External-beam radiotherapy followed by High Dose Rate (HDR) brachytherapy is the standard-of-care for treating gynecologic cancers. The enhanced soft-tissue contrast provided by Magnetic Resonance Imaging (MRI) makes it a valuable imaging modality for diagnosing and treating these cancers. However, in contrast to Computed Tomography (CT) imaging, the appearance of the brachytherapy catheters, through which radiation sources are inserted to reach the cancerous tissue later on, is often variable across images. This paper reports, for the first time, a new deep-learning-based method for fully automatic segmentation of multiple closely spaced brachytherapy catheters in intraoperative MRI. Represented in the data are 50 gynecologic cancer patients treated by MRI-guided HDR brachytherapy. For each patient, a single intraoperative MRI was used. 826 catheters in the images were manually segmented by an expert radiation physicist who is also a trained radiation oncologist. The number of catheters in a patient ranged between 10 and 35. A deep 3-dimensional Convolutional Neural Network (CNN) model was developed and trained. In order to make the learning process more robust, the network was trained 5 times, each time using a different combination of shown patients. Finally, each test case was processed by the 5 networks and the final segmentation was generated by voting on the obtained 5 candidate segmentations. 4-fold validation was executed and all the patients were segmented. An average distance error of 2.0±3.4 mm was achieved. False positive and false negative catheters were 6.7% and 1.5% respectively. Average Dice score was equal to 0.60±0.17. The algorithm is available for use in the open source software platform 3D Slicer allowing for wide scale testing and research discussion. In conclusion, to the best of our knowledge, fully automatic segmentation of multiple closely spaced catheters from intraoperative MR images was achieved for the first time in gynecological brachytherapy.
PURPOSE: To compare clinical outcomes of MR-based versus CT-based high-dose-rate interstitial brachytherapy (ISBT) for vaginal recurrence of endometrioid endometrial cancer (EC). METHODS AND MATERIALS: We reviewed 66 patients with vaginal recurrent EC; 18 had MR-based ISBT on a prospective clinical trial and 48 had CT-based treatment. Kaplan-Meier survival modeling was used to generate estimates for local control (LC), disease-free interval (DFI), and overall survival (OS), and multivariate Cox modeling was used to assess prognostic factors. Toxicities were evaluated and compared. RESULTS: Median followup was 33 months (CT 30 months, MR 35 months). Median cumulative equivalent dose in 2-Gy fractions was 75.5 Gy for MR-ISBT and 73.8 Gy for CT-ISBT (p = 0.58). MR patients were older (p = 0.03) and had larger tumor size (>4 cm vs. ≤ 4 cm) compared to CT patients (p = 0.04). For MR-based versus CT-based ISBT, 3-year KM rate for local control was 100% versus 78% (p = 0.04), DFI was 69% versus 55% (p = 0.1), and OS was 63% versus 75% (p = 0.81), respectively. On multivariate analysis, tumor Grade 3 was associated with worse OS (HR 3.57, 95% CI 1.25, 11.36) in a model with MR-ISBT (HR 0.56, 95% CI 0.16, 1.89). Toxicities were not significantly different between the two modalities. CONCLUSION: Despite worse patient prognostic features, MR-ISBT was associated with a significantly better (100%) 3-year local control, comparable survival, and improved DFI rates compared to CT. Toxicities did not differ compared to CT-ISBT patients. Tumor grade contributed as the most significant predictor for survival. Larger prospective studies are needed to assess the impact of MR-ISBT on survival outcomes.
PURPOSE: We designed and built dedicated active magnetic resonance (MR)-tracked (MRTR) stylets. We explored the role of MRTR in a prospective clinical trial. METHODS AND MATERIALS: Eleven gynecologic cancer patients underwent MRTR to rapidly optimize interstitial catheter placement. MRTR catheter tip location and orientation were computed and overlaid on images displayed on in-room monitors at rates of 6 to 16 frames per second. Three modes of actively tracked navigation were analyzed: coarse navigation to the approximate region around the tumor; fine-tuning, bringing the stylets to the desired location; and pullback, with MRTR stylets rapidly withdrawn from within the catheters, providing catheter trajectories for radiation treatment planning (RTP). Catheters with conventional stylets were inserted, forming baseline locations. MRTR stylets were substituted, and catheter navigation was performed by a clinician working inside the MRI bore, using monitor feedback. RESULTS: Coarse navigation allowed repositioning of the MRTR catheters tips by 16 mm (mean), relative to baseline, in 14 ± 5 s/catheter (mean ± standard deviation [SD]). The fine-tuning mode repositioned the catheter tips by a further 12 mm, in 24 ± 17 s/catheter. Pullback mode provided catheter trajectories with RTP point resolution of ∼1.5 mm, in 1 to 9 s/catheter. CONCLUSIONS: MRTR-based navigation resulted in rapid and optimal placement of interstitial brachytherapy catheters. Catheters were repositioned compared with the initial insertion without tracking. In pullback mode, catheter trajectories matched computed tomographic precision, enabling their use for RTP.
The gynecological cancer mortality rate, including cervical, ovarian, vaginal and vulvar cancers, is more than 20,000 annually in the US alone. In many countries, including the US, external-beam radiotherapy followed by high dose rate brachytherapy is the standard-of-care. The superior ability of MR to visualize soft tissue has led to an increase in its usage in planning and delivering brachytherapy treatment. A technical challenge associated with the use of MRI imaging for brachytherapy, in contrast to that of CT imaging, is the visualization of catheters that are used to place radiation sources into cancerous tissue. We describe here a precise, accurate method for achieving catheter segmentation and visualization. The algorithm, with the assistance of manually provided tip locations, performs segmentation using image-features, and is guided by a catheter-specific, estimated mechanical model. A final quality control step removes outliers or conflicting catheter trajectories. The mean Hausdorff error on a 54 patient, 760 catheter reference database was 1.49 mm; 51 of the outliers deviated more than two catheter widths (3.4 mm) from the gold standard, corresponding to catheter identification accuracy of 93% in a Syed-Neblett template. In a multi-user simulation experiment for evaluating RMS precision by simulating varying manually-provided superior tip positions, 3σ maximum errors were 2.44 mm. The average segmentation time for a single catheter was 3 s on a standard PC. The segmentation time, accuracy and precision, are promising indicators of the value of this method for clinical translation of MR-guidance in gynecologic brachytherapy and other catheter-based interventional procedures.
PURPOSE: To assess whether R2* mapping with a standard Monoexponential (ME) or a Gaussian Augmentation of the Monoexponential (GAME) decay model better characterizes gradient-echo signal decays in gynecological cancers after external beam radiation therapy at 3T, and evaluate implications of modeling for noninvasive identification of intratumoral hypoxia. MATERIALS AND METHODS: Multi-gradient-echo signals were acquired on 25 consecutive patients with gynecologic cancers and three healthy participants during inhalation of different oxygen concentrations at 3T. Data were fitted with both ME and GAME models. Models were compared using F-tests in tumors and muscles in patients, muscles, cervix, and uterus in healthy participants, and across oxygenation levels. RESULTS: GAME significantly improved fitting over ME (P < 0.05): Improvements with GAME covered 34% of tumor regions-of-interest on average, ranging from 6% (of a vaginal tumor) to 68% (of a cervical tumor) in individual tumors. Improvements with GAME were more prominent in areas that would be assumed hypoxic based on ME alone, reaching 90% as ME R2* approached 100 Hz. Gradient echo decay parameters at different oxygenation levels were not significantly different (P = 0.81). CONCLUSION: R2* may prove sensitive to hypoxia; however, inaccurate representations of underlying data may limit the success of quantitative assessments. Although the degree to which R2 or σ values correlate with hypoxia remains unknown, improved characterization with GAME increases the potential for determining any correlates of fit parameters with biomarkers, such as oxygenation status. J. MAGN. RESON. IMAGING 2016;44:1020-1030.
PURPOSE: To develop an active MR-tracking system to guide placement of metallic devices for radiation therapy. METHODS: An actively tracked metallic stylet for brachytherapy was constructed by adding printed-circuit micro-coils to a commercial stylet. The coil design was optimized by electromagnetic simulation, and has a radio-frequency lobe pattern extending ∼5 mm beyond the strong B0 inhomogeneity region near the metal surface. An MR-tracking sequence with phase-field dithering was used to overcome residual effects of B0 and B1 inhomogeneities caused by the metal, as well as from inductive coupling to surrounding metallic stylets. The tracking system was integrated with a graphical workstation for real-time visualization. The 3 Tesla MRI catheter-insertion procedures were tested in phantoms and ex vivo animal tissue, and then performed in three patients during interstitial brachytherapy. RESULTS: The tracking system provided high-resolution (0.6 × 0.6 × 0.6 mm(3) ) and rapid (16 to 40 frames per second, with three to one phase-field dithering directions) catheter localization in phantoms, animals, and three gynecologic cancer patients. CONCLUSION: This is the first demonstration of active tracking of the shaft of metallic stylet in MR-guided brachytherapy. It holds the promise of assisting physicians to achieve better targeting and improving outcomes in interstitial brachytherapy.
The application of magnetic resonance image (MRI)-guided brachytherapy has demonstrated significant growth during the past 2 decades. Clinical improvements in cervix cancer outcomes have been linked to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and resulted in mounting evidence of improved clinical outcome regarding local control, overall survival as well as morbidity. MRI-guided prostate high-dose-rate and low-dose-rate brachytherapies have improved the accuracy of target and organs-at-risk delineation, and the potential exists for improved dose prescription and reporting for the prostate gland and organs at risk. Furthermore, MRI-guided prostate brachytherapy has significant potential to identify prostate subvolumes and dominant lesions to allow for dose administration reflecting the differential risk of recurrence. MRI-guided brachytherapy involves advanced imaging, target concepts, and dose planning. The key issue for safe dissemination and implementation of high-quality MRI-guided brachytherapy is establishment of qualified multidisciplinary teams and strategies for training and education.
Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and/or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.
Segmentation of interstitial catheters from MRI needs to be addressed in order for MRI-based brachytherapy treatment planning to become part of the clinical practice of gynecologic cancer radiotherapy. This paper presents a validation study of a novel image-processing method for catheter segmentation. The method extends the distal catheter tip, interactively provided by the physician, to its proximal end, using knowledge of catheter geometry and appearance in MRI sequences. The validation study consisted of comparison of the algorithm results to expert manual segmentations, first on images of a phantom, and then on patient MRI images obtained during MRI-guided insertion of brachytherapy catheters for the treatment of gynecologic cancer. In the phantom experiment, the maximum disagreement between automatic and manual segmentation of the same MRI image, as computed using the Hausdorf distance, was 1.5 mm, which is of the same order as the MR image spatial resolution, while the disagreement between automatic segmentation of MR images and "ground truth", manual segmentation of CT images, was 3.5 mm. The segmentation method was applied to an IRB-approved retrospective database of 10 interstitial brachytherapy patients which included a total of 101 catheters. Compared with manual expert segmentations, the automatic method correctly segmented 93 out of 101 catheters, at an average rate of 0.3 seconds per catheter using a 3 GHz Intel Core i7 computer with 16 GB RAM and running Mac OS X 10.7. These results suggest that the proposed catheter segmentation is both technically and clinically feasible.
Gynecologic malignancies are a leading cause of death in women worldwide. Standard treatment for many primary and recurrent gynecologic cancer cases includes external-beam radiation followed by brachytherapy. Magnetic resonance (MR) imaging is beneficial in diagnostic evaluation, in mapping the tumor location to tailor radiation dose and in monitoring the tumor response to treatment. Initial studies of MR guidance in gynecologic brachytherapy demonstrate the ability to optimize tumor coverage and reduce radiation dose to normal tissues, resulting in improved outcomes for patients. In this article, we describe a methodology to aid applicator placement and treatment planning for 3 Tesla (3-T) MR-guided brachytherapy that was developed specifically for gynecologic cancers. This methodology has been used in 18 cases from September 2011 to May 2012 in the Advanced Multimodality Image Guided Operating (AMIGO) suite at Brigham and Women's Hospital. AMIGO comprises state-of-the-art tools for MR imaging, image analysis and treatment planning. An MR sequence using three-dimensional (3D)-balanced steady-state free precession in a 3-T MR scanner was identified as the best sequence for catheter identification with ballooning artifact at the tip. 3D treatment planning was performed using MR images. Items in development include software designed to support virtual needle trajectory planning that uses probabilistic bias correction, graph-based segmentation and image registration algorithms. The results demonstrate that 3-T MR image guidance has a role in gynecologic brachytherapy. These novel developments have the potential to improve targeted treatment to the tumor while sparing the normal tissues.
OBJECTIVE: Accurate biopsy sampling of the suspected lesions is critical for the diagnosis and clinical management of prostate cancer. Transperineal in-bore MRI-guided prostate biopsy (tpMRgBx) is a targeted biopsy technique that was shown to be safe, efficient, and accurate. Our goal was to develop an open source software platform to support evaluation, refinement, and translation of this biopsy approach. METHODS: We developed SliceTracker, a 3D Slicer extension to support tpMRgBx. We followed modular design of the implementation to enable customization of the interface and interchange of image segmentation and registration components to assess their effect on the processing time, precision, and accuracy of the biopsy needle placement. The platform and supporting documentation were developed to enable the use of software by an operator with minimal technical training to facilitate translation. Retrospective evaluation studied registration accuracy, effect of the prostate segmentation approach, and re-identification time of biopsy targets. Prospective evaluation focused on the total procedure time and biopsy targeting error (BTE). RESULTS: Evaluation utilized data from 73 retrospective and ten prospective tpMRgBx cases. Mean landmark registration error for retrospective evaluation was 1.88 ± 2.63 mm, and was not sensitive to the approach used for prostate gland segmentation. Prospectively, we observed target re-identification time of 4.60 ± 2.40 min and BTE of 2.40 ± 0.98 mm. CONCLUSION: SliceTracker is modular and extensible open source platform for supporting image processing aspects of the tpMRgBx procedure. It has been successfully utilized to support clinical research procedures at our site.
Patient-mounted needle guide devices for percutaneous ablation are vulnerable to patient motion. The objective of this study is to develop and evaluate a software system for an MRI-compatible patient-mounted needle guide device that can adaptively compensate for displacement of the device due to patient motion using a novel image-based automatic device-to-image registration technique. We have developed a software system for an MRI-compatible patient-mounted needle guide device for percutaneous ablation. It features fully-automated image-based device-to-image registration to track the device position, and a device controller to adjust the needle trajectory to compensate for the displacement of the device. We performed: (a) a phantom study using a clinical MR scanner to evaluate registration performance; (b) simulations using intraoperative time-series MR data acquired in 20 clinical cases of MRI-guided renal cryoablations to assess its impact on motion compensation; and (c) a pilot clinical study in three patients to test its feasibility during the clinical procedure. FRE, TRE, and success rate of device-to-image registration were [Formula: see text] mm, [Formula: see text] mm, and 98.3% for the phantom images. The simulation study showed that the motion compensation reduced the targeting error for needle placement from 8.2 mm to 5.4 mm (p < 0.0005) in patients under general anesthesia (GA), and from 14.4 mm to 10.0 mm ([Formula: see text]) in patients under monitored anesthesia care (MAC). The pilot study showed that the software registered the device successfully in a clinical setting. Our simulation study demonstrated that the software system could significantly improve targeting accuracy in patients treated under both MAC and GA. Intraprocedural image-based device-to-image registration was feasible.
PURPOSE: To develop and evaluate an approach to estimate the respiratory-induced motion of lesions in the chest and abdomen. MATERIALS AND METHODS: The proposed approach uses the motion of an initial reference needle inserted into a moving organ to estimate the lesion (target) displacement that is caused by respiration. The needles position is measured using an inertial measurement unit (IMU) sensor externally attached to the hub of an initially placed reference needle. Data obtained from the IMU sensor and the target motion are used to train a learning-based approach to estimate the position of the moving target. An experimental platform was designed to mimic respiratory motion of the liver. Liver motion profiles of human subjects provided inputs to the experimental platform. Variables including the insertion angle, target depth, target motion velocity and target proximity to the reference needle were evaluated by measuring the error of the estimated target position and processing time. RESULTS: The mean error of estimation of the target position ranged between 0.86 and 1.29 mm. The processing maximum training and testing time was 5 ms which is suitable for real-time target motion estimation using the needle position sensor. CONCLUSION: The external motion of an initially placed reference needle inserted into a moving organ can be used as a surrogate, measurable and accessible signal to estimate in real-time the position of a moving target caused by respiration; this technique could then be used to guide the placement of subsequently inserted needles directly into the target.
Brain shift during tumor resection compromises the spatial validity of registered preoperative imaging data that is critical to image-guided procedures. One current clinical solution to mitigate the effects is to reimage using intraoperative magnetic resonance (iMR) imaging. Although iMR has demonstrated benefits in accounting for preoperative-to-intraoperative tissue changes, its cost and encumbrance have limited its widespread adoption. While iMR will likely continue to be employed for challenging cases, a cost-effective model-based brain shift compensation strategy is desirable as a complementary technology for standard resections. We performed a retrospective study of [Formula: see text] tumor resection cases, comparing iMR measurements with intraoperative brain shift compensation predicted by our model-based strategy, driven by sparse intraoperative cortical surface data. For quantitative assessment, homologous subsurface targets near the tumors were selected on preoperative MR and iMR images. Once rigidly registered, intraoperative shift measurements were determined and subsequently compared to model-predicted counterparts as estimated by the brain shift correction framework. When considering moderate and high shift ([Formula: see text], [Formula: see text] measurements per case), the alignment error due to brain shift reduced from [Formula: see text] to [Formula: see text], representing [Formula: see text] correction. These first steps toward validation are promising for model-based strategies.
OBJECTIVE: The purpose of this article is to report our intermediate to long-term outcomes with image-guided percutaneous hepatic tumor cryoablation and to evaluate its technical success, technique efficacy, local tumor progression, and adverse event rate. MATERIALS AND METHODS: Between 1998 and 2014, 299 hepatic tumors (243 metastases and 56 primary tumors; mean diameter, 2.5 cm; median diameter, 2.2 cm; range, 0.3-7.8 cm) in 186 patients (95 women; mean age, 60.9 years; range, 29-88 years) underwent cryoablation during 236 procedures using CT (n = 126), MRI (n = 100), or PET/CT (n = 10) guidance. Technical success, technique efficacy at 3 months, local tumor progression (mean follow-up, 2.5 years; range, 2 months to 14.6 years), and adverse event rates were calculated. RESULTS: The technical success rate was 94.6% (279/295). The technique efficacy rate was 89.5% (231/258) and was greater for tumors smaller than 4 cm (93.4%; 213/228) than for larger tumors (60.0%; 18/30) (p < 0.0001). Local tumor progression occurred in 23.3% (60/258) of tumors and was significantly more common after the treatment of tumors 4 cm or larger (63.3%; 19/30) compared with smaller tumors (18.0%; 41/228) (p < 0.0001). Adverse events followed 33.8% (80/236) of procedures and were grade 3-5 in 10.6% (25/236) of cases. Grade 3 or greater adverse events more commonly followed the treatment of larger tumors (19.5%; 8/41) compared with smaller tumors (8.7%; 17/195) (p = 0.04). CONCLUSION: Image-guided percutaneous cryoablation of hepatic tumors is efficacious; however, tumors smaller than 4 cm are more likely to be treated successfully and without an adverse event.