Cone-Beam Computed Tomography (CBCT) is essential in medical imaging, and the Feldkamp-Davis-Kress (FDK) algorithm is a popular choice for reconstruction due to its efficiency. However, FDK is susceptible to noise and artifacts. While recent deep learning methods offer improved image quality, they often increase computational complexity and lack the interpretability of traditional methods. In this paper, we introduce an enhanced FDK-based neural network that maintains the classical algorithm's interpretability by selectively integrating trainable elements into the cosine weighting and filtering stages. Recognizing the challenge of a large parameter space inherent in 3D CBCT data, we leverage wavelet transformations to create sparse representations of the cosine weights and filters. This strategic sparsification reduces the parameter count by $93.75\%$ without compromising performance, accelerates convergence, and importantly, maintains the inference computational cost equivalent to the classical FDK algorithm. Our method not only ensures volumetric consistency and boosts robustness to noise, but is also designed for straightforward integration into existing CT reconstruction pipelines. This presents a pragmatic enhancement that can benefit clinical applications, particularly in environments with computational limitations.

This study aims to investigate the feasibility of a single general model to synthesize CT images across body sites, thorax, abdomen, and pelvis, to support treatment planning for MRI-only radiotherapy. A total of 157 patients who received MRI-guided radiation therapy in the thorax, abdomen, and pelvis on a 0.35T MRIdian Linac were included. A subset of 122 cases were used for model training and the remaining 35 cases were used for model validation. All patient datasets had semi-paired CT-simulation image and 0.35T MR image acquired using TrueFISP. A conditional generative adversarial network with a multi-planar method was used to generate synthetic CT images from 0.35T MR images. The effect of preprocessing methods (with and without bias field corrections) on the quality of synthetic CT was evaluated and found to be insignificant. The general models trained on all cases performed comparably to the site-specific models trained on individual body sites. For all models, the peak signal-to-noise ratios ranged from 31.7 to 34.9 and the structural index similarity measures ranged from 0.9547 to 0.9758. For the datasets with bias field corrections, the mean-absolute-errors in HU (general model versus site-specific model) were 49.7 ± 9.4 versus 49.5 ± 8.9, 48.7 ± 7.6 versus 43 ± 7.8 and 32.8 ± 5.5 versus 31.8 ± 5.3 for the thorax, abdomen, and pelvis, respectively. When comparing plans between synthetic CTs and ground truth CTs, the dosimetric difference was on average less than 0.5% (0.2 Gy) for target coverage and less than 2.1% (0.4 Gy) for organ-at-risk metrics for all body sites with either the general or specific models. Synthetic CT plans showed good agreement with mean gamma pass rates of >94% and >99% for 1%/1 mm and 2%/2 mm, respectively. This study has demonstrated the feasibility of using a general model for multiple body sites and the potential of using synthetic CT to support an MRI-guided radiotherapy workflow.

Multi-modal medical image fusion (MMIF) is increasingly recognized as an essential technique for enhancing diagnostic precision and facilitating effective clinical decision-making within computer-aided diagnosis systems. MMIF combines data from X-ray, MRI, CT, PET, SPECT, and ultrasound to create detailed, clinically useful images of patient anatomy and pathology. These integrated representations significantly advance diagnostic accuracy, lesion detection, and segmentation. This comprehensive review meticulously surveys the evolution, methodologies, algorithms, current advancements, and clinical applications of MMIF. We present a critical comparative analysis of traditional fusion approaches, including pixel-, feature-, and decision-level methods, and delves into recent advancements driven by deep learning, generative models, and transformer-based architectures. A critical comparative analysis is presented between these conventional methods and contemporary techniques, highlighting differences in robustness, computational efficiency, and interpretability. The article addresses extensive clinical applications across oncology, neurology, and cardiology, demonstrating MMIF's vital role in precision medicine through improved patient-specific therapeutic outcomes. Moreover, the review thoroughly investigates the persistent challenges affecting MMIF's broad adoption, including issues related to data privacy, heterogeneity, computational complexity, interpretability of AI-driven algorithms, and integration within clinical workflows. It also identifies significant future research avenues, such as the integration of explainable AI, adoption of privacy-preserving federated learning frameworks, development of real-time fusion systems, and standardization efforts for regulatory compliance.

Visual grounding is essential for precise perception and reasoning in multimodal large language models (MLLMs), especially in medical imaging domains. While existing medical visual grounding benchmarks primarily focus on single-image scenarios, real-world clinical applications often involve sequential images, where accurate lesion localization across different modalities and temporal tracking of disease progression (e.g., pre- vs. post-treatment comparison) require fine-grained cross-image semantic alignment and context-aware reasoning. To remedy the underrepresentation of image sequences in existing medical visual grounding benchmarks, we propose MedSG-Bench, the first benchmark tailored for Medical Image Sequences Grounding. It comprises eight VQA-style tasks, formulated into two paradigms of the grounding tasks, including 1) Image Difference Grounding, which focuses on detecting change regions across images, and 2) Image Consistency Grounding, which emphasizes detection of consistent or shared semantics across sequential images. MedSG-Bench covers 76 public datasets, 10 medical imaging modalities, and a wide spectrum of anatomical structures and diseases, totaling 9,630 question-answer pairs. We benchmark both general-purpose MLLMs (e.g., Qwen2.5-VL) and medical-domain specialized MLLMs (e.g., HuatuoGPT-vision), observing that even the advanced models exhibit substantial limitations in medical sequential grounding tasks. To advance this field, we construct MedSG-188K, a large-scale instruction-tuning dataset tailored for sequential visual grounding, and further develop MedSeq-Grounder, an MLLM designed to facilitate future research on fine-grained understanding across medical sequential images. The benchmark, dataset, and model are available at https://huggingface.co/MedSG-Bench

Deep learning models are increasingly being implemented for automated medical image analysis to inform patient care. Most models, however, lack uncertainty information, without which the reliability of model outputs cannot be ensured. Several uncertainty quantification (UQ) methods exist to capture model uncertainty. Yet, it is not clear which method is optimal for a given task. The purpose of this work was to investigate several commonly used UQ methods for the critical yet understudied task of metastatic lesion segmentation on whole body PET/CT. 
Approach:
59 whole body 68Ga-DOTATATE PET/CT images of patients undergoing theranostic treatment of metastatic neuroendocrine tumors were used in this work. A 3D U-Net was trained for lesion segmentation following five-fold cross validation. Uncertainty measures derived from four UQ methods-probability entropy, Monte Carlo dropout, deep ensembles, and test time augmentation-were investigated. Each uncertainty measure was assessed across four quantitative evaluations: (1) its ability to detect artificially degraded image data at low, medium, and high degradation magnitudes; (2) to detect false-positive (FP) predicted regions; (3) to recover false-negative (FN) predicted regions; and (3) to establish correlations with model biomarker extraction and segmentation performance metrics. 
Results: Test time augmentation and probability entropy respectively achieved the highest and lowest degraded image detection at low (AUC=0.54 vs. 0.68), medium (AUC=0.70 vs. 0.82), and high (AUC=0.83 vs. 0.90) degradation magnitudes. For detecting FPs, all UQ methods achieve strong performance, with AUC values ranging narrowly between 0.77 and 0.81. FN region recovery performance was strongest for test time augmentation and weakest for probability entropy. Performance for the correlation analysis was mixed, where the strongest performance was achieved by test time augmentation for SUVtotal capture (ρ=0.57) and segmentation Dice coefficient (ρ=0.72), by Monte Carlo dropout for SUVmean capture (ρ=0.35), and by probability entropy for segmentation cross entropy (ρ=0.96).
Significance: Overall, test time augmentation demonstrated superior uncertainty quantification performance and is recommended for use in metastatic lesion segmentation task. It also offers the advantage of being post hoc and computationally efficient. In contrast, probability entropy performed the worst, highlighting the need for advanced UQ approaches for this task.&#xD.

Positron Emission Tomography (PET) is an important clinical imaging tool but inevitably introduces radiation exposure to patients and healthcare providers. Reducing the tracer injection dose and eliminating the CT acquisition for attenuation correction can reduce the overall radiation dose, but often results in PET with high noise and bias. Thus, it is desirable to develop 3D methods to translate the non-attenuation-corrected low-dose PET (NAC-LDPET) into attenuation-corrected standard-dose PET (AC-SDPET). Recently, diffusion models have emerged as a new state-of-the-art deep learning method for image-to-image translation, better than traditional CNN-based methods. However, due to the high computation cost and memory burden, it is largely limited to 2D applications. To address these challenges, we developed a novel 2.5D Multi-view Averaging Diffusion Model (MADM) for 3D image-to-image translation with application on NAC-LDPET to AC-SDPET translation. Specifically, MADM employs separate diffusion models for axial, coronal, and sagittal views, whose outputs are averaged in each sampling step to ensure the 3D generation quality from multiple views. To accelerate the 3D sampling process, we also proposed a strategy to use the CNN-based 3D generation as a prior for the diffusion model. Our experimental results on human patient studies suggested that MADM can generate high-quality 3D translation images, outperforming previous CNN-based and Diffusion-based baseline methods. The code is available at https://github.com/tianqic/MADM.

Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is a multi-modality medical imaging technique widely used for screening and diagnosis of lesions and tumors, in which, CT can provide detailed anatomical structures, while PET can show metabolic activities. Nevertheless, it has disadvantages such as long scanning time, high cost, and relatively high radiation doses.

Purpose: We propose a deep learning model for the whole-body CT-to-PET synthesis task, generating high-quality synthetic PET images that are comparable to real ones in both clinical relevance and diagnostic value.

Material: We collect 102 pairs of 3D CT and PET scans, which are sliced into 27,240 pairs of 2D CT and PET images ( training: 21,855 pairs, validation: 2,810, testing: 2,575 pairs).

Methods: We propose a Transformer-enhanced Generative Adversarial Network (GAN) for whole-body CT-to-PET synthesis task. The CPGAN model uses residual blocks and Fully Connected Transformer Residual (FCTR) blocks to capture both local features and global contextual information. A customized loss function incorporating structural consistency is designed to improve the quality of synthesized PET images.

Results: Both quantitative and qualitative evaluation results demonstrate effectiveness of the CPGAN model. The mean and standard variance of NRMSE,PSNR and SSIM values on test set are (16.90 ± 12.27) × 10-4, 28.71 ± 2.67 and 0.926 ± 0.033, respectively, outperforming other seven state-of-the-art models. Three radiologists independently and blindly evaluated and gave subjective scores to 100 randomly chosen PET images (50 real and 50 synthetic). By Wilcoxon signed rank test, there are no statistical differences between the synthetic PET images and the real ones.

Conclusions: Despite the inherent limitations of CT images to directly reflect biological information of metabolic tissues, CPGAN model effectively synthesizes satisfying PET images from CT scans, which has potential in reducing the reliance on actual PET-CT scans.

We developed an AI-driven software solution to quantify metastatic bone disease from WB-DWI scans. Core technologies include: (i) a weakly-supervised Residual U-Net model generating a skeleton probability map to isolate bone; (ii) a statistical framework for WB-DWI intensity normalisation, obtaining a signal-normalised b=900s/mm^2 (b900) image; and (iii) a shallow convolutional neural network that processes outputs from (i) and (ii) to generate a mask of suspected bone lesions, characterised by higher b900 signal intensity due to restricted water diffusion. This mask is applied to the gADC map to extract TDV and gADC statistics. We tested the tool using expert-defined metastatic bone disease delineations on 66 datasets, assessed repeatability of imaging biomarkers (N=10), and compared software-based response assessment with a construct reference standard based on clinical, laboratory and imaging assessments (N=118). Dice score between manual and automated delineations was 0.6 for lesions within pelvis and spine, with an average surface distance of 2mm. Relative differences for log-transformed TDV (log-TDV) and median gADC were below 9% and 5%, respectively. Repeatability analysis showed coefficients of variation of 4.57% for log-TDV and 3.54% for median gADC, with intraclass correlation coefficients above 0.9. The software achieved 80.5% accuracy, 84.3% sensitivity, and 85.7% specificity in assessing response to treatment compared to the construct reference standard. Computation time generating a mask averaged 90 seconds per scan. Our software enables reproducible TDV and gADC quantification from WB-DWI scans for monitoring metastatic bone disease response, thus providing potentially useful measurements for clinical decision-making in APC patients.

Deep learning (DL) has become the dominant approach for medical image segmentation, yet ensuring the reliability and clinical applicability of these models requires addressing key challenges such as annotation variability, calibration, and uncertainty estimation. This is why we created the Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation (CURVAS), which highlights the critical role of multiple annotators in establishing a more comprehensive ground truth, emphasizing that segmentation is inherently subjective and that leveraging inter-annotator variability is essential for robust model evaluation. Seven teams participated in the challenge, submitting a variety of DL models evaluated using metrics such as Dice Similarity Coefficient (DSC), Expected Calibration Error (ECE), and Continuous Ranked Probability Score (CRPS). By incorporating consensus and dissensus ground truth, we assess how DL models handle uncertainty and whether their confidence estimates align with true segmentation performance. Our findings reinforce the importance of well-calibrated models, as better calibration is strongly correlated with the quality of the results. Furthermore, we demonstrate that segmentation models trained on diverse datasets and enriched with pre-trained knowledge exhibit greater robustness, particularly in cases deviating from standard anatomical structures. Notably, the best-performing models achieved high DSC and well-calibrated uncertainty estimates. This work underscores the need for multi-annotator ground truth, thorough calibration assessments, and uncertainty-aware evaluations to develop trustworthy and clinically reliable DL-based medical image segmentation models.

Chronic diseases are closely linked to alterations in body composition, yet there is a need for reliable biomarkers to assess disease risk and progression. This study aimed to develop and validate a biological age indicator based on body composition derived from dual-energy X-ray absorptiometry (DXA) scans, offering a novel approach to evaluating health status and predicting disease outcomes. A deep learning model was trained on a reference population from the UK Biobank to estimate body composition biological age (BCBA). The model's performance was assessed across various groups, including individuals with typical and atypical body composition, those with pre-existing diseases, and those who developed diseases after DXA imaging. Key metrics such as c-index were employed to examine BCBA's diagnostic and prognostic potential for type 2 diabetes, major adverse cardiovascular events (MACE), atherosclerotic cardiovascular disease (ASCVD), and hypertension. Here we show that BCBA strongly correlates with chronic disease diagnoses and risk prediction. BCBA demonstrated significant associations with type 2 diabetes (odds ratio 1.08 for females and 1.04 for males, p < 0.0005), MACE (odds ratio 1.10 for females and 1.11 for males, p < 0.0005), ASCVD (odds ratio 1.07 for females and 1.10 for males, p < 0.0005), and hypertension (odds ratio 1.06 for females and 1.04 for males, p < 0.0005). It outperformed standard cardiovascular risk profiles in predicting MACE and ASCVD. BCBA is a promising biomarker for assessing chronic disease risk and progression, with potential to improve clinical decision-making. Its integration into routine health assessments could aid early disease detection and personalised interventions.