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

Mesh-to-raster based non-rigid registration of multi-modal images

Region of interest (ROI) alignment in medical images plays a crucial role in diagnostics, procedure planning, treatment, and follow-up. Frequently, a model is represented as triangulated mesh while the patient data is provided from CAT scanners as pixel or voxel data. Previously, we presented a 2D method for curve-to-pixel registration. This paper contributes (i) a general mesh-to-raster (M2R) framework to register ROIs in multi-modal images; (ii) a 3D surface-to-voxel application, and (iii) a comprehensive quantitative evaluation in 2D using ground truth provided by the simultaneous truth and performance level estimation (STAPLE) method. The registration is formulated as a minimization problem where the objective consists of a data term, which involves the signed distance function of the ROI from the reference image, and a higher order elastic regularizer for the deformation. The evaluation is based on quantitative light-induced fluoroscopy (QLF) and digital photography (DP) of decalcified teeth. STAPLE is computed on 150 image pairs from 32 subjects, each showing one corresponding tooth in both modalities. The ROI in each image is manually marked by three experts (900 curves in total). In the QLF-DP setting, our approach significantly outperforms the mutual information-based registration algorithm implemented with the Insight Segmentation and Registration Toolkit (ITK) and Elastix

A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy

AbstractWe present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified

Biomechanical Modeling for Lung Tumor Motion Prediction during Brachytherapy and Radiotherapy

A novel technique is proposed to develop a biomechanical model for estimating lung’s tumor position as a function of respiration cycle time. Continuous tumor motion is a major challenge in lung cancer treatment techniques where the tumor needs to be targeted; e.g. in external beam radiotherapy and brachytherapy. If not accounted for, this motion leads to areas of radiation over and/or under dosage for normal tissue and tumors. In this thesis, biomechanical models were developed for lung tumor motion predication in two distinct cases of lung brachytherapy and lung external beam radiotherapy. The lung and other relevant surrounding organs geometries, loading, boundary conditions and mechanical properties were considered and incorporated properly for each case. While using material model with constant incompressibility is sufficient to model the lung tissue in the brachytherapy case, in external beam radiation therapy the tissue incompressibility varies significantly due to normal breathing. One of the main issues tackled in this research is characterizing lung tissue incompressibility variations and measuring its corresponding parameters as a function of respiration cycle time. Results obtained from an ex-vivo porcine deflated lung indicated feasibility and reliability of using the developed biomechanical model to predict tumor motion during brachytherapy. For external beam radiotherapy, in-silico studies indicated very significant impact of considering the lung tissue incompressibility on the accuracy of predicting tumor motion. Furthermore, ex-vivo porcine lung experiments demonstrated the capability and reliability of the proposed approach for predicting tumor motion as a function of cyclic time. As such, the proposed models have a good potential to be incorporated effectively in computer assisted lung radiotherapy treatment systems

A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy

AbstractWe present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified

4D-CT Lung Registration and its Application for Lung Radiation Therapy

Radiation therapy has been successful in treating lung cancer patients, but its efficacy is limited by the inability to account for the respiratory motion during treatment planning and radiation dose delivery. Physics-based lung deformation models facilitate the motion computation of both tumor and local lung tissue during radiation therapy. In this dissertation, a novel method is discussed to accurately register 3D lungs across the respiratory phases from 4D-CT datasets, which facilitates the estimation of the volumetric lung deformation models. This method uses multi-level and multi-resolution optical flow registration coupled with thin plate splines (TPS), to address registration issue of inconsistent intensity across respiratory phases. It achieves higher accuracy as compared to multi-resolution optical flow registration and other commonly used registration methods. Results of validation show that the lung registration is computed with 3 mm Target Registration Error (TRE) and approximately 3 mm Inverse Consistency Error (ICE). This registration method is further implemented in GPU based real time dose delivery simulation to assist radiation therapy planning

Toward adaptive radiotherapy for head and neck patients: Uncertainties in dose warping due to the choice of deformable registration algorithm.

The aims of this work were to evaluate the performance of several deformable image registration (DIR) algorithms implemented in our in-house software (NiftyReg) and the uncertainties inherent to using different algorithms for dose warping

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

Validation of an elastic registration technique to estimate anatomical lung modification in Non-Small-Cell Lung Cancer Tomotherapy

<p>Abstract</p> <p>Background</p> <p>The study of lung parenchyma anatomical modification is useful to estimate dose discrepancies during the radiation treatment of Non-Small-Cell Lung Cancer (NSCLC) patients. We propose and validate a method, based on free-form deformation and mutual information, to elastically register planning kVCT with daily MVCT images, to estimate lung parenchyma modification during Tomotherapy.</p> <p>Methods</p> <p>We analyzed 15 registrations between the planning kVCT and 3 MVCT images for each of the 5 NSCLC patients. Image registration accuracy was evaluated by visual inspection and, quantitatively, by Correlation Coefficients (CC) and Target Registration Errors (TRE). Finally, a lung volume correspondence analysis was performed to specifically evaluate registration accuracy in lungs.</p> <p>Results</p> <p>Results showed that elastic registration was always satisfactory, both qualitatively and quantitatively: TRE after elastic registration (average value of 3.6 mm) remained comparable and often smaller than voxel resolution. Lung volume variations were well estimated by elastic registration (average volume and centroid errors of 1.78% and 0.87 mm, respectively).</p> <p>Conclusions</p> <p>Our results demonstrate that this method is able to estimate lung deformations in thorax MVCT, with an accuracy within 3.6 mm comparable or smaller than the voxel dimension of the kVCT and MVCT images. It could be used to estimate lung parenchyma dose variations in thoracic Tomotherapy.</p