Rafe McBeth

Kuancheng Wang, Hai Siong Tan, Rafe Mcbeth

The field of Radiation Oncology is uniquely positioned to benefit from the use of artificial intelligence to fully automate the creation of radiation treatment plans for cancer therapy. This time-consuming and specialized task combines patient imaging with organ and tumor segmentation to generate a 3D radiation dose distribution to meet clinical treatment goals, similar to voxel-level dense prediction. In this work, we propose Swin UNETR++, that contains a lightweight 3D Dual Cross-Attention (DCA) module to capture the intra and inter-volume relationships of each patient's unique anatomy, which fully convolutional neural networks lack. Our model was trained, validated, and tested on the Open Knowledge-Based Planning dataset. In addition to metrics of Dose Score $\overline{S_{\text{Dose}}}$ and DVH Score $\overline{S_{\text{DVH}}}$ that quantitatively measure the difference between the predicted and ground-truth 3D radiation dose distribution, we propose the qualitative metrics of average volume-wise acceptance rate $\overline{R_{\text{VA}}}$ and average patient-wise clinical acceptance rate $\overline{R_{\text{PA}}}$ to assess the clinical reliability of the predictions. Swin UNETR++ demonstrates near-state-of-the-art performance on validation and test dataset (validation: $\overline{S_{\text{DVH}}}$=1.492 Gy, $\overline{S_{\text{Dose}}}$=2.649 Gy, $\overline{R_{\text{VA}}}$=88.58%, $\overline{R_{\text{PA}}}$=100.0%; test: $\overline{S_{\text{DVH}}}$=1.634 Gy, $\overline{S_{\text{Dose}}}$=2.757 Gy, $\overline{R_{\text{VA}}}$=90.50%, $\overline{R_{\text{PA}}}$=98.0%), establishing a basis for future studies to translate 3D dose predictions into a deliverable treatment plan, facilitating full automation.

Riqiang Gao, Mamadou Diallo, Han Liu et al.

Radiotherapy (RT) planning is complex, subjective, and time-intensive. Advances with artificial intelligence (AI) promise to improve its precision and efficiency, but progress is often limited by the scarcity of large, standardized datasets. To address this, we introduce the Automated Iterative RT Planning (AIRTP) system, a scalable solution for generating high-quality treatment plans. This scalable solution is designed to generate substantial volumes of consistently high-quality treatment plans, overcoming a key obstacle in the advancement of AI-driven RT planning. Our AIRTP pipeline adheres to clinical guidelines and automates essential steps, including organ-at-risk (OAR) contouring, helper structure creation, beam setup, optimization, and plan quality improvement, using AI integrated with RT planning software like Varian Eclipse. Furthermore, a novel approach for determining optimization parameters to reproduce 3D dose distributions, i.e. a method to convert dose predictions to deliverable treatment plans constrained by machine limitations is proposed. A comparative analysis of plan quality reveals that our automated pipeline produces treatment plans of quality comparable to those generated manually, which traditionally require several hours of labor per plan. Committed to public research, the first data release of our AIRTP pipeline includes nine cohorts covering head-and-neck and lung cancer sites to support an AAPM 2025 challenge. To our best knowledge, this dataset features more than 10 times number of plans compared to the largest existing well-curated public dataset. Repo: https://github.com/RiqiangGao/GDP-HMM_AAPMChallenge.

H. S. Tan, Kuancheng Wang, Rafe Mcbeth

In this work, we study various hybrid models of entropy-based and representativeness sampling techniques in the context of active learning in medical segmentation, in particular examining the role of UMAP (Uniform Manifold Approximation and Projection) as a technique for capturing representativeness. Although UMAP has been shown viable as a general purpose dimension reduction method in diverse areas, its role in deep learning-based medical segmentation has yet been extensively explored. Using the cardiac and prostate datasets in the Medical Segmentation Decathlon for validation, we found that a novel hybrid combination of Entropy-UMAP sampling technique achieved a statistically significant Dice score advantage over the random baseline ($3.2 \%$ for cardiac, $4.5 \%$ for prostate), and attained the highest Dice coefficient among the spectrum of 10 distinct active learning methodologies we examined. This provides preliminary evidence that there is an interesting synergy between entropy-based and UMAP methods when the former precedes the latter in a hybrid model of active learning.

Hai Siong Tan, Kuancheng Wang, Rafe Mcbeth

In this work, we present a novel application of an uncertainty-quantification framework called Deep Evidential Learning in the domain of radiotherapy dose prediction. Using medical images of the Open Knowledge-Based Planning Challenge dataset, we found that this model can be effectively harnessed to yield uncertainty estimates that inherited correlations with prediction errors upon completion of network training. This was achieved only after reformulating the original loss function for a stable implementation. We found that (i)epistemic uncertainty was highly correlated with prediction errors, with various association indices comparable or stronger than those for Monte-Carlo Dropout and Deep Ensemble methods, (ii)the median error varied with uncertainty threshold much more linearly for epistemic uncertainty in Deep Evidential Learning relative to these other two conventional frameworks, indicative of a more uniformly calibrated sensitivity to model errors, (iii)relative to epistemic uncertainty, aleatoric uncertainty demonstrated a more significant shift in its distribution in response to Gaussian noise added to CT intensity, compatible with its interpretation as reflecting data noise. Collectively, our results suggest that Deep Evidential Learning is a promising approach that can endow deep-learning models in radiotherapy dose prediction with statistical robustness. Towards enhancing its clinical relevance, we demonstrate how we can use such a model to construct the predicted Dose-Volume-Histograms' confidence intervals.

Hai Siong Tan, Kuancheng Wang, Rafe McBeth

We present the fundamental theory and implementation guidelines underlying Evidential Physics-Informed Neural Network (E-PINN) -- a novel class of uncertainty-aware PINN. It leverages the marginal distribution loss function of evidential deep learning for estimating uncertainty of outputs, and infers unknown parameters of the PDE via a learned posterior distribution. Validating our model on two illustrative case studies -- the 1D Poisson equation with a Gaussian source and the 2D Fisher-KPP equation, we found that E-PINN generated empirical coverage probabilities that were calibrated significantly better than Bayesian PINN and Deep Ensemble methods. To demonstrate real-world applicability, we also present a brief case study on applying E-PINN to analyze clinical glucose-insulin datasets that have featured in medical research on diabetes pathophysiology.

Hai Siong Tan, Kuancheng Wang, Rafe McBeth

We present a novel class of Physics-Informed Neural Networks that is formulated based on the principles of Evidential Deep Learning, where the model incorporates uncertainty quantification by learning parameters of a higher-order distribution. The dependent and trainable variables of the PDE residual loss and data-fitting loss terms are recast as functions of the hyperparameters of an evidential prior distribution. Our model is equipped with an information-theoretic regularizer that contains the Kullback-Leibler divergence between two inverse-gamma distributions characterizing predictive uncertainty. Relative to Bayesian-Physics-Informed-Neural-Networks, our framework appeared to exhibit higher sensitivity to data noise, preserve boundary conditions more faithfully and yield empirical coverage probabilities closer to nominal ones. Toward examining its relevance for data mining in scientific discoveries, we demonstrate how to apply our model to inverse problems involving 1D and 2D nonlinear differential equations.

Jace Grandinetti, Rafe McBeth

Large Language Models (LLMs) have achieved remarkable progress, yet their application in specialized fields, such as medical physics, remains challenging due to the need for domain-specific knowledge. This study introduces ARCoT (Adaptable Retrieval-based Chain of Thought), a framework designed to enhance the domain-specific accuracy of LLMs without requiring fine-tuning or extensive retraining. ARCoT integrates a retrieval mechanism to access relevant domain-specific information and employs step-back and chain-of-thought prompting techniques to guide the LLM's reasoning process, ensuring more accurate and context-aware responses. Benchmarking on a medical physics multiple-choice exam, our model outperformed standard LLMs and reported average human performance, demonstrating improvements of up to 68% and achieving a high score of 90%. This method reduces hallucinations and increases domain-specific performance. The versatility and model-agnostic nature of ARCoT make it easily adaptable to various domains, showcasing its significant potential for enhancing the accuracy and reliability of LLMs in specialized fields.

Hai Siong Tan, Kuancheng Wang, Rafe Mcbeth

In this work, we examine the effectiveness of an uncertainty quantification framework known as Evidential Deep Learning applied in the context of biomedical image segmentation. This class of models involves assigning Dirichlet distributions as priors for segmentation labels, and enables a few distinct definitions of model uncertainties. Using the cardiac and prostate MRI images available in the Medical Segmentation Decathlon for validation, we found that Evidential Deep Learning models with U-Net backbones generally yielded superior correlations between prediction errors and uncertainties relative to the conventional baseline equipped with Shannon entropy measure, Monte-Carlo Dropout and Deep Ensemble methods. We also examined these models' effectiveness in active learning, finding that relative to the standard Shannon entropy-based sampling, they yielded higher point-biserial uncertainty-error correlations while attaining similar performances in Dice-Sorensen coefficients. These superior features of EDL models render them well-suited for segmentation tasks that warrant a critical sensitivity in detecting large model errors.

Ti Bai, Anjali Balagopal, Michael Dohopolski et al.

Automatic segmentation of anatomical structures is critical for many medical applications. However, the results are not always clinically acceptable and require tedious manual revision. Here, we present a novel concept called artificial intelligence assisted contour revision (AIACR) and demonstrate its feasibility. The proposed clinical workflow of AIACR is as follows given an initial contour that requires a clinicians revision, the clinician indicates where a large revision is needed, and a trained deep learning (DL) model takes this input to update the contour. This process repeats until a clinically acceptable contour is achieved. The DL model is designed to minimize the clinicians input at each iteration and to minimize the number of iterations needed to reach acceptance. In this proof-of-concept study, we demonstrated the concept on 2D axial images of three head-and-neck cancer datasets, with the clinicians input at each iteration being one mouse click on the desired location of the contour segment. The performance of the model is quantified with Dice Similarity Coefficient (DSC) and 95th percentile of Hausdorff Distance (HD95). The average DSC/HD95 (mm) of the auto-generated initial contours were 0.82/4.3, 0.73/5.6 and 0.67/11.4 for three datasets, which were improved to 0.91/2.1, 0.86/2.4 and 0.86/4.7 with three mouse clicks, respectively. Each DL-based contour update requires around 20 ms. We proposed a novel AIACR concept that uses DL models to assist clinicians in revising contours in an efficient and effective way, and we demonstrated its feasibility by using 2D axial CT images from three head-and-neck cancer datasets.

Maryam Mashayekhi, Itzel Ramirez Tapia, Anjali Balagopal et al.

Typically, the current dose prediction models are limited to small amounts of data and require re-training for a specific site, often leading to suboptimal performance. We propose a site-agnostic, 3D dose distribution prediction model using deep learning that can leverage data from any treatment site, thus increasing the total data available to train the model. Applying our proposed model to a new target treatment site requires only a brief fine-tuning of the model to the new data and involves no modifications to the model input channels or its parameters. Thus, it can be efficiently adapted to a different treatment site, even with a small training dataset.

Dan Nguyen, Azar Sadeghnejad Barkousaraie, Gyanendra Bohara et al.

Recently, artificial intelligence technologies and algorithms have become a major focus for advancements in treatment planning for radiation therapy. As these are starting to become incorporated into the clinical workflow, a major concern from clinicians is not whether the model is accurate, but whether the model can express to a human operator when it does not know if its answer is correct. We propose to use Monte Carlo dropout (MCDO) and the bootstrap aggregation (bagging) technique on deep learning models to produce uncertainty estimations for radiation therapy dose prediction. We show that both models are capable of generating a reasonable uncertainty map, and, with our proposed scaling technique, creating interpretable uncertainties and bounds on the prediction and any relevant metrics. Performance-wise, bagging provides statistically significant reduced loss value and errors in most of the metrics investigated in this study. The addition of bagging was able to further reduce errors by another 0.34% for Dmean and 0.19% for Dmax, on average, when compared to the baseline framework. Overall, the bagging framework provided significantly lower MAE of 2.62, as opposed to the baseline framework's MAE of 2.87. The usefulness of bagging, from solely a performance standpoint, does highly depend on the problem and the acceptable predictive error, and its high upfront computational cost during training should be factored in to deciding whether it is advantageous to use it. In terms of deployment with uncertainty estimations turned on, both frameworks offer the same performance time of about 12 seconds. As an ensemble-based metaheuristic, bagging can be used with existing machine learning architectures to improve stability and performance, and MCDO can be applied to any deep learning models that have dropout as part of their architecture.

Dan Nguyen, Rafe McBeth, Azar Sadeghnejad Barkousaraie et al.

We propose a novel domain specific loss, which is a differentiable loss function based on the dose volume histogram, and combine it with an adversarial loss for the training of deep neural networks to generate Pareto optimal dose distributions. The mean squared error (MSE) loss, dose volume histogram (DVH) loss, and adversarial (ADV) loss were used to train 4 instances of the neural network model: 1) MSE, 2) MSE+ADV, 3) MSE+DVH, and 4) MSE+DVH+ADV. 70 prostate patients were acquired, and the dose influence arrays were calculated for each patient. 1200 Pareto surface plans per patient were generated by pseudo-randomizing the tradeoff weights (84,000 plans total). We divided the data into 54 training, 6 validation, and 10 testing patients. Each model was trained for 100,000 iterations, with a batch size of 2. The prediction time of each model is 0.052 seconds. Quantitatively, the MSE+DVH+ADV model had the lowest prediction error of 0.038 (conformation), 0.026 (homogeneity), 0.298 (R50), 1.65% (D95), 2.14% (D98), 2.43% (D99). The MSE model had the worst prediction error of 0.134 (conformation), 0.041 (homogeneity), 0.520 (R50), 3.91% (D95), 4.33% (D98), 4.60% (D99). For both the mean dose PTV error and the max dose PTV, Body, Bladder and rectum error, the MSE+DVH+ADV outperformed all other models. All model's predictions have an average mean and max dose error less than 2.8% and 4.2%, respectively. Expert human domain specific knowledge can be the largest driver in the performance improvement, and adversarial learning can be used to further capture nuanced features. The real-time prediction capabilities allow for a physician to quickly navigate the tradeoff space, and produce a dose distribution as a tangible endpoint for the dosimetrist to use for planning. This can considerably reduce the treatment planning time, allowing for clinicians to focus their efforts on challenging cases.