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Interpretable Machine Learning based Detection of Coeliac Disease

Jaeckle, F., Bryant, R., Denholm, J., Romero Diaz, J., Schreiber, B., Shenoy, V., Ekundayomi, D., Evans, S., Arends, M., Soilleux, E.

medrxiv logopreprintJun 4 2025
BackgroundCoeliac disease, an autoimmune disorder affecting approximately 1% of the global population, is typically diagnosed on a duodenal biopsy. However, inter-pathologist agreement on coeliac disease diagnosis is only around 80%. Existing machine learning solutions designed to improve coeliac disease diagnosis often lack interpretability, which is essential for building trust and enabling widespread clinical adoption. ObjectiveTo develop an interpretable AI model capable of segmenting key histological structures in duodenal biopsies, generating explainable segmentation masks, estimating intraepithelial lymphocyte (IEL)-to-enterocyte and villus-to-crypt ratios, and diagnosing coeliac disease. DesignSemantic segmentation models were trained to identify villi, crypts, IELs, and enterocytes using 49 annotated 2048x2048 patches at 40x magnification. IEL-to-enterocyte and villus-to-crypt ratios were calculated from segmentation masks, and a logistic regression model was trained on 172 images to diagnose coeliac disease based on these ratios. Evaluation was performed on an independent test set of 613 duodenal biopsy scans from a separate NHS Trust. ResultsThe villus-crypt segmentation model achieved a mean PR AUC of 80.5%, while the IEL-enterocyte model reached a PR AUC of 82%. The diagnostic model classified WSIs with 96% accuracy, 86% positive predictive value, and 98% negative predictive value on the independent test set. ConclusionsOur interpretable AI models accurately segmented key histological structures and diagnosed coeliac disease in unseen WSIs, demonstrating strong generalization performance. These models provide pathologists with reliable IEL-to-enterocyte and villus-to-crypt ratio estimates, enhancing diagnostic accuracy. Interpretable AI solutions like ours are essential for fostering trust among healthcare professionals and patients, complementing existing black-box methodologies. What is already known on this topicPathologist concordance in diagnosing coeliac disease from duodenal biopsies is consistently reported to be below 80%, highlighting diagnostic variability and the need for improved methods. Several recent studies have leveraged artificial intelligence (AI) to enhance coeliac disease diagnosis. However, most of these models operate as "black boxes," offering limited interpretability and transparency. The lack of explainability in AI-driven diagnostic tools prevents widespread adoption by healthcare professionals and reduces patient trust. What this study addsThis study presents an interpretable semantic segmentation algorithm capable of detecting the four key histological structures essential for diagnosing coeliac disease: crypts, villi, intraepithelial lymphocytes (IELs), and enterocytes. The model accurately estimates the IEL-to-enterocyte ratio and the villus-to-crypt ratio, the latter being an indicator of villous atrophy and crypt hyperplasia, thereby providing objective, reproducible metrics for diagnosis. The segmentation outputs allow for transparent, explainable decision-making, supporting pathologists in coeliac disease diagnosis with improved accuracy and confidence. This study presents an AI model that automates the estimation of the IEL-to-enterocyte ratio--a labour-intensive task currently performed manually by pathologists in limited biopsy regions. By minimising diagnostic variability and alleviating time constraints for pathologists, the model provides an efficient and practical solution to streamline the diagnostic workflow. Tested on an independent dataset from a previously unseen source, the model demonstrates explainability and generalizability, enhancing trust and encouraging adoption in routine clinical practice. Furthermore, this approach could set a new standard for AI-assisted duodenal biopsy evaluation, paving the way for the development of interpretable AI tools in pathology to address the critical challenges of limited pathologist availability and diagnostic inconsistencies.

Recent Advances in Medical Image Classification

Loan Dao, Ngoc Quoc Ly

arxiv logopreprintJun 4 2025
Medical image classification is crucial for diagnosis and treatment, benefiting significantly from advancements in artificial intelligence. The paper reviews recent progress in the field, focusing on three levels of solutions: basic, specific, and applied. It highlights advances in traditional methods using deep learning models like Convolutional Neural Networks and Vision Transformers, as well as state-of-the-art approaches with Vision Language Models. These models tackle the issue of limited labeled data, and enhance and explain predictive results through Explainable Artificial Intelligence.

Gender and Ethnicity Bias of Text-to-Image Generative Artificial Intelligence in Medical Imaging, Part 2: Analysis of DALL-E 3.

Currie G, Hewis J, Hawk E, Rohren E

pubmed logopapersJun 4 2025
Disparity among gender and ethnicity remains an issue across medicine and health science. Only 26%-35% of trainee radiologists are female, despite more than 50% of medical students' being female. Similar gender disparities are evident across the medical imaging professions. Generative artificial intelligence text-to-image production could reinforce or amplify gender biases. <b>Methods:</b> In March 2024, DALL-E 3 was utilized via GPT-4 to generate a series of individual and group images of medical imaging professionals: radiologist, nuclear medicine physician, radiographer, nuclear medicine technologist, medical physicist, radiopharmacist, and medical imaging nurse. Multiple iterations of images were generated using a variety of prompts. Collectively, 120 images were produced for evaluation of 524 characters. All images were independently analyzed by 3 expert reviewers from medical imaging professions for apparent gender and skin tone. <b>Results:</b> Collectively (individual and group images), 57.4% (<i>n</i> = 301) of medical imaging professionals were depicted as male, 42.4% (<i>n</i> = 222) as female, and 91.2% (<i>n</i> = 478) as having a light skin tone. The male gender representation was 65% for radiologists, 62% for nuclear medicine physicians, 52% for radiographers, 56% for nuclear medicine technologists, 62% for medical physicists, 53% for radiopharmacists, and 26% for medical imaging nurses. For all professions, this overrepresents men compared with women. There was no representation of persons with a disability. <b>Conclusion:</b> This evaluation reveals a significant overrepresentation of the male gender associated with generative artificial intelligence text-to-image production using DALL-E 3 across the medical imaging professions. Generated images have a disproportionately high representation of white men, which is not representative of the diversity of the medical imaging professions.

An Unsupervised XAI Framework for Dementia Detection with Context Enrichment

Singh, D., Brima, Y., Levin, F., Becker, M., Hiller, B., Hermann, A., Villar-Munoz, I., Beichert, L., Bernhardt, A., Buerger, K., Butryn, M., Dechent, P., Duezel, E., Ewers, M., Fliessbach, K., D. Freiesleben, S., Glanz, W., Hetzer, S., Janowitz, D., Goerss, D., Kilimann, I., Kimmich, O., Laske, C., Levin, J., Lohse, A., Luesebrink, F., Munk, M., Perneczky, R., Peters, O., Preis, L., Priller, J., Prudlo, J., Prychynenko, D., Rauchmann, B.-S., Rostamzadeh, A., Roy-Kluth, N., Scheffler, K., Schneider, A., Droste zu Senden, L., H. Schott, B., Spottke, A., Synofzik, M., Wiltfang, J., Jessen, F., W

medrxiv logopreprintJun 4 2025
IntroductionExplainable Artificial Intelligence (XAI) methods enhance the diagnostic efficiency of clinical decision support systems by making the predictions of a convolutional neural networks (CNN) on brain imaging more transparent and trustworthy. However, their clinical adoption is limited due to limited validation of the explanation quality. Our study introduces a framework that evaluates XAI methods by integrating neuroanatomical morphological features with CNN-generated relevance maps for disease classification. MethodsWe trained a CNN using brain MRI scans from six cohorts: ADNI, AIBL, DELCODE, DESCRIBE, EDSD, and NIFD (N=3253), including participants that were cognitively normal, with amnestic mild cognitive impairment, dementia due to Alzheimers disease and frontotemporal dementia. Clustering analysis benchmarked different explanation space configurations by using morphological features as proxy-ground truth. We implemented three post-hoc explanations methods: i) by simplifying model decisions, ii) explanation-by-example, and iii) textual explanations. A qualitative evaluation by clinicians (N=6) was performed to assess their clinical validity. ResultsClustering performance improved in morphology enriched explanation spaces, improving both homogeneity and completeness of the clusters. Post hoc explanations by model simplification largely delineated converters and stable participants, while explanation-by-example presented possible cognition trajectories. Textual explanations gave rule-based summarization of pathological findings. Clinicians qualitative evaluation highlighted challenges and opportunities of XAI for different clinical applications. ConclusionOur study refines XAI explanation spaces and applies various approaches for generating explanations. Within the context of AI-based decision support system in dementia research we found the explanations methods to be promising towards enhancing diagnostic efficiency, backed up by the clinical assessments.

A Review of Intracranial Aneurysm Imaging Modalities, from CT to State-of-the-Art MR.

Allaw S, Khabaz K, Given TC, Montas D, Alcazar-Felix RJ, Srinath A, Kass-Hout T, Carroll TJ, Hurley MC, Polster SP

pubmed logopapersJun 3 2025
Traditional guidance for intracranial aneurysm (IA) management is dichotomized by rupture status. Fundamental to the management of ruptured aneurysm is the detection and treatment of SAH, along with securing the aneurysm by the safest technique. On the other hand, unruptured aneurysms first require a careful assessment of their natural history versus treatment risk, including an imaging assessment of aneurysm size, location, and morphology, along with additional evidence-based risk factors such as smoking, hypertension, and family history. Unfortunately, a large proportion of ruptured aneurysms are in the lower risk size category (<7 mm), putting a premium on discovering a more refined noninvasive biomarker to detect and stratify aneurysm instability before rupture. In this review of aneurysm work-up, we cover the gamut of established imaging modalities (eg, CT, CTA, DSA, FLAIR, 3D TOF-MRA, contrast-enhanced-MRA) as well as more novel MR techniques (MR vessel wall imaging, dynamic contrast-enhanced MRI, computational fluid dynamics). Additionally, we evaluate the current landscape of artificial intelligence software and its integration into diagnostic and risk-stratification pipelines for IAs. These advanced MR techniques, increasingly complemented with artificial intelligence models, offer a paradigm shift by evaluating factors beyond size and morphology, including vessel wall inflammation, permeability, and hemodynamics. Additionally, we provide our institution's scan parameters for many of these modalities as a reference. Ultimately, this review provides an organized, up-to-date summary of the array of available modalities/sequences for IA imaging to help build protocols focused on IA characterization.

Evaluating the Diagnostic Accuracy of ChatGPT-4.0 for Classifying Multimodal Musculoskeletal Masses: A Comparative Study with Human Raters.

Bosbach WA, Schoeni L, Beisbart C, Senge JF, Mitrakovic M, Anderson SE, Achangwa NR, Divjak E, Ivanac G, Grieser T, Weber MA, Maurer MH, Sanal HT, Daneshvar K

pubmed logopapersJun 3 2025
Novel artificial intelligence tools have the potential to significantly enhance productivity in medicine, while also maintaining or even improving treatment quality. In this study, we aimed to evaluate the current capability of ChatGPT-4.0 to accurately interpret multimodal musculoskeletal tumor cases.We created 25 cases, each containing images from X-ray, computed tomography, magnetic resonance imaging, or scintigraphy. ChatGPT-4.0 was tasked with classifying each case using a six-option, two-choice question, where both a primary and a secondary diagnosis were allowed. For performance evaluation, human raters also assessed the same cases.When only the primary diagnosis was taken into account, the accuracy of human raters was greater than that of ChatGPT-4.0 by a factor of nearly 2 (87% vs. 44%). However, in a setting that also considered secondary diagnoses, the performance gap shrank substantially (accuracy: 94% vs. 71%). Power analysis relying on Cohen's w confirmed the adequacy of the sample set size (n: 25).The tested artificial intelligence tool demonstrated lower performance than human raters. Considering factors such as speed, constant availability, and potential future improvements, it appears plausible that artificial intelligence tools could serve as valuable assistance systems for doctors in future clinical settings. · ChatGPT-4.0 classifies musculoskeletal cases using multimodal imaging inputs.. · Human raters outperform AI in primary diagnosis accuracy by a factor of nearly two.. · Including secondary diagnoses improves AI performance and narrows the gap.. · AI demonstrates potential as an assistive tool in future radiological workflows.. · Power analysis confirms robustness of study findings with the current sample size.. · Bosbach WA, Schoeni L, Beisbart C et al. Evaluating the Diagnostic Accuracy of ChatGPT-4.0 for Classifying Multimodal Musculoskeletal Masses: A Comparative Study with Human Raters. Rofo 2025; DOI 10.1055/a-2594-7085.

Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias.

Wang D, Honnorat N, Toledo JB, Li K, Charisis S, Rashid T, Benet Nirmala A, Brandigampala SR, Mojtabai M, Seshadri S, Habes M

pubmed logopapersJun 3 2025
Concurrent neurodegenerative and vascular pathologies pose a diagnostic challenge in the clinical setting, with histopathology remaining the definitive modality for dementia-type diagnosis. To address this clinical challenge, we introduce a neuropathology-based, data-driven, multi-label deep-learning framework to identify and quantify in vivo biomarkers for Alzheimer's disease (AD), vascular dementia (VD) and Lewy body dementia (LBD) using antemortem T1-weighted MRI scans of 423 demented and 361 control participants from National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative datasets. Based on the best-performing deep-learning model, explainable heat maps were extracted to visualize disease patterns, and the novel Deep Signature of Pathology Atrophy REcognition (DeepSPARE) indices were developed, where a higher DeepSPARE score indicates more brain alterations associated with that specific pathology. A substantial discrepancy in clinical and neuropathological diagnosis was observed in the demented patients: 71% had more than one pathology, but 67% were diagnosed clinically as AD only. Based on these neuropathological diagnoses and leveraging cross-validation principles, the deep-learning model achieved the best performance, with a balanced accuracy of 0.844, 0.839 and 0.623 for AD, VD and LBD, respectively, and was used to generate the explainable deep-learning heat maps and DeepSPARE indices. The explainable deep-learning heat maps revealed distinct neuroimaging brain alteration patterns for each pathology: (i) the AD heat map highlighted bilateral hippocampal regions; (ii) the VD heat map emphasized white matter regions; and (iii) the LBD heat map exposed occipital alterations. The DeepSPARE indices were validated by examining their associations with cognitive testing and neuropathological and neuroimaging measures using linear mixed-effects models. The DeepSPARE-AD index was associated with Mini-Mental State Examination, the Trail Making Test B, memory, hippocampal volume, Braak stages, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores and Thal phases [false-discovery rate (FDR)-adjusted P < 0.05]. The DeepSPARE-VD index was associated with white matter hyperintensity volume and cerebral amyloid angiopathy (FDR-adjusted P < 0.001), and the DeepSPARE-LBD index was associated with Lewy body stages (FDR-adjusted P < 0.05). The findings were replicated in an out-of-sample Alzheimer's Disease Neuroimaging Initiative dataset by testing associations with cognitive, imaging, plasma and CSF measures. CSF and plasma tau phosphorylated at threonine-181 (pTau181) were significantly associated with DeepSPARE-AD in the AD and mild cognitive impairment amyloid-β positive (AD/MCIΑβ+) group (FDR-adjusted P < 0.001), and CSF α-synuclein was associated solely with DeepSPARE-LBD (FDR-adjusted P = 0.036). Overall, these findings demonstrate the advantages of our innovative deep-learning framework in detecting antemortem neuroimaging signatures linked to different pathologies. The newly deep-learning-derived DeepSPARE indices are precise, pathology-sensitive and single-valued non-invasive neuroimaging metrics, bridging the traditional widely available in vivo T1 imaging with histopathology.

Patient-specific prediction of glioblastoma growth via reduced order modeling and neural networks.

Cerrone D, Riccobelli D, Gazzoni S, Vitullo P, Ballarin F, Falco J, Acerbi F, Manzoni A, Zunino P, Ciarletta P

pubmed logopapersJun 3 2025
Glioblastoma is among the most aggressive brain tumors in adults, characterized by patient-specific invasion patterns driven by the underlying brain microstructure. In this work, we present a proof-of-concept for a mathematical model of GBL growth, enabling real-time prediction and patient-specific parameter identification from longitudinal neuroimaging data. The framework exploits a diffuse-interface mathematical model to describe the tumor evolution and a reduced-order modeling strategy, relying on proper orthogonal decomposition, trained on synthetic data derived from patient-specific brain anatomies reconstructed from magnetic resonance imaging and diffusion tensor imaging. A neural network surrogate learns the inverse mapping from tumor evolution to model parameters, achieving significant computational speed-up while preserving high accuracy. To ensure robustness and interpretability, we perform both global and local sensitivity analyses, identifying the key biophysical parameters governing tumor dynamics and assessing the stability of the inverse problem solution. These results establish a methodological foundation for future clinical deployment of patient-specific digital twins in neuro-oncology.

Super-resolution sodium MRI of human gliomas at 3T using physics-based generative artificial intelligence.

Raymond C, Yao J, Kolkovsky ALL, Feiweier T, Clifford B, Meyer H, Zhong X, Han F, Cho NS, Sanvito F, Oshima S, Salamon N, Liau LM, Patel KS, Everson RG, Cloughesy TF, Ellingson BM

pubmed logopapersJun 3 2025
Sodium neuroimaging provides unique insights into the cellular and metabolic properties of brain tumors. However, at 3T, sodium neuroimaging MRI's low signal-to-noise ratio (SNR) and resolution discourages routine clinical use. We evaluated the recently developed Anatomically constrained GAN using physics-based synthetic MRI artifacts" (ATHENA) for high-resolution sodium neuroimaging of brain tumors at 3T. We hypothesized the model would improve the image quality while preserving the inherent sodium information. 4,573 proton MRI scans from 1,390 suspected brain tumor patients were used for training. Sodium and proton MRI datasets from Twenty glioma patients were collected for validation. Twenty-four image-guided biopsies from seven patients were available for sodium-proton exchanger (NHE1) expression evaluation on immunohistochemistry. High-resolution synthetic sodium images were generated using the ATHENA model, then compared to native sodium MRI and NHE1 protein expression from image-guided biopsy samples. The ATHENA produced synthetic-sodium MR with significantly improved SNR (native SNR 18.20 ± 7.04; synthetic SNR 23.83 ± 9.33, P = 0.0079). The synthetic-sodium values were consistent with the native measurements (P = 0.2058), with a strong linear correlation within contrast-enhancing areas of the tumor (R<sup>2</sup> = 0.7565, P = 0.0005), T2-hyperintense (R<sup>2</sup> = 0.7325, P < 0.0001), and necrotic areas (R<sup>2</sup> = 0.7678, P < 0.0001). The synthetic-sodium MR and the relative NHE1 expression from image-guided biopsies were better correlated for the synthetic (ρ = 0.3269, P < 0.0001) than the native (ρ = 0.1732, P = 0.0276) with higher sodium signal in samples expressing elevated NHE1 (P < 0.0001). ATHENA generates high-resolution synthetic-sodium MRI at 3T, enabling clinically attainable multinuclear imaging for brain tumors that retain the inherent information from the native sodium. The resulting synthetic sodium significantly correlates with tissue expression, potentially supporting its utility as a non-invasive marker of underlying sodium homeostasis in brain tumors.

Current trends in glioma tumor segmentation: A survey of deep learning modules.

Shoushtari FK, Elahi R, Valizadeh G, Moodi F, Salari HM, Rad HS

pubmed logopapersJun 2 2025
Multiparametric Magnetic Resonance Imaging (mpMRI) is the gold standard for diagnosing brain tumors, especially gliomas, which are difficult to segment due to their heterogeneity and varied sub-regions. While manual segmentation is time-consuming and error-prone, Deep Learning (DL) automates the process with greater accuracy and speed. We conducted ablation studies on surveyed articles to evaluate the impact of "add-on" modules-addressing challenges like spatial information loss, class imbalance, and overfitting-on glioma segmentation performance. Advanced modules-such as atrous (dilated) convolutions, inception, attention, transformer, and hybrid modules-significantly enhance segmentation accuracy, efficiency, multiscale feature extraction, and boundary delineation, while lightweight modules reduce computational complexity. Experiments on the Brain Tumor Segmentation (BraTS) dataset (comprising low- and high-grade gliomas) confirm their robustness, with top-performing models achieving high Dice score for tumor sub-regions. This survey underscores the need for optimal module selection and placement to balance speed, accuracy, and interpretability in glioma segmentation. Future work should focus on improving model interpretability, lowering computational costs, and boosting generalizability. Tools like NeuroQuant® and Raidionics demonstrate potential for clinical translation. Further refinement could enable regulatory approval, advancing precision in brain tumor diagnosis and treatment planning.
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