A review of segmentation and deformable registration methods applied to adaptive cervical cancer radiation therapy treatment planning

Objective: Manual contouring and registration for radiotherapy treatment planning and online adaptation for cervical cancer radiation therapy in computed tomography (CT) and magnetic resonance images (MRI) are often necessary. However manual intervention is time consuming and may suffer from inter or intra-rater variability. In recent years a number of computer-guided automatic or semi-automatic segmentation and registration methods have been proposed. Segmentation and registration in CT and MRI for this purpose is a challenging task due to soft tissue deformation, inter-patient shape and appearance variation and anatomical changes over the course of treatment. The objective of this work is to provide a state-of-the-art review of computer-aided methods developed for adaptive treatment planning and radiation therapy planning for cervical cancer radiation therapy. Methods: Segmentation and registration methods published with the goal of cervical cancer treatment planning and adaptation have been identified from the literature (PubMed and Google Scholar). A comprehensive description of each method is provided. Similarities and differences of these methods are highlighted and the strengths and weaknesses of these methods are discussed. A discussion about choice of an appropriate method for a given modality is provided. Results: In the reviewed papers a Dice similarity coefficient of around 0.85 along with mean absolute surface distance of 2-4. mm for the clinically treated volume were reported for transfer of contours from planning day to the treatment day. Conclusions: Most segmentation and non-rigid registration methods have been primarily designed for adaptive re-planning for the transfer of contours from planning day to the treatment day. The use of shape priors significantly improved segmentation and registration accuracy compared to other models

Validating Dose Uncertainty Estimates Produced by AUTODIRECT: An Automated Program to Evaluate Deformable Image Registration Accuracy.

Deformable image registration is a powerful tool for mapping information, such as radiation therapy dose calculations, from one computed tomography image to another. However, deformable image registration is susceptible to mapping errors. Recently, an automated deformable image registration evaluation of confidence tool was proposed to predict voxel-specific deformable image registration dose mapping errors on a patient-by-patient basis. The purpose of this work is to conduct an extensive analysis of automated deformable image registration evaluation of confidence tool to show its effectiveness in estimating dose mapping errors. The proposed format of automated deformable image registration evaluation of confidence tool utilizes 4 simulated patient deformations (3 B-spline-based deformations and 1 rigid transformation) to predict the uncertainty in a deformable image registration algorithm's performance. This workflow is validated for 2 DIR algorithms (B-spline multipass from Velocity and Plastimatch) with 1 physical and 11 virtual phantoms, which have known ground-truth deformations, and with 3 pairs of real patient lung images, which have several hundred identified landmarks. The true dose mapping error distributions closely followed the Student t distributions predicted by automated deformable image registration evaluation of confidence tool for the validation tests: on average, the automated deformable image registration evaluation of confidence tool-produced confidence levels of 50%, 68%, and 95% contained 48.8%, 66.3%, and 93.8% and 50.1%, 67.6%, and 93.8% of the actual errors from Velocity and Plastimatch, respectively. Despite the sparsity of landmark points, the observed error distribution from the 3 lung patient data sets also followed the expected error distribution. The dose error distributions from automated deformable image registration evaluation of confidence tool also demonstrate good resemblance to the true dose error distributions. Automated deformable image registration evaluation of confidence tool was also found to produce accurate confidence intervals for the dose-volume histograms of the deformed dose

Optimization of Decision Making in Personalized Radiation Therapy using Deformable Image Registration

Cancer has become one of the dominant diseases worldwide, especially in western countries, and radiation therapy is one of the primary treatment options for 50% of all patients diagnosed. Radiation therapy involves the radiation delivery and planning based on radiobiological models derived primarily from clinical trials. Since 2015 improvements in information technologies and data storage allowed new models to be created using the large volumes of treatment data already available and correlate the actually delivered treatment with outcomes. The goals of this thesis are to 1) construct models of patient outcomes after receiving radiation therapy using available treatment and patient parameters and 2) provide a method to determine real accumulated radiation dose including the impact of registration uncertainties. In Chapter 2, a model was developed predicting overall survival for patients with hepatocellular carcinoma or liver metastasis receiving radiation therapy. These models show which patients benefit from curative radiation therapy based on liver function, and the survival benefit of increased radiation dose on survival. In Chapter 3, a method was developed to routinely evaluate deformable image registration (DIR) with computer-generated landmark pairs using the scale-invariant feature transform. The method presented in this chapter created landmark sets for comparing lung 4DCT images and provided the same evaluation of DIR as manual landmark sets. In Chapter 4, an investigation was performed on the impact of DIR error on dose accumulation using landmarked 4DCT images as the ground truth. The study demonstrated the relationship between dose gradient, DIR error and dose accumulation error, and presented a method to determine error bars on the dose accumulation process. In Chapter 5, a method was presented to determine quantitatively when to update a treatment plan during the course of a multi-fraction radiation treatment of head and neck cancer. This method investigated the ability to use only the planned dose with deformable image registration to predict dose changes caused by anatomical deformations. This thesis presents the fundamental elements of a decision support system including patient pre-treatment parameters and the actual delivered dose using DIR while considering registration uncertainties

Textural features for bladder cancer definition on CT images

Genitourinary cancer refers to the presence of tumours in the genital or urinary organs such as bladder, kidney and prostate. In 2008 the worldwide incidence of bladder cancer was 382,600 with a mortality of 150,282. Radiotherapy is one of the main treatment choices for genitourinary cancer where accurate delineation of the gross tumour volume (GTV) on computed tomography (CT) images is crucial for the success of this treatment. Limited CT resolution and contrast in soft tissue organs make this difficult and has led to significant inter- and intra- clinical variability in defining the extent of the GTV, especially at the junctions of different organs. In addition the introduction of new imaging techniques and modalities has significantly increased the number of the medical images that require contouring. More advanced image processing is required to help reduce contouring variability and assist in handling the increased volume of data. In this thesis image analysis methodologies were used to extract low-level features such as entropy, moment and correlation from radiotherapy planning CT images. These distinctive features were identified and used for defining the GTV and to implement a fully-automatic contouring system. The first key contribution is to demonstrate that second-order statistics from co-occurrence matrices (GTSDM) give higher accuracy in classifying soft tissue regions of interest (ROIs) into GTV and non-GTV. Loadings of the principal components (PCs) of the GTSDM features were found to be consistent over different patients. Exhaustive feature selection suggested that entropies and correlations produced consistently larger areas under receiver operating characteristic (AUROC) curves than first-order features. The second significant contribution is to demonstrate that in the bladder-prostate junction, where the largest inter-clinical variability is observed, the second-order principal entropy from stationery wavelet denoised CT images (DPE) increased the saliency of the bladder prostate junction. As a result thresholding of the DPE produced good agreement between gold standard clinical contours and those produced by this approach with Dice coefficients. The third contribution is to implement a fully automatic and reproducible system for bladder cancer GTV auto-contouring based on classifying second-order statistics. The Dice similarity coefficients (DSCs) were employed to evaluate the automatic contours. It was found that in the mid-range of the bladder the automatic contours are accurate, but in the inferior and superior ends of bladder automatic contours were more likely to have small DSCs with clinical contours, which reconcile with the fact of clinical variability in defining GTVs. A novel male bladder probability atlas was constructed based on the clinical contours and volume estimation from the classification results. Registration of the classification results with this probabilistic atlas consistently increases the DSCs of the inferior slices

Automatic Block-Matching Registration to Improve Lung Tumor Localization During Image-Guided Radiotherapy

To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed “blocks”, are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy

Deformable models for adaptive radiotherapy planning

Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85

SenseCare: A Research Platform for Medical Image Informatics and Interactive 3D Visualization

Clinical research on smart healthcare has an increasing demand for intelligent and clinic-oriented medical image computing algorithms and platforms that support various applications. To this end, we have developed SenseCare research platform for smart healthcare, which is designed to boost translational research on intelligent diagnosis and treatment planning in various clinical scenarios. To facilitate clinical research with Artificial Intelligence (AI), SenseCare provides a range of AI toolkits for different tasks, including image segmentation, registration, lesion and landmark detection from various image modalities ranging from radiology to pathology. In addition, SenseCare is clinic-oriented and supports a wide range of clinical applications such as diagnosis and surgical planning for lung cancer, pelvic tumor, coronary artery disease, etc. SenseCare provides several appealing functions and features such as advanced 3D visualization, concurrent and efficient web-based access, fast data synchronization and high data security, multi-center deployment, support for collaborative research, etc. In this paper, we will present an overview of SenseCare as an efficient platform providing comprehensive toolkits and high extensibility for intelligent image analysis and clinical research in different application scenarios.Comment: 11 pages, 10 figure

Applicability and usage of dose mapping/accumulation in radiotherapy

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping

Atlas-Based Methods in Radiotherapy Treatment of Head and Neck Cancer

Radiotherapy is one of the principal methods for treating head and neck cancer (HNC). It plays an important role in the curative and palliative treatment of HNC. It uses high-energy radiation beams to kill cancer cells by damaging their DNA. Radiotherapy planning depends upon complex algorithms to determine the best trajectories and intensities of those beams by simulating their effects passing through designated areas. This requires accurate segmentation of anatomical structures and knowledge of the relative electron density within a patient body. Computed tomography (CT) has been the modality of choice in radiotherapy planning. It offers a wealth of anatomical information and is critical in providing information about the relative electron density of tissues required to calculate radiation deposited at any one site. Manual segmentation is time-consuming and is becoming impractical with the increasing demand in image acquisition for planning. Recently, planning solely based on magnetic resonance (MR) imaging has gained popularity as it provides superior soft tissue contrast compared to CT imaging and can better facilitate the process of segmentation. However, MR imaging does not provide electron density information for dose calculation. With the growing volumes of data and data repositories, algorithms based on atlases have gained popularity as they provide prior information for structure segmentation and tissue classification. In this PhD thesis, I demonstrate that atlas-based methods can be used for segmenting head and neck structures giving results as comparable as manual segmentation. In addition, I demonstrate that those methods can be used to support radiotherapy treatment solely based on MR imaging by generating synthetic CT images. The radiation doses calculated from a synthetic and real CT image agreed well, showing the clinical feasibility of methods based on atlases. In conclusion, I show that atlas-based methods are clinically relevant in radiotherapy treatment