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Dec 8

An Explainable Diagnostic Framework for Neurodegenerative Dementias via Reinforcement-Optimized LLM Reasoning

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

  • 6 authors
·
May 26 2

A Machine Learning Approach for Identifying Anatomical Biomarkers of Early Mild Cognitive Impairment

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that primarily affects the aging population by impairing cognitive and motor functions. Early detection of AD through accessible methodologies like magnetic resonance imaging (MRI) is vital for developing effective interventions to halt or slow the disease's progression. This study aims to perform a comprehensive analysis of machine learning techniques for selecting MRI-based biomarkers and classifying individuals into healthy controls (HC) and unstable controls (uHC) who later show mild cognitive impairment within five years. The research utilizes MRI data from the Alzheimer's Disease Neuroinformatics Initiative (ADNI) and the Open Access Series of Imaging Studies 3 (OASIS-3), focusing on both HC and uHC participants. The study addresses the challenges of imbalanced data by testing classification methods on balanced and unbalanced datasets, and harmonizes data using polynomial regression to mitigate nuisance variables like age, gender, and intracranial volume. Results indicate that Gaussian Naive Bayes and RusBoost classifiers shows an optimal performance, achieving accuracies of up to 76.46% and 72.48% respectively on the ADNI dataset. For the OASIS-3 dataset, Kernel Naive Bayes and RusBoost yield accuracies ranging from 64.66% to 75.71%, improving further in age-matched datasets. Brain regions like the entorhinal cortex, hippocampus, lateral ventricle, and lateral orbitofrontal cortex are identified as significantly impacted during early cognitive decline. Despite limitations such as small sample sizes, the study's harmonization approach enhances the robustness of biomarker selection, suggesting the potential of this semi-automatic machine learning pipeline for early AD detection using MRI.

  • 6 authors
·
May 29, 2024

Anatomical Foundation Models for Brain MRIs

Deep Learning (DL) in neuroimaging has become increasingly relevant for detecting neurological conditions and neurodegenerative disorders. One of the most predominant biomarkers in neuroimaging is represented by brain age, which has been shown to be a good indicator for different conditions, such as Alzheimer's Disease. Using brain age for weakly supervised pre-training of DL models in transfer learning settings has also recently shown promising results, especially when dealing with data scarcity of different conditions. On the other hand, anatomical information of brain MRIs (e.g. cortical thickness) can provide important information for learning good representations that can be transferred to many downstream tasks. In this work, we propose AnatCL, an anatomical foundation model for brain MRIs that i.) leverages anatomical information in a weakly contrastive learning approach, and ii.) achieves state-of-the-art performances across many different downstream tasks. To validate our approach we consider 12 different downstream tasks for the diagnosis of different conditions such as Alzheimer's Disease, autism spectrum disorder, and schizophrenia. Furthermore, we also target the prediction of 10 different clinical assessment scores using structural MRI data. Our findings show that incorporating anatomical information during pre-training leads to more robust and generalizable representations. Pre-trained models can be found at: https://github.com/EIDOSLAB/AnatCL.

  • 4 authors
·
Aug 7, 2024

BRAINS: A Retrieval-Augmented System for Alzheimer's Detection and Monitoring

As the global burden of Alzheimer's disease (AD) continues to grow, early and accurate detection has become increasingly critical, especially in regions with limited access to advanced diagnostic tools. We propose BRAINS (Biomedical Retrieval-Augmented Intelligence for Neurodegeneration Screening) to address this challenge. This novel system harnesses the powerful reasoning capabilities of Large Language Models (LLMs) for Alzheimer's detection and monitoring. BRAINS features a dual-module architecture: a cognitive diagnostic module and a case-retrieval module. The Diagnostic Module utilizes LLMs fine-tuned on cognitive and neuroimaging datasets -- including MMSE, CDR scores, and brain volume metrics -- to perform structured assessments of Alzheimer's risk. Meanwhile, the Case Retrieval Module encodes patient profiles into latent representations and retrieves similar cases from a curated knowledge base. These auxiliary cases are fused with the input profile via a Case Fusion Layer to enhance contextual understanding. The combined representation is then processed with clinical prompts for inference. Evaluations on real-world datasets demonstrate BRAINS effectiveness in classifying disease severity and identifying early signs of cognitive decline. This system not only shows strong potential as an assistive tool for scalable, explainable, and early-stage Alzheimer's disease detection, but also offers hope for future applications in the field.

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

  • 96 authors
·
Feb 9, 2020

Enhancing Spatiotemporal Disease Progression Models via Latent Diffusion and Prior Knowledge

In this work, we introduce Brain Latent Progression (BrLP), a novel spatiotemporal disease progression model based on latent diffusion. BrLP is designed to predict the evolution of diseases at the individual level on 3D brain MRIs. Existing deep generative models developed for this task are primarily data-driven and face challenges in learning disease progressions. BrLP addresses these challenges by incorporating prior knowledge from disease models to enhance the accuracy of predictions. To implement this, we propose to integrate an auxiliary model that infers volumetric changes in various brain regions. Additionally, we introduce Latent Average Stabilization (LAS), a novel technique to improve spatiotemporal consistency of the predicted progression. BrLP is trained and evaluated on a large dataset comprising 11,730 T1-weighted brain MRIs from 2,805 subjects, collected from three publicly available, longitudinal Alzheimer's Disease (AD) studies. In our experiments, we compare the MRI scans generated by BrLP with the actual follow-up MRIs available from the subjects, in both cross-sectional and longitudinal settings. BrLP demonstrates significant improvements over existing methods, with an increase of 22% in volumetric accuracy across AD-related brain regions and 43% in image similarity to the ground-truth scans. The ability of BrLP to generate conditioned 3D scans at the subject level, along with the novelty of integrating prior knowledge to enhance accuracy, represents a significant advancement in disease progression modeling, opening new avenues for precision medicine. The code of BrLP is available at the following link: https://github.com/LemuelPuglisi/BrLP.

  • 3 authors
·
May 6, 2024

Is a PET all you need? A multi-modal study for Alzheimer's disease using 3D CNNs

Alzheimer's Disease (AD) is the most common form of dementia and often difficult to diagnose due to the multifactorial etiology of dementia. Recent works on neuroimaging-based computer-aided diagnosis with deep neural networks (DNNs) showed that fusing structural magnetic resonance images (sMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) leads to improved accuracy in a study population of healthy controls and subjects with AD. However, this result conflicts with the established clinical knowledge that FDG-PET better captures AD-specific pathologies than sMRI. Therefore, we propose a framework for the systematic evaluation of multi-modal DNNs and critically re-evaluate single- and multi-modal DNNs based on FDG-PET and sMRI for binary healthy vs. AD, and three-way healthy/mild cognitive impairment/AD classification. Our experiments demonstrate that a single-modality network using FDG-PET performs better than MRI (accuracy 0.91 vs 0.87) and does not show improvement when combined. This conforms with the established clinical knowledge on AD biomarkers, but raises questions about the true benefit of multi-modal DNNs. We argue that future work on multi-modal fusion should systematically assess the contribution of individual modalities following our proposed evaluation framework. Finally, we encourage the community to go beyond healthy vs. AD classification and focus on differential diagnosis of dementia, where fusing multi-modal image information conforms with a clinical need.

  • 6 authors
·
Jul 5, 2022

Automated speech- and text-based classification of neuropsychiatric conditions in a multidiagnostic setting

Speech patterns have been identified as potential diagnostic markers for neuropsychiatric conditions. However, most studies only compare a single clinical group to healthy controls, whereas clinical practice often requires differentiating between multiple potential diagnoses (multiclass settings). To address this, we assembled a dataset of repeated recordings from 420 participants (67 with major depressive disorder, 106 with schizophrenia and 46 with autism, as well as matched controls), and tested the performance of a range of conventional machine learning models and advanced Transformer models on both binary and multiclass classification, based on voice and text features. While binary models performed comparably to previous research (F1 scores between 0.54-0.75 for autism spectrum disorder, ASD; 0.67-0.92 for major depressive disorder, MDD; and 0.71-0.83 for schizophrenia); when differentiating between multiple diagnostic groups performance decreased markedly (F1 scores between 0.35-0.44 for ASD, 0.57-0.75 for MDD, 0.15-0.66 for schizophrenia, and 0.38-0.52 macro F1). Combining voice and text-based models yielded increased performance, suggesting that they capture complementary diagnostic information. Our results indicate that models trained on binary classification may learn to rely on markers of generic differences between clinical and non-clinical populations, or markers of clinical features that overlap across conditions, rather than identifying markers specific to individual conditions. We provide recommendations for future research in the field, suggesting increased focus on developing larger transdiagnostic datasets that include more fine-grained clinical features, and that can support the development of models that better capture the complexity of neuropsychiatric conditions and naturalistic diagnostic assessment.

  • 11 authors
·
Jan 13, 2023

ITCFN: Incomplete Triple-Modal Co-Attention Fusion Network for Mild Cognitive Impairment Conversion Prediction

Alzheimer's disease (AD) is a common neurodegenerative disease among the elderly. Early prediction and timely intervention of its prodromal stage, mild cognitive impairment (MCI), can decrease the risk of advancing to AD. Combining information from various modalities can significantly improve predictive accuracy. However, challenges such as missing data and heterogeneity across modalities complicate multimodal learning methods as adding more modalities can worsen these issues. Current multimodal fusion techniques often fail to adapt to the complexity of medical data, hindering the ability to identify relationships between modalities. To address these challenges, we propose an innovative multimodal approach for predicting MCI conversion, focusing specifically on the issues of missing positron emission tomography (PET) data and integrating diverse medical information. The proposed incomplete triple-modal MCI conversion prediction network is tailored for this purpose. Through the missing modal generation module, we synthesize the missing PET data from the magnetic resonance imaging and extract features using specifically designed encoders. We also develop a channel aggregation module and a triple-modal co-attention fusion module to reduce feature redundancy and achieve effective multimodal data fusion. Furthermore, we design a loss function to handle missing modality issues and align cross-modal features. These components collectively harness multimodal data to boost network performance. Experimental results on the ADNI1 and ADNI2 datasets show that our method significantly surpasses existing unimodal and other multimodal models. Our code is available at https://github.com/justinhxy/ITFC.

  • 11 authors
·
Jan 20

Machine Learning Workflow to Explain Black-box Models for Early Alzheimer's Disease Classification Evaluated for Multiple Datasets

Purpose: Hard-to-interpret Black-box Machine Learning (ML) were often used for early Alzheimer's Disease (AD) detection. Methods: To interpret eXtreme Gradient Boosting (XGBoost), Random Forest (RF), and Support Vector Machine (SVM) black-box models a workflow based on Shapley values was developed. All models were trained on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and evaluated for an independent ADNI test set, as well as the external Australian Imaging and Lifestyle flagship study of Ageing (AIBL), and Open Access Series of Imaging Studies (OASIS) datasets. Shapley values were compared to intuitively interpretable Decision Trees (DTs), and Logistic Regression (LR), as well as natural and permutation feature importances. To avoid the reduction of the explanation validity caused by correlated features, forward selection and aspect consolidation were implemented. Results: Some black-box models outperformed DTs and LR. The forward-selected features correspond to brain areas previously associated with AD. Shapley values identified biologically plausible associations with moderate to strong correlations with feature importances. The most important RF features to predict AD conversion were the volume of the amygdalae, and a cognitive test score. Good cognitive test performances and large brain volumes decreased the AD risk. The models trained using cognitive test scores significantly outperformed brain volumetric models (p<0.05). Cognitive Normal (CN) vs. AD models were successfully transferred to external datasets. Conclusion: In comparison to previous work, improved performances for ADNI and AIBL were achieved for CN vs. Mild Cognitive Impairment (MCI) classification using brain volumes. The Shapley values and the feature importances showed moderate to strong correlations.

  • 2 authors
·
May 12, 2022

Enforcing temporal consistency in Deep Learning segmentation of brain MR images

Longitudinal analysis has great potential to reveal developmental trajectories and monitor disease progression in medical imaging. This process relies on consistent and robust joint 4D segmentation. Traditional techniques are dependent on the similarity of images over time and the use of subject-specific priors to reduce random variation and improve the robustness and sensitivity of the overall longitudinal analysis. This is however slow and computationally intensive as subject-specific templates need to be rebuilt every time. The focus of this work to accelerate this analysis with the use of deep learning. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The state of art using 3D patches as inputs to modified Unet provides results around {0.91 pm 0.5} Dice and using multi-view atlas in CNNs provide around the same results. In this work, different models are explored, each offers better accuracy and fast results while increasing the segmentation quality. These methods are evaluated on 135 scans from the EADC-ADNI Harmonized Hippocampus Protocol. Proposed CNN based segmentation approaches demonstrate how 2D segmentation using prior slices can provide similar results to 3D segmentation while maintaining good continuity in the 3D dimension and improved speed. Just using 2D modified sagittal slices provide us a better Dice and longitudinal analysis for a given subject. For the ADNI dataset, using the simple UNet CNN technique gives us {0.84 pm 0.5} and while using modified CNN techniques on the same input yields {0.89 pm 0.5}. Rate of atrophy and RMS error are calculated for several test cases using various methods and analyzed.

  • 2 authors
·
Jun 13, 2019

AD-BERT: Using Pre-trained contextualized embeddings to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease

Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We first preprocessed the notes by deidentification, cleaning and splitting, and then pretrained a BERT model for AD (AD-BERT) based on the publicly available Bio+Clinical BERT on the preprocessed notes. The embeddings of all the sections of a patient's notes processed by AD-BERT were combined by MaxPooling to compute the probability of MCI-to-AD progression. For replication, we conducted a similar set of experiments on 2563 MCI patients identified at Weill Cornell Medicine (WCM) during the same timeframe. Results: Compared with the 7 baseline models, the AD-BERT model achieved the best performance on both datasets, with Area Under receiver operating characteristic Curve (AUC) of 0.8170 and F1 score of 0.4178 on NMEDW dataset and AUC of 0.8830 and F1 score of 0.6836 on WCM dataset. Conclusion: We developed a deep learning framework using BERT models which provide an effective solution for prediction of MCI-to-AD progression using clinical note analysis.

  • 12 authors
·
Nov 6, 2022

A Review of Deep Learning Approaches for Non-Invasive Cognitive Impairment Detection

This review paper explores recent advances in deep learning approaches for non-invasive cognitive impairment detection. We examine various non-invasive indicators of cognitive decline, including speech and language, facial, and motoric mobility. The paper provides an overview of relevant datasets, feature-extracting techniques, and deep-learning architectures applied to this domain. We have analyzed the performance of different methods across modalities and observed that speech and language-based methods generally achieved the highest detection performance. Studies combining acoustic and linguistic features tended to outperform those using a single modality. Facial analysis methods showed promise for visual modalities but were less extensively studied. Most papers focused on binary classification (impaired vs. non-impaired), with fewer addressing multi-class or regression tasks. Transfer learning and pre-trained language models emerged as popular and effective techniques, especially for linguistic analysis. Despite significant progress, several challenges remain, including data standardization and accessibility, model explainability, longitudinal analysis limitations, and clinical adaptation. Lastly, we propose future research directions, such as investigating language-agnostic speech analysis methods, developing multi-modal diagnostic systems, and addressing ethical considerations in AI-assisted healthcare. By synthesizing current trends and identifying key obstacles, this review aims to guide further development of deep learning-based cognitive impairment detection systems to improve early diagnosis and ultimately patient outcomes.

  • 6 authors
·
Oct 25, 2024

Deep SNP: An End-to-end Deep Neural Network with Attention-based Localization for Break-point Detection in SNP Array Genomic data

Diagnosis and risk stratification of cancer and many other diseases require the detection of genomic breakpoints as a prerequisite of calling copy number alterations (CNA). This, however, is still challenging and requires time-consuming manual curation. As deep-learning methods outperformed classical state-of-the-art algorithms in various domains and have also been successfully applied to life science problems including medicine and biology, we here propose Deep SNP, a novel Deep Neural Network to learn from genomic data. Specifically, we used a manually curated dataset from 12 genomic single nucleotide polymorphism array (SNPa) profiles as truth-set and aimed at predicting the presence or absence of genomic breakpoints, an indicator of structural chromosomal variations, in windows of 40,000 probes. We compare our results with well-known neural network models as well as Rawcopy though this tool is designed to predict breakpoints and in addition genomic segments with high sensitivity. We show, that Deep SNP is capable of successfully predicting the presence or absence of a breakpoint in large genomic windows and outperforms state-of-the-art neural network models. Qualitative examples suggest that integration of a localization unit may enable breakpoint detection and prediction of genomic segments, even if the breakpoint coordinates were not provided for network training. These results warrant further evaluation of DeepSNP for breakpoint localization and subsequent calling of genomic segments.

  • 12 authors
·
Jun 22, 2018

A Demographic-Conditioned Variational Autoencoder for fMRI Distribution Sampling and Removal of Confounds

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds.

  • 10 authors
·
May 13, 2024

How We Won BraTS-SSA 2025: Brain Tumor Segmentation in the Sub-Saharan African Population Using Segmentation-Aware Data Augmentation and Model Ensembling

Brain tumors, particularly gliomas, pose significant chall-enges due to their complex growth patterns, infiltrative nature, and the variability in brain structure across individuals, which makes accurate diagnosis and monitoring difficult. Deep learning models have been developed to accurately delineate these tumors. However, most of these models were trained on relatively homogenous high-resource datasets, limiting their robustness when deployed in underserved regions. In this study, we performed segmentation-aware offline data augmentation on the BraTS-Africa dataset to increase the data sample size and diversity to enhance generalization. We further constructed an ensemble of three distinct architectures, MedNeXt, SegMamba, and Residual-Encoder U-Net, to leverage their complementary strengths. Our best-performing model, MedNeXt, was trained on 1000 epochs and achieved the highest average lesion-wise dice and normalized surface distance scores of 0.86 and 0.81 respectively. However, the ensemble model trained for 500 epochs produced the most balanced segmentation performance across the tumour subregions. This work demonstrates that a combination of advanced augmentation and model ensembling can improve segmentation accuracy and robustness on diverse and underrepresented datasets. Code available at: https://github.com/SPARK-Academy-2025/SPARK-2025/tree/main/SPARK2025_BraTs_MODELS/SPARK_NeuroAshanti

  • 8 authors
·
Oct 3

Sparse Training via Boosting Pruning Plasticity with Neuroregeneration

Works on lottery ticket hypothesis (LTH) and single-shot network pruning (SNIP) have raised a lot of attention currently on post-training pruning (iterative magnitude pruning), and before-training pruning (pruning at initialization). The former method suffers from an extremely large computation cost and the latter usually struggles with insufficient performance. In comparison, during-training pruning, a class of pruning methods that simultaneously enjoys the training/inference efficiency and the comparable performance, temporarily, has been less explored. To better understand during-training pruning, we quantitatively study the effect of pruning throughout training from the perspective of pruning plasticity (the ability of the pruned networks to recover the original performance). Pruning plasticity can help explain several other empirical observations about neural network pruning in literature. We further find that pruning plasticity can be substantially improved by injecting a brain-inspired mechanism called neuroregeneration, i.e., to regenerate the same number of connections as pruned. We design a novel gradual magnitude pruning (GMP) method, named gradual pruning with zero-cost neuroregeneration (GraNet), that advances state of the art. Perhaps most impressively, its sparse-to-sparse version for the first time boosts the sparse-to-sparse training performance over various dense-to-sparse methods with ResNet-50 on ImageNet without extending the training time. We release all codes in https://github.com/Shiweiliuiiiiiii/GraNet.

  • 10 authors
·
Jun 18, 2021

SGUQ: Staged Graph Convolution Neural Network for Alzheimer's Disease Diagnosis using Multi-Omics Data

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

  • 7 authors
·
Oct 14, 2024

Clinically-Inspired Multi-Agent Transformers for Disease Trajectory Forecasting from Multimodal Data

Deep neural networks are often applied to medical images to automate the problem of medical diagnosis. However, a more clinically relevant question that practitioners usually face is how to predict the future trajectory of a disease. Current methods for prognosis or disease trajectory forecasting often require domain knowledge and are complicated to apply. In this paper, we formulate the prognosis prediction problem as a one-to-many prediction problem. Inspired by a clinical decision-making process with two agents -- a radiologist and a general practitioner -- we predict prognosis with two transformer-based components that share information with each other. The first transformer in this framework aims to analyze the imaging data, and the second one leverages its internal states as inputs, also fusing them with auxiliary clinical data. The temporal nature of the problem is modeled within the transformer states, allowing us to treat the forecasting problem as a multi-task classification, for which we propose a novel loss. We show the effectiveness of our approach in predicting the development of structural knee osteoarthritis changes and forecasting Alzheimer's disease clinical status directly from raw multi-modal data. The proposed method outperforms multiple state-of-the-art baselines with respect to performance and calibration, both of which are needed for real-world applications. An open-source implementation of our method is made publicly available at https://github.com/Oulu-IMEDS/CLIMATv2.

  • 4 authors
·
Oct 25, 2022

PathOrchestra: A Comprehensive Foundation Model for Computational Pathology with Over 100 Diverse Clinical-Grade Tasks

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

  • 27 authors
·
Mar 31

HA-HI: Synergising fMRI and DTI through Hierarchical Alignments and Hierarchical Interactions for Mild Cognitive Impairment Diagnosis

Early diagnosis of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) utilizing multi-modal magnetic resonance imaging (MRI) is a pivotal area of research. While various regional and connectivity features from functional MRI (fMRI) and diffusion tensor imaging (DTI) have been employed to develop diagnosis models, most studies integrate these features without adequately addressing their alignment and interactions. This limits the potential to fully exploit the synergistic contributions of combined features and modalities. To solve this gap, our study introduces a novel Hierarchical Alignments and Hierarchical Interactions (HA-HI) method for MCI and SCD classification, leveraging the combined strengths of fMRI and DTI. HA-HI efficiently learns significant MCI- or SCD- related regional and connectivity features by aligning various feature types and hierarchically maximizing their interactions. Furthermore, to enhance the interpretability of our approach, we have developed the Synergistic Activation Map (SAM) technique, revealing the critical brain regions and connections that are indicative of MCI/SCD. Comprehensive evaluations on the ADNI dataset and our self-collected data demonstrate that HA-HI outperforms other existing methods in diagnosing MCI and SCD, making it a potentially vital and interpretable tool for early detection. The implementation of this method is publicly accessible at https://github.com/ICI-BCI/Dual-MRI-HA-HI.git.

  • 7 authors
·
Jan 2, 2024

The order in speech disorder: a scoping review of state of the art machine learning methods for clinical speech classification

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

  • 4 authors
·
Mar 3

Dale meets Langevin: A Multiplicative Denoising Diffusion Model

Gradient descent has proven to be a powerful and effective technique for optimization in numerous machine learning applications. Recent advances in computational neuroscience have shown that learning in standard gradient descent optimization formulation is not consistent with learning in biological systems. This has opened up interesting avenues for building biologically inspired learning techniques. One such approach is inspired by Dale's law, which states that inhibitory and excitatory synapses do not swap roles during the course of learning. The resulting exponential gradient descent optimization scheme leads to log-normally distributed synaptic weights. Interestingly, the density that satisfies the Fokker-Planck equation corresponding to the stochastic differential equation (SDE) with geometric Brownian motion (GBM) is the log-normal density. Leveraging this connection, we start with the SDE governing geometric Brownian motion, and show that discretizing the corresponding reverse-time SDE yields a multiplicative update rule, which surprisingly, coincides with the sampling equivalent of the exponential gradient descent update founded on Dale's law. Furthermore, we propose a new formalism for multiplicative denoising score-matching, subsuming the loss function proposed by Hyvaerinen for non-negative data. Indeed, log-normally distributed data is positive and the proposed score-matching formalism turns out to be a natural fit. This allows for training of score-based models for image data and results in a novel multiplicative update scheme for sample generation starting from a log-normal density. Experimental results on MNIST, Fashion MNIST, and Kuzushiji datasets demonstrate generative capability of the new scheme. To the best of our knowledge, this is the first instance of a biologically inspired generative model employing multiplicative updates, founded on geometric Brownian motion.

Towards a deep learning approach for classifying treatment response in glioblastomas

Glioblastomas are the most aggressive type of glioma, having a 5-year survival rate of 6.9%. Treatment typically involves surgery, followed by radiotherapy and chemotherapy, and frequent magnetic resonance imaging (MRI) scans to monitor disease progression. To assess treatment response, radiologists use the Response Assessment in Neuro-Oncology (RANO) criteria to categorize the tumor into one of four labels based on imaging and clinical features: complete response, partial response, stable disease, and progressive disease. This assessment is very complex and time-consuming. Since deep learning (DL) has been widely used to tackle classification problems, this work aimed to implement the first DL pipeline for the classification of RANO criteria based on two consecutive MRI acquisitions. The models were trained and tested on the open dataset LUMIERE. Five approaches were tested: 1) subtraction of input images, 2) different combinations of modalities, 3) different model architectures, 4) different pretraining tasks, and 5) adding clinical data. The pipeline that achieved the best performance used a Densenet264 considering only T1-weighted, T2-weighted, and Fluid Attenuated Inversion Recovery (FLAIR) images as input without any pretraining. A median Balanced Accuracy of 50.96% was achieved. Additionally, explainability methods were applied. Using Saliency Maps, the tumor region was often successfully highlighted. In contrast, Grad-CAM typically failed to highlight the tumor region, with some exceptions observed in the Complete Response and Progressive Disease classes, where it effectively identified the tumor region. These results set a benchmark for future studies on glioblastoma treatment response assessment based on the RANO criteria while emphasizing the heterogeneity of factors that might play a role when assessing the tumor's response to treatment.

  • 6 authors
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Apr 25

Diffusion-Driven Generation of Minimally Preprocessed Brain MRI

The purpose of this study is to present and compare three denoising diffusion probabilistic models (DDPMs) that generate 3D T_1-weighted MRI human brain images. Three DDPMs were trained using 80,675 image volumes from 42,406 subjects spanning 38 publicly available brain MRI datasets. These images had approximately 1 mm isotropic resolution and were manually inspected by three human experts to exclude those with poor quality, field-of-view issues, and excessive pathology. The images were minimally preprocessed to preserve the visual variability of the data. Furthermore, to enable the DDPMs to produce images with natural orientation variations and inhomogeneity, the images were neither registered to a common coordinate system nor bias field corrected. Evaluations included segmentation, Frechet Inception Distance (FID), and qualitative inspection. Regarding results, all three DDPMs generated coherent MR brain volumes. The velocity and flow prediction models achieved lower FIDs than the sample prediction model. However, all three models had higher FIDs compared to real images across multiple cohorts. In a permutation experiment, the generated brain regional volume distributions differed statistically from real data. However, the velocity and flow prediction models had fewer statistically different volume distributions in the thalamus and putamen. In conclusion this work presents and releases the first 3D non-latent diffusion model for brain data without skullstripping or registration. Despite the negative results in statistical testing, the presented DDPMs are capable of generating high-resolution 3D T_1-weighted brain images. All model weights and corresponding inference code are publicly available at https://github.com/piksl-research/medforj .

  • 4 authors
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Oct 29

GAITGen: Disentangled Motion-Pathology Impaired Gait Generative Model -- Bringing Motion Generation to the Clinical Domain

Gait analysis is crucial for the diagnosis and monitoring of movement disorders like Parkinson's Disease. While computer vision models have shown potential for objectively evaluating parkinsonian gait, their effectiveness is limited by scarce clinical datasets and the challenge of collecting large and well-labelled data, impacting model accuracy and risk of bias. To address these gaps, we propose GAITGen, a novel framework that generates realistic gait sequences conditioned on specified pathology severity levels. GAITGen employs a Conditional Residual Vector Quantized Variational Autoencoder to learn disentangled representations of motion dynamics and pathology-specific factors, coupled with Mask and Residual Transformers for conditioned sequence generation. GAITGen generates realistic, diverse gait sequences across severity levels, enriching datasets and enabling large-scale model training in parkinsonian gait analysis. Experiments on our new PD-GaM (real) dataset demonstrate that GAITGen outperforms adapted state-of-the-art models in both reconstruction fidelity and generation quality, accurately capturing critical pathology-specific gait features. A clinical user study confirms the realism and clinical relevance of our generated sequences. Moreover, incorporating GAITGen-generated data into downstream tasks improves parkinsonian gait severity estimation, highlighting its potential for advancing clinical gait analysis.

  • 9 authors
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Mar 28

Amplifying Pathological Detection in EEG Signaling Pathways through Cross-Dataset Transfer Learning

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labelled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labelling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labelled data was available. Our findings indicate a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better on transfer and learning from a larger and diverse dataset.

  • 6 authors
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Sep 19, 2023

Prototype Learning to Create Refined Interpretable Digital Phenotypes from ECGs

Prototype-based neural networks offer interpretable predictions by comparing inputs to learned, representative signal patterns anchored in training data. While such models have shown promise in the classification of physiological data, it remains unclear whether their prototypes capture an underlying structure that aligns with broader clinical phenotypes. We use a prototype-based deep learning model trained for multi-label ECG classification using the PTB-XL dataset. Then without modification we performed inference on the MIMIC-IV clinical database. We assess whether individual prototypes, trained solely for classification, are associated with hospital discharge diagnoses in the form of phecodes in this external population. Individual prototypes demonstrate significantly stronger and more specific associations with clinical outcomes compared to the classifier's class predictions, NLP-extracted concepts, or broader prototype classes across all phecode categories. Prototype classes with mixed significance patterns exhibit significantly greater intra-class distances (p < 0.0001), indicating the model learned to differentiate clinically meaningful variations within diagnostic categories. The prototypes achieve strong predictive performance across diverse conditions, with AUCs ranging from 0.89 for atrial fibrillation to 0.91 for heart failure, while also showing substantial signal for non-cardiac conditions such as sepsis and renal disease. These findings suggest that prototype-based models can support interpretable digital phenotyping from physiologic time-series data, providing transferable intermediate phenotypes that capture clinically meaningful physiologic signatures beyond their original training objectives.

  • 6 authors
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Aug 2

Context-Aware Attention Layers coupled with Optimal Transport Domain Adaptation methods for recognizing dementia from spontaneous speech

Alzheimer's disease (AD) constitutes a complex neurocognitive disease and is the main cause of dementia. Although many studies have been proposed targeting at diagnosing dementia through spontaneous speech, there are still limitations. Existing state-of-the-art approaches, which propose multimodal methods, train separately language and acoustic models, employ majority-vote approaches, and concatenate the representations of the different modalities either at the input level, i.e., early fusion, or during training. Also, some of them employ self-attention layers, which calculate the dependencies between representations without considering the contextual information. In addition, no prior work has taken into consideration the model calibration. To address these limitations, we propose some new methods for detecting AD patients, which capture the intra- and cross-modal interactions. First, we convert the audio files into log-Mel spectrograms, their delta, and delta-delta and create in this way an image per audio file consisting of three channels. Next, we pass each transcript and image through BERT and DeiT models respectively. After that, context-based self-attention layers, self-attention layers with a gate model, and optimal transport domain adaptation methods are employed for capturing the intra- and inter-modal interactions. Finally, we exploit two methods for fusing the self and cross-attended features. For taking into account the model calibration, we apply label smoothing. We use both performance and calibration metrics. Experiments conducted on the ADReSS Challenge dataset indicate the efficacy of our introduced approaches over existing research initiatives with our best performing model reaching Accuracy and F1-score up to 91.25% and 91.06% respectively.

  • 2 authors
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May 25, 2023

Hopfield Networks is All You Need

We introduce a modern Hopfield network with continuous states and a corresponding update rule. The new Hopfield network can store exponentially (with the dimension of the associative space) many patterns, retrieves the pattern with one update, and has exponentially small retrieval errors. It has three types of energy minima (fixed points of the update): (1) global fixed point averaging over all patterns, (2) metastable states averaging over a subset of patterns, and (3) fixed points which store a single pattern. The new update rule is equivalent to the attention mechanism used in transformers. This equivalence enables a characterization of the heads of transformer models. These heads perform in the first layers preferably global averaging and in higher layers partial averaging via metastable states. The new modern Hopfield network can be integrated into deep learning architectures as layers to allow the storage of and access to raw input data, intermediate results, or learned prototypes. These Hopfield layers enable new ways of deep learning, beyond fully-connected, convolutional, or recurrent networks, and provide pooling, memory, association, and attention mechanisms. We demonstrate the broad applicability of the Hopfield layers across various domains. Hopfield layers improved state-of-the-art on three out of four considered multiple instance learning problems as well as on immune repertoire classification with several hundreds of thousands of instances. On the UCI benchmark collections of small classification tasks, where deep learning methods typically struggle, Hopfield layers yielded a new state-of-the-art when compared to different machine learning methods. Finally, Hopfield layers achieved state-of-the-art on two drug design datasets. The implementation is available at: https://github.com/ml-jku/hopfield-layers

  • 16 authors
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Jul 16, 2020

ISLES'24: Final Infarct Prediction with Multimodal Imaging and Clinical Data. Where Do We Stand?

Accurate estimation of brain infarction (i.e., irreversibly damaged tissue) is critical for guiding treatment decisions in acute ischemic stroke. Reliable infarct prediction informs key clinical interventions, including the need for patient transfer to comprehensive stroke centers, the potential benefit of additional reperfusion attempts during mechanical thrombectomy, decisions regarding secondary neuroprotective treatments, and ultimately, prognosis of clinical outcomes. This work introduces the Ischemic Stroke Lesion Segmentation (ISLES) 2024 challenge, which focuses on the prediction of final infarct volumes from pre-interventional acute stroke imaging and clinical data. ISLES24 provides a comprehensive, multimodal setting where participants can leverage all clinically and practically available data, including full acute CT imaging, sub-acute follow-up MRI, and structured clinical information, across a train set of 150 cases. On the hidden test set of 98 cases, the top-performing model, a multimodal nnU-Net-based architecture, achieved a Dice score of 0.285 (+/- 0.213) and an absolute volume difference of 21.2 (+/- 37.2) mL, underlining the significant challenges posed by this task and the need for further advances in multimodal learning. This work makes two primary contributions: first, we establish a standardized, clinically realistic benchmark for post-treatment infarct prediction, enabling systematic evaluation of multimodal algorithmic strategies on a longitudinal stroke dataset; second, we analyze current methodological limitations and outline key research directions to guide the development of next-generation infarct prediction models.

  • 40 authors
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Aug 20, 2024

A Knowledge-enhanced Pathology Vision-language Foundation Model for Cancer Diagnosis

Deep learning has enabled the development of highly robust foundation models for various pathological tasks across diverse diseases and patient cohorts. Among these models, vision-language pre-training, which leverages large-scale paired data to align pathology image and text embedding spaces, and provides a novel zero-shot paradigm for downstream tasks. However, existing models have been primarily data-driven and lack the incorporation of domain-specific knowledge, which limits their performance in cancer diagnosis, especially for rare tumor subtypes. To address this limitation, we establish a Knowledge-enhanced Pathology (KEEP) foundation model that harnesses disease knowledge to facilitate vision-language pre-training. Specifically, we first construct a disease knowledge graph (KG) that covers 11,454 human diseases with 139,143 disease attributes, including synonyms, definitions, and hypernym relations. We then systematically reorganize the millions of publicly available noisy pathology image-text pairs, into 143K well-structured semantic groups linked through the hierarchical relations of the disease KG. To derive more nuanced image and text representations, we propose a novel knowledge-enhanced vision-language pre-training approach that integrates disease knowledge into the alignment within hierarchical semantic groups instead of unstructured image-text pairs. Validated on 18 diverse benchmarks with more than 14,000 whole slide images (WSIs), KEEP achieves state-of-the-art performance in zero-shot cancer diagnostic tasks. Notably, for cancer detection, KEEP demonstrates an average sensitivity of 89.8% at a specificity of 95.0% across 7 cancer types. For cancer subtyping, KEEP achieves a median balanced accuracy of 0.456 in subtyping 30 rare brain cancers, indicating strong generalizability for diagnosing rare tumors.

  • 11 authors
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Dec 17, 2024

MultiConAD: A Unified Multilingual Conversational Dataset for Early Alzheimer's Detection

Dementia is a progressive cognitive syndrome with Alzheimer's disease (AD) as the leading cause. Conversation-based AD detection offers a cost-effective alternative to clinical methods, as language dysfunction is an early biomarker of AD. However, most prior research has framed AD detection as a binary classification problem, limiting the ability to identify Mild Cognitive Impairment (MCI)-a crucial stage for early intervention. Also, studies primarily rely on single-language datasets, mainly in English, restricting cross-language generalizability. To address this gap, we make three key contributions. First, we introduce a novel, multilingual dataset for AD detection by unifying 16 publicly available dementia-related conversational datasets. This corpus spans English, Spanish, Chinese, and Greek and incorporates both audio and text data derived from a variety of cognitive assessment tasks. Second, we perform finer-grained classification, including MCI, and evaluate various classifiers using sparse and dense text representations. Third, we conduct experiments in monolingual and multilingual settings, finding that some languages benefit from multilingual training while others perform better independently. This study highlights the challenges in multilingual AD detection and enables future research on both language-specific approaches and techniques aimed at improving model generalization and robustness.

  • 3 authors
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Feb 26

Synthetic Generation and Latent Projection Denoising of Rim Lesions in Multiple Sclerosis

Quantitative susceptibility maps from magnetic resonance images can provide both prognostic and diagnostic information in multiple sclerosis, a neurodegenerative disease characterized by the formation of lesions in white matter brain tissue. In particular, susceptibility maps provide adequate contrast to distinguish between "rim" lesions, surrounded by deposited paramagnetic iron, and "non-rim" lesion types. These paramagnetic rim lesions (PRLs) are an emerging biomarker in multiple sclerosis. Much effort has been devoted to both detection and segmentation of such lesions to monitor longitudinal change. As paramagnetic rim lesions are rare, addressing this problem requires confronting the class imbalance between rim and non-rim lesions. We produce synthetic quantitative susceptibility maps of paramagnetic rim lesions and show that inclusion of such synthetic data improves classifier performance and provide a multi-channel extension to generate accompanying contrasts and probabilistic segmentation maps. We exploit the projection capability of our trained generative network to demonstrate a novel denoising approach that allows us to train on ambiguous rim cases and substantially increase the minority class. We show that both synthetic lesion synthesis and our proposed rim lesion label denoising method best approximate the unseen rim lesion distribution and improve detection in a clinically interpretable manner. We release our code and generated data at https://github.com/agr78/PRLx-GAN upon publication.

  • 9 authors
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May 29

fastHDMI: Fast Mutual Information Estimation for High-Dimensional Data

In this paper, we introduce fastHDMI, a Python package designed for efficient variable screening in high-dimensional datasets, particularly neuroimaging data. This work pioneers the application of three mutual information estimation methods for neuroimaging variable selection, a novel approach implemented via fastHDMI. These advancements enhance our ability to analyze the complex structures of neuroimaging datasets, providing improved tools for variable selection in high-dimensional spaces. Using the preprocessed ABIDE dataset, we evaluate the performance of these methods through extensive simulations. The tests cover a range of conditions, including linear and nonlinear associations, as well as continuous and binary outcomes. Our results highlight the superiority of the FFTKDE-based mutual information estimation for feature screening in continuous nonlinear outcomes, while binning-based methods outperform others for binary outcomes with nonlinear probability preimages. For linear simulations, both Pearson correlation and FFTKDE-based methods show comparable performance for continuous outcomes, while Pearson excels in binary outcomes with linear probability preimages. A comprehensive case study using the ABIDE dataset further demonstrates fastHDMI's practical utility, showcasing the predictive power of models built from variables selected using our screening techniques. This research affirms the computational efficiency and methodological strength of fastHDMI, significantly enriching the toolkit available for neuroimaging analysis.

  • 5 authors
·
Oct 13, 2024

The Imaging Database for Epilepsy And Surgery (IDEAS)

Magnetic resonance imaging (MRI) is a crucial tool to identify brain abnormalities in a wide range of neurological disorders. In focal epilepsy MRI is used to identify structural cerebral abnormalities. For covert lesions, machine learning and artificial intelligence algorithms may improve lesion detection if abnormalities are not evident on visual inspection. The success of this approach depends on the volume and quality of training data. Herein, we release an open-source dataset of preprocessed MRI scans from 442 individuals with drug-refractory focal epilepsy who had neurosurgical resections, and detailed demographic information. The MRI scan data includes the preoperative 3D T1 and where available 3D FLAIR, as well as a manually inspected complete surface reconstruction and volumetric parcellations. Demographic information includes age, sex, age of onset of epilepsy, location of surgery, histopathology of resected specimen, occurrence and frequency of focal seizures with and without impairment of awareness, focal to bilateral tonic-clonic seizures, number of anti-seizure medications (ASMs) at time of surgery, and a total of 1764 patient years of post-surgical follow up. Crucially, we also include resection masks delineated from post-surgical imaging. To demonstrate the veracity of our data, we successfully replicated previous studies showing long-term outcomes of seizure freedom in the range of around 50%. Our imaging data replicates findings of group level atrophy in patients compared to controls. Resection locations in the cohort were predominantly in the temporal and frontal lobes. We envisage our dataset, shared openly with the community, will catalyse the development and application of computational methods in clinical neurology.

  • 15 authors
·
Jun 10, 2024

Raidionics: an open software for pre- and postoperative central nervous system tumor segmentation and standardized reporting

For patients suffering from central nervous system tumors, prognosis estimation, treatment decisions, and postoperative assessments are made from the analysis of a set of magnetic resonance (MR) scans. Currently, the lack of open tools for standardized and automatic tumor segmentation and generation of clinical reports, incorporating relevant tumor characteristics, leads to potential risks from inherent decisions' subjectivity. To tackle this problem, the proposed Raidionics open-source software has been developed, offering both a user-friendly graphical user interface and stable processing backend. The software includes preoperative segmentation models for each of the most common tumor types (i.e., glioblastomas, lower grade gliomas, meningiomas, and metastases), together with one early postoperative glioblastoma segmentation model. Preoperative segmentation performances were quite homogeneous across the four different brain tumor types, with an average Dice around 85% and patient-wise recall and precision around 95%. Postoperatively, performances were lower with an average Dice of 41%. Overall, the generation of a standardized clinical report, including the tumor segmentation and features computation, requires about ten minutes on a regular laptop. The proposed Raidionics software is the first open solution enabling an easy use of state-of-the-art segmentation models for all major tumor types, including preoperative and postsurgical standardized reports.

  • 7 authors
·
Apr 28, 2023

How connectivity structure shapes rich and lazy learning in neural circuits

In theoretical neuroscience, recent work leverages deep learning tools to explore how some network attributes critically influence its learning dynamics. Notably, initial weight distributions with small (resp. large) variance may yield a rich (resp. lazy) regime, where significant (resp. minor) changes to network states and representation are observed over the course of learning. However, in biology, neural circuit connectivity could exhibit a low-rank structure and therefore differs markedly from the random initializations generally used for these studies. As such, here we investigate how the structure of the initial weights -- in particular their effective rank -- influences the network learning regime. Through both empirical and theoretical analyses, we discover that high-rank initializations typically yield smaller network changes indicative of lazier learning, a finding we also confirm with experimentally-driven initial connectivity in recurrent neural networks. Conversely, low-rank initialization biases learning towards richer learning. Importantly, however, as an exception to this rule, we find lazier learning can still occur with a low-rank initialization that aligns with task and data statistics. Our research highlights the pivotal role of initial weight structures in shaping learning regimes, with implications for metabolic costs of plasticity and risks of catastrophic forgetting.

  • 6 authors
·
Oct 12, 2023

ImageFlowNet: Forecasting Multiscale Image-Level Trajectories of Disease Progression with Irregularly-Sampled Longitudinal Medical Images

Advances in medical imaging technologies have enabled the collection of longitudinal images, which involve repeated scanning of the same patients over time, to monitor disease progression. However, predictive modeling of such data remains challenging due to high dimensionality, irregular sampling, and data sparsity. To address these issues, we propose ImageFlowNet, a novel model designed to forecast disease trajectories from initial images while preserving spatial details. ImageFlowNet first learns multiscale joint representation spaces across patients and time points, then optimizes deterministic or stochastic flow fields within these spaces using a position-parameterized neural ODE/SDE framework. The model leverages a UNet architecture to create robust multiscale representations and mitigates data scarcity by combining knowledge from all patients. We provide theoretical insights that support our formulation of ODEs, and motivate our regularizations involving high-level visual features, latent space organization, and trajectory smoothness. We validate ImageFlowNet on three longitudinal medical image datasets depicting progression in geographic atrophy, multiple sclerosis, and glioblastoma, demonstrating its ability to effectively forecast disease progression and outperform existing methods. Our contributions include the development of ImageFlowNet, its theoretical underpinnings, and empirical validation on real-world datasets. The official implementation is available at https://github.com/KrishnaswamyLab/ImageFlowNet.

  • 11 authors
·
Jun 20, 2024