Treatment Planning Strategies for Interstitial Ultrasound Ablation of Prostate Cancer.

PURPOSE: To develop patient-specific 3D models using Finite-Difference Time-Domain (FDTD) simulations and pre-treatment planning tools for the selective thermal ablation of prostate cancer with interstitial ultrasound. This involves the integration with a FDA 510(k) cleared catheter-based ultrasound interstitial applicators and delivery system. METHODS: A 3D generalized "prostate" model was developed to generate temperature and thermal dose profiles for different applicator operating parameters and anticipated perfusion ranges. A priori planning, based upon these pre-calculated lethal thermal dose and iso-temperature clouds, was devised for iterative device selection and positioning. Full 3D patient-specific anatomic modeling of actual placement of single or multiple applicators to conformally ablate target regions can be applied, with optional integrated pilot-point temperature-based feedback control and urethral/rectum cooling. These numerical models were verified against previously reported ex-vivo experimental results obtained in soft tissues. RESULTS: For generic prostate tissue, 360 treatment schemes were simulated based on the number of transducers (1-4), applied power (8-20 W/cm2), heating time (5, 7.5, 10 min), and blood perfusion (0, 2.5, 5 kg/m3/s) using forward treatment modelling. Selectable ablation zones ranged from 0.8-3.0 cm and 0.8-5.3 cm in radial and axial directions, respectively. 3D patient-specific thermal treatment modeling for 12 Cases of T2/T3 prostate disease demonstrate applicability of workflow and technique for focal, quadrant and hemi-gland ablation. A temperature threshold (e.g., Tthres = 52 °C) at the treatment margin, emulating placement of invasive temperature sensing, can be applied for pilot-point feedback control to improve conformality of thermal ablation. Also, binary power control (e.g., Treg = 45 °C) can be applied which will regulate the applied power level to maintain the surrounding temperature to a safe limit or maximum threshold until the set heating time. CONCLUSIONS: Prostate-specific simulations of interstitial ultrasound applicators were used to generate a library of thermal-dose distributions to visually optimize and set applicator positioning and directivity during a priori treatment planning pre-procedure. Anatomic 3D forward treatment planning in patient-specific models, along with optional temperature-based feedback control, demonstrated single and multi-applicator implant strategies to effectively ablate focal disease while affording protection of normal tissues.

What happens to brain outside the thermal ablation zones? An assessment of needle-based therapeutic ultrasound in survival swine.

BACKGROUND: In stereotactic radiosurgery, isodose lines must be considered to determine how surrounding tissue is affected. In thermal ablative therapy, such as laser interstitial thermal therapy (LITT), transcranial MR-guided focused ultrasound (tcMRgFUS), and needle-based therapeutic ultrasound (NBTU), how the surrounding area is affected has not been well studied. OBJECTIVE: We aimed to quantify the transition zone surrounding the ablation core created by magnetic resonance-guided robotically-assisted (MRgRA) delivery of NBTU using multi-slice volumetric 2-D magnetic resonance thermal imaging (MRTI) and subsequent characterization of the resultant tissue damage using histopathologic analysis. METHODS: Four swine underwent MRgRA NBTU using varying duration and wattage for treatment delivery. Serial MRI images were obtained, and the most representative were overlaid with isodose lines and compared to brain tissue acquired postmortem which underwent histopathologic analysis. These results were also compared to predicted volumes using a finite element analysis model. Contralateral brain tissue was used for control data. RESULTS: Intraoperative MRTI thermal isodose contours were characterized and comprehensively mapped to post-operative MRI images and qualitatively compared with histological tissue sections postmortem. NBTU 360° ablations induced smaller lesion volumes (33.19 mm3; 120 s, 3 W; 30.05 mm3, 180 s, 4 W) versus 180° ablations (77.20 mm3, 120 s, 3 W; 109.29 mm3; 180 s; 4 W). MRTI/MRI overlay demonstrated the lesion within the proximal isodose lines. The ablation-zone was characterized by dense macrophage infiltration and glial/neuronal loss as demonstrated by glial fibrillary acidic protein (GFAP) and neurofilament (NF) absence and avid CD163 staining. The transition-zone between lesion and normal brain demonstrated decreased macrophage infiltration and measured ∼345 microns (n - 3). We did not detect overt hemorrhages or signs of edema in the adjacent spared tissue. CONCLUSION: We successfully performed MRgRA NBTU ablation in swine and demonstrated minimal histologic changes extended past the ablation-zone. The lesion was characterized by macrophage infiltration and glial/neuronal loss which decreased through the transition-zone.

Predicting ablation zones with multislice volumetric 2-D magnetic resonance thermal imaging.

BACKGROUND: High-intensity focused ultrasound (HIFU) serves as a noninvasive stereotactic system for the ablation of brain metastases; however, treatments are limited to simple geometries and energy delivery is limited by the high acoustic attenuation of the calvarium. Minimally-invasive magnetic resonance-guided robotically-assisted (MRgRA) needle-based therapeutic ultrasound (NBTU) using multislice volumetric 2-D magnetic resonance thermal imaging (MRTI) overcomes these limitations and has potential to produce less collateral tissue damage than current methods. OBJECTIVE: To correlate multislice volumetric 2-D MRTI volumes with histologically confirmed regions of tissue damage in MRgRA NBTU. METHODS: Seven swine underwent a total of 8 frontal MRgRA NBTU lesions. MRTI ablation volumes were compared to histologic tissue damage on brain sections stained with 2,3,5-triphenyltetrazolium chloride (TTC). Bland-Altman analyses and correlation trends were used to compare MRTI and TTC ablation volumes. RESULTS: Data from the initial and third swine's ablations were excluded due to sub-optimal tissue staining. For the remaining ablations (n = 6), the limits of agreement between the MRTI and histologic volumes ranged from -0.149 cm3 to 0.252 cm3 with a mean difference of 0.052 ± 0.042 cm3 (11.1%). There was a high correlation between the MRTI and histology volumes (r2 = 0.831) with a strong linear relationship (r = 0.868). CONCLUSION: We used a volumetric MRTI technique to accurately track thermal changes during MRgRA NBTU in preparation for human trials. Improved volumetric coverage with MRTI enhanced our delivery of therapy and has far-reaching implications for focused ultrasound in the broader clinical setting.

Dual-sectored transurethral ultrasound for thermal treatment of stress urinary incontinence: in silico studies in 3D anatomical models.

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.

Robotic Assisted MRI-Guided Interventional Interstitial MR-Guided Focused Ultrasound Ablation in a Swine Model.

BACKGROUND: Ablative lesions are current treatments for epilepsy and brain tumors. Interstitial magnetic resonance (MR) guided focused ultrasound (iMRgFUS) may be an alternate ablation technique which limits thermal tissue charring as compared to laser therapy (LITT) and can produce larger ablation patterns nearer the surface than transcranial MR guided focused ultrasound (tcMRgFUS). OBJECTIVE: To describe our experience with interstitial focused ultrasound (iFUS) ablations in swine, using MR-guided robotically assisted (MRgRA) delivery. METHODS: In an initial 3 animals, we optimized the workflow of the robot in the MR suite and made modifications to the robotic arm to allow range of motion. Then, 6 farm pigs (4 acute, 2 survival) underwent 7 iMRgFUS ablations using MRgRA. We altered dosing to explore differences between thermal dosing in brain as compared to other tissues. Imaging was compared to gross examination. RESULTS: Our work culminated in adjustments to the MRgRA, iMRgFUS probes, and dosing, culminating in 2 survival surgeries; swine had ablations with no neurological sequelae at 2 wk postprocedure. Immediately following iMRgFUS therapy, diffusion-weighted imaging, and T1 weighted MR were accurate reflections of the ablation volume. T2 and fluid-attenuated inversion-recovery (FLAIR) images were accurate reflections of ablation volume 1-wk postprocedure. CONCLUSION: We successfully performed MRgRA iFUS ablation in swine and found intraoperative and postoperative imaging to correlate with histological examination. These data are useful to validate our system and to guide imaging follow-up for thermal ablation lesions in brain tissue from our therapy, tcMRgFUS, and LITT.

Phase II study of intraoperative dosimetry for prostate brachytherapy using registered ultrasound and fluoroscopy.

PURPOSE: To assess the performance of a system of intraoperative dosimetry and obtain estimates of dosimetry outcomes achieved when utilizing the system in a Phase II clinical trial. METHODS AND MATERIALS: Forty-five patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed and dose was tracked intraoperatively using intraoperative registered ultrasound and fluoroscopy (iRUF). Three-dimensional seed locations were computed from X-rays and registered to ultrasound for intraoperative dosimetry, followed by adaptive plan modification to achieve prostate V100 ≥95% and ≥95% D90. Time required for iRUF was recorded. Postoperative CT/MRI scans were performed 1 day after the implantation and used as reference for dosimetric analysis. Dosimetric parameters for the prostate and urethra were compared between standard ultrasound-based dosimetry (USD), iRUF, and postoperative CT/MRI. RESULTS: Mean total time for iRUF was <30 min. A mean of four seeds (0-12) were added per implant to correct cold spots discovered by iRUF. Day 1 CT/MRI prostate V100 was ≥95% for 44/45 patients; 1 patient had Day 1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF dosimetry had significantly smaller mean differences and higher correlations for all prostate and urethral dosimetric parameters examined than USD. Both USD and iRUF tended to overestimate dose, but with less bias in iRUF than USD. CONCLUSIONS: Intraoperative dosimetry utilizing iRUF was associated with acceptable increase in procedure time and enabled very high rates of achieving excellent prostate dose coverage. iRUF intraoperative dosimetry approximated postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and urethra.

A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies.

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

Magnetic resonance-guided interstitial high-intensity focused ultrasound for brain tumor ablation.

Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors' interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery.

Intraoperative Registered Ultrasound and Fluoroscopy (iRUF) for dose calculation during prostate brachytherapy: Improved accuracy compared to standard ultrasound-based dosimetry.

BACKGROUND AND PURPOSE: Intraoperative transrectal ultrasound dosimetry during low-dose-rate prostate brachytherapy is imprecise due to sonographic distortion caused by seed echoes and needle tracks that obscure seed positions or create false signals as well as traumatic edema. Here we report the results of a pilot study comparing a combined ultrasound and fluoroscopy-based seed localization method (iRUF) to standard ultrasound-based dosimetry (USD). MATERIAL AND METHODS: Eighty patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed using standard USD for intraoperative dose tracking. Upon implant completion, six X-ray images were intraoperatively acquired using a mobile C-arm and transverse ultrasound images of the implanted prostate were also acquired. Three-dimensional seed locations were reconstructed from X-ray images and registered to the ultrasound for iRUF dosimetry. Day 1 CT/MRI scans were performed for post-implant dosimetry. Prostate and urethral dosimetric parameters were separately calculated for analysis on iRUF, USD, and CT/MRI data sets. Differences and similarities between dosimetric values measured by iRUF, USD, and CT/MRI were assessed based on root mean squared differences, intraclass correlation coefficients (ICC), and Wilcoxon signed rank test. RESULTS: Data from 66 eligible patients were analyzed. Compared to CT/MRI, iRUF dosimetry showed higher correlation with overall ICC of 0.42 (0.01 for USD) and significantly smaller root mean squared differences (overall 16.5 vs 21.5 for iRUF and USD) than USD for all prostate and urethral dosimetric parameters examined. USD demonstrated a tendency to overestimate dose to the prostate when compared to iRUF. CONCLUSIONS: iRUF approximated post-implant CT/MRI prostate and urethral dosimetry to a greater degree than USD. A phase II trial utilizing iRUF for intraoperative dynamic plan modification is underway, with the goal to confirm capability to minimize and correct for prostate underdosage not otherwise detected.

An image-guidance system for dynamic dose calculation in prostate brachytherapy using ultrasound and fluoroscopy.

PURPOSE: Brachytherapy is a standard option of care for prostate cancer patients but may be improved by dynamic dose calculation based on localized seed positions. The American Brachytherapy Society states that the major current limitation of intraoperative treatment planning is the inability to localize the seeds in relation to the prostate. An image-guidance system was therefore developed to localize seeds for dynamic dose calculation. METHODS: The proposed system is based on transrectal ultrasound (TRUS) and mobile C-arm fluoroscopy, while using a simple fiducial with seed-like markers to compute pose from the nonencoded C-arm. Three or more fluoroscopic images and an ultrasound volume are acquired and processed by a pipeline of algorithms: (1) seed segmentation, (2) fiducial detection with pose estimation, (3) seed matching with reconstruction, and (4) fluoroscopy-to-TRUS registration. RESULTS: The system was evaluated on ten phantom cases, resulting in an overall mean error of 1.3 mm. The system was also tested on 37 patients and each algorithm was evaluated. Seed segmentation resulted in a 1% false negative rate and 2% false positive rate. Fiducial detection with pose estimation resulted in a 98% detection rate. Seed matching with reconstruction had a mean error of 0.4 mm. Fluoroscopy-to-TRUS registration had a mean error of 1.3 mm. Moreover, a comparison of dose calculations between the authors' intraoperative method and an independent postoperative method shows a small difference of 7% and 2% forD90 and V100, respectively. Finally, the system demonstrated the ability to detect cold spots and required a total processing time of approximately 1 min. CONCLUSIONS: The proposed image-guidance system is the first practical approach to dynamic dose calculation, outperforming earlier solutions in terms of robustness, ease of use, and functional completeness.

Interstitial ultrasound ablation of vertebral and paraspinal tumours: parametric and patient-specific simulations.

PURPOSE: Theoretical parametric and patient-specific models are applied to assess the feasibility of interstitial ultrasound ablation of tumours in and near the spine and to identify potential treatment delivery strategies. METHODS: 3D patient-specific finite element models (n = 11) of interstitial ultrasound ablation of tumours associated with the spine were generated. Gaseous nerve insulation and various applicator configurations, frequencies (3 and 7 MHz), placement trajectories, and tumour locations were simulated. Parametric studies with multilayered models investigated the impacts of tumour attenuation, tumour dimension, and the thickness of bone insulating critical structures. Temperature and thermal dose were calculated to define ablation (>240 equivalent minutes at 43 °C (EM43 °C)) and safety margins (<45 °C and <6 EM43 °C), and to determine performance and required delivery parameters. RESULTS: Osteolytic tumours (≤44 mm) encapsulated by bone could be successfully ablated with 7 MHz interstitial ultrasound (8.1-16.6 W/cm(2), 120-5900 J, 0.4-15 min). Ablation of tumours (94.6-100% volumetric) 0-14.5 mm from the spinal canal was achieved within 3-15 min without damaging critical nerves. 3 MHz devices provided faster ablation (390 versus 930 s) of an 18 mm diameter osteoblastic (high bone content) volume than 7 MHz devices. Critical anatomy in proximity to the tumour could be protected by selection of appropriate applicator configurations, active sectors, and applied power schemas, and through gaseous insulation. Preferential ultrasound absorption at bone surfaces facilitated faster, more effective ablations in osteolytic tumours and provided isolation of ablative energies and temperatures. CONCLUSIONS: Parametric and patient-specific studies demonstrated the feasibility and potential advantages of interstitial ultrasound ablation treatment of paraspinal and osteolytic vertebral tumours.

Approaches for modelling interstitial ultrasound ablation of tumours within or adjacent to bone: theoretical and experimental evaluations.

PURPOSE: The objectives of this study were to develop numerical models of interstitial ultrasound ablation of tumours within or adjacent to bone, to evaluate model performance through theoretical analysis, and to validate the models and approximations used through comparison to experiments. METHODS: 3D transient biothermal and acoustic finite element models were developed, employing four approximations of 7-MHz ultrasound propagation at bone/soft tissue interfaces. The various approximations considered or excluded reflection, refraction, angle-dependence of transmission coefficients, shear mode conversion, and volumetric heat deposition. Simulations were performed for parametric and comparative studies. Experiments within ex vivo tissues and phantoms were performed to validate the models by comparison to simulations. Temperature measurements were conducted using needle thermocouples or magnetic resonance temperature imaging (MRTI). Finite element models representing heterogeneous tissue geometries were created based on segmented MR images. RESULTS: High ultrasound absorption at bone/soft tissue interfaces increased the volumes of target tissue that could be ablated. Models using simplified approximations produced temperature profiles closely matching both more comprehensive models and experimental results, with good agreement between 3D calculations and MRTI. The correlation coefficients between simulated and measured temperature profiles in phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models. CONCLUSIONS: Models using approximations of interstitial ultrasound energy deposition around bone/soft tissue interfaces produced temperature distributions in close agreement with comprehensive simulations and experimental measurements. These models may be applied to accurately predict temperatures produced by interstitial ultrasound ablation of tumours near and within bone, with applications toward treatment planning.

An Autoclavable Steerable Cannula Manual Deployment Device: Design and Accuracy Analysis.

Accessing a specific, predefined location identified in medical images is a common interventional task for biopsies and drug or therapy delivery. While conventional surgical needles provide little steerability, concentric tube continuum devices enable steering through curved trajectories. These devices are usually developed as robotic systems. However, manual actuation of concentric tube devices is particularly useful for initial transfer into the clinic since the Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval process of manually operated devices is simple compared to their motorized counterparts. In this paper, we present a manual actuation device for the deployment of steerable cannulas. The design focuses on compactness, modularity, usability, and sterilizability. Further, the kinematic mapping from joint space to Cartesian space is detailed for an example concentric tube device. Assessment of the device's accuracy was performed in free space, as well as in an image-guided surgery setting, using tracked 2D ultrasound.

Automated intraoperative calibration for prostate cancer brachytherapy.

PURPOSE: Prostate cancer brachytherapy relies on an accurate spatial registration between the implant needles and the TRUS image, called "calibration". The authors propose a new device and a fast, automatic method to calibrate the brachytherapy system in the operating room, with instant error feedback. METHODS: A device was CAD-designed and precision-engineered, which mechanically couples a calibration phantom with an exact replica of the standard brachytherapy template. From real-time TRUS images acquired from the calibration device and processed by the calibration system, the coordinate transformation between the brachytherapy template and the TRUS images was computed automatically. The system instantly generated a report of the target reconstruction accuracy based on the current calibration outcome. RESULTS: Four types of validation tests were conducted. First, 50 independent, real-time calibration trials yielded an average of 0.57 ± 0.13 mm line reconstruction error (LRE) relative to ground truth. Second, the averaged LRE was 0.37 ± 0.25 mm relative to ground truth in tests with six different commercial TRUS scanners operating at similar imaging settings. Furthermore, testing with five different commercial stepper systems yielded an average of 0.29 ± 0.16 mm LRE relative to ground truth. Finally, the system achieved an average of 0.56 ± 0.27 mm target registration error (TRE) relative to ground truth in needle insertion tests through the template in a water tank. CONCLUSIONS: The proposed automatic, intraoperative calibration system for prostate cancer brachytherapy has achieved high accuracy, precision, and robustness.

Point-to-volume registration of prostate implants to ultrasound.

Ultrasound-Fluoroscopy fusion is a key step toward intraoperative dosimetry for prostate brachytherapy. We propose a method for intensity-based registration of fluoroscopy to ultrasound that obviates the need for seed segmentation required for seed-based registration. We employ image thresholding and morphological and Gaussian filtering to enhance the image intensity distribution of ultrasound volume. Finally, we find the registration parameters by maximizing a point-to-volume similarity metric. We conducted an experiment on a ground truth phantom and achieved registration error of 0.7 +/- 0.2 mm. Our clinical results on 5 patient data sets show excellent visual agreement between the registered seeds and the ultrasound volume with a seed-to-seed registration error of 1.8 +/- 0.9mm. With low registration error, high computational speed and no need for manual seed segmentation, our method is promising for clinical application.

Dynamic intraoperative dosimetry for prostate brachytherapy using a nonisocentric C-arm.

PURPOSE: To evaluate a prototypical system of dynamic intraoperative dosimetry for prostate brachytherapy using registered ultrasound and fluoroscopy (RUF) with a nonisocentric C-arm (GE OEC, Salt Lake City, UT) and to compare intraoperative dosimetry of RUF as well as ultrasound-based seed localization (USD) with Day 0 CT dosimetry. METHODS: Seed positions were independently determined using RUF and USD. RUF uses a radio-opaque fiducial for registration to ultrasound and 3-dimensional reconstruction of seeds relative to prostate using nonisocentric C-arm fluoroscopy. Postimplant CT was performed on Day 0. Squared differences between dosimetric measures for RUF vs. CT and USD vs. CT were calculated and mean squared differences evaluated. Paired t test was used to evaluate which method was more closely aligned with CT. Accuracies of USD and RUF compared with CT were estimated using a nonparametric approach. RESULTS: Six patients were treated and compared with USD. RUF identified areas of underdosage intraoperatively in all patients and median 5 additional seeds were placed. In 40 of 42 measures, RUF was equally or more closely correlated with CT than USD. USD showed statistically significant variation from CT for 6 of 7 parameters compared with 1 of 7 parameters for RUF. Mean squared differences from CT were significantly smaller for RUF in 4 of 7 parameters compared with USD. CONCLUSIONS: Dynamic intraoperative dosimetry is possible with a conventional nonisocentric C-arm. Compared with an USD method, RUF-based intraoperative dosimetry was more closely aligned with immediate postimplant CT. RUF identified areas of underdosage, which were not detected using USD.

Percutaneous computed tomography fluoroscopy-guided conformal ultrasonic ablation of vertebral tumors in a rabbit tumor model. Laboratory investigation.

OBJECT: Radiofrequency ablation (RFA) has proven to be effective for treatment of malignant and benign tumors in numerous anatomical sites outside the spine. The major challenge of using RFA for spinal tumors is difficulty protecting the spinal cord and nerves from damage. However, conforming ultrasound energy to match the exact anatomy of the tumor may provide successful ablation in such sensitive locations. In a rabbit model of vertebral body tumor, the authors have successfully ablated tumors using an acoustic ablator placed percutaneously via computed tomography fluoroscopic (CTF) guidance. METHODS: Using CTF guidance, 12 adult male New Zealand White rabbits were injected with VX2 carcinoma cells in the lowest lumbar vertebral body. At 21 days, a bone biopsy needle was placed into the geographical center of the lesion, down which an acoustic ablator was inserted. Three multisensor thermocouple arrays were placed around the lesion to provide measurement of tissue temperature during ablation, at thermal doses ranging from 100 to 1,000,000 TEM (thermal equivalent minutes at 43°C), and tumor volumes were given a tumoricidal dose of acoustic energy. Animals were monitored for 24 hours and then sacrificed. Pathological specimens were obtained to determine the extent of tumor death and surrounding tissue damage. Measured temperature distributions were used to reconstruct volumetric doses of energy delivered to tumor tissue, and such data were correlated with pathological findings. RESULTS: All rabbits were successfully implanted with VX2 cells, leading to a grossly apparent spinal and paraspinal tissue mass. The CTF guidance provided accurate placement of the acoustic ablator in all tumors, as corroborated through gross and microscopic histology. Significant tumor death was noted in all specimens without collateral damage to nearby nerve tissue. Tissue destruction just beyond the margin of the tumor was noted in some but not all specimens. No neurological deficits occurred in response to ablation. Reconstruction of measured temperature data allowed accurate assessment of volumetric dose delivered to tissues. CONCLUSIONS: Using a rabbit intravertebral tumor model, the authors have successfully delivered tumoricidal doses of acoustic energy via a therapeutic ultrasound ablation probe placed percutaneously with CTF guidance. The authors have thus established the first technical and preclinical feasibility study of controlled ultrasound ablation of spinal tumors in vivo.

Automatic segmentation of seeds and fluoroscope tracking (FTRAC) fiducial in prostate brachytherapy x-ray images.

C-arm X-ray fluoroscopy-based radioactive seed localization for intraoperative dosimetry of prostate brachytherapy is an active area of research. The fluoroscopy tracking (FTRAC) fiducial is an image-based tracking device composed of radio-opaque BBs, lines, and ellipses that provides an effective means for pose estimation so that three-dimensional reconstruction of the implanted seeds from multiple X-ray images can be related to the ultrasound-computed prostate volume. Both the FTRAC features and the brachytherapy seeds must be segmented quickly and accurately during the surgery, but current segmentation algorithms are inhibitory in the operating room (OR). The first reason is that current algorithms require operators to manually select a region of interest (ROI), preventing automatic pipelining from image acquisition to seed reconstruction. Secondly, these algorithms fail often, requiring operators to manually correct the errors. We propose a fast and effective ROI-free automatic FTRAC and seed segmentation algorithm to minimize such human intervention. The proposed algorithm exploits recent image processing tools to make seed reconstruction as easy and convenient as possible. Preliminary results on 162 patient images show this algorithm to be fast, effective, and accurate for all features to be segmented. With near perfect success rates and subpixel differences to manual segmentation, our automatic FTRAC and seed segmentation algorithm shows promising results to save crucial time in the OR while reducing errors.

Robotic assistance for ultrasound guided prostate brachytherapy.

We present a robotically assisted prostate brachytherapy system and test results in training phantoms. The system consists of a transrectal ultrasound (TRUS) and a spatially co-registered robot 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 and uses the same coordinate system. Established clinical hardware, workflow and calibration are left intact. In these experiments, we recorded the first insertion attempt without adjustment. All clinically relevant locations were reached. Non-parallel needle trajectories were achieved. The pre-insertion transverse and rotational errors (measured with Polaris optical tracker relative to the template's coordinate frame) were 0.25mm (STD = 0.17mm) and 0.75 degrees (STD = 0.37 degrees). The needle tip placement errors measured in TRUS were 1.04mm (STD = 0.50mm). The system is in Phase-I clinical feasibility and safety trials, under Institutional Review Board approval.