Purpose: To develop and validate a robust and accurate registration pipeline for automatic contour propagation for online adaptive Intensity-Modulated Proton Therapy (IMPT) of prostate cancer using elastix software and deep learning. Methods: A three-dimensional (3D) Convolutional Neural Network was trained for automatic bladder segmentation of the computed tomography (CT) scans. The automatic bladder segmentation alongside the computed tomography (CT) scan is jointly optimized to add explicit knowledge about the underlying anatomy to the registration algorithm. We included three datasets from different institutes and CT manufacturers. The first was used for training and testing the ConvNet, where the second and the third were used for evaluation of the proposed pipeline. The system performance was quantified geometrically using the dice similarity coefficient (DSC), the mean surface distance (MSD), and the 95% Hausdorff distance (HD). The propagated contours were validated clinically through generating the associated IMPT plans and compare it with the IMPT plans based on the manual delineations. Propagated contours were considered clinically acceptable if their treatment plans met the dosimetric coverage constraints on the manual contours. Results: The bladder segmentation network achieved a DSC of 88% and 82% on the test datasets. The proposed registration pipeline achieved a MSD of 1.29 ± 0.39, 1.48 ± 1.16, and 1.49 ± 0.44 mm for the prostate, seminal vesicles, and lymph nodes, respectively, on the second dataset and a MSD of 2.31 ± 1.92 and 1.76 ± 1.39 mm for the prostate and seminal vesicles on the third dataset. The automatically propagated contours met the dose coverage constraints in 86%, 91%, and 99% of the cases for the prostate, seminal vesicles, and lymph nodes, respectively. A Conservative Success Rate (CSR) of 80% was obtained, compared to 65% when only using intensity-based registration. Conclusion: The proposed registration pipeline obtained highly promising results for generating treatment plans adapted to the daily anatomy. With 80% of the automatically generated treatment plans directly usable without manual correction, a substantial improvement in system robustness was reached compared to a previous approach. The proposed method therefore facilitates more precise proton therapy of prostate cancer, potentially leading to fewer treatment-related adverse side effects.

Objective: Our goal was to investigate the performance of an open source deformable image registration package, elastix, for fast and robust contour propagation in the context of online-adaptive intensity-modulated proton therapy (IMPT) for prostate cancer. Methods: A planning and 7–10 repeat CT scans were available of 18 prostate cancer patients. Automatic contour propagation of repeat CT scans was performed using elastix and compared with manual delineations in terms of geometric accuracy and runtime. Dosimetric accuracy was quantified by generating IMPT plans using the propagated contours expanded with a 2 mm (prostate) and 3.5 mm margin (seminal vesicles and lymph nodes) and calculating dosimetric coverage based on the manual delineation. A coverage of V_95% ≥ 98% (at least 98% of the target volumes receive at least 95% of the prescribed dose) was considered clinically acceptable. Results: Contour propagation runtime varied between 3 and 30 s for different registration settings. For the fastest setting, 83 in 93 (89.2%), 73 in 93 (78.5%), and 91 in 93 (97.9%) registrations yielded clinically acceptable dosimetric coverage of the prostate, seminal vesicles, and lymph nodes, respectively. For the prostate, seminal vesicles, and lymph nodes the Dice Similarity Coefficient (DSC) was 0.87 ± 0.05, 0.63 ± 0.18, and 0.89 ± 0.03 and the mean surface distance (MSD) was 1.4 ± 0.5 mm, 2.0 ± 1.2 mm, and 1.5 ± 0.4 mm, respectively. Conclusion: With a dosimetric success rate of 78.5–97.9%, this software may facilitate online adaptive IMPT of prostate cancer using a fast, free and open implementation.

Stochastic gradient descent (SGD) is commonly used to solve (parametric) image registration problems. In the case of badly scaled problems, SGD, however, only exhibits sublinear convergence properties. In this paper, we propose an efficient preconditioner estimation method to improve the convergence rate of SGD. Based on the observed distribution of voxel displacements in the registration, we estimate the diagonal entries of a preconditioning matrix, thus rescaling the optimization cost function. The preconditioner is efficient to compute and employ and can be used for mono-modal as well as multi-modal cost functions, in combination with different transformation models, such as the rigid, the affine, and the B-spline model. Experiments on different clinical datasets show that the proposed method, indeed, improves the convergence rate compared with SGD with speedups around 25 in all tested settings while retaining the same level of registration accuracy.

In recent years, machine learning approaches have been successfully applied to the field of neuroimaging for classification and regression tasks. However, many approaches do not give an intuitive relation between the raw features and the diagnosis. Therefore, they are difficult for clinicians to interpret. Moreover, most approaches treat the features extracted from the brain (for example, voxelwise gray matter concentration maps from brain MRI) as independent variables and ignore their spatial and anatomical relations. In this paper, we present a new Support Vector Machine (SVM)-based learning method for the classification of Alzheimer's disease (AD), which integrates spatial-anatomical information. In this way, spatial-neighbor features in the same anatomical region are encouraged to have similar weights in the SVM model. Secondly, we introduce a group lasso penalty to induce structure sparsity, which may help clinicians to assess the key regions involved in the disease. For solving this learning problem, we use an accelerated proximal gradient descent approach. We tested our method on the subset of ADNI data selected by Cuingnet et al. (2011) for Alzheimer's disease classification, as well as on an independent larger dataset from ADNI. Good classification performance is obtained for distinguishing cognitive normals (CN) vs. AD, as well as on distinguishing between various sub-types (e.g. CN vs. Mild Cognitive Impairment). The model trained on Cuignet's dataset for AD vs. CN classification was directly used without re-training to the independent larger dataset. Good performance was achieved, demonstrating the generalizability of the proposed methods. For all experiments, the classification results are comparable or better than the state-of-the-art, while the weight map more clearly indicates the key regions related to Alzheimer's disease.