Needle release mechanism enabling multiple insertions with an ultrasound-guided prostate brachytherapy robot.

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.

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation.

PURPOSE: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. METHODS AND MATERIALS: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. RESULTS: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). CONCLUSIONS: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.

Deformable registration of X-ray to MRI for post-implant dosimetry in prostate brachytherapy.

Post-implant dosimetric assessment in prostate brachytherapy is typically performed using CT as the standard imaging modality. However, poor soft tissue contrast in CT causes significant variability in target contouring, resulting in incorrect dose calculations for organs of interest. CT-MR fusion-based approach has been advocated taking advantage of the complementary capabilities of CT (seed identification) and MRI (soft tissue visibility), and has proved to provide more accurate dosimetry calculations. However, seed segmentation in CT requires manual review, and the accuracy is limited by the reconstructed voxel resolution. In addition, CT deposits considerable amount of radiation to the patient. In this paper, we propose an X-ray and MRI based post-implant dosimetry approach. Implanted seeds are localized using three X-ray images by solving a combinatorial optimization problem, and the identified seeds are registered to MR images by an intensity-based points-to-volume registration. We pre-process the MR images using geometric and Gaussian filtering. To accommodate potential soft tissue deformation, our registration is performed in two steps, an initial affine transformation and local deformable registration. An evolutionary optimizer in conjunction with a points-to-volume similarity metric is used for the affine registration. Local prostate deformation and seed migration are then adjusted by the deformable registration step with external and internal force constraints. We tested our algorithm on six patient data sets, achieving registration error of (1.2±0.8) mm in < 30 sec. Our proposed approach has the potential to be a fast and cost-effective solution for post-implant dosimetry with equivalent accuracy as the CT-MR fusion-based approach.

Transurethral light delivery for prostate photoacoustic imaging.

Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

In vivo visualization of prostate brachytherapy seeds with photoacoustic imaging.

We conducted a canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans. A fiber coupled to a 1064-nm Nd:YAG laser was inserted into high-dose-rate brachytherapy needles, which diffused light spherically. These needles were inserted through the perineum into the prostate for interstitial light delivery and the resulting acoustic waves were detected with a transrectal ultrasound probe. Postoperative computed tomography images and ex vivo photoacoustic images confirmed seed locations. Limitations with insufficient light delivery were mitigated with short-lag spatial coherence (SLSC) beamforming, providing a 10-20 dB contrast improvement over delay-and-sum (DAS) beamforming for pulse energies ranging from 6.8 to 10.5 mJ with a fiber-seed distance as large as 9.5 mm. For the same distance and the same range of energy densities, signal-to-noise ratios (SNRs) were similar while the contrast-to-noise ratio (CNR) was higher in SLSC compared to DAS images. Challenges included visualization of signals associated with the interstitial fiber tip and acoustic reverberations between seeds separated by ≤ 2 mm. Results provide insights into the potential for clinical translation to humans.

AAPM and GEC-ESTRO guidelines for image-guided robotic brachytherapy: report of Task Group 192.

In the last decade, there have been significant developments into integration of robots and automation tools with brachytherapy delivery systems. These systems aim to improve the current paradigm by executing higher precision and accuracy in seed placement, improving calculation of optimal seed locations, minimizing surgical trauma, and reducing radiation exposure to medical staff. Most of the applications of this technology have been in the implantation of seeds in patients with early-stage prostate cancer. Nevertheless, the techniques apply to any clinical site where interstitial brachytherapy is appropriate. In consideration of the rapid developments in this area, the American Association of Physicists in Medicine (AAPM) commissioned Task Group 192 to review the state-of-the-art in the field of robotic interstitial brachytherapy. This is a joint Task Group with the Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO). All developed and reported robotic brachytherapy systems were reviewed. Commissioning and quality assurance procedures for the safe and consistent use of these systems are also provided. Manual seed placement techniques with a rigid template have an estimated in vivo accuracy of 3-6 mm. In addition to the placement accuracy, factors such as tissue deformation, needle deviation, and edema may result in a delivered dose distribution that differs from the preimplant or intraoperative plan. However, real-time needle tracking and seed identification for dynamic updating of dosimetry may improve the quality of seed implantation. The AAPM and GEC-ESTRO recommend that robotic systems should demonstrate a spatial accuracy of seed placement ≤1.0 mm in a phantom. This recommendation is based on the current performance of existing robotic brachytherapy systems and propagation of uncertainties. During clinical commissioning, tests should be conducted to ensure that this level of accuracy is achieved. These tests should mimic the real operating procedure as closely as possible. Additional recommendations on robotic brachytherapy systems include display of the operational state; capability of manual override; documented policies for independent check and data verification; intuitive interface displaying the implantation plan and visualization of needle positions and seed locations relative to the target anatomy; needle insertion in a sequential order; robot-clinician and robot-patient interactions robustness, reliability, and safety while delivering the correct dose at the correct site for the correct patient; avoidance of excessive force on radioactive sources; delivery confirmation of the required number or position of seeds; incorporation of a collision avoidance system; system cleaning, decontamination, and sterilization procedures. These recommendations are applicable to end users and manufacturers of robotic brachytherapy systems.

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.

Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial.

BACKGROUND: Radiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial. METHODS: Fifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS). RESULTS: Of the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months. CONCLUSION: The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

Short-lag spatial coherence beamforming of photoacoustic images for enhanced visualization of prostate brachytherapy seeds.

Prostate brachytherapy, administered by implanting tiny radioactive seeds to treat prostate cancer, currently relies on transrectal ultrasound imaging for intraoperative visualization of the metallic seeds. Photoacoustic (PA) imaging has been suggested as a feasible alternative to ultrasound imaging due to its superior sensitivity to metal surrounded by tissue. However, PA images suffer from poor contrast when seeds are distant from the light source. We propose a transperineal light delivery method and investigate the application of a short-lag spatial coherence (SLSC) beamformer to enhance low-contrast photoacoustic signals that are distant from this type of light source. Performance is compared to a conventional delay-and-sum beamformer. A pure gelatin phantom was implanted with black ink-coated brachytherapy seeds and the mean contrast was improved by 3-25 dB with the SLSC beamformer for fiber-seed distances ranging 0.6-6.3 cm, when approximately 10% of the receive aperture elements were included in the short-lag sum. For fiber-seed distances greater than 3-4 cm, the mean contrast-to-noise ratio (CNR) was approximately doubled with the SLSC beamformer, while mean signal-to-noise ratios (SNR) were mostly similar with both beamformers. Lateral resolution was decreased by 2 mm, but improved with larger short-lag values at the expense of poorer CNR and SNR. Similar contrast and CNR improvements were achieved with an uncoated brachytherapy seed implanted in ex vivo tissue. Results indicate that the SLSC beamformer has potential to enhance the visualization of prostate brachytherapy seeds that are distant from the light source.

Molecularly targeted agents as radiosensitizers in cancer therapy--focus on prostate cancer.

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.

The effect of anterior proton beams in the setting of a prostate-rectum spacer.

Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS.

Sunitinib plus androgen deprivation and radiation therapy for patients with localized high-risk prostate cancer: results from a multi-institutional phase 1 study.

PURPOSE: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. METHODS AND MATERIALS: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. RESULTS: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. CONCLUSIONS: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer: analysis of dosimetric outcomes.

PURPOSE: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

An overlap-volume-histogram based method for rectal dose prediction and automated treatment planning in the external beam prostate radiotherapy following hydrogel injection.

PURPOSE: Hydrogel injected between the rectum and prostate prior to radiotherapy provides a possible means of increased dose sparing to the rectum. Here the authors evaluate the overlap volume histogram (OVH) metric as a means to predict the rectal dose following hydrogel injection. Whether OVH predicted dose can serve as the dose objective or constraint for automated treatment planning was also investigated. METHODS: Treatment planning was performed on 21 prostate cancer patients both pre- and posthydrogel injection, with five-field IMRT delivering 78 Gy to the planning target volume (PTV). The authors quantify the geometrical relationship between the rectum and the prostate PTV using an OVH metric which determines the fractional volume of the rectum that is within a specified distance of the PTV. For an OVH distance the authors selected, L(20), the PTV expansion distance at which 20% of the rectum overlaps. The authors calculated the rectal dose, D(20), received by 20% of the rectum volume on the dose volume histogram. Linear regression was used to examine the correlation between the L(20) and D(20), and between ΔL(20) and ΔD(20) (i.e., the change of L(20) and D(20) posthydrogel injection). Additionally, rectal dose D(15), D(25), D(35), D(50), and bladder dose D(15) were predicted from the OVH (L(15), L(25), L(35), L(50), for rectum and L(15) for bladder) by the L(x)-D(x) linear regression. The predicted doses were applied to the objectives for automated treatment planning of ten plans from five patients. Automatically generated plans were compared with plans manually generated on trial-and-error basis. RESULTS: The rectal L(20) was increased and dose D(20) decreased due to the enlarged separation of rectum caused by the hydrogel injection. Linear regression showed an inverse linear correlation between L(20) and D(20), and between ΔL(20) and ΔD(20) (r(2) = 0.77, 0.60, respectively; p < 0.0001). The increase in rectal sparing (ΔD(20)) is only weakly correlated with the volume of injected hydrogel (r(2) = 0.17; p = 0.07), indicating OVH is a more predictive indicator of rectal sparing than the volume of hydrogel itself. Application of the predicted rectum and bladder doses to automated planning produced acceptable treatment plans, with rectal dose reduced for eight of ten plans. CONCLUSIONS: The OVH metric can predict the rectal dose in the external beam prostate radiotherapy for patients with hydrogel injection. The predicted doses can be applied to the objectives of optimization in automated treatment planning to produce acceptable treatment plans.

A Dynamic Dosimetry System for Prostate Brachytherapy.

The lack of dynamic dosimetry tools for permanent prostate brachytherapy causes otherwise avoidable problems in prostate cancer patient care. The goal of this work is to satisfy this need in a readily adoptable manner. Using the ubiquitous ultrasound scanner and mobile non-isocentric C-arm, we show that dynamic dosimetry is now possible with only the addition of an arbitrarily configured marker-based fiducial. Not only is the system easily configured from accessible hardware, but it is also simple and convenient, requiring little training from technicians. Furthermore, the proposed system is built upon robust algorithms of seed segmentation, fiducial detection, seed reconstruction, and image registration. All individual steps of the pipeline have been thoroughly tested, and the system as a whole has been validated on a study of 25 patients. The system has shown excellent results of accurately computing dose, and does so with minimal manual intervention, therefore showing promise for widespread adoption of dynamic dosimetry.

Ultrasound-fluoroscopy registration for prostate brachytherapy dosimetry.

Prostate brachytherapy is a treatment for prostate cancer using radioactive seeds that are permanently implanted in the prostate. The treatment success depends on adequate coverage of the target gland with a therapeutic dose, while sparing the surrounding tissue. Since seed implantation is performed under transrectal ultrasound (TRUS) imaging, intraoperative localization of the seeds in ultrasound can provide physicians with dynamic dose assessment and plan modification. However, since all the seeds cannot be seen in the ultrasound images, registration between ultrasound and fluoroscopy is a practical solution for intraoperative dosimetry. In this manuscript, we introduce a new image-based nonrigid registration method that obviates the need for manual seed segmentation in TRUS images and compensates for the prostate displacement and deformation due to TRUS probe pressure. First, we filter the ultrasound images for subsequent registration using thresholding and Gaussian blurring. Second, a computationally efficient point-to-volume similarity metric, an affine transformation and an evolutionary optimizer are used in the registration loop. A phantom study showed final registration errors of 0.84 ± 0.45 mm compared to ground truth. In a study on data from 10 patients, the registration algorithm showed overall seed-to-seed errors of 1.7 ± 1.0 mm and 1.5 ± 0.9 mm for rigid and nonrigid registration methods, respectively, performed in approximately 30s per patient.

Behavior of tip-steerable needles in ex vivo and in vivo tissue.

Robotic needle steering is a promising technique to improve the effectiveness of needle-based clinical procedures, such as biopsies and ablation, by computer-controlled, curved insertions of needles within solid organs. In this paper, we explore the capabilities, challenges, and clinical relevance of asymmetric-tip needle steering through experiments in ex vivo and in vivo tissue. We evaluate the repeatability of needle insertion in inhomogeneous biological tissue and compare ex vivo and in vivo needle curvature and insertion forces. Steerable needles curved more in kidney than in liver and prostate, likely due to differences in tissue properties. Pre-bent needles produced higher insertion forces in liver and more curvature in vivo than ex vivo. When compared to straight stainless steel needles, steerable needles did not cause a measurable increase in tissue damage and did not exert more force during insertion. The minimum radius of curvature achieved by prebent needles was 5.23 cm in ex vivo tissue, and 10.4 cm in in vivo tissue. The curvatures achieved by bevel tip needles were negligible for in vivo tissue. The minimum radius of curvature for bevel tip needles in ex vivo tissue was 16.4 cm; however, about half of the bevel tip needles had negligible curvatures. We also demonstrate a potential clinical application of needle steering by targeting and ablating overlapping regions of cadaveric canine liver.

Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system.

Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.

Automatic segmentation of radiographic fiducial and seeds from X-ray images in prostate brachytherapy.

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.