Brachytherapy Seed and Applicator Localization via Iterative Forward Projection Matching Algorithm using Digital X-ray Projections

Interstitial and intracavitary brachytherapy plays an essential role in management of several malignancies. However, the achievable accuracy of brachytherapy treatment for prostate and cervical cancer is limited due to the lack of intraoperative planning and adaptive replanning. A major problem in implementing TRUS-based intraoperative planning is an inability of TRUS to accurately localize individual seed poses (positions and orientations) relative to the prostate volume during or after the implantation. For the locally advanced cervical cancer patient, manual drawing of the source positions on orthogonal films can not localize the full 3D intracavitary brachytherapy (ICB) applicator geometry. A new iterative forward projection matching (IFPM) algorithm can explicitly localize each individual seed/applicator by iteratively matching computed projections of the post-implant patient with the measured projections. This thesis describes adaptation and implementation of a novel IFPM algorithm that addresses hitherto unsolved problems in localization of brachytherapy seeds and applicators. The prototype implementation of 3-parameter point-seed IFPM algorithm was experimentally validated using a set of a few cone-beam CT (CBCT) projections of both the phantom and post-implant patient’s datasets. Geometric uncertainty due to gantry angle inaccuracy was incorporated. After this, IFPM algorithm was extended to 5-parameter elongated line-seed model which automatically reconstructs individual seed orientation as well as position. The accuracy of this algorithm was tested using both the synthetic-measured projections of clinically-realistic Model-6711 125I seed arrangements and measured projections of an in-house precision-machined prostate implant phantom that allows the orientations and locations of up to 100 seeds to be set to known values. The seed reconstruction error for simulation was less than 0.6 mm/3o. For the physical phantom experiments, IFPM absolute accuracy for position, polar angle, and azimuthal angel were (0.78 ± 0.57) mm, (5.8 ± 4.8)o, and (6.8 ± 4.0)o, respectively. It avoids the need to match corresponding seeds in each projection and accommodates incomplete data, overlapping seed clusters, and highly-migrated seeds. IFPM was further generalized from 5-parameter to 6-parameter model which was needed to reconstruct 3D pose of arbitrary-shape applicators. The voxelized 3D model of the applicator was obtained from external complex combinatorial geometric modeling. It is then integrated into the forward projection matching method for computing the 2D projections of the 3D ICB applicators, iteratively. The applicator reconstruction error for simulation was about 0.5 mm/2o. The residual 2D registration error (positional difference) between computed and actual measured applicator images was less than 1 mm for the intrauterine tandem and about 1.5 mm for the bilateral colpostats in each detector plane. By localizing the applicator’s internal structure and the sources, the effect of intra and inter-applicator attenuation can be included in the resultant dose distribution and CBCT metal streaking artifact mitigation. The localization accuracy of better than 1 mm and 6o has the potential to support more accurate Monte Carlo-based or 2D TG-43 dose calculations in clinical practice. It is hoped the clinical implementation of IFPM approach to localize elongated line-seed/applicator for intraoperative brachytherapy planning may have a positive impact on the treatment of prostate and cervical cancers

Segmentation, separation and pose estimation of prostate brachytherapy seeds in CT images.

International audienceIn this paper, we address the development of an automatic approach for the computation of pose information (position + orientation) of prostate brachytherapy loose seeds from 3D CT images. From an initial detection of a set of seed candidates in CT images using a threshold and connected component method, the orientation of each individual seed is estimated by using the principal components analysis (PCA) method. The main originality of this approach is the ability to classify the detected objects based on a priori intensity and volume information and to separate groups of closely spaced seeds using three competing clustering methods: the standard and a modified k-means method and a Gaussian mixture model with an Expectation-Maximization algorithm. Experiments were carried out on a series of CT images of two phantoms and patients. The fourteen patients correspond to a total of 1063 implanted seeds. Detections are compared to manual segmentation and to related work in terms of detection performance and calculation time. This automatic method has proved to be accurate and fast including the ability to separate groups of seeds in a reliable way and to determine the orientation of each seed. Such a method is mandatory to be able to compute precisely the real dose delivered to the patient post-operatively instead of assuming the alignment of seeds along the theoretical insertion direction of the brachytherapy needles

Therapeutic applications of radioactive sources: from image-guided brachytherapy to radio-guided surgical resection

It is well known nowadays that radioactivity can destroy the living cells it interacts with. It is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. However, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medical applications. Here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. In brachytherapy (BT), the radioactive sources are used for internal radiation treatment. Current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomography, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. Radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. Radioactive seed localization (RSL) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of RSL in a clinic through our experiences at the Netherlands Cancer Institute.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Therapeutic applications of radioactive sources: From image-guided brachytherapyto radio-guided surgical resection

It is well known nowadays that radioactivity can destroy the living cells it interacts with. it is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. however, since then, new techniques have been invented that make creative use of the same radioactivity properties of these sources for medi- cal applications. here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. in brachytherapy (BT), the radioactive sources are used for internal radiation treatment. current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomog- raphy, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. radioactive seed localization (rSl) is increasingly popular as an alternative tumor localization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemply the implementation of rSl in a clinic through our experi- ences at the netherlands cancer institute

SEED LOCALIZATION IN IMAGE-GUIDED PROSTATE BRACHYTHERAPY INTRAOPERATIVE DOSIMETRY SYSTEMS

Prostate cancer is the most common cancer among men in the United States. Many treatments are available, but prostate brachytherapy is acknowledged as a standard treatment for patients with localized cancer. Prostate brachytherapy is a minimally invasive surgery involving the permanent implantation of approximately 100 grain-sized radioactive seeds into the prostate. While effective, contemporary practice of brachytherapy is suboptimal because it spreads the stages of planning, implant, and dosimetry over several weeks. Although brachytherapy is now moving towards intraoperative treatment planning (ITP) which integrates all three stages into a single day in the operating room,the American Brachytherapy Society states, “the major current limitation of ITP is the inability to localize the seeds in relation to the prostate.” While the procedure is traditionally guided by transrectal ultrasound (TRUS), poor image quality prevents TRUS from accurately localizing seeds to compute dosimetry intraoperatively. Alternative methods exist, but are generally impractical to implement in clinics worldwide. The subject of this dissertation is the development of two intraoperative dosimetry systems to practically solve the problem of seed localization in ITP. The first system fuses TRUS with X-ray fluoroscopy using the ubiquitous non-isocentric mobile C-arm.The primary contributions of this dissertation include an automatic fiducial and seed segmentation algorithm for fluoroscopic images, as well as a next generation intraoperative dosimetry system based on a fiducial with seed-like markers. Results from over 30 patients prove that both contributions are significant for localizing seeds with high accuracy and demonstrate the capability of detecting cold spots. The second intraoperative dosimetry system is based on photoacoustic imaging, and uses the already implemented TRUS probe to detect ultrasonic waves converted from electromagnetic waves generated by a laser. The primary contributions of this dissertation therefore also include a prototype benchtop photoacoustic system and an improved clinical version usable in the operating room. Results from gelatin phantoms, an ex vivo dog prostate, and an in vivo dog study reveal that multiple seeds are clearly visible with high contrast using photoacoustic imaging at clinically safe laser energies.Together, both systems significantly progress the latest technologies to provide optimal care to patients through ITP

Tools for improving high-dose-rate prostate cancer brachytherapy using three-dimensional ultrasound and magnetic resonance imaging

High-dose-rate brachytherapy (HDR-BT) is an interstitial technique for the treatment of intermediate and high-risk localized prostate cancer that involves placement of a radiation source directly inside the prostate using needles. Dose-escalated whole-gland treatments have led to improvements in survival, and tumour-targeted treatments may offer future improvements in therapeutic ratio. The efficacy of tumour-targeted HDR-BT depends on imaging tools to enable accurate dose delivery to prostate sub-volumes. This thesis is focused on implementing ultrasound tools to improve HDR-BT needle localization accuracy and efficiency, and evaluating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for tumour localization. First, we implemented a device enabling sagittally-reconstructed 3D (SR3D) ultrasound, which provides sub-millimeter resolution in the needle insertion direction. We acquired SR3D and routine clinical images in a cohort of 12 consecutive eligible HDR-BT patients, with a total of 194 needles. The SR3D technique provided needle insertion depth errors within 5 mm for 93\% of needles versus 76\% for the clinical imaging technique, leading to increased precision in dose delivered to the prostate. Second, we implemented an algorithm to automatically segment multiple HDR-BT needles in a SR3D image. The algorithm was applied to the SR3D images from the first patient cohort, demonstrating mean execution times of 11.0 s per patient and successfully segmenting 82\% of needles within 3 mm. Third, we augmented SR3D imaging with live-2D sagittal ultrasound for needle tip localization. This combined technique was applied to another cohort of 10 HDR-BT patients, reducing insertion depth errors compared to routine imaging from a range of [-8.1 mm, 7.7 mm] to [-6.2 mm, 5.9 mm]. Finally, we acquired DCE-MRI in 16 patients scheduled to undergo prostatectomy, using either high spatial resolution or high temporal resolution imaging, and compared the images to whole-mount histology. The high spatial resolution images demonstrated improved high-grade cancer classification compared to the high temporal resolution images, with areas under the receiver operating characteristic curve of 0.79 and 0.70, respectively. In conclusion, we have translated and evaluated specialized imaging tools for HDR-BT which are ready to be tested in a clinical trial investigating tumour-targeted treatment

Software and Hardware-based Tools for Improving Ultrasound Guided Prostate Brachytherapy

Minimally invasive procedures for prostate cancer diagnosis and treatment, including biopsy and brachytherapy, rely on medical imaging such as two-dimensional (2D) and three-dimensional (3D) transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) for critical tasks such as target definition and diagnosis, treatment guidance, and treatment planning. Use of these imaging modalities introduces challenges including time-consuming manual prostate segmentation, poor needle tip visualization, and variable MR-US cognitive fusion. The objective of this thesis was to develop, validate, and implement software- and hardware-based tools specifically designed for minimally invasive prostate cancer procedures to overcome these challenges. First, a deep learning-based automatic 3D TRUS prostate segmentation algorithm was developed and evaluated using a diverse dataset of clinical images acquired during prostate biopsy and brachytherapy procedures. The algorithm significantly outperformed state-of-the-art fully 3D CNNs trained using the same dataset while a segmentation time of 0.62 s demonstrated a significant reduction compared to manual segmentation. Next, the impact of dataset size, image quality, and image type on segmentation performance using this algorithm was examined. Using smaller training datasets, segmentation accuracy was shown to plateau with as little as 1000 training images, supporting the use of deep learning approaches even when data is scarce. The development of an image quality grading scale specific to 3D TRUS images will allow for easier comparison between algorithms trained using different datasets. Third, a power Doppler (PD) US-based needle tip localization method was developed and validated in both phantom and clinical cases, demonstrating reduced tip error and variation for obstructed needles compared to conventional US. Finally, a surface-based MRI-3D TRUS deformable image registration algorithm was developed and implemented clinically, demonstrating improved registration accuracy compared to manual rigid registration and reduced variation compared to the current clinical standard of physician cognitive fusion. These generalizable and easy-to-implement tools have the potential to improve workflow efficiency and accuracy for minimally invasive prostate procedures

A Review on Advances in Intra-operative Imaging for Surgery and Therapy: Imagining the Operating Room of the Future

none4openZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria FrancescaZaffino, Paolo; Moccia, Sara; De Momi, Elena; Spadea, Maria Francesc