Organizations: Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA 30308, USA · Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA
Head-and-neck (HN) proton therapy is highly sensitive to anatomical change over a 4-to-6-week course, as tumor shrinkage, weight loss, and setup variation can misposition the Bragg peak near critical organs such as the parotids, oral cavity, brainstem, and spinal cord, leading to target underdosing or organ-at-risk overdosing. Online adaptive proton therapy replans on the anatomy of the day, yet standard workflows rely on offline replanning that requires repeated CT acquisition and roughly a week of preparation, adding burden, cost, and delay. We investigate whether a patient's treatment-day anatomy can be predicted before image acquisition by transferring longitudinal change from a population database. We propose a digital-twin framework built on a pretrained foundation-model deformable registration network used without patient-specific training. A first registration aligns a prior patient's planning CT to the target and carries the prior's during-treatment quality assurance CT (QACT) into the target frame; a second registration estimates the prior's planning-to-QACT change, which is then applied to the target's own planning CT to synthesize predicted CTs (pdCTs) with propagated contours. Using 88 HN patients, each with a planning CT and three QACTs, we show that pdCTs better match treatment-day anatomy than the static planning CT. Compared with the planning CT alone, normalized cross-correlation improves by 22.8%, Dice for organs-at-risk by 20.2%, and CT-number error decreases by 23.4%. Gains are largest for patients with major anatomical change and negligible when anatomy is stable. This cross-patient motion transfer leverages the digital-twin concept to anticipate treatment-day anatomy, enabling personalized online adaptive proton therapy without repeated imaging.
Patient-specific anatomical models provide individualized context for surgical planning, image-guided intervention, and algorithm development. However, most CT-derived models are static: they preserve the body configuration captured at scan time, but cannot represent how the same anatomy would appear after patient repositioning. This limitation is especially important for radiographic imaging, where appearance depends jointly on imaging geometry and patient pose. We present a proof-of-concept for constructing a patient-specific articulated digital twin from a single full-body CT scan. The method fits a parametric human body model (SMPL) to obtain a patient-aligned kinematic scaffold, binds segmented bones and organs to an anatomy-aware rig, and retargets body-pose changes while preserving skeletal geometry. On three full-body CT subjects, the fitted scaffold achieved 15.8 ± 4.0 mm chamfer distance and 95.9 ± 1.8% skeletal enclosure. Recomposition at the acquisition pose preserved major radiographic structure, with overall SSIM of 0.872 ± 0.016 and PSNR of 18.5 ± 1.4 dB across paired DRRs. Across unseen target poses, the resulting twins enabled articulation while maintaining high skeletal enclosure (94.4 ± 0.4%). As a feasibility demonstration, we render the articulated twin as pose-dependent DRRs. These results suggest the feasibility of extending static, view-controllable CT simulation toward pose-controllable anatomical twins for future synthetic imaging and positioning studies.
Brain tumor progression exhibits spatially heterogeneous growth, patient-specific treatment response, and complex interactions with surrounding anatomy, making accurate long-term prediction challenging. We propose an AI-augmented adaptive digital twin (DT) framework for brain tumor evolution prediction and treatment scheduling. The framework integrates an interpretable reaction--diffusion (RD) model, a 3D residual learning module for model-form correction, patient-specific DT updating during recursive rollout, and model predictive control (MPC) for constrained chemotherapy and radiotherapy scheduling. Experiments on 387 synthetic tumor trajectories with 120-step evolution show that the baseline RD model captures tumor location and overall temporal behavior but underestimates heterogeneous tumor burden during long-horizon prediction. Hybrid RD--residual modeling reduces masked voxel-wise mean squared error by 84.3% and increases Dice overlap by 43.5% relative to the RD baseline under dense simulated observations. Online DT updating further reduces mean squared error by 45.9% and improves Dice overlap by 9.6% compared with the non-updated hybrid model. In MPC-based scheduling simulations, the updated DT controller reduces final tumor burden by 22.4% relative to a fixed treatment schedule under the terminal-burden objective. Together, these results demonstrate a unified framework for patient-specific initialization, mechanistic modeling, adaptive learning, and constrained treatment optimization. Although validated using patient-data-informed synthetic trajectories rather than clinical longitudinal data, the proposed framework establishes a foundation for future translation to real-world adaptive treatment planning.
In proton therapy, plans are typically optimized on a single planning CT, making robustness evaluation essential under anatomical changes. However, current scenarios often rely on simplified perturbations that poorly capture complex, patient-specific variability. We propose SynthRCT, a scalable conditional generative framework for 3D anatomical deformation synthesis. Based on a conditional variational autoencoder, SynthRCT learns a latent deformation space and decodes sampled latent codes into local stationary velocity fields conditioned on an input anatomy. Local fields are assembled into coherent full-volume transformations, enabling memory-scalable generation for large field-of-view CT data. We validate the approach on respiratory 4DCT data with multiple breathing-phase anatomies per subject. SynthRCT enables patient-specific sampling of plausible anatomical transformations beyond predefined robustness scenarios. Code available at: https://github.com/TomasGuija/SynthRCT.
Tomas Guija-Valiente, Blanca Rodriguez-Gonzalez, Norberto Malpica