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Characterizing ASD Subtypes Using Morphological Features from sMRI with Unsupervised Learning.

Raj A, Ratnaik R, Sengar SS, Fredo ARJ

pubmed logopapersMay 15 2025
In this study, we attempted to identify the subtypes of autism spectrum disorder (ASD) with the help of anatomical alterations found in structural magnetic resonance imaging (sMRI) data of the ASD brain and machine learning tools. Initially, the sMRI data was preprocessed using the FreeSurfer toolbox. Further, the brain regions were segmented into 148 regions of interest using the Destrieux atlas. Features such as volume, thickness, surface area, and mean curvature were extracted for each brain region. We performed principal component analysis independently on the volume, thickness, surface area, and mean curvature features and identified the top 10 features. Further, we applied k-means clustering on these top 10 features and validated the number of clusters using Elbow and Silhouette method. Our study identified two clusters in the dataset which significantly shows the existence of two subtypes in ASD. We identified the features such as volume of scaled lh_G_front middle, thickness of scaled rh_S_temporal transverse, area of scaled lh_S_temporal sup, and mean curvature of scaled lh_G_precentral as the significant features discriminating the two clusters with statistically significant p-value (p<0.05). Thus, our proposed method is effective for the identification of ASD subtypes and can also be useful for the screening of other similar neurological disorders.

Machine learning-based prognostic subgrouping of glioblastoma: A multicenter study.

Akbari H, Bakas S, Sako C, Fathi Kazerooni A, Villanueva-Meyer J, Garcia JA, Mamourian E, Liu F, Cao Q, Shinohara RT, Baid U, Getka A, Pati S, Singh A, Calabrese E, Chang S, Rudie J, Sotiras A, LaMontagne P, Marcus DS, Milchenko M, Nazeri A, Balana C, Capellades J, Puig J, Badve C, Barnholtz-Sloan JS, Sloan AE, Vadmal V, Waite K, Ak M, Colen RR, Park YW, Ahn SS, Chang JH, Choi YS, Lee SK, Alexander GS, Ali AS, Dicker AP, Flanders AE, Liem S, Lombardo J, Shi W, Shukla G, Griffith B, Poisson LM, Rogers LR, Kotrotsou A, Booth TC, Jain R, Lee M, Mahajan A, Chakravarti A, Palmer JD, DiCostanzo D, Fathallah-Shaykh H, Cepeda S, Santonocito OS, Di Stefano AL, Wiestler B, Melhem ER, Woodworth GF, Tiwari P, Valdes P, Matsumoto Y, Otani Y, Imoto R, Aboian M, Koizumi S, Kurozumi K, Kawakatsu T, Alexander K, Satgunaseelan L, Rulseh AM, Bagley SJ, Bilello M, Binder ZA, Brem S, Desai AS, Lustig RA, Maloney E, Prior T, Amankulor N, Nasrallah MP, O'Rourke DM, Mohan S, Davatzikos C

pubmed logopapersMay 15 2025
Glioblastoma (GBM) is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification. We developed a highly reproducible, personalized prognostication, and clinical subgrouping system using machine learning (ML) on routine clinical data, magnetic resonance imaging (MRI), and molecular measures from 2838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, and III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]). The ML model stratified patients into distinct prognostic subgroups with HRs between subgroups I-II and I-III of 1.62 (95% CI: 1.43-1.84, P < .001) and 3.48 (95% CI: 2.94-4.11, P < .001), respectively. Analysis of imaging features revealed several tumor properties contributing unique prognostic value, supporting the feasibility of a generalizable prognostic classification system in a diverse cohort. Our ML model demonstrates extensive reproducibility and online accessibility, utilizing routine imaging data rather than complex imaging protocols. This platform offers a unique approach to personalized patient management and clinical trial stratification in GBM.

Machine learning for grading prediction and survival analysis in high grade glioma.

Li X, Huang X, Shen Y, Yu S, Zheng L, Cai Y, Yang Y, Zhang R, Zhu L, Wang E

pubmed logopapersMay 15 2025
We developed and validated a magnetic resonance imaging (MRI)-based radiomics model for the classification of high-grade glioma (HGG) and determined the optimal machine learning (ML) approach. This retrospective analysis included 184 patients (59 grade III lesions and 125 grade IV lesions). Radiomics features were extracted from MRI with T1-weighted imaging (T1WI). The least absolute shrinkage and selection operator (LASSO) feature selection method and seven classification methods including logistic regression, XGBoost, Decision Tree, Random Forest (RF), Adaboost, Gradient Boosting Decision Tree, and Stacking fusion model were used to differentiate HGG. Performance was compared on AUC, sensitivity, accuracy, precision and specificity. In the non-fusion models, the best performance was achieved by using the XGBoost classifier, and using SMOTE to deal with the data imbalance to improve the performance of all the classifiers. The Stacking fusion model performed the best, with an AUC = 0.95 (sensitivity of 0.84; accuracy of 0.85; F1 score of 0.85). MRI-based quantitative radiomics features have good performance in identifying the classification of HGG. The XGBoost method outperforms the classifiers in the non-fusion model and the Stacking fusion model outperforms the non-fusion model.

Deep normative modelling reveals insights into early-stage Alzheimer's disease using multi-modal neuroimaging data.

Lawry Aguila A, Lorenzini L, Janahi M, Barkhof F, Altmann A

pubmed logopapersMay 15 2025
Exploring the early stages of Alzheimer's disease (AD) is crucial for timely intervention to help manage symptoms and set expectations for affected individuals and their families. However, the study of the early stages of AD involves analysing heterogeneous disease cohorts which may present challenges for some modelling techniques. This heterogeneity stems from the diverse nature of AD itself, as well as the inclusion of undiagnosed or 'at-risk' AD individuals or the presence of comorbidities which differentially affect AD biomarkers within the cohort. Normative modelling is an emerging technique for studying heterogeneous disorders that can quantify how brain imaging-based measures of individuals deviate from a healthy population. The normative model provides a statistical description of the 'normal' range that can be used at subject level to detect deviations, which may relate to pathological effects. In this work, we applied a deep learning-based normative model, pre-trained on MRI scans in the UK Biobank, to investigate ageing and identify abnormal age-related decline. We calculated deviations, relative to the healthy population, in multi-modal MRI data of non-demented individuals in the external EPAD (ep-ad.org) cohort and explored these deviations with the aim of determining whether normative modelling could detect AD-relevant subtle differences between individuals. We found that aggregate measures of deviation based on the entire brain correlated with measures of cognitive ability and biological phenotypes, indicating the effectiveness of a general deviation metric in identifying AD-related differences among individuals. We then explored deviations in individual imaging features, stratified by cognitive performance and genetic risk, across different brain regions and found that the brain regions showing deviations corresponded to those affected by AD such as the hippocampus. Finally, we found that 'at-risk' individuals in the EPAD cohort exhibited increasing deviation over time, with an approximately 6.4 times greater t-statistic in a pairwise t-test compared to a 'super-healthy' cohort. This study highlights the capability of deep normative modelling approaches to detect subtle differences in brain morphology among individuals at risk of developing AD in a non-demented population. Our findings allude to the potential utility of normative deviation metrics in monitoring disease progression.

"MR Fingerprinting for Imaging Brain Hemodynamics and Oxygenation".

Coudert T, Delphin A, Barrier A, Barbier EL, Lemasson B, Warnking JM, Christen T

pubmed logopapersMay 15 2025
Over the past decade, several studies have explored the potential of magnetic resonance fingerprinting (MRF) for the quantification of brain hemodynamics, oxygenation, and perfusion. Recent advances in simulation models and reconstruction frameworks have also significantly enhanced the accuracy of vascular parameter estimation. This review provides an overview of key vascular MRF studies, emphasizing advancements in geometrical models for vascular simulations, novel sequences, and state-of-the-art reconstruction techniques incorporating machine learning and deep learning algorithms. Both pre-clinical and clinical applications are discussed. Based on these findings, we outline future directions and development areas that need to be addressed to facilitate their clinical translation. EVIDENCE LEVEL: N/A. TECHNICAL EFFICACY: Stage 1.

A CVAE-based generative model for generalized B<sub>1</sub> inhomogeneity corrected chemical exchange saturation transfer MRI at 5 T.

Zhang R, Zhang Q, Wu Y

pubmed logopapersMay 15 2025
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful tool to image endogenous or exogenous macromolecules. CEST contrast highly depends on radiofrequency irradiation B<sub>1</sub> level. Spatial inhomogeneity of B<sub>1</sub> field would bias CEST measurement. Conventional interpolation-based B<sub>1</sub> correction method required CEST dataset acquisition under multiple B<sub>1</sub> levels, substantially prolonging scan time. The recently proposed supervised deep learning approach reconstructed B<sub>1</sub> inhomogeneity corrected CEST effect at the identical B<sub>1</sub> as of the training data, hindering its generalization to other B<sub>1</sub> levels. In this study, we proposed a Conditional Variational Autoencoder (CVAE)-based generative model to generate B<sub>1</sub> inhomogeneity corrected Z spectra from single CEST acquisition. The model was trained from pixel-wise source-target paired Z spectra under multiple B<sub>1</sub> with target B<sub>1</sub> as a conditional variable. Numerical simulation and healthy human brain imaging at 5 T were respectively performed to evaluate the performance of proposed model in B<sub>1</sub> inhomogeneity corrected CEST MRI. Results showed that the generated B<sub>1</sub>-corrected Z spectra agreed well with the reference averaged from regions with subtle B<sub>1</sub> inhomogeneity. Moreover, the performance of the proposed model in correcting B<sub>1</sub> inhomogeneity in APT CEST effect, as measured by both MTR<sub>asym</sub> and [Formula: see text] at 3.5 ppm, were superior over conventional Z/contrast-B<sub>1</sub>-interpolation and other deep learning methods, especially when target B<sub>1</sub> were not included in sampling or training dataset. In summary, the proposed model allows generalized B<sub>1</sub> inhomogeneity correction, benefiting quantitative CEST MRI in clinical routines.

Joint resting state and structural networks characterize pediatric bipolar patients compared to healthy controls: a multimodal fusion approach.

Yi X, Ma M, Wang X, Zhang J, Wu F, Huang H, Xiao Q, Xie A, Liu P, Grecucci A

pubmed logopapersMay 15 2025
Pediatric bipolar disorder (PBD) is a highly debilitating condition, characterized by alternating episodes of mania and depression, with intervening periods of remission. Limited information is available about the functional and structural abnormalities in PBD, particularly when comparing type I with type II subtypes. Resting-state brain activity and structural grey matter, assessed through MRI, may provide insight into the neurobiological biomarkers of this disorder. In this study, Resting state Regional Homogeneity (ReHo) and grey matter concentration (GMC) data of 58 PBD patients, and 21 healthy controls matched for age, gender, education and IQ, were analyzed in a data fusion unsupervised machine learning approach known as transposed Independent Vector Analysis. Two networks significantly differed between BPD and HC. The first network included fronto- medial regions, such as the medial and superior frontal gyrus, the cingulate, and displayed higher ReHo and GMC values in PBD compared to HC. The second network included temporo-posterior regions, as well as the insula, the caudate and the precuneus and displayed lower ReHo and GMC values in PBD compared to HC. Additionally, two networks differ between type-I vs type-II in PBD: an occipito-cerebellar network with increased ReHo and GMC in type-I compared to type-II, and a fronto-parietal network with decreased ReHo and GMC in type-I compared to type-II. Of note, the first network positively correlated with depression scores. These findings shed new light on the functional and structural abnormalities displayed by pediatric bipolar patients.

Zero-Shot Multi-modal Large Language Model v.s. Supervised Deep Learning: A Comparative Study on CT-Based Intracranial Hemorrhage Subtyping

Yinuo Wang, Yue Zeng, Kai Chen, Cai Meng, Chao Pan, Zhouping Tang

arxiv logopreprintMay 14 2025
Introduction: Timely identification of intracranial hemorrhage (ICH) subtypes on non-contrast computed tomography is critical for prognosis prediction and therapeutic decision-making, yet remains challenging due to low contrast and blurring boundaries. This study evaluates the performance of zero-shot multi-modal large language models (MLLMs) compared to traditional deep learning methods in ICH binary classification and subtyping. Methods: We utilized a dataset provided by RSNA, comprising 192 NCCT volumes. The study compares various MLLMs, including GPT-4o, Gemini 2.0 Flash, and Claude 3.5 Sonnet V2, with conventional deep learning models, including ResNet50 and Vision Transformer. Carefully crafted prompts were used to guide MLLMs in tasks such as ICH presence, subtype classification, localization, and volume estimation. Results: The results indicate that in the ICH binary classification task, traditional deep learning models outperform MLLMs comprehensively. For subtype classification, MLLMs also exhibit inferior performance compared to traditional deep learning models, with Gemini 2.0 Flash achieving an macro-averaged precision of 0.41 and a macro-averaged F1 score of 0.31. Conclusion: While MLLMs excel in interactive capabilities, their overall accuracy in ICH subtyping is inferior to deep networks. However, MLLMs enhance interpretability through language interactions, indicating potential in medical imaging analysis. Future efforts will focus on model refinement and developing more precise MLLMs to improve performance in three-dimensional medical image processing.

A multi-layered defense against adversarial attacks in brain tumor classification using ensemble adversarial training and feature squeezing.

Yinusa A, Faezipour M

pubmed logopapersMay 14 2025
Deep learning, particularly convolutional neural networks (CNNs), has proven valuable for brain tumor classification, aiding diagnostic and therapeutic decisions in medical imaging. Despite their accuracy, these models are vulnerable to adversarial attacks, compromising their reliability in clinical settings. In this research, we utilized a VGG16-based CNN model to classify brain tumors, achieving 96% accuracy on clean magnetic resonance imaging (MRI) data. To assess robustness, we exposed the model to Fast Gradient Sign Method (FGSM) and Projected Gradient Descent (PGD) attacks, which reduced accuracy to 32% and 13%, respectively. We then applied a multi-layered defense strategy, including adversarial training with FGSM and PGD examples and feature squeezing techniques such as bit-depth reduction and Gaussian blurring. This approach improved model resilience, achieving 54% accuracy on FGSM and 47% on PGD adversarial examples. Our results highlight the importance of proactive defense strategies for maintaining the reliability of AI in medical imaging under adversarial conditions.

Fed-ComBat: A Generalized Federated Framework for Batch Effect Harmonization in Collaborative Studies

Silva, S., Lorenzi, M., Altmann, A., Oxtoby, N.

biorxiv logopreprintMay 14 2025
In neuroimaging research, the utilization of multi-centric analyses is crucial for obtaining sufficient sample sizes and representative clinical populations. Data harmonization techniques are typically part of the pipeline in multi-centric studies to address systematic biases and ensure the comparability of the data. However, most multi-centric studies require centralized data, which may result in exposing individual patient information. This poses a significant challenge in data governance, leading to the implementation of regulations such as the GDPR and the CCPA, which attempt to address these concerns but also hinder data access for researchers. Federated learning offers a privacy-preserving alternative approach in machine learning, enabling models to be collaboratively trained on decentralized data without the need for data centralization or sharing. In this paper, we present Fed-ComBat, a federated framework for batch effect harmonization on decentralized data. Fed-ComBat extends existing centralized linear methods, such as ComBat and distributed as d-ComBat, and nonlinear approaches like ComBat-GAM in accounting for potentially nonlinear and multivariate covariate effects. By doing so, Fed-ComBat enables the preservation of nonlinear covariate effects without requiring centralization of data and without prior knowledge of which variables should be considered nonlinear or their interactions, differentiating it from ComBat-GAM. We assessed Fed-ComBat and existing approaches on simulated data and multiple cohorts comprising healthy controls (CN) and subjects with various disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD). The results of our study show that Fed-ComBat performs better than centralized ComBat when dealing with nonlinear effects and is on par with centralized methods like ComBat-GAM. Through experiments using synthetic data, Fed-ComBat demonstrates a superior ability to reconstruct the target unbiased function, achieving a 35% improvement (RMSE=0.5952) compared to d-ComBat (RMSE=0.9162) and a 12% improvement compared to our proposal to federate ComBat-GAM, d-ComBat-GAM (RMSE=0.6751). Additionally, Fed-ComBat achieves comparable results to centralized methods like ComBat-GAM for MRI-derived phenotypes without requiring prior knowledge of potential nonlinearities.
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