Aberrant functional connectivity (FC) between brain networks has been indicated closely associated with bipolar disorder (BD). However, the previous findings of specific brain network connectivity patterns have been inconsistent, and the clinical utility of FCs for predicting treatment outcomes in bipolar depression was underexplored. To identify robust neuro-biomarkers of bipolar depression, a connectome-based analysis was conducted on resting-state functional MRI (rs-fMRI) data of 580 bipolar depression patients and 116 healthy controls (HCs). A subsample of 148 patients underwent a 4-week quetiapine treatment with post-treatment clinical assessment. Adopting machine learning, a predictive model based on pre-treatment brain connectome was then constructed to predict treatment response and identify the efficacy-specific networks. Distinct brain network connectivity patterns were observed in bipolar depression compared to HCs. Elevated intra-network connectivity was identified within the default mode network (DMN), sensorimotor network (SMN), and subcortical network (SC); and as to the inter-network connectivity, increased FCs were between the DMN, SMN and frontoparietal (FPN), ventral attention network (VAN), and decreased FCs were between the SC and cortical networks, especially the DMN and FPN. And the global network topology analyses revealed decreased global efficiency and increased characteristic path length in BD compared to HC. Further, the support vector regression model successfully predicted the efficacy of quetiapine treatment, as indicated by a high correspondence between predicted and actual HAMD reduction ratio values (r_(df=147)=0.4493, p = 2*10^-4). The identified efficacy-specific networks primarily encompassed FCs between the SMN and SC, and between the FPN, DMN, and VAN. These identified networks further predicted treatment response with r = 0.3940 in the subsequent validation with an independent cohort (n = 43). These findings presented the characteristic aberrant patterns of brain network connectome in bipolar depression and demonstrated the predictive potential of pre-treatment network connectome for quetiapine response. Promisingly, the identified connectivity networks may serve as functional targets for future precise treatments for bipolar depression.

Features of new bleeding on conventional imaging in cerebral cavernous malformations (CCMs) often disappear after several weeks, yet the risk of rebleeding persists long thereafter. Increases in mean lesional quantitative susceptibility mapping (QSM) ≥ 6% on MRI during 1 year of prospective surveillance have been associated with new symptomatic hemorrhage (SH) during that period. The authors hypothesized that QSM at a single time point reflects features of hemorrhage in the prior year or potential bleeding in the subsequent year. Twenty-eight features were extracted from 265 QSM acquisitions in 120 patients enrolled in a prospective trial readiness project, and machine learning methods examined associations with SH and biomarker bleed (QSM increase ≥ 6%) in prior and subsequent years. QSM features including sum variance, variance, and correlation had lower average values in lesions with SH in the prior year (p < 0.05, false discovery rate corrected). A support-vector machine classifier recurrently selected sum average, mean lesional QSM, sphericity, and margin sharpness features to distinguish biomarker bleeds in the prior year (area under the curve = 0.61, 95% CI 0.52-0.70; p = 0.02). No QSM features were associated with a subsequent bleed. These results provide proof of concept that machine learning may derive features of QSM reflecting prior hemorrhagic activity, meriting further investigation. Clinical trial registration no.: NCT03652181 (ClinicalTrials.gov).

Recent advances in the treatment of acute ischemic stroke contribute to improved patient outcomes, yet the mechanisms driving long-term disease trajectory are not well-understood. Current trends in the literature emphasize the distributed disruptive impact of stroke lesions on brain network organization. While most studies use population-derived data to investigate lesion interference on healthy tissue, the potential for individualized treatment strategies remains underexplored due to a lack of availability and effective utilization of the necessary clinical imaging data. To validate the potential for individualized patient evaluation, we explored and compared the differential information in network models based on normative and individual data. We further present our novel deep learning approach providing usable and accurate estimates of individual stroke impact utilizing minimal imaging data, thus bridging the data gap hindering individualized treatment planning. We created normative and individual disconnectomes for each of 78 patients (mean age 65.1 years, 32 females) from two independent cohort studies. MRI data and Barthel Index, as a measure of activities of daily living, were collected in the acute and early sub-acute phase after stroke (baseline) and at three months post stroke incident. Disconnectomes were subsequently described using 12 network metrics, including clustering coefficient and transitivity. Metrics were first compared between disconnectomes and further utilized as features in a classifier to predict a patients disease trajectory, as defined by three months Barthel Index. We then developed a deep learning architecture based on graph convolution and trained it to predict properties of the individual disconnectomes from the normative disconnectomes. Both disconnectomes showed statistically significant differences in topology and predictive power. Normative disconnectomes included a statistically significant larger number of connections (N=604 for normative versus N=210 for individual) and agreement between network properties ranged from r2=0.01 for clustering coefficient to r2=0.8 for assortativity, highlighting the impact of disconnectome choice on subsequent analysis. To predict patient deficit severity, individual data achieved an AUC score of 0.94 compared to an AUC score of 0.85 for normative based features. Our deep learning estimates showed high correlation with individual features (mean r2=0.94) and a comparable performance with an AUC score of 0.93. We were able to show how normative data-based analysis of stroke disconnections provides limited information regarding patient recovery. In contrast, individual data provided higher prognostic precision. We presented a novel approach to curb the need for individual data while retaining most of the differential information encoding individual patient disease trajectory.

Mechanical thrombectomy has become the standard of care in patients with stroke due to large vessel occlusion (LVO). However, only 50% of successfully treated patients show a favorable outcome. We developed and evaluated interpretable deep learning models to predict functional outcomes in terms of the modified Rankin Scale score alongside individualized treatment effects (ITEs) using data of 449 LVO stroke patients from a randomized clinical trial. Besides clinical variables, we considered non-contrast CT (NCCT) and angiography (CTA) scans which were integrated using novel foundation models to make use of advanced imaging information. Clinical variables had a good predictive power for binary functional outcome prediction (AUC of 0.719 [0.666, 0.774]) which could slightly be improved when adding CTA imaging (AUC of 0.737 [0.687, 0.795]). Adding NCCT scans or a combination of NCCT and CTA scans to clinical features yielded no improvement. The most important clinical predictor for functional outcome was pre-stroke disability. While estimated ITEs were well calibrated to the average treatment effect, discriminatory ability was limited indicated by a C-for-Benefit statistic of around 0.55 in all models. In summary, the models allowed us to jointly integrate CT imaging and clinical features while achieving state-of-the-art prediction performance and ITE estimates. Yet, further research is needed to particularly improve ITE estimation.

Early-onset Alzheimer's disease (EOAD) population is a clinically, genetically and pathologically heterogeneous condition. Identifying biomarkers related to disease progression is crucial for advancing clinical trials and improving therapeutic strategies. This study aims to differentiate EOAD patients with varying rates of progression using Brain Age Gap Estimation (BrainAGE)-based clustering algorithm applied to structural magnetic resonance images (MRI). A retrospective analysis of a longitudinal cohort consisting of 142 participants who met the criteria for early-onset probable Alzheimer's disease was conducted. Participants were assessed clinically, neuropsychologically and with structural MRI at baseline and annually for 6 years. A Brain Age Gap Estimation (BrainAGE) deep learning model pre-trained on 3,227 3D T1-weighted MRI of healthy subjects was used to extract encoded MRI representations at baseline. Then, k-means clustering was performed on these encoded representations to stratify the population. The resulting clusters were then analyzed for disease severity, cognitive phenotype and brain volumes at baseline and longitudinally. The optimal number of clusters was determined to be 2. Clusters differed significantly in BrainAGE scores (5.44 [± 8] years vs 15.25 [± 5 years], p < 0.001). The high BrainAGE cluster was associated with older age (p = 0.001) and higher proportion of female patients (p = 0.005), as well as greater disease severity based on Mini Mental State Examination (MMSE) scores (19.32 [±4.62] vs 14.14 [±6.93], p < 0.001) and gray matter volume (0.35 [±0.03] vs 0.32 [±0.02], p < 0.001). Longitudinal analyses revealed significant differences in disease progression (MMSE decline of -2.35 [±0.15] pts/year vs -3.02 [±0.25] pts/year, p = 0.02; CDR 1.58 [±0.10] pts/year vs 1.99 [±0.16] pts/year, p = 0.03). K-means clustering of BrainAGE encoded representations stratified EOAD patients based on varying rates of disease progression. These findings underscore the potential of using BrainAGE as a biomarker for better understanding and managing EOAD.

Accurately predicting cognitive scores based on structural MRI holds significant clinical value for understanding the pathological stages of dementia and forecasting Alzheimer's disease (AD). Some existing deep learning methods often depend on anatomical priors, overlooking individual-specific structural differences during AD progression. To address these limitations, this work proposes a deep neural network that incorporates Transformer attention to jointly predict multiple cognitive scores, including ADAS, CDRSB, and MMSE. The architecture first employs a 3D convolutional neural network backbone to encode sMRI, capturing preliminary local structural information. Then an improved Transformer attention block integrated with 3D positional encoding and 3D convolutional layer to adaptively capture discriminative imaging features across the brain, thereby focusing on key cognitive-related regions effectively. Finally, an attention-aware regression network enables the joint prediction of multiple clinical scores. Experimental results demonstrate that our method outperforms some existing traditional and deep learning methods based on the ADNI dataset. Further qualitative analysis reveals that the dementia-related brain regions identified by the model hold important biological significance, effectively enhancing the performance of cognitive score prediction. Our code is publicly available at: https://github.com/lshsx/CTA_MRI.

Recent evidence suggests that modeling higher-order interactions (HOIs) in functional magnetic resonance imaging (fMRI) data can enhance the diagnostic accuracy of machine learning systems. However, effectively extracting and utilizing HOIs remains a significant challenge. In this work, we propose MvHo-IB, a novel multi-view learning framework that integrates both pairwise interactions and HOIs for diagnostic decision-making, while automatically compressing task-irrelevant redundant information. MvHo-IB introduces several key innovations: (1) a principled method that combines O-information from information theory with a matrix-based Renyi alpha-order entropy estimator to quantify and extract HOIs, (2) a purpose-built Brain3DCNN encoder to effectively utilize these interactions, and (3) a new multi-view learning information bottleneck objective to enhance representation learning. Experiments on three benchmark fMRI datasets demonstrate that MvHo-IB achieves state-of-the-art performance, significantly outperforming previous methods, including recent hypergraph-based techniques. The implementation of MvHo-IB is available at https://github.com/zky04/MvHo-IB.

Mental processing delineates the functions of human mind encompassing a wide range of motor, sensory, emotional, and cognitive processes, each of which is underlain by the neuroanatomical substrates. Identifying accurate representation of functional neuroanatomy substrates of mental processing could inform understanding of its neural mechanism. The challenge is that it is unclear whether a specific mental process possesses a 'functional neuroanatomy fingerprint', i.e., a unique and reliable pattern of functional neuroanatomy that underlies the mental process. To address this question, we utilized a multi-task deep learning model to disentangle the functional neuroanatomy fingerprint of seven different and representative mental processes including Emotion, Gambling, Language, Motor, Relational, Social, and Working Memory. Results based on the functional magnetic resonance imaging data of two independent cohorts of 1235 subjects from the US and China consistently show that each of the seven mental processes possessed a functional neuroanatomy fingerprint, which is represented by a unique set of functional activity weights of whole-brain regions characterizing the degree of each region involved in the mental process. The functional neuroanatomy fingerprint of a specific mental process exhibits high discrimination ability (93% classification accuracy and AUC of 0.99) with those of the other mental processes, and is robust across different datasets and using different brain atlases. This study provides a solid functional neuroanatomy foundation for investigating the neural mechanism of mental processing.

Accurately and efficiently identifying mitotic figures (MFs) is crucial for diagnosing and grading various cancers, including glioblastoma (GBM), a highly aggressive brain tumour requiring precise and timely intervention. Traditional manual counting of MFs in whole slide images (WSIs) is labour-intensive and prone to interobserver variability. Our study introduces a deep active learning framework that addresses these challenges with minimal human intervention. We utilized a dataset of GBM WSIs from The Cancer Genome Atlas (TCGA). Our framework integrates convolutional neural networks (CNNs) with an active learning strategy. Initially, a CNN is trained on a small, annotated dataset. The framework then identifies uncertain samples from the unlabelled data pool, which are subsequently reviewed by experts. These ambiguous cases are verified and used for model retraining. This iterative process continues until the model achieves satisfactory performance. Our approach achieved 81.75% precision and 82.48% recall for MF detection. For MF subclass classification, it attained an accuracy of 84.1%. Furthermore, this approach significantly reduced annotation time - approximately 900 min across 66 WSIs - cutting the effort nearly in half compared to traditional methods. Our deep active learning framework demonstrates a substantial improvement in both efficiency and accuracy for MF detection and classification in GBM WSIs. By reducing reliance on large annotated datasets, it minimizes manual effort while maintaining high performance. This methodology can be generalized to other medical imaging tasks, supporting broader applications in the healthcare domain.

Brain tumors pose a critical health threat requiring timely and accurate classification for effective treatment. Traditional MRI analysis is labor-intensive and prone to variability, necessitating reliable automated solutions. This study explores lightweight deep learning models for multi-class brain tumor classification across four categories: glioma, meningioma, pituitary tumors, and no tumor. We investigate the performance of MobileNetV3 and SqueezeNet individually, and a feature-fusion hybrid model that combines their embedding layers. We utilized a publicly available MRI dataset containing 7023 images with a consistent internal split (65% training, 17% validation, 18% test) to ensure reliable evaluation. MobileNetV3 offers deep semantic understanding through its expressive features, while SqueezeNet provides minimal computational overhead. Their feature-level integration creates a balanced approach between diagnostic accuracy and deployment efficiency. Experiments conducted with consistent hyperparameters and preprocessing showed MobileNetV3 achieved the highest test accuracy (99.31%) while maintaining a low parameter count (3.47M), making it suitable for real-world deployment. Grad-CAM visualizations were employed for model explainability, highlighting tumor-relevant regions and helping visualize the specific areas contributing to predictions. Our proposed models outperform several baseline architectures like VGG16 and InceptionV3, achieving high accuracy with significantly fewer parameters. These results demonstrate that well-optimized lightweight networks can deliver accurate and interpretable brain tumor classification.