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Guiding Registration with Emergent Similarity from Pre-Trained Diffusion Models

Nurislam Tursynbek, Hastings Greer, Basar Demir, Marc Niethammer

arxiv logopreprintJun 3 2025
Diffusion models, while trained for image generation, have emerged as powerful foundational feature extractors for downstream tasks. We find that off-the-shelf diffusion models, trained exclusively to generate natural RGB images, can identify semantically meaningful correspondences in medical images. Building on this observation, we propose to leverage diffusion model features as a similarity measure to guide deformable image registration networks. We show that common intensity-based similarity losses often fail in challenging scenarios, such as when certain anatomies are visible in one image but absent in another, leading to anatomically inaccurate alignments. In contrast, our method identifies true semantic correspondences, aligning meaningful structures while disregarding those not present across images. We demonstrate superior performance of our approach on two tasks: multimodal 2D registration (DXA to X-Ray) and monomodal 3D registration (brain-extracted to non-brain-extracted MRI). Code: https://github.com/uncbiag/dgir

Redefining diagnostic lesional status in temporal lobe epilepsy with artificial intelligence.

Gleichgerrcht E, Kaestner E, Hassanzadeh R, Roth RW, Parashos A, Davis KA, Bagić A, Keller SS, Rüber T, Stoub T, Pardoe HR, Dugan P, Drane DL, Abrol A, Calhoun V, Kuzniecky RI, McDonald CR, Bonilha L

pubmed logopapersJun 3 2025
Despite decades of advancements in diagnostic MRI, 30%-50% of temporal lobe epilepsy (TLE) patients remain categorized as 'non-lesional' (i.e. MRI negative) based on visual assessment by human experts. MRI-negative patients face diagnostic uncertainty and significant delays in treatment planning. Quantitative MRI studies have demonstrated that MRI-negative patients often exhibit a TLE-specific pattern of temporal and limbic atrophy that might be too subtle for the human eye to detect. This signature pattern could be translated successfully into clinical use via advances in artificial intelligence in computer-aided MRI interpretation, thereby improving the detection of brain 'lesional' patterns associated with TLE. Here, we tested this hypothesis by using a three-dimensional convolutional neural network applied to a dataset of 1178 scans from 12 different centres, which was able to differentiate TLE from healthy controls with high accuracy (85.9% ± 2.8%), significantly outperforming support vector machines based on hippocampal (74.4% ± 2.6%) and whole-brain (78.3% ± 3.3%) volumes. Our analysis focused subsequently on a subset of patients who achieved sustained seizure freedom post-surgery as a gold standard for confirming TLE. Importantly, MRI-negative patients from this cohort were accurately identified as TLE 82.7% ± 0.9% of the time, an encouraging finding given that clinically these were all patients considered to be MRI negative (i.e. not radiographically different from controls). The saliency maps from the convolutional neural network revealed that limbic structures, particularly medial temporal, cingulate and orbitofrontal areas, were most influential in classification, confirming the importance of the well-established TLE signature atrophy pattern for diagnosis. Indeed, the saliency maps were similar in MRI-positive and MRI-negative TLE groups, suggesting that even when humans cannot distinguish more subtle levels of atrophy, these MRI-negative patients are on the same continuum common across all TLE patients. As such, artificial intelligence can identify TLE lesional patterns, and artificial intelligence-aided diagnosis has the potential to enhance the neuroimaging diagnosis of TLE greatly and to redefine the concept of 'lesional' TLE.

Multi-modal brain MRI synthesis based on SwinUNETR

Haowen Pang, Weiyan Guo, Chuyang Ye

arxiv logopreprintJun 3 2025
Multi-modal brain magnetic resonance imaging (MRI) plays a crucial role in clinical diagnostics by providing complementary information across different imaging modalities. However, a common challenge in clinical practice is missing MRI modalities. In this paper, we apply SwinUNETR to the synthesize of missing modalities in brain MRI. SwinUNETR is a novel neural network architecture designed for medical image analysis, integrating the strengths of Swin Transformer and convolutional neural networks (CNNs). The Swin Transformer, a variant of the Vision Transformer (ViT), incorporates hierarchical feature extraction and window-based self-attention mechanisms, enabling it to capture both local and global contextual information effectively. By combining the Swin Transformer with CNNs, SwinUNETR merges global context awareness with detailed spatial resolution. This hybrid approach addresses the challenges posed by the varying modality characteristics and complex brain structures, facilitating the generation of accurate and realistic synthetic images. We evaluate the performance of SwinUNETR on brain MRI datasets and demonstrate its superior capability in generating clinically valuable images. Our results show significant improvements in image quality, anatomical consistency, and diagnostic value.

Radiomics-Based Differentiation of Primary Central Nervous System Lymphoma and Solitary Brain Metastasis Using Contrast-Enhanced T1-Weighted Imaging: A Retrospective Machine Learning Study.

Xia X, Qiu J, Tan Q, Du W, Gou Q

pubmed logopapersJun 3 2025
To develop and evaluate radiomics-based models using contrast-enhanced T1-weighted imaging (CE-T1WI) for the non-invasive differentiation of primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (SBM), aiming to improve diagnostic accuracy and support clinical decision-making. This retrospective study included a cohort of 324 patients pathologically diagnosed with PCNSL (n=115) or SBM (n=209) between January 2014 and December 2024. Tumor regions were manually segmented on CE-T1WI, and a comprehensive set of 1561 radiomic features was extracted. To identify the most important features, a two-step approach for feature selection was utilized, which involved the use of least absolute shrinkage and selection operator (LASSO) regression. Multiple machine learning classifiers were trained and validated to assess diagnostic performance. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. The effectiveness of the radiomics-based models was further assessed using decision curve analysis, which incorporated a risk threshold of 0.5 to balance both false positives and false negatives. 23 features were identified through LASSO regression. All classifiers demonstrated robust performance in terms of area under the curve (AUC) and accuracy, with 15 out of 20 classifiers achieving AUC values exceeding 0.9. In the 10-fold cross-validation, the artificial neural network (ANN) classifier achieved the highest AUC of 0.9305, followed by the support vector machine with polynomial kernels (SVMPOLY) classifier at 0.9226. Notably, the independent test revealed that the support vector machine with radial basis function (SVMRBF) classifier performed best, with an AUC of 0.9310 and the highest accuracy of 0.8780. The selected models-SVMRBF, SVMPOLY, ensemble learning with LDA (ELDA), ANN, random forest (RF), and grading boost with random undersampling boosting (GBRUSB)-all showed significant clinical utility, with their standardized net benefits (sNBs) surpassing 0.6. These results underline the potential of the radiomics-based models in reliably distinguishing PCNSL from SBM. The application of radiomic-driven models based on CE-T1WI has demonstrated encouraging potential for accurately distinguishing between PCNSL and SBM. The SVMRBF classifier showed the greatest diagnostic efficacy of all the classifiers tested, indicating its potential clinical utility in differential diagnosis.

Computer-Aided Decision Support Systems of Alzheimer's Disease Diagnosis - A Systematic Review.

Günaydın T, Varlı S

pubmed logopapersJun 3 2025
The incidence of Alzheimer's disease is rising with the increasing elderly population worldwide. While no cure exists, early diagnosis can significantly slow disease progression. Computer-aided diagnostic systems are becoming critical tools for assisting in the early detection of Alzheimer's disease. In this systematic review, we aim to evaluate recent advancements in computer-aided decision support systems for Alzheimer's disease diagnosis, focusing on data modalities, machine learning methods, and performance metrics. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published between 2021 and 2024 were retrieved from PubMed, IEEEXplore and Web of Science, using search terms related to Alzheimer's disease classification, neuroimaging, machine learning, and diagnostic performance. A total of 39 studies met the inclusion criteria, focusing on the use of Magnetic Resonance Imaging, Positron Emission Tomography, and biomarkers for Alzheimer's disease classification using machine learning models. Multimodal approaches, combining Magnetic Resonance Imaging with Positron Emission Tomography and Cognitive assessments, outperformed single-modality studies in diagnostic accuracy reliability. Convolutional Neural Networks were the most commonly used machine learning models, followed by hybrid models and Random Forest. The highest accuracy reported for binary classification was 100%, while multi-class classification achieved up to 99.98%. Techniques like Synthetic Minority Over-sampling Technique and data augmentation were frequently employed to address data imbalance, improving model generalizability. Our review highlights the advantages of using multimodal data in computer-aided decision support systems for more accurate Alzheimer's disease diagnosis. However, we also identified several limitations, including data imbalance, small sample sizes, and the lack of external validation in most studies. Future research should utilize larger, more diverse datasets, incorporate longitudinal data, and validate models in real-world clinical trials. Additionally, there is a growing need for explainability in machine learning models to ensure they are interpretable and trusted in clinical settings. While computer-aided decision support systems show great promise in improving the early diagnosis of Alzheimer's disease, further work is needed to enhance their robustness, generalizability, and clinical applicability. By addressing these challenges, computer-aided decision support systems could play a pivotal role in the early detection and management of Alzheimer's disease, potentially improving patient outcomes and reducing healthcare costs.

Prediction of etiology and prognosis based on hematoma location of spontaneous intracerebral hemorrhage: a multicenter diagnostic study.

Liang J, Tan W, Xie S, Zheng L, Li C, Zhong Y, Li J, Zhou C, Zhang Z, Zhou Z, Gong P, Chen X, Zhang L, Cheng X, Zhang Q, Lu G

pubmed logopapersJun 3 2025
The location of the hemorrhagic of spontaneous intracerebral hemorrhage (sICH) is clinically pivotal for both identifying its etiology and prognosis, but comprehensive and quantitative modeling approach has yet to be thoroughly explored. We employed lesion-symptom mapping to extract the location features of sICH. We registered patients' non-contrast computed tomography image and hematoma masks with standard human brain templates to identify specific affected brain regions. Then, we generated hemorrhage probabilistic maps of different etiologies and prognoses. By integrating radiomics and clinical features into multiple logistic regression models, we developed and validated optimal etiological and prognostic models across three centers, comprising 1162 sICH patients. Hematomas of different etiology have unique spatial distributions. The location-based features demonstrated robust classification of the etiology of spontaneous intracerebral hemorrhage (sICH), with a mean area under the curve (AUC) of 0.825 across diverse datasets. These features provided significant incremental value when integrated into predictive models (fusion model mean AUC = 0.915), outperforming models relying solely on clinical features (mean AUC = 0.828). In prognostic assessments, both hematoma location (mean AUC = 0.762) and radiomic features (mean AUC = 0.837) contributed substantial incremental predictive value, as evidenced by the fusion model's mean AUC of 0.873, compared to models utilizing clinical features alone (mean AUC = 0.771). Our results show that location features were more intrinsically robust, generalizable relative, strong interpretability to the complex modeling of radiomics, our approach demonstrated a novel interpretable, streamlined, comprehensive etiologic classification and prognostic prediction framework for sICH.

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.

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.

petBrain: A New Pipeline for Amyloid, Tau Tangles and Neurodegeneration Quantification Using PET and MRI

Pierrick Coupé, Boris Mansencal, Floréal Morandat, Sergio Morell-Ortega, Nicolas Villain, Jose V. Manjón, Vincent Planche

arxiv logopreprintJun 3 2025
INTRODUCTION: Quantification of amyloid plaques (A), neurofibrillary tangles (T2), and neurodegeneration (N) using PET and MRI is critical for Alzheimer's disease (AD) diagnosis and prognosis. Existing pipelines face limitations regarding processing time, variability in tracer types, and challenges in multimodal integration. METHODS: We developed petBrain, a novel end-to-end processing pipeline for amyloid-PET, tau-PET, and structural MRI. It leverages deep learning-based segmentation, standardized biomarker quantification (Centiloid, CenTauR, HAVAs), and simultaneous estimation of A, T2, and N biomarkers. The pipeline is implemented as a web-based platform, requiring no local computational infrastructure or specialized software knowledge. RESULTS: petBrain provides reliable and rapid biomarker quantification, with results comparable to existing pipelines for A and T2. It shows strong concordance with data processed in ADNI databases. The staging and quantification of A/T2/N by petBrain demonstrated good agreement with CSF/plasma biomarkers, clinical status, and cognitive performance. DISCUSSION: petBrain represents a powerful and openly accessible platform for standardized AD biomarker analysis, facilitating applications in clinical research.

Machine learning for classification of pediatric bipolar disorder with and without psychotic symptoms based on thalamic subregional structural volume.

Gao W, Zhang K, Jiao Q, Su L, Cui D, Lu S, Yang R

pubmed logopapersJun 3 2025
The thalamus plays a crucial role in sensory processing, emotional regulation, and cognitive functions, and its dysregulation may be implicated in psychosis. The aim of the present study was to examine the differences in thalamic subregional volumes between pediatric bipolar disorder patients with (P-PBD) and without psychotic symptoms (NP-PBD). Participants including 28 P-PBD, 26 NP-PBD, and 18 healthy controls (HCs) underwent structural magnetic resonance imaging (sMRI) scanning using a 3.0T MRI scanner. All T1-weighted imaging data were processed by FreeSurfer 7.4.0 software. The volumetric differences of thalamic subregions among three groups were compared by using analyses of covariance (ANCOVA) and post-hoc analyses. Additionally, we applied a standard support vector classification (SVC) model for pairwise comparison among the three groups to identify brain regions with significant volumetric differences. The ANCOVA revealed that significant volumetric differences were observed in the left pulvinar anterior (L_PuA) and left reuniens medial ventral (L_MV-re) thalamus among three groups. Post-hoc analysis revealed that patients with P-PBD exhibited decreased volumes in the L_PuA and L_MV-re when compared to the NP-PBD group and HCs, respectively. Furthermore, the SVC model revealed that the L_MV-re volume exhibited the best capacity to discriminate P-PBD from NP-PBD and HCs. The present findings demonstrated that reduced thalamic subregional volumes in the L_PuA and L_MV-re might be associated with psychotic symptoms in PBD.
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