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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.

Objective: Treatment of brain tumors requires high precision in order to ensure sufficient treatment while minimizing damage to surrounding healthy tissue. Ablation of such tumors using needle-based therapeutic ultrasound (NBTU) under real-time magnetic resonance imaging (MRI) can fulfill this need. However, the constrained space and strong magnetic field in the MRI bore restricts patient access limiting precise placement of the NBTU ablation tool. A surgical robot compatible with use inside the bore of an MRI scanner can alleviate these challenges. Methods: We present preclinical trials of a robotic system for NBTU ablation of brain tumors under real-time MRI guidance. The system comprises of an updated robotic manipulator and corresponding control electronics, the NBTU ablation system and applications for planning, navigation and monitoring of the system. Results: The robotic system had a mean translational and rotational accuracy of 1.39 $\pm$ 0.64 mm and 1.27 $\pm \;\text{0.56}^{\circ }$ in gelatin phantoms and 3.13 $\pm$ 1.41 mm and 5.58 $\pm \;\text{3.59}^{\circ }$ in 10 porcine trials while causing a maximum reduction in signal to noise ratio (SNR) of 10.3%. Conclusion: The integrated robotic system can place NBTU ablator at a desired target location in porcine brain and monitor the ablation in realtime via magnetic resonance thermal imaging (MRTI). Significance: Further optimization of this system could result in a clinically viable system for use in human trials for various diagnostic or therapeutic neurosurgical interventions.

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 (

Purpose: While the interaction between a needle and the surrounding tissue is known to cause a significant targeting error in prostate biopsy leading to false-negative results, few studies have demonstrated how it impacts in the actual procedure. We performed a pilot study on robot-assisted MRI-guided prostate biopsy with an emphasis on the in-depth analysis of the needle-tissue interaction in-vivo. Methods: The data were acquired during in-bore transperineal prostate biopsies in patients using a 4 degrees-of-freedom (DoF) MRI-compatible robot. The anatomical structures in the pelvic area and the needle path were reconstructed from MR images, and quantitatively analyzed. We analyzed each structure individually and also proposed a mathematical model to investigate the influence of those structures in the targeting error using the mixed-model regression. Results: The median targeting error in 188 insertions (27 patients) was 6.3mm. Both the individual anatomical structure analysis and the mixed-model analysis showed that the deviation resulted from the contact between the needle and the skin as the main source of error. On contrary, needle bending inside the tissue (expressed as needle curvature) did not vary among insertions with targeting errors above and below the average. The analysis indicated that insertions crossing the bulbospongiosus presented a targeting error lower than the average. The mixed-model analysis demonstrated that the distance between the needle guide and the patient skin, the deviation at the entry point, and the path length inside the pelvic diaphragm had a statistically significant contribution to the targeting error (pl0.05). Conclusions: Our results indicate that the errors associated with the elastic contact between the needle and the skin were more prominent than the needle bending along the insertion. Our findings will help to improve the preoperative planning of transperineal prostate biopsies.

In this article, we combine a review of the wide range of tissue dielectric studies and applications (e.g., safety, imaging, therapy) being pursued by the bioelectromagnetics community with a description of one specific application of dielectric measurements (in vivo tumor classification). The tumor measurements were acquired over a frequency range of 0.01-4.0 GHz using a technique based on the impedance change recorded by a short antenna when placed near or in a lossy dielectric. Substantial differences (up to 300%) were found between the dielectric properties of tumors (mammary adenocarcinoma, melanoma, lung carcinoma, glioblastoma and ependymoblastoma) and normal host tissues. Such differences reflect the known heterogeneity of abnormal cell growth in cancer. In addition, in vivo human measurements of breast carcinoma, normal skin and breast tissue indicate that a maximum differential power absorption (30% higher in tumor) occurs between 1.0 and 2.0 GHz. This information, when combined with tumor size, geometry, and anatomical location, enable the design and development of effective systems for the detection of tumors and for electromagnetically induced differential hyperthermia treatment. Finally, we also discuss these results in the context of other impedance and dielectric approaches used to characterize normal and neoplastic cells and tissues.

Herein we report a bi-modal cancer treatment technique using therapeutic ultrasound in the presence of a novel sorafenib loaded nanobubble for hepatocellular carcinoma. Therapeutic ultrasound was used for improving fusion-triggered drug release from nanobubbles leading to enhanced cytotoxicity in HepG2 cells by greater than two folds improvement in IC50 values. This strategy could also be made compatible with catheter-based devices to derive a highly localized treatment approach, a concept that might be extendable to metastatic cancers as well.

We present a robotic system for transrectal ultrasound-guided prostate brachytherapy that employs a quick release mechanism to enable multiple needles to be inserted into the prostate prior to plan optimization. The mechanism consists of two actuated fingers that act as needle guides, thereby allowing insertion of both parallel and angled needles. Path planning, including reordering of needles within a batch, is required to avoid collisions with previously inserted needles. We perform two phantom experiments using clinical implant plans. The extra time required for the robotic motions, including finger actuation, is less than three minutes for the entire procedure. Mean position error is measured to be less than 0.5 mm, presumably due to the design of the needle guides, which have a toroidal shape to enable needle angulation.

This paper presents the development, preclinical evaluation, and preliminary clinical study of a robotic system for targeted transperineal prostate biopsy under direct interventional magnetic resonance imaging (MRI) guidance. The clinically integrated robotic system is developed based on a modular design approach, comprised of surgical navigation application, robot control software, MRI robot controller hardware, and robotic needle placement manipulator. The system provides enabling technologies for MRI-guided procedures. It can be easily transported and setup for supporting the clinical workflow of interventional procedures, and the system is readily extensible and reconfigurable to other clinical applications. Preclinical evaluation of the system is performed with phantom studies in a 3 Tesla MRI scanner, rehearsing the proposed clinical workflow, and demonstrating an in-plane targeting error of 1.5[Formula: see text]mm. The robotic system has been approved by the institutional review board (IRB) for clinical trials. A preliminary clinical study is conducted with the patient consent, demonstrating the targeting errors at two biopsy target sites to be 4.0[Formula: see text]mm and 3.7[Formula: see text]mm, which is sufficient to target a clinically significant tumor foci. First-in-human trials to evaluate the system’s effectiveness and accuracy for MR image-guided prostate biopsy are underway.

In minimally invasive prostate percutaneous interventions, Magnetic Resonance Imaging (MRI) compatible robotic assistive systems developed over the years tend to have multiple degrees of freedom (DOF) to accomplish complex surgical tasks. This paper presents a novel design of an MRI-compatible transmission that allows one driving motor to control a multiplexed DOF robot system. The transmission could reduce the number of motors in the system, while maintaining the functionality of the system, by controlling each motion sequentially rather than simultaneously. A series of preliminary experiments as well as a targeting accuracy test are conducted to evaluate the accuracy of the system.

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: C-arm fluoroscopy reconstruction, such as that used in prostate brachytherapy, requires that the relative poses of the individual C-arm fluoroscopy images must be known prior to reconstruction. Radiographic fiducials can provide excellent C-arm pose tracking, but they need to be segmented in the image. The authors report an automated and unsupervised method that does not require prior segmentation of the fiducial. Methods: The authors compute the individual C-arm poses relative to a stationary radiographic fiducial of known geometry. The authors register a filtered 2D fluoroscopy image of the fiducial to its 3D model by using image intensity alone without prior segmentation. To enhance the C-arm images, the authors investigated a three-step cascade filter and a line enhancement filter. The authors tested the method on a composite fiducial containing beads, straight lines, and ellipses. Ground-truth C-arm pose was provided by a clinically proven method. Results: Using 111 clinical C-arm images and {+-}10 deg. and {+-}10 mm random perturbation around the ground-truth pose, a total of 2775 cases were evaluated. The average rotation and translation errors were 0.62 deg. (STD=0.31 deg.) and 0.72 mm (STD=0.55 mm) for the three-step filter and 0.67 deg. (STD=0.40 deg.) and 0.87 mm (STD=0.27 mm) usingmore » the line enhancement filter. Conclusions: The C-arm pose tracking method was sufficiently accurate and robust on human patient data for subsequent 3D implant reconstruction.« less

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.

The success of prostate brachytherapy critically depends on delivering adequate dose to the prostate gland. Intraoperative localization of the implanted seeds provides potential for dose evaluation and optimization during therapy. A reduced-dimensionality matching algorithm for prostate brachytherapy seed reconstruction (REDMAPS) that uses multiple X-ray fluoroscopy images obtained from different poses is proposed. The seed reconstruction problem is formulated as a combinatorial optimization problem, and REDMAPS finds a solution in a clinically acceptable amount of time using dimensionality reduction to create a smaller space of possible solutions. Dimensionality reduction is possible since the optimal solution has approximately zero cost when the poses of the acquired images are known to be within a small error. REDMAPS is also formulated to address the "hidden seed problem" in which seeds overlap on one or more observed images. REDMAPS uses a pruning algorithm to avoid unnecessary computation of cost metrics and the reduced problem is solved using linear programming. REDMAPS was first evaluated and its parameters tuned using simulations. It was then validated using five phantom and 21 patient datasets. REDMAPS was successful in reconstructing the seeds with an overall seed matching rate above 99% and a reconstruction error below 1 mm in less than 5 s.

Purpose: In prostate brachytherapy, transrectal ultrasound(TRUS) is used to visualize the anatomy, while implanted seeds can be visualized by fluoroscopy. Intraoperative dosimetry optimization is possible using a combination of TRUS and fluoroscopy, but requires localization of the fluoroscopy-derived seed cloud, relative to the anatomy as seen on TRUS. The authors propose to develop a method of registration of TRUSimages and the implants reconstructed from fluoroscopy. Methods: A phantom was implanted with 48 seeds then imaged with TRUS and CT. Seeds were reconstructed from CT yielding a cloud of seeds. Fiducial-based ground-truth registration was established between the TRUS and CT.TRUSimages are filtered, compounded, and registered to the reconstructed implants by using an intensity-based metric. The authors evaluated a volume-to-volume and point-to-volume registration scheme. In total, seven TRUS filtering techniques and three image similarity metrics were analyzed. The method was also tested on human subject data captured from a brachytherapy procedure. Results: For volume-to-volume registration, noise reduction filter and normalized correlation metrics yielded the best result: An average of 0.54 ± 0.11 mm seed localization error relative to ground truth. 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 fluoroscopyimages showed 81 radioactive seeds implanted inside the prostate. A qualitative analysis showed clinically correct agreement between the seeds visible in TRUS and reconstructed from intraoperative fluoroscopyimaging. The measured registration error compared to the manually selected seed locations by the clinician was 2.86 ± 1.26 mm . Conclusions: Fully automated registration between TRUS and the reconstructed seeds performed well in ground-truth phantom experiments and qualitative observation showed adequate performance on early clinical patient data.

Background Clinical use of image-guided needle placement robots has lagged behind laboratory-demonstrated robotic capability. Bridging this gap requires reliable and easy-to-use robotic systems. Methods Our system for image-guided needle placement requires only simple, low-cost components and minimal, entirely off-line calibration. It rapidly aligns needles to planned entry paths using 3D ultrasound (US) reconstructed from freehand 2D scans. We compare system accuracy against clinical standard manual needle placement. Results The US-guided robotic system is significantly more accurate than single manual insertions. When several manual withdrawals and reinsertions are allowed, accuracy becomes equivalent. In ex vivo experiments, robotic repeatability was 1.56 mm, compared to 3.19 and 4.63 mm for two sets of manual insertions. In an in vivo experiment with heartbeat and respiratory effects, robotic system accuracy was 5.5 mm. Conclusions A 3D US-guided robot can eliminate error bias and reduce invasiveness (the number of insertions required) compared to manual needle insertion. Remaining future challenges include target motion compensation. Copyright  2008 John Wiley & Sons, Ltd.

PURPOSE: To report the preliminary experimental results obtained with a robot-assisted trans- rectal ultrasound (TRUS)-guided prostate brachytherapy system. METHODS AND MATERIALS: The system consists of a TRUS unit, a spatially coregistered needle insertion robot, and an FDA-approved treatment planning and image-registered implant sys- tem. The robot receives each entry/target coordinate pair of the implant plan, inserts a preloaded needle, and then the seeds are deposited. The needles/sources are tracked in TRUS, thus allowing the plan to be updated as the procedure progresses. RESULTS: The first insertion attempt was recorded for each needle, without adjustment. All clin- ically relevant locations were reached in a prostate phantom. Nonparallel and parallel needle trajec- tories were demonstrated. Based on TRUS, the average transverse placement error was 2 mm (worst case 2.5 mm, 80% less than 2 mm), and the average sagittal error was 2.5 mm (worst case 5.0 mm, 70% less than 2.5 mm). CONCLUSIONS: The concept and technical viability of robot-assisted brachytherapy were dem- onstrated in phantoms. The kinematically decoupled robotic assistant device is inherently safe. Overall performance was promising, but further optimization is necessary to prove the possibility of improved dosimetry. 2006 American Brachytherapy Society. 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.

The success of prostate brachytherapy critically depends on delivering adequate dose to the prostate gland, and the capability of intraoperatively localizing implanted seeds provides potential for dose evaluation and optimization during therapy. REDMAPS is a recently reported algorithm that carries out seed localization by detecting, matching and reconstructing seeds in only a few seconds from three acquired x-ray images (Lee et al 2011 IEEE Trans. Med. Imaging 29 38–51). In this paper, we present an automatic pose correction (APC) process that is combined with REDMAPS to allow for both more accurate seed reconstruction and the use of images with relatively large pose errors. APC uses a set of reconstructed seeds as a fiducial and corrects the image pose by minimizing the overall projection error. The seed matching and APC are iteratively computed until a stopping condition is met. Simulations and clinical studies show that APC significantly improves the reconstructions with an overall average matching rate of ≥99.4%, reconstruction error of ≤0.5 mm, and the matching solution optimality of ≥99.8%.

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, real-time dosimetry would be ideal to allow for rapid evaluation of the implant quality intra-operatively. However, such a mechanism requires an imaging system that is both real-time and which provides, via multiple C-arm fluoroscopy images, clear information describing the three-dimensional position of the seeds deposited within the prostate. Thus, accurate tracking of the C-arm poses proves to be of critical importance to the process. Methodology: We compute the pose of the C-arm relative to a stationary radiographic fiducial of known geometry by employing a hybrid registration framework. Firstly, by means of an ellipse segmentation algorithm and a 2D/3D feature based registration, we exploit known FTRAC geometry to recover an initial estimate of the C-arm pose. Using this estimate, we then initialize the intensity-based registration which serves to recover a refined and accurate estimation of the C-arm pose. Results: Ground-truth pose was established for each C-arm image through a published and clinically tested segmentation-based method. Using 169 clinical C-arm images and a ±10° and ±10 mm random perturbation of the ground-truth pose, the average rotation and translation errors were 0.68° (std = 0.06°) and 0.64 mm (std = 0.24 mm). Conclusion: Fully automated C-arm pose estimation using a 2D/3D hybrid registration scheme was found to be clinically robust based on human patient data. Copyright 2011 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.

Prostate brachytherapy guided by transrectal ultrasound is a common treatment option for early stage prostate cancer. Prostate cancer accounts for 28% of cancer cases and 11% of cancer deaths in men with 217,730 estimated new cases and 32,050 estimated deaths in 2010 in the United States alone. The major current limitation is the inability to reliably localize implanted radiation seeds spatially in relation to the prostate. Multimodality approaches that incorporate X-ray for seed localization have been proposed, but they require both accurate tracking of the imaging device and segmentation of the seeds. Some use image-based radiographic fiducials to track the X-ray device, but manual intervention is needed to select proper regions of interest for segmenting both the tracking fiducial and the seeds, to evaluate the segmentation results, and to correct the segmentations in the case of segmentation failure, thus requiring a significant amount of extra time in the operating room. In this paper, we present an automatic segmentation algorithm that simultaneously segments the tracking fiducial and brachytherapy seeds, thereby minimizing the need for manual intervention. In addition, through the innovative use of image processing techniques such as mathematical morphology, Hough transforms, and RANSAC, our method can detect and separate overlapping seeds that are common in brachytherapy implant images. Our algorithm was validated on 55 phantom and 206 patient images, successfully segmenting both the fiducial and seeds with a mean seed segmentation rate of 96% and sub-millimeter accuracy.

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.

Intraoperative dosimetry in prostate brachytherapy requires localization of the implanted radioactive seeds. A tomosynthesis-based seed reconstruction method is proposed. A three-dimensional volume is reconstructed from Gaussian-blurred projection images and candidate seed locations are computed from the reconstructed volume. A false positive seed removal process, formulated as an optimal coverage problem, iteratively removes ldquoghostrdquo seeds that are created by tomosynthesis reconstruction. In an effort to minimize pose errors that are common in conventional C-arms, initial pose parameter estimates are iteratively corrected by using the detected candidate seeds as fiducials, which automatically ldquofocusesrdquo the collected images and improves successive reconstructed volumes. Simulation results imply that the implanted seed locations can be estimated with a detection rate of ges97.9% and ges99.3% from three and four images, respectively, when the C-arm is calibrated and the pose of the C-arm is known. The algorithm was also validated on phantom data sets successfully localizing the implanted seeds from four or five images. In a Phase-1 clinical trial, we were able to localize the implanted seeds from five intraoperative fluoroscopy images with 98.8% (STD=1.6) overall detection rate.

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.

In prostate brachytherapy, x-ray fluoroscopy has been used for intra-operative dosimetry to provide qualitative assessment of implant quality. More recent developments have made possible 3D localization of the implanted radioactive seeds. This is usually modeled as an assignment problem and solved by resolving the correspondence of seeds. It is, however, NP-hard, and the problem is even harder in practice due to the significant number of hidden seeds. In this paper, we propose an algorithm that can find an optimal solution from multiple projection images with hidden seeds. It solves an equivalent problem with reduced dimensional complexity, thus allowing us to find an optimal solution in polynomial time. Simulation results show the robustness of the algorithm. It was validated on 5 phantom and 18 patient datasets, successfully localizing the seeds with detection rate ofor = 97.6% and reconstruction error ofor = 1.2 mm. This is considered to be clinically excellent performance.

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.

Purpose: Interstitial high intensity therapeutic ultrasound (HITU) applicators can be used to ablate tissue percutaneously, allowing for minimally-invasive treatment without ionizing radiation [1,2]. The purpose of this study was to evaluate the feasibility and usability of combining multielement interstitial HITU applicators with a clinical magnetic resonance imaging (MRI)-guided focused ultrasound software platform. Methods: The Sonalleve software platform (Philips Healthcare, Vantaa, Finland) combines anatomical MRI for target selection and multi-planar MRI thermometry to provide real-time temperature information. The MRI-compatible interstitial US applicators (Acoustic MedSystems, Savoy, IL, USA) had 1–4 cylindrical US elements, each 1 cm long with either 180° or 360° of active surface. Each applicator (4 Fr diameter, enclosed within a 13 Fr flexible catheter) was inserted into a tissue-mimicking agar-silica phantom. Degassed water was circulated around the transducers for cooling and coupling. Based on the location of the applicator, a virtual transducer overlay was added to the software to assist targeting and to allow automatic thermometry slice placement. The phantom was sonicated at 7 MHz for 5 minutes with 6–8 W of acoustic power for each element. MR thermometry data were collected during and after sonication. Results: Preliminary testing indicated that the applicator location could be identified in themore » planning images and the transducer locations predicted within 1 mm accuracy using the overlay. Ablation zones (thermal dose ≥ 240 CEM43) for 2 active, adjacent US elements ranged from 18 mm × 24 mm (width × length) to 25 mm × 25 mm for the 6 W and 8 W sonications, respectively. Conclusion: The combination of interstitial HITU applicators and this software platform holds promise for novel approaches in minimally-invasive MRI-guided therapy, especially when bony structures or air-filled cavities may preclude extracorporeal HIFU.[1] Diederich et al. IEEE UFFFC 46.5 (1999): 1218.[2] Chopra et al. PMB 50.21 (2005): 4957. Funding support was provided by Philips Healthcare and in-kind support from Acoustic MedSystems Inc. Ari Partanen is a paid employee of Philips Healthcare. Goutam Ghoshal and Everette Clif Burdette are paid employees of Acoustic MedSystems Inc.« less

Purpose: C-arm fluoroscopy is ubiquitous in contemporary surgery, but it lacks the ability to accurately reconstruct 3D information. A major obstacle in fluoroscopic reconstruction is discerning the pose of the X-ray image, in 3D space. Optical/magnetic trackers are prohibitively expensive, intrusive and cumbersome. Method: We present single-image-based fluoroscope tracking (FTRAC) with the use of an external radiographic fiducial consisting of a mathematically optimized set of points, lines, and ellipses. The fiducial encodes six degrees of freedom in a single image by creating a unique view from any direction. A non-linear optimizer can rapidly compute the pose of the fiducial using this image. The current embodiment has salient attributes: small dimensions (3 x 3 x 5 cm), it need not be close to the anatomy of interest and can be segmented automatically. Results: We tested the fiducial and the pose recovery method on synthetic data and also experimentally on a precisely machined mechanical phantom. Pose recovery had an error of 0.56 mm in translation and 0.33° in orientation. Object reconstruction had a mean error of 0.53 mm with 0.16 mm STD. Conclusion: The method offers accuracies similar to commercial tracking systems, and is sufficiently robust for intra-operative quantitative C-arm fluoroscopy.

Purpose: The purpose of the work is to describe a new algorithm for the automatic detection of implanted radioactive seeds within the prostate. The algorithm is based on the traditional Hough transform. A method of quality assurance is described as well as a quantitative phantom study to determine the accuracy of the algorithm. Methods and Materials: An algorithm is described which is based on the Hough transform. The Hough transform is a well known transform traditionally used to automatically segment lines and other well defined geometric objects from images. The traditional Hough transform is extended to three-dimensions and applied to CTimages of seed implanted prostate glands. A method based on digitally reconstructed radiographs is described to quality assure the determined three-dimensional positions of the detected seeds. Two phantom studies utilizing eight seeds and nine seeds are described. All eight seeds form a contiguous a square while the nine seed phantom describes seeds which are placed side-by-side in groups of two and three. The algorithm is applied to the CT scans of both phantoms and the seed positions determined. Results: The algorithm has been commercially developed and used to perform postsurgical dosimetric assessment on approximately 1000 patients. Using the described quality assurance tool it was determined that the algorithm accurately determined the seed positions in all 1000 patients. The algorithm was also applied to the eight seed phantom. The algorithm successfully found all eight seeds as well as their seed coordinates. The average radial error was determined to be 0.9 mm. For the nine seed phantom, the algorithm correctly identified all nine seeds, with an average radial error of 3 mm. Conclusions: The described algorithm is a robust, accurate, automatic, three-dimensional application for CT based seed determination.

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.

Purpose: Prostate brachytherapy is a common treatment method for low-risk prostate cancer patients. Intraoperative treatment planning is known to improve the treatment procedure and the outcome. The current limitation of intraoperative treatment planning is the inability to localize the seeds in relation to the prostate. We developed an image-guidance system to fulfill this need to achieve intraoperative dynamic dosimetry in prostate brachytherapy. Methods: Our system is based on standard imaging equipments available in the operating room, including the transrectal ultrasound (TRUS) and the mobile C-arm. A simple fiducial is added to compute the C-arm pose. Three fluoroscopic images and an ultrasound volume of the seeds and the prostate are acquired and processed by four image processing algorithms: seed segmentation, fiducial detection with pose estimation, seed reconstruction, and seeds-to-TRUS registration. The updated seed positions allow the physician to assess the quality of implantation and dynamically adjust the treatment plan during the course of surgery to achieve improved exit dosimetry. Results: The system was tested on 10 phantoms and 37 patients. Seed segmentation resulted in a 1% false negative and 2% false positive rates. Fiducial detection with pose estimation resulted in a detection rate of 98%. Seed reconstruction had a mean reconstructionmore » error of 0.4 mm. Seeds-to-TRUS registration had a mean registration error of 1.3 mm. The total processing time from image acquisition to registration was approximately 1 minute. Conclusion: We present an image-guidance system for intraoperative dynamic dosimetry in prostate brachytherapy. Using standard imaging equipments and a simple fiducial, our system can be easily adopted in any clinics. Robust image processing algorithms enable accurate and fast computation of the delivered dose. Especially, the system enables detection of possible hot/cold spots during the surgery, allowing the physician to address these in the operating room rather than requiring additional therapy afterwards. This research was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) under grant 2R44CA099374 and grant 1R01CA151395, and in part by the Department of Defense (DoD) under grant W81XWH-05-1-0407.« less

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 system for optimizing the planning, registration, targeting, and delivery of conformal, external beam radiation therapy of prostate cancer and other soft tissue diseases. Real-time ultrasound imaging during planning and treatment employing an ultrasound probe (41) is used for localization of soft tissue treatment targets and fused with radiographic or CT data for conformal treatment optimization. The fusion technique provides accurate localization of the prostate volume in real time. A spatial registration system (30,40) is used to track and record the relative spatial position of the ultrasound probe (41).

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.

Freezing studies were conducted using rat platelets to determine if electromagnetic thawing could be used to improve the survival time and recovery of platelets over that obtainable with conventional techniques. A total of 130 experiments were conducted. Seventy-four control experiments not involving freezing and 56 experimental freezings of rat platelets were performed. In most freezing experiments, 51Cr-labeled platelets were maintained in a mixture of RCD-20% plasma-6% Me2SO. In this medium, the mean survival and recovery of unfrozen control platelets were 3.50 days and 67%, respectively. The results for frozen-thawed platelets were not encouraging. Using the same incubation mixture, the mean survival time was 1.18 days and the mean recovery was 7%, yielding a platelet viability index of 3.5%. Changing the thawing method (electromagnetic or waterbath), Me2SO concentration (6 or 10%), buffer medium (RCD-20% plasma or plasma), or freezing or thawing rate did not improve the results. When these same methods were applied in humans, platelets could be successfully frozen and thawed. It would therefore appear that the rat model is an inappropriate one in which to develop improved techniques for freezing and thawing human platelets.