Justin Roper

Shaoyan Pan, Chih-Wei Chang, Junbo Peng et al.

This study aims to develop a novel Cycle-guided Denoising Diffusion Probability Model (CG-DDPM) for cross-modality MRI synthesis. The CG-DDPM deploys two DDPMs that condition each other to generate synthetic images from two different MRI pulse sequences. The two DDPMs exchange random latent noise in the reverse processes, which helps to regularize both DDPMs and generate matching images in two modalities. This improves image-to-image translation ac-curacy. We evaluated the CG-DDPM quantitatively using mean absolute error (MAE), multi-scale structural similarity index measure (MSSIM), and peak sig-nal-to-noise ratio (PSNR), as well as the network synthesis consistency, on the BraTS2020 dataset. Our proposed method showed high accuracy and reliable consistency for MRI synthesis. In addition, we compared the CG-DDPM with several other state-of-the-art networks and demonstrated statistically significant improvements in the image quality of synthetic MRIs. The proposed method enhances the capability of current multimodal MRI synthesis approaches, which could contribute to more accurate diagnosis and better treatment planning for patients by synthesizing additional MRI modalities.

Shaoyan Pan, Elham Abouei, Junbo Peng et al.

Objective: Positron Emission Tomography (PET) has been a commonly used imaging modality in broad clinical applications. One of the most important tradeoffs in PET imaging is between image quality and radiation dose: high image quality comes with high radiation exposure. Improving image quality is desirable for all clinical applications while minimizing radiation exposure is needed to reduce risk to patients. Approach: We introduce PET Consistency Model (PET-CM), an efficient diffusion-based method for generating high-quality full-dose PET images from low-dose PET images. It employs a two-step process, adding Gaussian noise to full-dose PET images in the forward diffusion, and then denoising them using a PET Shifted-window Vision Transformer (PET-VIT) network in the reverse diffusion. The PET-VIT network learns a consistency function that enables direct denoising of Gaussian noise into clean full-dose PET images. PET-CM achieves state-of-the-art image quality while requiring significantly less computation time than other methods. Results: In experiments comparing eighth-dose to full-dose images, PET-CM demonstrated impressive performance with NMAE of 1.278+/-0.122%, PSNR of 33.783+/-0.824dB, SSIM of 0.964+/-0.009, NCC of 0.968+/-0.011, HRS of 4.543, and SUV Error of 0.255+/-0.318%, with an average generation time of 62 seconds per patient. This is a significant improvement compared to the state-of-the-art diffusion-based model with PET-CM reaching this result 12x faster. Similarly, in the quarter-dose to full-dose image experiments, PET-CM delivered competitive outcomes, achieving an NMAE of 0.973+/-0.066%, PSNR of 36.172+/-0.801dB, SSIM of 0.984+/-0.004, NCC of 0.990+/-0.005, HRS of 4.428, and SUV Error of 0.151+/-0.192% using the same generation process, which underlining its high quantitative and clinical precision in both denoising scenario.

Huiqiao Xie, Yang Lei, Yabo Fu et al.

CBCTs in image-guided radiotherapy provide crucial anatomy information for patient setup and plan evaluation. Longitudinal CBCT image registration could quantify the inter-fractional anatomic changes. The purpose of this study is to propose an unsupervised deep learning based CBCT-CBCT deformable image registration. The proposed deformable registration workflow consists of training and inference stages that share the same feed-forward path through a spatial transformation-based network (STN). The STN consists of a global generative adversarial network (GlobalGAN) and a local GAN (LocalGAN) to predict the coarse- and fine-scale motions, respectively. The network was trained by minimizing the image similarity loss and the deformable vector field (DVF) regularization loss without the supervision of ground truth DVFs. During the inference stage, patches of local DVF were predicted by the trained LocalGAN and fused to form a whole-image DVF. The local whole-image DVF was subsequently combined with the GlobalGAN generated DVF to obtain final DVF. The proposed method was evaluated using 100 fractional CBCTs from 20 abdominal cancer patients in the experiments and 105 fractional CBCTs from a cohort of 21 different abdominal cancer patients in a holdout test. Qualitatively, the registration results show great alignment between the deformed CBCT images and the target CBCT image. Quantitatively, the average target registration error (TRE) calculated on the fiducial markers and manually identified landmarks was 1.91+-1.11 mm. The average mean absolute error (MAE), normalized cross correlation (NCC) between the deformed CBCT and target CBCT were 33.42+-7.48 HU, 0.94+-0.04, respectively. This promising registration method could provide fast and accurate longitudinal CBCT alignment to facilitate inter-fractional anatomic changes analysis and prediction.

Yuheng Li, Jacob Wynne, Jing Wang et al.

Biparametric magnetic resonance imaging (bpMRI) has demonstrated promising results in prostate cancer (PCa) detection using convolutional neural networks (CNNs). Recently, transformers have achieved competitive performance compared to CNNs in computer vision. Large scale transformers need abundant annotated data for training, which are difficult to obtain in medical imaging. Self-supervised learning (SSL) utilizes unlabeled data to generate meaningful semantic representations without the need for costly annotations, enhancing model performance on tasks with limited labeled data. We introduce a novel end-to-end Cross-Shaped windows (CSwin) transformer UNet model, CSwin UNet, to detect clinically significant prostate cancer (csPCa) in prostate bi-parametric MR imaging (bpMRI) and demonstrate the effectiveness of our proposed self-supervised pre-training framework. Using a large prostate bpMRI dataset with 1500 patients, we first pretrain CSwin transformer using multi-task self-supervised learning to improve data-efficiency and network generalizability. We then finetune using lesion annotations to perform csPCa detection. Five-fold cross validation shows that self-supervised CSwin UNet achieves 0.888 AUC and 0.545 Average Precision (AP), significantly outperforming four comparable models (Swin UNETR, DynUNet, Attention UNet, UNet). Using a separate bpMRI dataset with 158 patients, we evaluate our method robustness to external hold-out data. Self-supervised CSwin UNet achieves 0.79 AUC and 0.45 AP, still outperforming all other comparable methods and demonstrating good generalization to external data.

Shansong Wang, Mojtaba Safari, Qiang Li et al.

Vision foundation models (VFMs) are pre-trained on extensive image datasets to learn general representations for diverse types of data. These models can subsequently be fine-tuned for specific downstream tasks, significantly boosting performance across a broad range of applications. However, existing vision foundation models that claim to be applicable to various clinical tasks are mostly pre-trained on 3D computed tomography (CT), which benefits from the availability of extensive 3D CT databases. Significant differences between CT and magnetic resonance imaging (MRI) in imaging principles, signal characteristics, and data distribution may hinder their practical performance and versatility in MRI-specific applications. Here, we propose Triad, a vision foundation model for 3D MRI. Triad adopts a widely used autoencoder architecture to learn robust representations from 131,170 3D MRI volumes and uses organ-independent imaging descriptions to constrain the semantic distribution of the visual modality. The above pre-training dataset is called Triad-131K, which is currently the largest 3D MRI pre-training dataset. We evaluate Triad across three tasks, namely, organ/tumor segmentation, organ/cancer classification, and medical image registration, in two data modalities (within-domain and out-of-domain) settings using 25 downstream datasets. By initializing models with Triad's pre-trained weights, nnUNet-Triad improves segmentation performance by 2.51% compared to nnUNet-Scratch across 17 datasets. Swin-B-Triad achieves a 3.97% improvement over Swin-B-Scratch in classification tasks across five datasets. SwinUNETR-Triad improves by 4.00% compared to SwinUNETR-Scratch in registration tasks across two datasets. Our study demonstrates that pre-training can improve performance when the data modalities and organs of upstream and downstream tasks are consistent.

Shansong Wang, Zhecheng Jin, Mingzhe Hu et al.

CLIP models pretrained on natural images with billion-scale image-text pairs have demonstrated impressive capabilities in zero-shot classification, cross-modal retrieval, and open-ended visual answering. However, transferring this success to biomedicine is hindered by the scarcity of large-scale biomedical image-text corpora, the heterogeneity of image modalities, and fragmented data standards across institutions. These limitations hinder the development of a unified and generalizable biomedical foundation model trained from scratch. To overcome this, we introduce MMKD-CLIP, a generalist biomedical foundation model developed via Multiple Medical CLIP Knowledge Distillation. Rather than relying on billion-scale raw data, MMKD-CLIP distills knowledge from nine state-of-the-art domain-specific or generalist biomedical CLIP models, each pretrained on millions of biomedical image-text pairs. Our two-stage training pipeline first performs CLIP-style pretraining on over 2.9 million biomedical image-text pairs from 26 image modalities, followed by feature-level distillation using over 19.2 million feature pairs extracted from teacher models. We evaluate MMKD-CLIP on 58 diverse biomedical datasets, encompassing over 10.8 million biomedical images across nine image modalities. The evaluation spans six core task types: zero-shot classification, linear probing, cross-modal retrieval, visual question answering, survival prediction, and cancer diagnosis. MMKD-CLIP consistently outperforms all teacher models while demonstrating remarkable robustness and generalization across image domains and task settings. These results underscore that multi-teacher knowledge distillation is a scalable and effective paradigm for building high-performing biomedical foundation models under the practical constraints of real-world data availability.

Yang Lei, Luke A. Matkovic, Justin Roper et al.

This paper aims to create a deep learning framework that can estimate the deformation vector field (DVF) for directly registering abdominal MRI-CT images. The proposed method assumed a diffeomorphic deformation. By using topology-preserved deformation features extracted from the probabilistic diffeomorphic registration model, abdominal motion can be accurately obtained and utilized for DVF estimation. The model integrated Swin transformers, which have demonstrated superior performance in motion tracking, into the convolutional neural network (CNN) for deformation feature extraction. The model was optimized using a cross-modality image similarity loss and a surface matching loss. To compute the image loss, a modality-independent neighborhood descriptor (MIND) was used between the deformed MRI and CT images. The surface matching loss was determined by measuring the distance between the warped coordinates of the surfaces of contoured structures on the MRI and CT images. The deformed MRI image was assessed against the CT image using the target registration error (TRE), Dice similarity coefficient (DSC), and mean surface distance (MSD) between the deformed contours of the MRI image and manual contours of the CT image. When compared to only rigid registration, DIR with the proposed method resulted in an increase of the mean DSC values of the liver and portal vein from 0.850 and 0.628 to 0.903 and 0.763, a decrease of the mean MSD of the liver from 7.216 mm to 3.232 mm, and a decrease of the TRE from 26.238 mm to 8.492 mm. The proposed deformable image registration method based on a diffeomorphic transformer provides an effective and efficient way to generate an accurate DVF from an MRI-CT image pair of the abdomen. It could be utilized in the current treatment planning workflow for liver radiotherapy.

Yuan Gao, Shaoyan Pan, Mingzhe Hu et al.

Cone-beam CT (CBCT) is widely used in clinical radiotherapy for image-guided treatment, improving setup accuracy, adaptive planning, and motion management. However, slow gantry rotation limits performance by introducing motion artifacts, blurring, and increased dose. This work aims to develop a clinically feasible method for reconstructing high-quality CBCT volumes from consecutive limited-angle acquisitions, addressing imaging challenges in time- or dose-constrained settings. We propose a limited-angle (LA) geometry-integrated cycle-domain (LA-GICD) framework for CBCT reconstruction, comprising two denoising diffusion probabilistic models (DDPMs) connected via analytic cone-beam forward and back projectors. A Projection-DDPM completes missing projections, followed by back-projection, and an Image-DDPM refines the volume. This dual-domain design leverages complementary priors from projection and image spaces to achieve high-quality reconstructions from limited-angle (<= 90 degrees) scans. Performance was evaluated against full-angle reconstruction. Four board-certified medical physicists conducted assessments. A total of 78 planning CTs in common CBCT geometries were used for training and evaluation. The method achieved a mean absolute error of 35.5 HU, SSIM of 0.84, and PSNR of 29.8 dB, with visibly reduced artifacts and improved soft-tissue clarity. LA-GICD's geometry-aware dual-domain learning, embedded in analytic forward/backward operators, enabled artifact-free, high-contrast reconstructions from a single 90-degree scan, reducing acquisition time and dose four-fold. LA-GICD improves limited-angle CBCT reconstruction with strong data fidelity and anatomical realism. It offers a practical solution for short-arc acquisitions, enhancing CBCT use in radiotherapy by providing clinically applicable images with reduced scan time and dose for more accurate, personalized treatments.

Zach Eidex, Mojtaba Safari, Jie Ding et al.

Objective: Gadolinium-based contrast agents (GBCAs) are commonly employed with T1w MRI to enhance lesion visualization but are restricted in patients at risk of nephrogenic systemic fibrosis and variations in GBCA administration can introduce imaging inconsistencies. This study develops an efficient 3D deep-learning framework to generate T1-contrast enhanced images (T1C) from pre-contrast multiparametric MRI. Approach: We propose the 3D latent rectified flow (T1C-RFlow) model for generating high-quality T1C images. First, T1w and T2-FLAIR images are input into a pretrained autoencoder to acquire an efficient latent space representation. A rectified flow diffusion model is then trained in this latent space representation. The T1C-RFlow model was trained on a curated dataset comprised of the BraTS 2024 glioma (GLI; 1480 patients), meningioma (MEN; 1141 patients), and metastases (MET; 1475 patients) datasets. Selected patients were split into train (N=2860), validation (N=612), and test (N=614) sets. Results: Both qualitative and quantitative results demonstrate that the T1C-RFlow model outperforms benchmark 3D models (pix2pix, DDPM, Diffusion Transformers (DiT-3D)) trained in the same latent space. T1C-RFlow achieved the following metrics - GLI: NMSE 0.044 +/- 0.047, SSIM 0.935 +/- 0.025; MEN: NMSE 0.046 +/- 0.029, SSIM 0.937 +/- 0.021; MET: NMSE 0.098 +/- 0.088, SSIM 0.905 +/- 0.082. T1C-RFlow had the best tumor reconstruction performance and significantly faster denoising times (6.9 s/volume, 200 steps) than conventional DDPM models in both latent space (37.7s, 1000 steps) and patch-based in image space (4.3 hr/volume). Significance: Our proposed method generates synthetic T1C images that closely resemble ground truth T1C in much less time than previous diffusion models. Further development may permit a practical method for contrast-agent-free MRI for brain tumors.

Mingzhe Hu, Yuan Gao, Yuheng Li et al.

Purpose: Accurate segmentation of clinical target volumes (CTV) and organs-at-risk is crucial for optimizing gynecologic brachytherapy (GYN-BT) treatment planning. However, anatomical variability, low soft-tissue contrast in CT imaging, and limited annotated datasets pose significant challenges. This study presents GynBTNet, a novel multi-stage learning framework designed to enhance segmentation performance through self-supervised pretraining and hierarchical fine-tuning strategies. Methods: GynBTNet employs a three-stage training strategy: (1) self-supervised pretraining on large-scale CT datasets using sparse submanifold convolution to capture robust anatomical representations, (2) supervised fine-tuning on a comprehensive multi-organ segmentation dataset to refine feature extraction, and (3) task-specific fine-tuning on a dedicated GYN-BT dataset to optimize segmentation performance for clinical applications. The model was evaluated against state-of-the-art methods using the Dice Similarity Coefficient (DSC), 95th percentile Hausdorff Distance (HD95), and Average Surface Distance (ASD). Results: Our GynBTNet achieved superior segmentation performance, significantly outperforming nnU-Net and Swin-UNETR. Notably, it yielded a DSC of 0.837 +/- 0.068 for CTV, 0.940 +/- 0.052 for the bladder, 0.842 +/- 0.070 for the rectum, and 0.871 +/- 0.047 for the uterus, with reduced HD95 and ASD compared to baseline models. Self-supervised pretraining led to consistent performance improvements, particularly for structures with complex boundaries. However, segmentation of the sigmoid colon remained challenging, likely due to anatomical ambiguities and inter-patient variability. Statistical significance analysis confirmed that GynBTNet's improvements were significant compared to baseline models.

Shaoyan Pan, Elham Abouei, Jacob Wynne et al.

Magnetic resonance imaging (MRI)-based synthetic computed tomography (sCT) simplifies radiation therapy treatment planning by eliminating the need for CT simulation and error-prone image registration, ultimately reducing patient radiation dose and setup uncertainty. We propose an MRI-to-CT transformer-based denoising diffusion probabilistic model (MC-DDPM) to transform MRI into high-quality sCT to facilitate radiation treatment planning. MC-DDPM implements diffusion processes with a shifted-window transformer network to generate sCT from MRI. The proposed model consists of two processes: a forward process which adds Gaussian noise to real CT scans, and a reverse process in which a shifted-window transformer V-net (Swin-Vnet) denoises the noisy CT scans conditioned on the MRI from the same patient to produce noise-free CT scans. With an optimally trained Swin-Vnet, the reverse diffusion process was used to generate sCT scans matching MRI anatomy. We evaluated the proposed method by generating sCT from MRI on a brain dataset and a prostate dataset. Qualitative evaluation was performed using the mean absolute error (MAE) of Hounsfield unit (HU), peak signal to noise ratio (PSNR), multi-scale Structure Similarity index (MS-SSIM) and normalized cross correlation (NCC) indexes between ground truth CTs and sCTs. MC-DDPM generated brain sCTs with state-of-the-art quantitative results with MAE 43.317 HU, PSNR 27.046 dB, SSIM 0.965, and NCC 0.983. For the prostate dataset, MC-DDPM achieved MAE 59.953 HU, PSNR 26.920 dB, SSIM 0.849, and NCC 0.948. In conclusion, we have developed and validated a novel approach for generating CT images from routine MRIs using a transformer-based DDPM. This model effectively captures the complex relationship between CT and MRI images, allowing for robust and high-quality synthetic CT (sCT) images to be generated in minutes.