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Objective: To assess the performance of a probabilistic deep learning based algorithm for predicting inter-fraction anatomical changes in head and neck patients. Approach: A probabilistic daily anatomy model for head and neck patients $(\mathrm{DAM}_{\mathrm{HN}})$ is built on the variational autoencoder architecture. The model approximates the generative joint conditional probability distribution of the repeat computed tomography (rCT) images and their corresponding masks on the planning CT images (pCT) and their masks. The model outputs deformation vector fields, which are used to produce possible rCTs and associated masks. The dataset is composed of 93 patients (i.e., 367 pCT - rCT pairs), 9 (i.e., 37 pairs) of which were set aside for final testing. The performance of the model is assessed based on the reconstruction accuracy and the generative performance for the set aside patients. Main results: The model achieves a DICE score of 0.92 and an image similarity score of 0.65 on the test set. The generated parotid glands volume change distributions and center of mass shift distributions were also assessed. For both, the medians of the distributions are close to the true ones, and the distributions are broad enough to encompass the real observed changes. Moreover, the generated images display anatomical changes in line with the literature reported ones, such as the medial shifts of the parotids glands. Significance: $(\mathrm{DAM}_{\mathrm{HN}})$ is capable of generating realistic anatomies observed during the course of the treatment and has applications in anatomical robust optimization, treatment planning based on plan library approaches and robustness evaluation against inter-fractional changes.

$\textbf{Purpose:}$ To assess the viability of a physics-based, deterministic and adjoint-capable algorithm for performing treatment planning system independent dose calculations and for computing dosimetric differences caused by anatomical changes. $\textbf{Methods:}$ A semi-numerical approach is employed to solve two partial differential equations for the proton phase-space density which determines the deposited dose. Lateral hetereogeneities are accounted for by an optimized (Gaussian) beam splitting scheme. Adjoint theory is applied to approximate the change in the deposited dose caused by a new underlying patient anatomy. $\textbf{Results:}$ The quality of the dose engine was benchmarked through three-dimensional gamma index comparisons against Monte Carlo simulations done in TOPAS. The worst passing rate for the gamma index with (1 mm, 1 %, 10 % dose cut-off) criteria is 95.62 %. The effect of delivering treatment plans on repeat CTs was also tested. For a non-robustly optimized plan the adjoint component was accurate to 6.2 % while for a robustly optimized plan it was accurate to 1 %. $\textbf{Conclusions:}$ YODA is capable of accurate dose computations in both single and multi spot irradiations when compared to TOPAS. Moreover, it is able to compute dosimetric differences due to anatomical changes with small to moderate errors thereby facilitating its use for patient-specific quality assurance in online adaptive proton therapy.

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: 1) MRI-to-CT and 2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (>0.87/0.90) and gamma pass rates for photon (>98.1%/99.0%) and proton (>97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy., Comment: Preprint submitted to Medical Image Analysis

In radiotherapy, the internal movement of organs between treatment sessions causes errors in the final radiation dose delivery. Motion models can be used to simulate motion patterns and assess anatomical robustness before delivery. Traditionally, such models are based on principal component analysis (PCA) and are either patient-specific (requiring several scans per patient) or population-based, applying the same deformations to all patients. We present a hybrid approach which, based on population data, allows to predict patient-specific inter-fraction variations for an individual patient. We propose a deep learning probabilistic framework that generates deformation vector fields (DVFs) warping a patient's planning computed tomography (CT) into possible patient-specific anatomies. This daily anatomy model (DAM) uses few random variables capturing groups of correlated movements. Given a new planning CT, DAM estimates the joint distribution over the variables, with each sample from the distribution corresponding to a different deformation. We train our model using dataset of 312 CT pairs from 38 prostate cancer patients. For 2 additional patients (22 CTs), we compute the contour overlap between real and generated images, and compare the sampled and ground truth distributions of volume and center of mass changes. With a DICE score of 0.86 and a distance between prostate contours of 1.09 mm, DAM matches and improves upon PCA-based models. The distribution overlap further indicates that DAM's sampled movements match the range and frequency of clinically observed daily changes on repeat CTs. Conditioned only on a planning CT and contours of a new patient without any pre-processing, DAM can accurately predict CTs seen during following treatment sessions, which can be used for anatomically robust treatment planning and robustness evaluation against inter-fraction anatomical changes.

Fast dose calculation is critical for online and real time adaptive therapy workflows. While modern physics-based dose algorithms must compromise accuracy to achieve low computation times, deep learning models can potentially perform dose prediction tasks with both high fidelity and speed. We present a deep learning algorithm that, exploiting synergies between Transformer and convolutional layers, accurately predicts broad photon beam dose distributions in few milliseconds. The proposed improved Dose Transformer Algorithm (iDoTA) maps arbitrary patient geometries and beam information (in the form of a 3D projected shape resulting from a simple ray tracing calculation) to their corresponding 3D dose distribution. Treating the 3D CT input and dose output volumes as a sequence of 2D slices along the direction of the photon beam, iDoTA solves the dose prediction task as sequence modeling. The proposed model combines a Transformer backbone routing long-range information between all elements in the sequence, with a series of 3D convolutions extracting local features of the data. We train iDoTA on a dataset of 1700 beam dose distributions, using 11 clinical volumetric modulated arc therapy (VMAT) plans (from prostate, lung and head and neck cancer patients with 194-354 beams per plan) to assess its accuracy and speed. iDoTA predicts individual photon beams in ~50 milliseconds with a high gamma pass rate of 97.72% (2 mm, 2%). Furthermore, estimating full VMAT dose distributions in 6-12 seconds, iDoTA achieves state-of-the-art performance with a 99.51% (2 mm, 2%) pass rate. Offering the sub-second speed needed in online and real-time adaptive treatments, iDoTA represents a new state of the art in data-driven photon dose calculation. The proposed model can massively speed-up current photon workflows, reducing calculation times from few minutes to just a few seconds.

In this paper we propose a solution to the need for a fast particle transport algorithm in Online Adaptive Proton Therapy capable of cheaply, but accurately computing the changes in patient dose metrics as a result of changes in the system parameters. We obtain the proton phase-space density through the product of the numerical solution to the one-dimensional Fokker-Planck equation and the analytical solution to the Fermi-Eyges equation. Moreover, a corresponding adjoint system was derived and solved for the adjoint flux. The proton phase-space density together with the adjoint flux and the metric (chosen as the energy deposited by the beam in a variable region of interest) allowed assessing the accuracy of our algorithm to different perturbation ranges in the system parameters and regions of interest. The algorithm achieved negligible errors ($1.1 \times 10^{-6}$ $\%$ to $3.6 \times 10^{-3}$ $\%$) for small perturbation ranges ($-40 \text{ HU to } 40 \text{ HU}$) and small to moderate errors ($3 \text{ $\%$ to } 17 \text{ $\%$}$) -- in line with the well-known limitation of adjoint approaches -- for large perturbation ranges ($-400 \text{ HU to } 400 \text{ HU}$) in the case of most clinical interest where the region of interest surrounds the Bragg peak. Given these results coupled with the capability of further improving the timing performance it can be concluded that our algorithm presents a viable solution for the specific purpose of Online Adaptive Proton Therapy.

Next generation online and real-time adaptive radiotherapy workflows require precise particle transport simulations in sub-second times, which is unfeasible with current analytical pencil beam algorithms (PBA) or stochastic Monte Carlo (MC) methods. We present a data-driven millisecond speed dose calculation algorithm (DoTA) accurately predicting the dose deposited by mono-energetic proton pencil beams for arbitrary energies and patient geometries. Given the forward-scattering nature of protons, we frame 3D particle transport as modeling a sequence of 2D geometries in the beam's eye view. DoTA combines convolutional neural networks extracting spatial features (e.g., tissue and density contrasts) with a transformer self-attention backbone that routes information between the sequence of geometry slices and a vector representing the beam's energy, and is trained to predict low noise MC simulations of proton beamlets using 80,000 different head and neck, lung, and prostate geometries. Predicting beamlet doses in 5 ms with a very high gamma pass rate of 99.37% (1%, 3 mm) compared to the ground truth MC calculations, DoTA significantly improves upon analytical pencil beam algorithms both in precision and speed. Offering MC accuracy 100 times faster than PBAs for pencil beams, our model calculates full treatment plan doses in 10 to 15 s depending on the number of beamlets, achieving a 99.70% (2%, 2 mm) gamma pass rate across 9 test patients. Outperforming all previous analytical pencil beam and deep learning based approaches, DoTA represents a new state of the art in data-driven dose calculation and can directly compete with the speed of even commercial GPU MC approaches. Providing the sub-second speed required for adaptive treatments, straightforward implementations could offer similar benefits to other steps of the radiotherapy workflow or other modalities such as helium or carbon treatments.

Particle physics simulations are the cornerstone of nuclear engineering applications. Among them radiotherapy (RT) is crucial for society, with 50% of cancer patients receiving radiation treatments. For the most precise targeting of tumors, next generation RT treatments aim for real-time correction during radiation delivery, necessitating particle transport algorithms that yield precise dose distributions in sub-second times even in highly heterogeneous patient geometries. This is infeasible with currently available, purely physics based simulations. In this study, we present a data-driven dose calculation algorithm predicting the dose deposited by mono-energetic proton beams for arbitrary energies and patient geometries. Our approach frames particle transport as sequence modeling, where convolutional layers extract important spatial features into tokens and the transformer self-attention mechanism routes information between such tokens in the sequence and a beam energy token. We train our network and evaluate prediction accuracy using computationally expensive but accurate Monte Carlo (MC) simulations, considered the gold standard in particle physics. Our proposed model is 33 times faster than current clinical analytic pencil beam algorithms, improving upon their accuracy in the most heterogeneous and challenging geometries. With a relative error of 0.34% and very high gamma pass rate of 99.59% (1%, 3 mm), it also greatly outperforms the only published similar data-driven proton dose algorithm, even at a finer grid resolution. Offering MC precision 400 times faster, our model could overcome a major obstacle that has so far prohibited real-time adaptive proton treatments and significantly increase cancer treatment efficacy. Its potential to model physics interactions of other particles could also boost heavy ion treatment planning procedures limited by the speed of traditional methods.

One of the main problems with biomedical signals is the limited amount of patient-specific data and the significant amount of time needed to record the sufficient number of samples needed for diagnostic and treatment purposes. In this study, we present a framework to simultaneously generate and classify biomedical time series based on a modified Adversarial Autoencoder (AAE) algorithm and one-dimensional convolutions. Our work is based on breathing time series, with specific motivation to capture breathing motion during radiotherapy lung cancer treatments. First, we explore the potential in using the Variational Autoencoder (VAE) and AAE algorithms to model breathing from individual patients. We extend the AAE algorithm to allow joint semi-supervised classification and generation of different types of signals. To simplify the modeling task, we introduce a pre-processing and post-processing compressing algorithm that transforms the multi-dimensional time series into vectors containing time and position values, which are transformed back into time series through an additional neural network. By incorporating few labeled samples during training, our model outperforms other purely discriminative networks in classifying breathing baseline shift irregularities from a dataset completely different from the training set. To our knowledge, the presented framework is the first approach that unifies generation and classification within a single model for this type of biomedical data, enabling both computer aided diagnosis and augmentation of labeled samples within a single framework.

In a previous paper (Lathouwers and Perk\'o, 2019) we have developed an efficient angular multigrid preconditioner for the Boltzmann transport equation with forward-peaked scatter modeled by the Fokker-Planck approximation. The discretization was based on a completely discontinuous Galerkin finite element scheme both for space and angle. The scheme was found to be highly effective on isotropically and anisotropically refined angular meshes. The purpose of this paper is to extend the method to non-Fokker-Planck models describing the forward scatter by general Legendre expansions. As smoother the standard source iteration is used whereas solution on the coarsest angular mesh is effected by a special sweep procedure that is able to solve this problem with highly anisotropic scatter using only a small number of iterations. An efficient scheme is obtained by lowering the scatter order in the multigrid preconditioner. A set of test problems is presented to illustrate the effectivity of the method, i.e. in less iterations than the single-mesh case and more importantly with reduced computational effort.