral and elevation offsets. Conclusions: The authors found properly adjusting the TRUS imaging settings to lower the ultrasound gain and power effectively minimized the appearance of elevation beamwidth artifacts and in turn reduced the localization errors of the needle tip. V C 2012 American Association of Physicists in Medicine. [DOI: 10.1118/1.3669488]

PURPOSE: Optimization of prostate brachytherapy is constrained by tissue deflection of needles and fixed spacing of template holes. We developed and clinically tested a robotic guide toward the goal of allowing greater freedom of needle placement. METHODS AND MATERIALS: The robot consists of a small tubular needle guide attached to a robotically controlled arm. The apparatus is mounted and calibrated to operate in the same coor- dinate frame as a standard template. Translation in x and y directions over the perineum � 40 mm are possible. Needle insertion is performed manually. RESULTS: Five patients were treated in an institutional review board-approved study. Confirma- tory measurements of robotic movements for initial 3 patients using infrared tracking showed mean error of 0.489 mm (standard deviation, 0.328 mm). Fine adjustments in needle positioning were possible when tissue deflection was encountered; adjustments were performed in 54 (30.2%) of 179 needles placed, with 36 (20.1%) of 179 adjustments ofO2 mm. Twenty-seven insertions were intentionally altered to positions between the standard template grid to improve the dosimetric plan or avoid structures such as pubic bone and blood vessels. CONCLUSIONS: Robotic needle positioning provided a means of compensating for needle deflections and the ability to intentionally place needles into areas between the standard template holes. To our knowledge, these results represent the first clinical testing of such a system. Future work will be incorporation of direct control of the robot by the physician, adding software algo- rithms to help avoid robot collisions with the ultrasound, and testing the angulation capability in the clinical setting. 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

This study presents the initial evaluation of an applicator designed for transurethral ultrasound thermotherapy (TUST) of prostate tissue in the treatment of benign prostatic hyperplasia (BPH) and cancer. A tubular multitransducer applicator, consisting of four piezoceramic tubes (2.5 mm diameter, 6 mm long, 6.8 MHz) under separate power control, was designed to fit within a semiflexible water-cooled temperature-regulated delivery catheter to be placed within the prostatic urethra during therapy. Sonication patterns were tailored to produce power depositions which avoid nontargeted tissues, such as the rectum. Computer simulations have demonstrated that 1.4-2.0 cm radial therapeutic zones (temperatures /spl ges/50-55/spl deg/C, thermal doses >300 EM/sub 43/) with concurrent sparing of the urethral mucosa can be produced within prostate tissue having blood perfusion as high as 10 kg m/sup -3/ s/sup -1/ within 15-30 min. Acoustic distributions and power output measurements of a prototype applicator have demonstrated acoustic power levels approaching 10 W per each sectored transducer segment are attainable, with beam profiles collimated within the transducer length and with desired circumferential distributions. In vivo thermal dosimetry characterizations of these transurethral applicators have indicated that therapeutic temperatures between 50 and 90/spl deg/C are attainable, controllable in the longitudinal and circumferential directions, and have effective radial heating. These results clearly indicate that transurethral ultrasound applicators have potential to provide improved spatial localization and control of the heating distribution over existing transurethral thermal therapy techniques for both hyperthermia and thermal coagulative therapy of the prostate.

Purpose: Ultrasound (US) elevation beamwidth causes a certain type of image artifact around the anechoic areas of the tissue. It is generally assumed that the US image is of zero thickness, which contradicts the fact that the acoustic beam can only be mechanically focused at a depth resulting in a finite, non-uniformed elevation beamwidth. We suspect that elevation beamwidth artifacts contribute to target reconstruction error in computer-assisted interventions. This paper introduces a method for characterization of the beamwidth for transrectal ultrasound (TRUS) used in prostate brachythyerapy. In particular, we measure how the US sectionthickness varies along the beam's axial depth. Method: We developed a beam-profiling device (a TRUS-bridge phantom) specifically tailored for standard brachytherapy ultrasound imaging systems to generate a complete section-thickness profile of a given TRUS transducer. The device was designed in CAD software and prototyped by a 3D printer. Result: The experimental results demonstrated that the TRUS beam in the elevation direction is focused closely to the transducer and theoretically the transducer would provide a better elevational resolution within that range. Conclusion: We presented a beam profiling phantom to measure the section-thickness of a transrectal ultrasound transducer for operating room use. However, there are some limitations which need to be addressed, for example, phantom sterilization and the speed of sound in the current medium of experiment which is not the same as that of biological tissues.

Motivation: In prostate brachytherapy, transrectal ultrasound (TRUS) is used to visualize the anatomy, while implanted seeds can be seen in C-arm fluoroscopy or CT. Intra-operative dosimetry optimization requires localization of the implants in TRUS relative to the anatomy. This could be achieved by registration of TRUS images and the implants reconstructed from fluoroscopy or CT. Methods: TRUS images are filtered, compounded, and registered on the reconstructed implants by using an intensity-based metric based on a 3D point-to-volume registration scheme. A phantom was implanted with 48 seeds, imaged with TRUS and CT/X-ray. Ground-truth registration was established between the two. Seeds were reconstructed from CT/X-ray. Seven TRUS filtering techniques and two image similarity metrics were analyzed as well. Results: For point-to-volume registration, noise reduction combined with beam profile filter and mean squares metrics yielded the best result: an average of 0.38 ± 0.19 mm seed localization error relative to the ground-truth. In human patient data C-arm fluoroscopy images showed 81 radioactive seeds implanted inside the prostate. A qualitative analysis showed clinically correct agreement between the seeds visible in TRUS and reconstructed from intra-operative fluoroscopy imaging. The measured registration error compared to the manually selected seed locations by the clinician was 2.86 ± 1.26 mm. Conclusion: Fully automated seed localization in TRUS performed excellently on ground-truth phantom, adequate in clinical data and was time efficient having an average runtime of 90 seconds. Copyright 2010 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.

Three dimensional heat-induced echo-strain imaging is a potentially useful tool for monitoring the formation of thermal lesions during ablative therapy. Heat-induced echo-strain, known as thermal strain, is due to the changes in the speed of propagating ultrasound signals and to tissue expansion during heat deposition. This paper presents a complete system for targeting and intraoperative monitoring of thermal ablation by high intensity focused acoustic applicators. A special software interface has been developed to enable motor motion control of 3D mechanical probes and rapid acquisition of 3D-RF data (ultrasound raw data after the beam-forming unit). Ex-vivo phantom and tissue studies were performed in a controlled laboratory environment. While B-mode ultrasound does not clearly identify the development of either necrotic lesions or the deposited thermal dose, the proposed 3D echo-strain imaging can visualize these changes, demonstrating agreement with temperature sensor readings and gross-pathology. Current results also demonstrate feasibility for realtime computation through a parallelized implementation for the algorithm used. Typically, 125 frames per volume can be processed in less than a second. We also demonstrate motion compensation that can account for shift within frames due to either tissue movement or positional error in the US 3D imaging probe.

We present a robotically assisted prostate brachytherapy system and test results in training phantoms and Phase-I clinical trials. The system consists of a transrectal ultrasound (TRUS) and a spatially co-registered robot, fully integrated with an FDA-approved commercial treatment planning system. The salient feature of the system is a small parallel robot affixed to the mounting posts of the template. The robot replaces the template interchangeably, using the same coordinate system. Established clinical hardware, workflow and calibration remain intact. In all phantom experiments, we recorded the first insertion attempt without adjustment. All clinically relevant locations in the prostate were reached. Non-parallel needle trajectories were achieved. The pre-insertion transverse and rotational errors (measured with a Polaris optical tracker relative to the template's coordinate frame) were 0.25 mm (STD=0.17 mm) and 0.75 degrees (STD=0.37 degrees). In phantoms, needle tip placement errors measured in TRUS were 1.04 mm (STD=0.50mm). A Phase-I clinical feasibility and safety trial has been successfully completed with the system. We encountered needle tip positioning errors of a magnitude greater than 4mm in only 2 of 179 robotically guided needles, in contrast to manual template guidance where errors of this magnitude are much more common. Further clinical trials are necessary to determine whether the apparent benefits of the robotic assistant will lead to improvements in clinical efficacy and outcomes.

PURPOSE: In prostate brachytherapy, determining the 3D location of the seeds relative to surrounding structures is necessary for calculating dosimetry. Ultrasound imaging provides the ability to visualize soft tissues, and implanted seeds can be reconstructed from C-arm fluoroscopy. Registration between these two complementary modalities would allow us to make immediate provisions for dosimetric deviation from the optimal implant plan. METHODS: We propose intensity-based registration between ultrasound and a reconstructed model of seeds from fluoroscopy. The ultrasound images are pre-processed with recursive thresholding and phase congruency. Then a 3D ultrasound volume is reconstructed and registered to the implant model using mutual information. RESULTS: A standard training phantom was implanted with 49 seeds. Average registration error between corresponding seeds relative to the ground truth is 0.09 mm. The effect of false positives in ultrasound was investigated by masking seeds from the fluoroscopy reconstructed model. The registration error remained below 0.5 mm at a rate of 30% false positives. CONCLUSION: Our method promises to be clinically adequate, where requirements for registration is 1.5 mm.

Uterine myomas (fibroids) are the most common pelvic tumors occurring in women, and are the leading cause of hysterectomy. Symptoms can be severe, and traditional treatments involve either surgical removal of the uterus (hysterectomy), or the fibroids (myomectomy). Interstitial ultrasound technologies have demonstrated potential for hyperthermia and high temperature thermal therapy in the treatment of benign and malignant tumors. These ultrasound devices offer favorable energy penetration allowing large volumes of tissue to be treated in short periods of time, as well as axial and angular control of heating to conform thermal treatment to a targeted tissue, while protecting surrounding tissues from thermal damage. The goal of this project is to evaluate interstitial ultrasound for controlled thermal coagulation of fibroids. Multi-element applicators were fabricated using tubular transducers, some of which were sectored to produce 180° directional heating patterns, and integrated with water cooling. Human uterine fibroids were obtained after routine myomectomies, and instrumented with thermocouples spaced at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 cm from the applicator. Power levels ranging from 8-15 W per element were applied for up to 15 minute heating periods. Results demonstrated that therapeutic temperatures >50° C and cytotoxic thermal doses (t43) extended beyond 2 cm radially from the applicator (>4 cm diameter). It is anticipated that this system will make a significant contribution toward the treatment of uterine fibroids.

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180° active sectors, ∼7.5 MHz ) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm×10 mm OD, 80 ml min −1 ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n=2) while using MRthermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1–contrast enhanced MRimages, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced ∼180° directed zones of thermal coagulation within targeted tissue which extended 15–20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially ∼18 mm and ∼25 mm from base to apex, respectively. Peak temperatures around 90 ° C were measured, with ∼50 ° C –52 ° C corresponding to outer boundary t 43 =240 min at ∼15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.

Reviews recent advances in interstitial and intracavitary ultrasound applicators designed for high-temperature thermal therapy and hyperthermia. Design and performance characteristics determined by acoustic measurements, in vitro and in vivo studies are presented. These results demonstrate the ability of this ultrasound technology to provide highly controllable zones of thermal coagulation or temperature elevation.

Two interstitial ultrasound applicator design configurations were evaluated for high-temperature thermal therapy using computer simulations, acoustic beam measurements, and in vivo temperature measurements. Simulated transient temperature rises and cumulative thermal dose distributions indicate that these applicators can produce target temperatures greater than 50/spl deg/C and corresponding thermal doses greater than 300-600 EM43/spl deg/C within 5 min at a radial depth of 1 cm in moderately perfused tissues. Temperature distributions achieved with prototype applicators in vivo were in good agreement with theoretical calculations, and further demonstrate that the devices are practicable, sufficient power output levels can be obtained, and heating profiles can be shaped to protect non-targeted critical normal tissues. This preliminary study demonstrates that these interstitial ultrasound applicators have potential to provide controlled thermal ablation (necrosis) of small cancerous lesions, and deserve further investigation for possible implementation in sites such as prostate and brain.

This preliminary investigation demonstrates that using implantable ultrasound applicators (with energy directed away from the rectum and nontargeted tissue) in combination with a directional transurethral ultrasound applicator have potential to provide controlled thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

The purpose of this study was to determine the feasibility of using a transurethral ultrasound applicator in combination with implantable ultrasound applicators for inducing thermal coagulation and necrosis of localized cancer lesions or benign disease within the prostate gland. The potential to treat target zones in the anterior and lateral portions of the prostate with the angularly directive transurethral applicator, while simultaneously treating regions of extracapsular extension and zones in the posterior prostate with the directive implantable applicators in combination with a rectal cooling bolus, is evaluated. Biothermal computer simulations, acoustic characterizations, and in vivo thermal dosimetry experiments with canine prostates were used to evaluate the performance of each applicator type and combinations thereof. Simulations have demonstrated that transurethral applicators with 180-270 degrees acoustic active zones can direct therapeutic heating patterns to the anterior and lateral prostate, implantable needles can isolate heating to the posterior gland while avoiding rectal tissue, and that the combination of applicators can be used to produce conformal heating to the whole gland. Single implantable applicators (1.8 mm OD x 10 mm long, approximately 180 degrees active sector, approximately 7 MHz, direct-coupled type) produced directional thermal lesions within in vivo prostate, with temperatures >50 degrees C extending more than 10 mm radially after 10-15 min. Combination of interstitial applicators (1-2) and a transurethral applicator (3-2.5 mm OD x 6 mm long, approximately 180 degrees active sector, 6.8 MHz, 6 mm OD delivery catheter) produced conforming temperature distributions (48-85 degrees C) and zones of acute thermal damage within 15 min. The preliminary results of this investigation demonstrate that implantable directional ultrasound applicators, in combination with a transurethral ultrasound applicator, have the potential to provide thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

The purpose of this study was to determine the feasibility of using a transurethral ultrasound applicator in combination with implantable ultrasound applicators for inducing thermal coagulation and necrosis of localized cancer lesions or BPH within the prostate gland. The concept being evaluated is the potential to treat target zones in the anterior and lateral portions of the prostate with the transurethral applicator, while simultaneously treating regions of extracapsular extension and zones in the posterior prostate with the directive implantable applicators in combination with a rectal cooling bolus. Biothermal computer simulations, acoustic characterizations, and in vivo thermal dosimetry experiments were used to evaluate the performance of each applicator type and combinations thereof. The preliminary results of this investigation demonstrate that implantable ultrasound applicators, in combination with a transurethral ultrasound applicator, have the potential to provide thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

Purpose/Objective(s): The ability to more accurately determine dosimetry intraoperatively during permanent prostate brachytherapy may assist clinicians in improving dosimetric and clinical results. Our purpose was to compare a novel system of registered ultrasound and fluoroscopy (RUF) with the current method of ultrasound (US) based seed localization (a.k.a. real time) for intraoperatively predicting dosimetry, using post-implant CT as a standard.

A thermotherapy device for use in treating cancer. The thermotherapy device includes a radio frequency power source for energizing transducers to output ultrasound waves to heat a patient treatment site. The transducers are arranged in a cylindrical shape to treat the patient and a variable number of ultrasound transducers can provide a customized therapy treatment.