Zohaib Salahuddin

Karim Lekadir, Aasa Feragen, Abdul Joseph Fofanah et al. · eth-zurich

Despite major advances in artificial intelligence (AI) for medicine and healthcare, the deployment and adoption of AI technologies remain limited in real-world clinical practice. In recent years, concerns have been raised about the technical, clinical, ethical and legal risks associated with medical AI. To increase real world adoption, it is essential that medical AI tools are trusted and accepted by patients, clinicians, health organisations and authorities. This work describes the FUTURE-AI guideline as the first international consensus framework for guiding the development and deployment of trustworthy AI tools in healthcare. The FUTURE-AI consortium was founded in 2021 and currently comprises 118 inter-disciplinary experts from 51 countries representing all continents, including AI scientists, clinicians, ethicists, and social scientists. Over a two-year period, the consortium defined guiding principles and best practices for trustworthy AI through an iterative process comprising an in-depth literature review, a modified Delphi survey, and online consensus meetings. The FUTURE-AI framework was established based on 6 guiding principles for trustworthy AI in healthcare, i.e. Fairness, Universality, Traceability, Usability, Robustness and Explainability. Through consensus, a set of 28 best practices were defined, addressing technical, clinical, legal and socio-ethical dimensions. The recommendations cover the entire lifecycle of medical AI, from design, development and validation to regulation, deployment, and monitoring. FUTURE-AI is a risk-informed, assumption-free guideline which provides a structured approach for constructing medical AI tools that will be trusted, deployed and adopted in real-world practice. Researchers are encouraged to take the recommendations into account in proof-of-concept stages to facilitate future translation towards clinical practice of medical AI.

Zohaib Salahuddin, Abdalla Ibrahim, Sheng Kuang et al.

Routine computed tomography (CT) scans often detect a wide range of renal cysts, some of which may be malignant. Early and precise localization of these cysts can significantly aid quantitative image analysis. Current segmentation methods, however, do not offer sufficient interpretability at the feature and pixel levels, emphasizing the necessity for an explainable framework that can detect and rectify model inaccuracies. We developed an interpretable segmentation framework and validated it on a multi-centric dataset. A Variational Autoencoder Generative Adversarial Network (VAE-GAN) was employed to learn the latent representation of 3D input patches and reconstruct input images. Modifications in the latent representation using the gradient of the segmentation model generated counterfactual explanations for varying dice similarity coefficients (DSC). Radiomics features extracted from these counterfactual images, using a ground truth cyst mask, were analyzed to determine their correlation with segmentation performance. The DSCs for the original and VAE-GAN reconstructed images for counterfactual image generation showed no significant differences. Counterfactual explanations highlighted how variations in cyst image features influence segmentation outcomes and showed model discrepancies. Radiomics features correlating positively and negatively with dice scores were identified. The uncertainty of the predicted segmentation masks was estimated using posterior sampling of the weight space. The combination of counterfactual explanations and uncertainty maps provided a deeper understanding of the image features within the segmented renal cysts that lead to high uncertainty. The proposed segmentation framework not only achieved high segmentation accuracy but also increased interpretability regarding how image features impact segmentation performance.

Xian Zhong, Zohaib Salahuddin, Yi Chen et al.

Artificial intelligence (AI)-based decision support systems have demonstrated value in predicting post-hepatectomy liver failure (PHLF) in hepatocellular carcinoma (HCC). However, they often lack transparency, and the impact of model explanations on clinicians' decisions has not been thoroughly evaluated. Building on prior research, we developed a variational autoencoder-multilayer perceptron (VAE-MLP) model for preoperative PHLF prediction. This model integrated counterfactuals and layerwise relevance propagation (LRP) to provide insights into its decision-making mechanism. Additionally, we proposed a methodological framework for evaluating the explainability of AI systems. This framework includes qualitative and quantitative assessments of explanations against recognized biomarkers, usability evaluations, and an in silico clinical trial. Our evaluations demonstrated that the model's explanation correlated with established biomarkers and exhibited high usability at both the case and system levels. Furthermore, results from the three-track in silico clinical trial showed that clinicians' prediction accuracy and confidence increased when AI explanations were provided.

Shruti Atul Mali, Zohaib Salahuddin, Yumeng Zhang et al.

Colorectal liver metastases (CRLM) are a major cause of cancer-related mortality, and reliable detection on CT remains challenging in multi-centre settings. We developed a foundation model-based AI pipeline for patient-level classification and lesion-level detection of CRLM on contrast-enhanced CT, integrating uncertainty quantification and explainability. CT data from the EuCanImage consortium (n=2437) and an external TCIA cohort (n=197) were used. Among several pretrained models, UMedPT achieved the best performance and was fine-tuned with an MLP head for classification and an FCOS-based head for lesion detection. The classification model achieved an AUC of 0.90 and a sensitivity of 0.82 on the combined test set, with a sensitivity of 0.85 on the external cohort. Excluding the most uncertain 20 percent of cases improved AUC to 0.91 and balanced accuracy to 0.86. Decision curve analysis showed clinical benefit for threshold probabilities between 0.30 and 0.40. The detection model identified 69.1 percent of lesions overall, increasing from 30 percent to 98 percent across lesion size quartiles. Grad-CAM highlighted lesion-corresponding regions in high-confidence cases. These results demonstrate that foundation model-based pipelines can support robust and interpretable CRLM detection and classification across heterogeneous CT data.

Sergey Primakov, Elizaveta Lavrova, Zohaib Salahuddin et al.

Medical image analysis plays a key role in precision medicine as it allows the clinicians to identify anatomical abnormalities and it is routinely used in clinical assessment. Data curation and pre-processing of medical images are critical steps in the quantitative medical image analysis that can have a significant impact on the resulting model performance. In this paper, we introduce a precision-medicine-toolbox that allows researchers to perform data curation, image pre-processing and handcrafted radiomics extraction (via Pyradiomics) and feature exploration tasks with Python. With this open-source solution, we aim to address the data preparation and exploration problem, bridge the gap between the currently existing packages, and improve the reproducibility of quantitative medical imaging research.

Sina Amirrajab, Zohaib Salahuddin, Sheng Kuang et al.

Text to image latent diffusion models have recently advanced medical image synthesis, but applications to 3D CT generation remain limited. Existing approaches rely on simplified prompts, neglecting the rich semantic detail in full radiology reports, which reduces text image alignment and clinical fidelity. We propose Report2CT, a radiology report conditional latent diffusion framework for synthesizing 3D chest CT volumes directly from free text radiology reports, incorporating both findings and impression sections using multiple text encoder. Report2CT integrates three pretrained medical text encoders (BiomedVLP CXR BERT, MedEmbed, and ClinicalBERT) to capture nuanced clinical context. Radiology reports and voxel spacing information condition a 3D latent diffusion model trained on 20000 CT volumes from the CT RATE dataset. Model performance was evaluated using Frechet Inception Distance (FID) for real synthetic distributional similarity and CLIP based metrics for semantic alignment, with additional qualitative and quantitative comparisons against GenerateCT model. Report2CT generated anatomically consistent CT volumes with excellent visual quality and text image alignment. Multi encoder conditioning improved CLIP scores, indicating stronger preservation of fine grained clinical details in the free text radiology reports. Classifier free guidance further enhanced alignment with only a minor trade off in FID. We ranked first in the VLM3D Challenge at MICCAI 2025 on Text Conditional CT Generation and achieved state of the art performance across all evaluation metrics. By leveraging complete radiology reports and multi encoder text conditioning, Report2CT advances 3D CT synthesis, producing clinically faithful and high quality synthetic data.

Yumeng Zhang, Zohaib Salahuddin, Danial Khan et al.

Background: Accurate MRI-based identification of extramural vascular invasion (EVI) and mesorectal fascia invasion (MFI) is pivotal for risk-stratified management of rectal cancer, yet visual assessment is subjective and vulnerable to inter-institutional variability. Purpose: To develop and externally evaluate a multicenter, foundation-model-driven framework that automatically classifies EVI and MFI on axial and sagittal T2-weighted MRI. Methods: This retrospective study used 331 pre-treatment rectal cancer MRI examinations from three European hospitals. After TotalSegmentator-guided rectal patch extraction, a self-supervised frequency-domain harmonization pipeline was trained to minimize scanner-related contrast shifts. Four classifiers were compared: ResNet50, SeResNet, the universal biomedical pretrained transformer (UMedPT) with a lightweight MLP head, and a logistic-regression variant using frozen UMedPT features (UMedPT_LR). Results: UMedPT_LR achieved the best EVI detection when axial and sagittal features were fused (AUC = 0.82; sensitivity = 0.75; F1 score = 0.73), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.74). The highest MFI performance was attained by UMedPT on axial harmonized images (AUC = 0.77), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.75). Frequency-domain harmonization improved MFI classification but variably affected EVI performance. Conventional CNNs (ResNet50, SeResNet) underperformed, especially in F1 score and balanced accuracy. Conclusion: These findings demonstrate that combining foundation model features, harmonization, and multi-view fusion significantly enhances diagnostic performance in rectal MRI.

Shruti Atul Mali, Zohaib Salahuddin, Danial Khan et al.

Purpose: To evaluate the impact of harmonization and multi-region CT image feature integration on survival prediction in non-small cell lung cancer (NSCLC) patients, using handcrafted radiomics, pretrained foundation model (FM) features, and clinical data from a multicenter dataset. Methods: We analyzed CT scans and clinical data from 876 NSCLC patients (604 training, 272 test) across five centers. Features were extracted from the whole lung, tumor, mediastinal nodes, coronary arteries, and coronary artery calcium (CAC). Handcrafted radiomics and FM deep features were harmonized using ComBat, reconstruction kernel normalization (RKN), and RKN+ComBat. Regularized Cox models predicted overall survival; performance was assessed using the concordance index (C-index), 5-year time-dependent area under the curve (t-AUC), and hazard ratio (HR). SHapley Additive exPlanations (SHAP) values explained feature contributions. A consensus model used agreement across top region of interest (ROI) models to stratify patient risk. Results: TNM staging showed prognostic utility (C-index = 0.67; HR = 2.70; t-AUC = 0.85). The clinical + tumor radiomics model with ComBat achieved a C-index of 0.7552 and t-AUC of 0.8820. FM features (50-voxel cubes) combined with clinical data yielded the highest performance (C-index = 0.7616; t-AUC = 0.8866). An ensemble of all ROIs and FM features reached a C-index of 0.7142 and t-AUC of 0.7885. The consensus model, covering 78% of valid test cases, achieved a t-AUC of 0.92, sensitivity of 97.6%, and specificity of 66.7%. Conclusion: Harmonization and multi-region feature integration improve survival prediction in multicenter NSCLC data. Combining interpretable radiomics, FM features, and consensus modeling enables robust risk stratification across imaging centers.

Danial Khan, Zohaib Salahuddin, Yumeng Zhang et al.

We present a fully automated, anatomically guided deep learning pipeline for prostate cancer (PCa) risk stratification using routine MRI. The pipeline integrates three key components: an nnU-Net module for segmenting the prostate gland and its zones on axial T2-weighted MRI; a classification module based on the UMedPT Swin Transformer foundation model, fine-tuned on 3D patches with optional anatomical priors and clinical data; and a VAE-GAN framework for generating counterfactual heatmaps that localize decision-driving image regions. The system was developed using 1,500 PI-CAI cases for segmentation and 617 biparametric MRIs with metadata from the CHAIMELEON challenge for classification (split into 70% training, 10% validation, and 20% testing). Segmentation achieved mean Dice scores of 0.95 (gland), 0.94 (peripheral zone), and 0.92 (transition zone). Incorporating gland priors improved AUC from 0.69 to 0.72, with a three-scale ensemble achieving top performance (AUC = 0.79, composite score = 0.76), outperforming the 2024 CHAIMELEON challenge winners. Counterfactual heatmaps reliably highlighted lesions within segmented regions, enhancing model interpretability. In a prospective multi-center in-silico trial with 20 clinicians, AI assistance increased diagnostic accuracy from 0.72 to 0.77 and Cohen's kappa from 0.43 to 0.53, while reducing review time per case by 40%. These results demonstrate that anatomy-aware foundation models with counterfactual explainability can enable accurate, interpretable, and efficient PCa risk assessment, supporting their potential use as virtual biopsies in clinical practice.

Zohaib Salahuddin, Henry C Woodruff, Avishek Chatterjee et al.

Artificial Intelligence has emerged as a useful aid in numerous clinical applications for diagnosis and treatment decisions. Deep neural networks have shown same or better performance than clinicians in many tasks owing to the rapid increase in the available data and computational power. In order to conform to the principles of trustworthy AI, it is essential that the AI system be transparent, robust, fair and ensure accountability. Current deep neural solutions are referred to as black-boxes due to a lack of understanding of the specifics concerning the decision making process. Therefore, there is a need to ensure interpretability of deep neural networks before they can be incorporated in the routine clinical workflow. In this narrative review, we utilized systematic keyword searches and domain expertise to identify nine different types of interpretability methods that have been used for understanding deep learning models for medical image analysis applications based on the type of generated explanations and technical similarities. Furthermore, we report the progress made towards evaluating the explanations produced by various interpretability methods. Finally we discuss limitations, provide guidelines for using interpretability methods and future directions concerning the interpretability of deep neural networks for medical imaging analysis.

Karim Lekadir, Richard Osuala, Catherine Gallin et al.

The recent advancements in artificial intelligence (AI) combined with the extensive amount of data generated by today's clinical systems, has led to the development of imaging AI solutions across the whole value chain of medical imaging, including image reconstruction, medical image segmentation, image-based diagnosis and treatment planning. Notwithstanding the successes and future potential of AI in medical imaging, many stakeholders are concerned of the potential risks and ethical implications of imaging AI solutions, which are perceived as complex, opaque, and difficult to comprehend, utilise, and trust in critical clinical applications. Addressing these concerns and risks, the FUTURE-AI framework has been proposed, which, sourced from a global multi-domain expert consensus, comprises guiding principles for increased trust, safety, and adoption for AI in healthcare. In this paper, we transform the general FUTURE-AI healthcare principles to a concise and specific AI implementation guide tailored to the needs of the medical imaging community. To this end, we carefully assess each building block of the FUTURE-AI framework consisting of (i) Fairness, (ii) Universality, (iii) Traceability, (iv) Usability, (v) Robustness and (vi) Explainability, and respectively define concrete best practices based on accumulated AI implementation experiences from five large European projects on AI in Health Imaging. We accompany our concrete step-by-step medical imaging development guide with a practical AI solution maturity checklist, thus enabling AI development teams to design, evaluate, maintain, and deploy technically, clinically and ethically trustworthy imaging AI solutions into clinical practice.

Jaime Simarro, Zohaib Salahuddin, Ahmed Gouda et al.

Identification and segmentation of breast masses in mammograms face complex challenges, owing to the highly variable nature of malignant densities with regards to their shape, contours, texture and orientation. Additionally, classifiers typically suffer from high class imbalance in region candidates, where normal tissue regions vastly outnumber malignant masses. This paper proposes a rigorous segmentation method, supported by morphological enhancement using grayscale linear filters. A novel cascaded ensemble of support vector machines (SVM) is used to effectively tackle the class imbalance and provide significant predictions. For True Positive Rate (TPR) of 0.35, 0.69 and 0.82, the system generates only 0.1, 0.5 and 1.0 False Positives/Image (FPI), respectively.

Zohaib Salahuddin, Matthias Lenga, Hannes Nickisch

We propose a deep learning-based automatic coronary artery tree centerline tracker (AuCoTrack) extending the vessel tracker by Wolterink (arXiv:1810.03143). A dual pathway Convolutional Neural Network (CNN) operating on multi-scale 3D inputs predicts the direction of the coronary arteries as well as the presence of a bifurcation. A similar multi-scale dual pathway 3D CNN is trained to identify coronary artery endpoints for terminating the tracking process. Two or more continuation directions are derived based on the bifurcation detection. The iterative tracker detects the entire left and right coronary artery trees based on only two ostium landmarks derived from a model-based segmentation of the heart. The 3D CNNs were trained on a proprietary dataset consisting of 43 CCTA scans. An average sensitivity of 87.1% and clinically relevant overlap of 89.1% was obtained relative to a refined manual segmentation. In addition, the MICCAI 2008 Coronary Artery Tracking Challenge (CAT08) training and test datasets were used to benchmark the algorithm and to assess its generalization. An average overlap of 93.6% and a clinically relevant overlap of 96.4% were obtained. The proposed method achieved better overlap scores than the current state-of-the-art automatic centerline extraction techniques on the CAT08 dataset with a vessel detection rate of 95%.