Gynecologic HDR Brachytherapy

 

Patients treated in AMIGO often have very large tumors that may have spread to surrounding structures. Image-guided interstitial catheter placement increases the likelihood that the catheters will be properly placed in the center of the tumor, thereby improving radiation dosimetry. The physician is able to see the tumor with much greater accuracy using MRI in AMIGO than is possible with other imaging modalities and it allows direct placement of an interstitial catheter into the tumor and away from the normal tissue, minimizing future toxicity to the patient. In the case of larger tumors that often require insertion of multiple catheters, each area of the tumor can be treated with the appropriate dose. AMIGO, with its unique integration of surgery, PET/CT, MRI, and brachytherapy, offers many possibilities for translational research with the potential for improving patient care for patients with gynecologic tumors. In terms of MRI, AMIGO facilitates assessment of potentially biologically active residual regions of tumors. In the laboratory, biopsied tissue obtained during AMIGO imaging allows correlation between imaging and pathology. The ultimate goal is to use these novel approaches to increase disease-free intervals and minimize long-term toxicities frequently associated with radiation treatment.

The workflow shown below is for a patient who was diagnosed using PET/CT and MR with a 0.5 cm mass in the cervix, extending back toward the pelvic side wall. The tumor is fixed at the side wall, causing a hydronephrosis (stage IIIb cervical cancer). On the basis of the images, the patient is an ideal candidate for the AMIGO suite because of the tumor location and the difficulty in accessing the tumor using standard approaches.

Gynecologic HDR Brachytherapy Workflow in AMIGO

Initial assessment. The patient is brought into the main operating room and placed in dorsal lithotomy position. The perineum is prepped and draped. A speculum is then inserted to visualize the cervix and the cervical os. A clinical examination is performed.
Applicator placement. A catheter is placed in the bladder, clamped, and the bladder filled with 150-200 cc. of saline, allowing a clear ultrasound picture of the intracervical and intrauterine canal. A single stitch at the cervical apex may be placed to pull the cervix towards the surgeon/radiologist to allow easier insertion to ensure that the cervix does not extend into the abdomen. The process of dilating the cervix using serial dilators begins, using an intrauterine sound to measure the length of the intrauterine canal. The required length of the tandem is determined and the applicator is inserted. The tandem holds the radiation seeds; treatment will be delivered later the same day in a shielded for radiation brachytherapy suite.
Applicator placement. Following dilation, the tandem is easily inserted and verified through US as in the proper position at the top of the fundus and inside the center of the cervix. An obturator is then placed over the tandem.
Applicator placement. The template is then placed. It rests on the surface of the patient’s perineum and is sutured at four corners.
Intraoperative Imaging. The patient is brought into the MR room on a MR compatible table top that is unique to the AMIGO suite. She is placed on the AMIGO MR table following transfer and brought through to the back of the 3T MR. A series of MR images are taken to delineate the tumor seen with the tandem in place. Then, a series of interstitial brachytherapy catheters are inserted, directly into the tumor, as seen on the MR.
Intraoperative Imaging. A series of MR images are obtained. Location of the needles is determined on an axial sequence to determine whether it covers the lateral extension to the side wall.
Intraoperative Imaging. Additional needles are placed to ensure accurate coverage. A real-time series of approximately 1 minute T2W monitoring catheter sequences is used to confirm adequate placement. Physicians view the scans on the MR imaging screens outside of the room. MR screens inside the MR room confirm the placement of additional insertion, as needed.
Intraoperative Imaging. Upon insertion of all the needles and confirmation of adequate placement, a final series of MR images is obtained, allowing the beginning of contouring the tumor volume on the MR.
Treatment. The patient is brought to the CT and a quick CT scan obtained for verification of the needle locations. The CT images assist the radiation physicist with digitization of the catheters for radiation treatment planning. Upon completion of treatment planning, the radiation sources are inserted in a dedicated brachytherapy suite in the Department of Radiation Oncology.

Book Chapters

Robert A. Cormack. Image-Guided Brachytherapy. Ch.26. Part IV. Image-Guided Therapy Delivery Systems. In Ferenc A. Jolesz (Ed.), Intraoperative Imaging and Image-Guided Therapy. New York, NY: Springer; 2014. pp. 387-98.

Select Publications

Paolo Zaffino, Guillaume Pernelle, Andre Mastmeyer, Alireza Mehrtash, Hongtao Zhang, Ron Kikinis, Tina Kapur, and Maria Francesca Spadea. 8/2019. “Fully Automatic Catheter Segmentation in MRI with 3D Convolutional Neural Networks: Application to MRI-guided Gynecologic Brachytherapy.” Phys Med Biol, 64, 16, Pp. 165008.Abstract
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.
Jose de Arcos, Ehud J Schmidt, Wei Wang, Junichi Tokuda, Kamal Vij, Ravi T Seethamraju, Antonio L Damato, Charles L Dumoulin, Robert A Cormack, and Akila N Viswanathan. 2017. “Prospective Clinical Implementation of a Novel Magnetic Resonance Tracking Device for Real-Time Brachytherapy Catheter Positioning.” Int J Radiat Oncol Biol Phys, 99, 3, Pp. 618-26.Abstract
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.
Sophia C Kamran, Matthias M Manuel, Paul Catalano, Linda Cho, Antonio L Damato, Larissa J Lee, Ehud J Schmidt, and Akila N Viswanathan. 2017. “MR- versus CT-based High-dose-rate Interstitial Brachytherapy for Vaginal Recurrence of Endometrial Cancer.” Brachytherapy, 16, 6, Pp. 1159-68.Abstract
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.
Andre Mastmeyer, Guillaume Pernelle, Ruibin Ma, Lauren Barber, and Tina Kapur. 2017. “Accurate Model-based Segmentation of Gynecologic Brachytherapy Catheter Collections in MRI-images.” Med Image Anal, 42, Pp. 173-88.Abstract
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.
Pelin A Ciris, Mukund Balasubramanian, Antonio L Damato, Ravi T Seethamraju, Clare M Tempany-Afdhal, Robert V. Mulkern, and Akila N Viswanathan. 2016. “Characterizing Gradient Echo Signal Decays in Gynecologic Cancers at 3T using a Gaussian Augmentation of the Monoexponential (GAME) Model.” J Magn Reson Imaging, 44, 4, Pp. 1020-30.Abstract

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.

Wei Wang, Charles L Dumoulin, Akila N Viswanathan, Zion TH Tse, Alireza Mehrtash, Wolfgang Loew, Isaiah Norton, Junichi Tokuda, Ravi T Seethamraju, Tina Kapur, Antonio L Damato, Robert A Cormack, and Ehud J Schmidt. 2015. “Real-time Active MR-tracking of Metallic Stylets in MR-guided Radiation Therapy.” Magn Reson Med, 73, 5, Pp. 1803-11.Abstract

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.

Kari Tanderup, Akila N Viswanathan, Christian Kirisits, and Steven J Frank. 2014. “Magnetic Resonance Image Guided Brachytherapy.” Semin Radiat Oncol, 24, 3, Pp. 181-91.Abstract
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.
Alireza Mehrtash, Antonio Damato, Guillaume Pernelle, Lauren Barber, Nabgha Farhat, Akila Viswanathan, Robert Cormack, and Tina Kapur. 2014. “EM-Navigated Catheter Placement for Gynecologic Brachytherapy: An Accuracy Study.” Proc SPIE Int Soc Opt Eng, 9036, Pp. 90361F.Abstract
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.
Guillaume Pernelle, Alireza Mehrtash, Lauren Barber, Antonio Damato, Wei Wang, Ravi Teja Seethamraju, Ehud Schmidt, Robert A Cormack, William M Wells III, Akila Viswanathan, and Tina Kapur. 2013. “Validation of Catheter Segmentation for MR-guided Gynecologic Cancer Brachytherapy.” Med Image Comput Comput Assist Interv, 16, Pt 3, Pp. 380-7.Abstract

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.

Tina Kapur, Jan Egger, Antonio Damato, Ehud J Schmidt, and Akila N Viswanathan. 2012. “3T MR-guided Brachytherapy for Gynecologic Malignancies.” Magn Reson Imaging, 30, 9, Pp. 1279-90.Abstract

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.