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Explainable AI Methods for Neuroimaging: Systematic Failures of Common Tools, the Need for Domain-Specific Validation, and a Proposal for Safe Application

Nys Tjade Siegel, James H. Cole, Mohamad Habes, Stefan Haufe, Kerstin Ritter, Marc-André Schulz

arxiv logopreprintAug 4 2025
Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.

Joint Lossless Compression and Steganography for Medical Images via Large Language Models

Pengcheng Zheng, Xiaorong Pu, Kecheng Chen, Jiaxin Huang, Meng Yang, Bai Feng, Yazhou Ren, Jianan Jiang

arxiv logopreprintAug 3 2025
Recently, large language models (LLMs) have driven promis ing progress in lossless image compression. However, di rectly adopting existing paradigms for medical images suf fers from an unsatisfactory trade-off between compression performance and efficiency. Moreover, existing LLM-based compressors often overlook the security of the compres sion process, which is critical in modern medical scenarios. To this end, we propose a novel joint lossless compression and steganography framework. Inspired by bit plane slicing (BPS), we find it feasible to securely embed privacy messages into medical images in an invisible manner. Based on this in sight, an adaptive modalities decomposition strategy is first devised to partition the entire image into two segments, pro viding global and local modalities for subsequent dual-path lossless compression. During this dual-path stage, we inno vatively propose a segmented message steganography algo rithm within the local modality path to ensure the security of the compression process. Coupled with the proposed anatom ical priors-based low-rank adaptation (A-LoRA) fine-tuning strategy, extensive experimental results demonstrate the su periority of our proposed method in terms of compression ra tios, efficiency, and security. The source code will be made publicly available.

External evaluation of an open-source deep learning model for prostate cancer detection on bi-parametric MRI.

Johnson PM, Tong A, Ginocchio L, Del Hoyo JL, Smereka P, Harmon SA, Turkbey B, Chandarana H

pubmed logopapersAug 3 2025
This study aims to evaluate the diagnostic accuracy of an open-source deep learning (DL) model for detecting clinically significant prostate cancer (csPCa) in biparametric MRI (bpMRI). It also aims to outline the necessary components of the model that facilitate effective sharing and external evaluation of PCa detection models. This retrospective diagnostic accuracy study evaluated a publicly available DL model trained to detect PCa on bpMRI. External validation was performed on bpMRI exams from 151 biologically male patients (mean age, 65 ± 8 years). The model's performance was evaluated using patient-level classification of PCa with both radiologist interpretation and histopathology serving as the ground truth. The model processed bpMRI inputs to generate lesion probability maps. Performance was assessed using the area under the receiver operating characteristic curve (AUC) for PI-RADS ≥ 3, PI-RADS ≥ 4, and csPCa (defined as Gleason ≥ 7) at an exam level. The model achieved AUCs of 0.86 (95% CI: 0.80-0.92) and 0.91 (95% CI: 0.85-0.96) for predicting PI-RADS ≥ 3 and ≥ 4 exams, respectively, and 0.78 (95% CI: 0.71-0.86) for csPCa. Sensitivity and specificity for csPCa were 0.87 and 0.53, respectively. Fleiss' kappa for inter-reader agreement was 0.51. The open-source DL model offers high sensitivity to clinically significant prostate cancer. The study underscores the importance of sharing model code and weights to enable effective external validation and further research. Question Inter-reader variability hinders the consistent and accurate detection of clinically significant prostate cancer in MRI. Findings An open-source deep learning model demonstrated reproducible diagnostic accuracy, achieving AUCs of 0.86 for PI-RADS ≥ 3 and 0.78 for CsPCa lesions. Clinical relevance The model's high sensitivity for MRI-positive lesions (PI-RADS ≥ 3) may provide support for radiologists. Its open-source deployment facilitates further development and evaluation across diverse clinical settings, maximizing its potential utility.

Functional immune state classification of unlabeled live human monocytes using holotomography and machine learning

Lee, M., Kim, G., Lee, M. S., Shin, J. W., Lee, J. H., Ryu, D. H., Kim, Y. S., Chung, Y., Kim, K. S., Park, Y.

biorxiv logopreprintAug 3 2025
Sepsis is an abnormally dysregulated immune response against infection in which the human immune system ranges from a hyper-inflammatory phase to an immune-suppressive phase. Current assessment methods are limiting owing to time-consuming and laborious sample preparation protocols. We propose a rapid label-free imaging-based technique to assess the immune status of individual human monocytes. High-resolution intracellular compositions of individual monocytes are quantitatively measured in terms of the three-dimensional distribution of refractive index values using holotomography, which are then analyzed using machine-learning algorithms to train for the classification into three distinct immune states: normal, hyper-inflammation, and immune suppression. The immune status prediction accuracy of the machine-learning holotomography classifier was 83.7% and 99.9% for one and six cell measurements, respectively. Our results suggested that this technique can provide a rapid deterministic method for the real-time evaluation of the immune status of an individual.

LoRA-based methods on Unet for transfer learning in Subarachnoid Hematoma Segmentation

Cristian Minoccheri, Matthew Hodgman, Haoyuan Ma, Rameez Merchant, Emily Wittrup, Craig Williamson, Kayvan Najarian

arxiv logopreprintAug 3 2025
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological emergency with mortality rates exceeding 30%. Transfer learning from related hematoma types represents a potentially valuable but underexplored approach. Although Unet architectures remain the gold standard for medical image segmentation due to their effectiveness on limited datasets, Low-Rank Adaptation (LoRA) methods for parameter-efficient transfer learning have been rarely applied to convolutional neural networks in medical imaging contexts. We implemented a Unet architecture pre-trained on computed tomography scans from 124 traumatic brain injury patients across multiple institutions, then fine-tuned on 30 aneurysmal SAH patients from the University of Michigan Health System using 3-fold cross-validation. We developed a novel CP-LoRA method based on tensor CP-decomposition and introduced DoRA variants (DoRA-C, convDoRA, CP-DoRA) that decompose weight matrices into magnitude and directional components. We compared these approaches against existing LoRA methods (LoRA-C, convLoRA) and standard fine-tuning strategies across different modules on a multi-view Unet model. LoRA-based methods consistently outperformed standard Unet fine-tuning. Performance varied by hemorrhage volume, with all methods showing improved accuracy for larger volumes. CP-LoRA achieved comparable performance to existing methods while using significantly fewer parameters. Over-parameterization with higher ranks consistently yielded better performance than strictly low-rank adaptations. This study demonstrates that transfer learning between hematoma types is feasible and that LoRA-based methods significantly outperform conventional Unet fine-tuning for aneurysmal SAH segmentation.

TopoImages: Incorporating Local Topology Encoding into Deep Learning Models for Medical Image Classification

Pengfei Gu, Hongxiao Wang, Yejia Zhang, Huimin Li, Chaoli Wang, Danny Chen

arxiv logopreprintAug 3 2025
Topological structures in image data, such as connected components and loops, play a crucial role in understanding image content (e.g., biomedical objects). % Despite remarkable successes of numerous image processing methods that rely on appearance information, these methods often lack sensitivity to topological structures when used in general deep learning (DL) frameworks. % In this paper, we introduce a new general approach, called TopoImages (for Topology Images), which computes a new representation of input images by encoding local topology of patches. % In TopoImages, we leverage persistent homology (PH) to encode geometric and topological features inherent in image patches. % Our main objective is to capture topological information in local patches of an input image into a vectorized form. % Specifically, we first compute persistence diagrams (PDs) of the patches, % and then vectorize and arrange these PDs into long vectors for pixels of the patches. % The resulting multi-channel image-form representation is called a TopoImage. % TopoImages offers a new perspective for data analysis. % To garner diverse and significant topological features in image data and ensure a more comprehensive and enriched representation, we further generate multiple TopoImages of the input image using various filtration functions, which we call multi-view TopoImages. % The multi-view TopoImages are fused with the input image for DL-based classification, with considerable improvement. % Our TopoImages approach is highly versatile and can be seamlessly integrated into common DL frameworks. Experiments on three public medical image classification datasets demonstrate noticeably improved accuracy over state-of-the-art methods.

Less is More: AMBER-AFNO -- a New Benchmark for Lightweight 3D Medical Image Segmentation

Andrea Dosi, Semanto Mondal, Rajib Chandra Ghosh, Massimo Brescia, Giuseppe Longo

arxiv logopreprintAug 3 2025
This work presents the results of a methodological transfer from remote sensing to healthcare, adapting AMBER -- a transformer-based model originally designed for multiband images, such as hyperspectral data -- to the task of 3D medical datacube segmentation. In this study, we use the AMBER architecture with Adaptive Fourier Neural Operators (AFNO) in place of the multi-head self-attention mechanism. While existing models rely on various forms of attention to capture global context, AMBER-AFNO achieves this through frequency-domain mixing, enabling a drastic reduction in model complexity. This design reduces the number of trainable parameters by over 80% compared to UNETR++, while maintaining a FLOPs count comparable to other state-of-the-art architectures. Model performance is evaluated on two benchmark 3D medical datasets -- ACDC and Synapse -- using standard metrics such as Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD), demonstrating that AMBER-AFNO achieves competitive or superior accuracy with significant gains in training efficiency, inference speed, and memory usage.

M$^3$AD: Multi-task Multi-gate Mixture of Experts for Alzheimer's Disease Diagnosis with Conversion Pattern Modeling

Yufeng Jiang, Hexiao Ding, Hongzhao Chen, Jing Lan, Xinzhi Teng, Gerald W. Y. Cheng, Zongxi Li, Haoran Xie, Jung Sun Yoo, Jing Cai

arxiv logopreprintAug 3 2025
Alzheimer's disease (AD) progression follows a complex continuum from normal cognition (NC) through mild cognitive impairment (MCI) to dementia, yet most deep learning approaches oversimplify this into discrete classification tasks. This study introduces M$^3$AD, a novel multi-task multi-gate mixture of experts framework that jointly addresses diagnostic classification and cognitive transition modeling using structural MRI. We incorporate three key innovations: (1) an open-source T1-weighted sMRI preprocessing pipeline, (2) a unified learning framework capturing NC-MCI-AD transition patterns with demographic priors (age, gender, brain volume) for improved generalization, and (3) a customized multi-gate mixture of experts architecture enabling effective multi-task learning with structural MRI alone. The framework employs specialized expert networks for diagnosis-specific pathological patterns while shared experts model common structural features across the cognitive continuum. A two-stage training protocol combines SimMIM pretraining with multi-task fine-tuning for joint optimization. Comprehensive evaluation across six datasets comprising 12,037 T1-weighted sMRI scans demonstrates superior performance: 95.13% accuracy for three-class NC-MCI-AD classification and 99.15% for binary NC-AD classification, representing improvements of 4.69% and 0.55% over state-of-the-art approaches. The multi-task formulation simultaneously achieves 97.76% accuracy in predicting cognitive transition. Our framework outperforms existing methods using fewer modalities and offers a clinically practical solution for early intervention. Code: https://github.com/csyfjiang/M3AD.

Medical Image De-Identification Resources: Synthetic DICOM Data and Tools for Validation

Michael W. Rutherford, Tracy Nolan, Linmin Pei, Ulrike Wagner, Qinyan Pan, Phillip Farmer, Kirk Smith, Benjamin Kopchick, Laura Opsahl-Ong, Granger Sutton, David Clunie, Keyvan Farahani, Fred Prior

arxiv logopreprintAug 3 2025
Medical imaging research increasingly depends on large-scale data sharing to promote reproducibility and train Artificial Intelligence (AI) models. Ensuring patient privacy remains a significant challenge for open-access data sharing. Digital Imaging and Communications in Medicine (DICOM), the global standard data format for medical imaging, encodes both essential clinical metadata and extensive protected health information (PHI) and personally identifiable information (PII). Effective de-identification must remove identifiers, preserve scientific utility, and maintain DICOM validity. Tools exist to perform de-identification, but few assess its effectiveness, and most rely on subjective reviews, limiting reproducibility and regulatory confidence. To address this gap, we developed an openly accessible DICOM dataset infused with synthetic PHI/PII and an evaluation framework for benchmarking image de-identification workflows. The Medical Image de-identification (MIDI) dataset was built using publicly available de-identified data from The Cancer Imaging Archive (TCIA). It includes 538 subjects (216 for validation, 322 for testing), 605 studies, 708 series, and 53,581 DICOM image instances. These span multiple vendors, imaging modalities, and cancer types. Synthetic PHI and PII were embedded into structured data elements, plain text data elements, and pixel data to simulate real-world identity leaks encountered by TCIA curation teams. Accompanying evaluation tools include a Python script, answer keys (known truth), and mapping files that enable automated comparison of curated data against expected transformations. The framework is aligned with the HIPAA Privacy Rule "Safe Harbor" method, DICOM PS3.15 Confidentiality Profiles, and TCIA best practices. It supports objective, standards-driven evaluation of de-identification workflows, promoting safer and more consistent medical image sharing.

Deep learning-driven incidental detection of vertebral fractures in cancer patients: advancing diagnostic precision and clinical management.

Mniai EM, Laletin V, Tselikas L, Assi T, Bonnet B, Camez AO, Zemmouri A, Muller S, Moussa T, Chaibi Y, Kiewsky J, Quenet S, Avare C, Lassau N, Balleyguier C, Ayobi A, Ammari S

pubmed logopapersAug 2 2025
Vertebral compression fractures (VCFs) are the most prevalent skeletal manifestations of osteoporosis in cancer patients. Yet, they are frequently missed or not reported in routine clinical radiology, adversely impacting patient outcomes and quality of life. This study evaluates the diagnostic performance of a deep-learning (DL)-based application and its potential to reduce the miss rate of incidental VCFs in a high-risk cancer population. We retrospectively analysed thoraco-abdomino-pelvic (TAP) CT scans from 1556 patients with stage IV cancer collected consecutively over a 4-month period (September-December 2023) in a tertiary cancer center. A DL-based application flagged cases positive for VCFs, which were subsequently reviewed by two expert radiologists for validation. Additionally, grade 3 fractures identified by the application were independently assessed by two expert interventional radiologists to determine their eligibility for vertebroplasty. Of the 1556 cases, 501 were flagged as positive for VCF by the application, with 436 confirmed as true positives by expert review, yielding a positive predictive value (PPV) of 87%. Common causes of false positives included sclerotic vertebral metastases, scoliosis, and vertebrae misidentification. Notably, 83.5% (364/436) of true positive VCFs were absent from radiology reports, indicating a substantial non-report rate in routine practice. Ten grade 3 fractures were overlooked or not reported by radiologists. Among them, 9 were deemed suitable for vertebroplasty by expert interventional radiologists. This study underscores the potential of DL-based applications to improve the detection of VCFs. The analyzed tool can assist radiologists in detecting more incidental vertebral fractures in adult cancer patients, optimising timely treatment and reducing associated morbidity and economic burden. Moreover, it might enhance patient access to interventional treatments such as vertebroplasty. These findings highlight the transformative role that DL can play in optimising clinical management and outcomes for osteoporosis-related VCFs in cancer patients.
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