Mojtaba Safari

Zach Eidex, Mojtaba Safari, Jacob Wynne et al.

Purpose: Apparent diffusion coefficient (ADC) maps derived from diffusion weighted (DWI) MRI provides functional measurements about the water molecules in tissues. However, DWI is time consuming and very susceptible to image artifacts, leading to inaccurate ADC measurements. This study aims to develop a deep learning framework to synthesize ADC maps from multi-parametric MR images. Methods: We proposed the multiparametric residual vision transformer model (MPR-ViT) that leverages the long-range context of ViT layers along with the precision of convolutional operators. Residual blocks throughout the network significantly increasing the representational power of the model. The MPR-ViT model was applied to T1w and T2- fluid attenuated inversion recovery images of 501 glioma cases from a publicly available dataset including preprocessed ADC maps. Selected patients were divided into training (N=400), validation (N=50) and test (N=51) sets, respectively. Using the preprocessed ADC maps as ground truth, model performance was evaluated and compared against the Vision Convolutional Transformer (VCT) and residual vision transformer (ResViT) models. Results: The results are as follows using T1w + T2-FLAIR MRI as inputs: MPR-ViT - PSNR: 31.0 +/- 2.1, MSE: 0.009 +/- 0.0005, SSIM: 0.950 +/- 0.015. In addition, ablation studies showed the relative impact on performance of each input sequence. Both qualitative and quantitative results indicate that the proposed MR- ViT model performs favorably against the ground truth data. Conclusion: We show that high-quality ADC maps can be synthesized from structural MRI using a MPR- VCT model. Our predicted images show better conformality to the ground truth volume than ResViT and VCT predictions. These high-quality synthetic ADC maps would be particularly useful for disease diagnosis and intervention, especially when ADC maps have artifacts or are unavailable.

Zach Eidex, Mojtaba Safari, Richard L. J. Qiu et al.

Objective: Gadolinium-based contrast agents (GBCAs) are commonly used in MRI scans of patients with gliomas to enhance brain tumor characterization using T1-weighted (T1W) MRI. However, there is growing concern about GBCA toxicity. This study develops a deep-learning framework to generate T1-postcontrast (T1C) from pre-contrast multiparametric MRI. Approach: We propose the tumor-aware vision transformer (TA-ViT) model that predicts high-quality T1C images. The predicted tumor region is significantly improved (P < .001) by conditioning the transformer layers from predicted segmentation maps through adaptive layer norm zero mechanism. The predicted segmentation maps were generated with the multi-parametric residual (MPR) ViT model and transformed into a latent space to produce compressed, feature-rich representations. The TA-ViT model predicted T1C MRI images of 501 glioma cases. Selected patients were split into training (N=400), validation (N=50), and test (N=51) sets. Main Results: Both qualitative and quantitative results demonstrate that the TA-ViT model performs superior against the benchmark MRP-ViT model. Our method produces synthetic T1C MRI with high soft tissue contrast and more accurately reconstructs both the tumor and whole brain volumes. The synthesized T1C images achieved remarkable improvements in both tumor and healthy tissue regions compared to the MRP-ViT model. For healthy tissue and tumor regions, the results were as follows: NMSE: 8.53 +/- 4.61E-4; PSNR: 31.2 +/- 2.2; NCC: 0.908 +/- .041 and NMSE: 1.22 +/- 1.27E-4, PSNR: 41.3 +/- 4.7, and NCC: 0.879 +/- 0.042, respectively. Significance: The proposed method generates synthetic T1C images that closely resemble real T1C images. Future development and application of this approach may enable contrast-agent-free MRI for brain tumor patients, eliminating the risk of GBCA toxicity and simplifying the MRI scan protocol.

Mojtaba Safari, Shansong Wang, Vanessa L Wildman et al.

Background: High-resolution MRI is critical for diagnosis, but long acquisition times limit clinical use. Super-resolution (SR) can enhance resolution post-scan, yet existing deep learning methods face fidelity-efficiency trade-offs. Purpose: To develop a computationally efficient and accurate deep learning framework for MRI SR that preserves anatomical detail for clinical integration. Materials and Methods: We propose a novel SR framework combining multi-head selective state-space models (MHSSM) with a lightweight channel MLP. The model uses 2D patch extraction with hybrid scanning to capture long-range dependencies. Each MambaFormer block integrates MHSSM, depthwise convolutions, and gated channel mixing. Evaluation used 7T brain T1 MP2RAGE maps (n=142) and 1.5T prostate T2w MRI (n=334). Comparisons included Bicubic interpolation, GANs (CycleGAN, Pix2pix, SPSR), transformers (SwinIR), Mamba (MambaIR), and diffusion models (I2SB, Res-SRDiff). Results: Our model achieved superior performance with exceptional efficiency. For 7T brain data: SSIM=0.951+-0.021, PSNR=26.90+-1.41 dB, LPIPS=0.076+-0.022, GMSD=0.083+-0.017, significantly outperforming all baselines (p<0.001). For prostate data: SSIM=0.770+-0.049, PSNR=27.15+-2.19 dB, LPIPS=0.190+-0.095, GMSD=0.087+-0.013. The framework used only 0.9M parameters and 57 GFLOPs, reducing parameters by 99.8% and computation by 97.5% versus Res-SRDiff, while outperforming SwinIR and MambaIR in accuracy and efficiency. Conclusion: The proposed framework provides an efficient, accurate MRI SR solution, delivering enhanced anatomical detail across datasets. Its low computational demand and state-of-the-art performance show strong potential for clinical translation.

Mojtaba Safari, Shansong Wang, Zach Eidex et al.

Objective:This study introduces a residual error-shifting mechanism that drastically reduces sampling steps while preserving critical anatomical details, thus accelerating MRI reconstruction. Approach:We propose a novel diffusion-based SR framework called Res-SRDiff, which integrates residual error shifting into the forward diffusion process. This enables efficient HR image reconstruction by aligning the degraded HR and LR distributions.We evaluated Res-SRDiff on ultra-high-field brain T1 MP2RAGE maps and T2-weighted prostate images, comparing it with Bicubic, Pix2pix, CycleGAN, and a conventional denoising diffusion probabilistic model with vision transformer backbone (TM-DDPM), using quantitative metrics such as peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), gradient magnitude similarity deviation (GMSD), and learned perceptual image patch similarity (LPIPS). Main results: Res-SRDiff significantly outperformed all comparative methods in terms of PSNR, SSIM, and GMSD across both datasets, with statistically significant improvements (p-values<<0.05). The model achieved high-fidelity image restoration with only four sampling steps, drastically reducing computational time to under one second per slice, which is substantially faster than conventional TM-DDPM with around 20 seconds per slice. Qualitative analyses further demonstrated that Res-SRDiff effectively preserved fine anatomical details and lesion morphology in both brain and pelvic MRI images. Significance: Our findings show that Res-SRDiff is an efficient and accurate MRI SR method, markedly improving computational efficiency and image quality. Integrating residual error shifting into the diffusion process allows for rapid and robust HR image reconstruction, enhancing clinical MRI workflows and advancing medical imaging research. The source at:https://github.com/mosaf/Res-SRDiff

Yifei Zhang, Jiashuo Zhang, Mojtaba Safari et al.

Low-dose chest computed tomography (LDCT) inherently captures both pulmonary and cardiac structures, offering a unique opportunity for joint assessment of lung and cardiovascular health. However, most existing approaches treat these domains as independent tasks, overlooking their physiological interplay and shared imaging biomarkers. We propose an Explainable Cross-Disease Reasoning Framework that enables interpretable cardiopulmonary risk assessment from a single LDCT scan. The framework introduces an agentic reasoning process that emulates clinical diagnostic thinking-first perceiving pulmonary findings, then reasoning through established medical knowledge, and finally deriving a cardiovascular judgment with explanatory rationale. It integrates three synergistic components: a pulmonary perception module that summarizes lung abnormalities, a knowledge-guided reasoning module that infers their cardiovascular implications, and a cardiac representation module that encodes structural biomarkers. Their outputs are fused to produce a holistic cardiovascular risk prediction that is both accurate and physiologically grounded. Experiments on the NLST cohort demonstrate that the proposed framework achieves state-of-the-art performance for CVD screening and mortality prediction, outperforming single-disease and purely image-based baselines. Beyond quantitative gains, the framework provides human-verifiable reasoning that aligns with cardiological understanding, revealing coherent links between pulmonary abnormalities and cardiac stress mechanisms. Overall, this work establishes a unified and explainable paradigm for cardiovascular analysis from LDCT, bridging the gap between image-based prediction and mechanism-based medical interpretation.

Shansong Wang, Mingzhe Hu, Qiang Li et al.

Recent advances in large language models (LLMs) have enabled general-purpose systems to perform increasingly complex domain-specific reasoning without extensive fine-tuning. In the medical domain, decision-making often requires integrating heterogeneous information sources, including patient narratives, structured data, and medical images. This study positions GPT-5 as a generalist multimodal reasoner for medical decision support and systematically evaluates its zero-shot chain-of-thought reasoning performance on both text-based question answering and visual question answering tasks under a unified protocol. We benchmark GPT-5, GPT-5-mini, GPT-5-nano, and GPT-4o-2024-11-20 against standardized splits of MedQA, MedXpertQA (text and multimodal), MMLU medical subsets, USMLE self-assessment exams, and VQA-RAD. Results show that GPT-5 consistently outperforms all baselines, achieving state-of-the-art accuracy across all QA benchmarks and delivering substantial gains in multimodal reasoning. On MedXpertQA MM, GPT-5 improves reasoning and understanding scores by +29.26% and +26.18% over GPT-4o, respectively, and surpasses pre-licensed human experts by +24.23% in reasoning and +29.40% in understanding. In contrast, GPT-4o remains below human expert performance in most dimensions. A representative case study demonstrates GPT-5's ability to integrate visual and textual cues into a coherent diagnostic reasoning chain, recommending appropriate high-stakes interventions. Our results show that, on these controlled multimodal reasoning benchmarks, GPT-5 moves from human-comparable to above human-expert performance. This improvement may substantially inform the design of future clinical decision-support systems.

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.

Mingzhe Hu, Zach Eidex, Shansong Wang et al.

Radiology, radiation oncology, and medical physics require decision-making that integrates medical images, textual reports, and quantitative data under high-stakes conditions. With the introduction of GPT-5, it is critical to assess whether recent advances in large multimodal models translate into measurable gains in these safety-critical domains. We present a targeted zero-shot evaluation of GPT-5 and its smaller variants (GPT-5-mini, GPT-5-nano) against GPT-4o across three representative tasks. We present a targeted zero-shot evaluation of GPT-5 and its smaller variants (GPT-5-mini, GPT-5-nano) against GPT-4o across three representative tasks: (1) VQA-RAD, a benchmark for visual question answering in radiology; (2) SLAKE, a semantically annotated, multilingual VQA dataset testing cross-modal grounding; and (3) a curated Medical Physics Board Examination-style dataset of 150 multiple-choice questions spanning treatment planning, dosimetry, imaging, and quality assurance. Across all datasets, GPT-5 achieved the highest accuracy, with substantial gains over GPT-4o up to +20.00% in challenging anatomical regions such as the chest-mediastinal, +13.60% in lung-focused questions, and +11.44% in brain-tissue interpretation. On the board-style physics questions, GPT-5 attained 90.7% accuracy (136/150), exceeding the estimated human passing threshold, while GPT-4o trailed at 78.0%. These results demonstrate that GPT-5 delivers consistent and often pronounced performance improvements over GPT-4o in both image-grounded reasoning and domain-specific numerical problem-solving, highlighting its potential to augment expert workflows in medical imaging and therapeutic physics.

Alexandru Florea, Shansong Wang, Mingzhe Hu et al.

The transition from task-specific artificial intelligence toward general-purpose foundation models raises fundamental questions about their capacity to support the integrated reasoning required in clinical medicine, where diagnosis demands synthesis of ambiguous patient narratives, laboratory data, and multimodal imaging. This landscape commentary provides the first controlled, cross-sectional evaluation of the GPT-5 family (GPT-5, GPT-5 Mini, GPT-5 Nano) against its predecessor GPT-4o across a diverse spectrum of clinically grounded tasks, including medical education examinations, text-based reasoning benchmarks, and visual question-answering in neuroradiology, digital pathology, and mammography using a standardized zero-shot chain-of-thought protocol. GPT-5 demonstrated substantial gains in expert-level textual reasoning, with absolute improvements exceeding 25 percentage-points on MedXpertQA. When tasked with multimodal synthesis, GPT-5 effectively leveraged this enhanced reasoning capacity to ground uncertain clinical narratives in concrete imaging evidence, achieving state-of-the-art or competitive performance across most VQA benchmarks and outperforming GPT-4o by margins of 10-40% in mammography tasks requiring fine-grained lesion characterization. However, performance remained moderate in neuroradiology (44% macro-average accuracy) and lagged behind domain-specific models in mammography, where specialized systems exceed 80% accuracy compared to GPT-5's 52-64%. These findings indicate that while GPT-5 represents a meaningful advance toward integrated multimodal clinical reasoning, mirroring the clinician's cognitive process of biasing uncertain information with objective findings, generalist models are not yet substitutes for purpose-built systems in highly specialized, perception-critical tasks.

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.

Mojtaba Safari, Shansong Wang, Qiang Li et al.

Objective. Motion artifacts in brain MRI, mainly from rigid head motion, degrade image quality and hinder downstream applications. Conventional methods to mitigate these artifacts, including repeated acquisitions or motion tracking, impose workflow burdens. This study introduces Res-MoCoDiff, an efficient denoising diffusion probabilistic model specifically designed for MRI motion artifact correction.Approach.Res-MoCoDiff exploits a novel residual error shifting mechanism during the forward diffusion process to incorporate information from motion-corrupted images. This mechanism allows the model to simulate the evolution of noise with a probability distribution closely matching that of the corrupted data, enabling a reverse diffusion process that requires only four steps. The model employs a U-net backbone, with attention layers replaced by Swin Transformer blocks, to enhance robustness across resolutions. Furthermore, the training process integrates a combined l1+l2 loss function, which promotes image sharpness and reduces pixel-level errors. Res-MoCoDiff was evaluated on both an in-silico dataset generated using a realistic motion simulation framework and an in-vivo MR-ART dataset. Comparative analyses were conducted against established methods, including CycleGAN, Pix2pix, and a diffusion model with a vision transformer backbone, using quantitative metrics such as PSNR, SSIM, and NMSE.Main results. The proposed method demonstrated superior performance in removing motion artifacts across minor, moderate, and heavy distortion levels. Res-MoCoDiff consistently achieved the highest SSIM and the lowest NMSE values, with a PSNR of up to 41.91+-2.94 dB for minor distortions. Notably, the average sampling time was reduced to 0.37 seconds per batch of two image slices, compared with 101.74 seconds for conventional approaches.

Mojtaba Safari, Zach Eidex, Shaoyan Pan et al.

Purpose: To propose a self-supervised deep learning-based compressed sensing MRI (DL-based CS-MRI) method named "Adaptive Self-Supervised Consistency Guided Diffusion Model (ASSCGD)" to accelerate data acquisition without requiring fully sampled datasets. Materials and Methods: We used the fastMRI multi-coil brain axial T2-weighted (T2-w) dataset from 1,376 cases and single-coil brain quantitative magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) T1 maps from 318 cases to train and test our model. Robustness against domain shift was evaluated using two out-of-distribution (OOD) datasets: multi-coil brain axial postcontrast T1 -weighted (T1c) dataset from 50 cases and axial T1-weighted (T1-w) dataset from 50 patients. Data were retrospectively subsampled at acceleration rates R in {2x, 4x, 8x}. ASSCGD partitions a random sampling pattern into two disjoint sets, ensuring data consistency during training. We compared our method with ReconFormer Transformer and SS-MRI, assessing performance using normalized mean squared error (NMSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM). Statistical tests included one-way analysis of variance (ANOVA) and multi-comparison Tukey's Honesty Significant Difference (HSD) tests. Results: ASSCGD preserved fine structures and brain abnormalities visually better than comparative methods at R = 8x for both multi-coil and single-coil datasets. It achieved the lowest NMSE at R in {4x, 8x}, and the highest PSNR and SSIM values at all acceleration rates for the multi-coil dataset. Similar trends were observed for the single-coil dataset, though SSIM values were comparable to ReconFormer at R in {2x, 8x}. These results were further confirmed by the voxel-wise correlation scatter plots. OOD results showed significant (p << 10^-5 ) improvements in undersampled image quality after reconstruction.