Recon-all-clinical: Cortical surface reconstruction and analysis of heterogeneous clinical brain MRI

Surface-based analysis of the cerebral cortex is ubiquitous in human neuroimaging with MRI. It is crucial for cortical registration, parcellation, and thickness estimation. Traditionally, these analyses require high-resolution, isotropic scans with good gray-white matter contrast, typically a 1mm T1-weighted scan. This excludes most clinical MRI scans, which are often anisotropic and lack the necessary T1 contrast. To enable large-scale neuroimaging studies using vast clinical data, we introduce recon-all-clinical, a novel method for cortical reconstruction, registration, parcellation, and thickness estimation in brain MRI scans of any resolution and contrast. Our approach employs a hybrid analysis method that combines a convolutional neural network (CNN) trained with domain randomization to predict signed distance functions (SDFs) and classical geometry processing for accurate surface placement while maintaining topological and geometric constraints. The method does not require retraining for different acquisitions, thus simplifying the analysis of heterogeneous clinical datasets. We tested recon-all-clinical on multiple datasets, including over 19,000 clinical scans. The method consistently produced precise cortical reconstructions and high parcellation accuracy across varied MRI contrasts and resolutions. Cortical thickness estimates are precise enough to capture aging effects independently of MRI contrast, although accuracy varies with slice thickness. Our method is publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/recon-all-clinical, enabling researchers to perform detailed cortical analysis on the huge amounts of already existing clinical MRI scans. This advancement may be particularly valuable for studying rare diseases and underrepresented populations where research-grade MRI data is scarce.

Two-layer retrieval augmented generation framework for low-resource medical question-answering: proof of concept using Reddit data

Retrieval augmented generation (RAG) provides the capability to constrain generative model outputs, and mitigate the possibility of hallucination, by providing relevant in-context text. The number of tokens a generative large language model (LLM) can incorporate as context is finite, thus limiting the volume of knowledge from which to generate an answer. We propose a two-layer RAG framework for query-focused answer generation and evaluate a proof-of-concept for this framework in the context of query-focused summary generation from social media forums, focusing on emerging drug-related information. The evaluations demonstrate the effectiveness of the two-layer framework in resource constrained settings to enable researchers in obtaining near real-time data from users.

Reddit-Impacts: A Named Entity Recognition Dataset for Analyzing Clinical and Social Effects of Substance Use Derived from Social Media

Substance use disorders (SUDs) are a growing concern globally, necessitating enhanced understanding of the problem and its trends through data-driven research. Social media are unique and important sources of information about SUDs, particularly since the data in such sources are often generated by people with lived experiences. In this paper, we introduce Reddit-Impacts, a challenging Named Entity Recognition (NER) dataset curated from subreddits dedicated to discussions on prescription and illicit opioids, as well as medications for opioid use disorder. The dataset specifically concentrates on the lesser-studied, yet critically important, aspects of substance use--its clinical and social impacts. We collected data from chosen subreddits using the publicly available Application Programming Interface for Reddit. We manually annotated text spans representing clinical and social impacts reported by people who also reported personal nonmedical use of substances including but not limited to opioids, stimulants and benzodiazepines. Our objective is to create a resource that can enable the development of systems that can automatically detect clinical and social impacts of substance use from text-based social media data. The successful development of such systems may enable us to better understand how nonmedical use of substances affects individual health and societal dynamics, aiding the development of effective public health strategies. In addition to creating the annotated data set, we applied several machine learning models to establish baseline performances. Specifically, we experimented with transformer models like BERT, and RoBERTa, one few-shot learning model DANN by leveraging the full training dataset, and GPT-3.5 by using one-shot learning, for automatic NER of clinical and social impacts. The dataset has been made available through the 2024 SMM4H shared tasks.

CARE-SD: Classifier-based analysis for recognizing and eliminating stigmatizing and doubt marker labels in electronic health records: model development and validation

Objective: To detect and classify features of stigmatizing and biased language in intensive care electronic health records (EHRs) using natural language processing techniques. Materials and Methods: We first created a lexicon and regular expression lists from literature-driven stem words for linguistic features of stigmatizing patient labels, doubt markers, and scare quotes within EHRs. The lexicon was further extended using Word2Vec and GPT 3.5, and refined through human evaluation. These lexicons were used to search for matches across 18 million sentences from the de-identified Medical Information Mart for Intensive Care-III (MIMIC-III) dataset. For each linguistic bias feature, 1000 sentence matches were sampled, labeled by expert clinical and public health annotators, and used to supervised learning classifiers. Results: Lexicon development from expanded literature stem-word lists resulted in a doubt marker lexicon containing 58 expressions, and a stigmatizing labels lexicon containing 127 expressions. Classifiers for doubt markers and stigmatizing labels had the highest performance, with macro F1-scores of .84 and .79, positive-label recall and precision values ranging from .71 to .86, and accuracies aligning closely with human annotator agreement (.87). Discussion: This study demonstrated the feasibility of supervised classifiers in automatically identifying stigmatizing labels and doubt markers in medical text, and identified trends in stigmatizing language use in an EHR setting. Additional labeled data may help improve lower scare quote model performance. Conclusions: Classifiers developed in this study showed high model performance and can be applied to identify patterns and target interventions to reduce stigmatizing labels and doubt markers in healthcare systems.

Leveraging Pre-trained and Transformer-derived Embeddings from EHRs to Characterize Heterogeneity Across Alzheimer's Disease and Related Dementias

Alzheimer's disease is a progressive, debilitating neurodegenerative disease that affects 50 million people globally. Despite this substantial health burden, available treatments for the disease are limited and its fundamental causes remain poorly understood. Previous work has suggested the existence of clinically-meaningful sub-types, which it is suggested may correspond to distinct etiologies, disease courses, and ultimately appropriate treatments. Here, we use unsupervised learning techniques on electronic health records (EHRs) from a cohort of memory disorder patients to characterise heterogeneity in this disease population. Pre-trained embeddings for medical codes as well as transformer-derived Clinical BERT embeddings of free text are used to encode patient EHRs. We identify the existence of sub-populations on the basis of comorbidities and shared textual features, and discuss their clinical significance.

Cortical analysis of heterogeneous clinical brain MRI scans for large-scale neuroimaging studies

Surface analysis of the cortex is ubiquitous in human neuroimaging with MRI, e.g., for cortical registration, parcellation, or thickness estimation. The convoluted cortical geometry requires isotropic scans (e.g., 1mm MPRAGEs) and good gray-white matter contrast for 3D reconstruction. This precludes the analysis of most brain MRI scans acquired for clinical purposes. Analyzing such scans would enable neuroimaging studies with sample sizes that cannot be achieved with current research datasets, particularly for underrepresented populations and rare diseases. Here we present the first method for cortical reconstruction, registration, parcellation, and thickness estimation for clinical brain MRI scans of any resolution and pulse sequence. The methods has a learning component and a classical optimization module. The former uses domain randomization to train a CNN that predicts an implicit representation of the white matter and pial surfaces (a signed distance function) at 1mm isotropic resolution, independently of the pulse sequence and resolution of the input. The latter uses geometry processing to place the surfaces while accurately satisfying topological and geometric constraints, thus enabling subsequent parcellation and thickness estimation with existing methods. We present results on 5mm axial FLAIR scans from ADNI and on a highly heterogeneous clinical dataset with 5,000 scans. Code and data are publicly available at https://surfer.nmr.mgh.harvard.edu/fswiki/recon-all-clinical

Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets

Every year, millions of brain MRI scans are acquired in hospitals, which is a figure considerably larger than the size of any research dataset. Therefore, the ability to analyse such scans could transform neuroimaging research. Yet, their potential remains untapped, since no automated algorithm can cope with the high variability in clinical acquisitions (MR contrast, resolution, orientation, etc.). Here we present SynthSeg+, an AI segmentation suite that enables, for the first time, robust analysis of heterogeneous clinical datasets. Specifically, in addition to whole-brain segmentation, SynthSeg+ also performs cortical parcellation, intracranial volume estimation, and automated detection of faulty segmentations (mainly caused by scans of very low quality). We demonstrate SynthSeg+ in seven experiments, including an ageing study on 14,000 scans, where it accurately replicates atrophy patterns observed on data of much higher quality. SynthSeg+ is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry in wide-ranging settings.

Multi-confound regression adversarial network for deep learning-based diagnosis on highly heterogenous clinical data

Automated disease detection in medical images using deep learning holds promise to improve the diagnostic ability of radiologists, but routinely collected clinical data frequently contains technical and demographic confounding factors that differ between hospitals, negatively affecting the robustness of diagnostic deep learning models. Thus, there is a critical need for deep learning models that can train on imbalanced datasets without overfitting to site-specific confounding factors. In this work, we developed a novel deep learning architecture, MUCRAN (Multi-Confound Regression Adversarial Network), to train a deep learning model on highly heterogeneous clinical data while regressing demographic and technical confounding factors. We trained MUCRAN using 16,821 clinical T1 Axial brain MRIs collected from Massachusetts General Hospital before 2019 and tested it using post-2019 data to distinguish Alzheimer's disease (AD) patients, identified using both prescriptions of AD drugs and ICD codes, from a non-medicated control group. In external validation tests using MRI data from other hospitals, the model showed a robust performance of over 90% accuracy on newly collected data. This work shows the feasibility of deep learning-based diagnosis in real-world clinical data.

Robust Segmentation of Brain MRI in the Wild with Hierarchical CNNs and no Retraining

Retrospective analysis of brain MRI scans acquired in the clinic has the potential to enable neuroimaging studies with sample sizes much larger than those found in research datasets. However, analysing such clinical images "in the wild" is challenging, since subjects are scanned with highly variable protocols (MR contrast, resolution, orientation, etc.). Nevertheless, recent advances in convolutional neural networks (CNNs) and domain randomisation for image segmentation, best represented by the publicly available method SynthSeg, may enable morphometry of clinical MRI at scale. In this work, we first evaluate SynthSeg on an uncurated, heterogeneous dataset of more than 10,000 scans acquired at Massachusetts General Hospital. We show that SynthSeg is generally robust, but frequently falters on scans with low signal-to-noise ratio or poor tissue contrast. Next, we propose SynthSeg+, a novel method that greatly mitigates these problems using a hierarchy of conditional segmentation and denoising CNNs. We show that this method is considerably more robust than SynthSeg, while also outperforming cascaded networks and state-of-the-art segmentation denoising methods. Finally, we apply our approach to a proof-of-concept volumetric study of ageing, where it closely replicates atrophy patterns observed in research studies conducted on high-quality, 1mm, T1-weighted scans. The code and trained model are publicly available at https://github.com/BBillot/SynthSeg.

Using Deep Learning to Identify Patients with Cognitive Impairment in Electronic Health Records

Dementia is a neurodegenerative disorder that causes cognitive decline and affects more than 50 million people worldwide. Dementia is under-diagnosed by healthcare professionals - only one in four people who suffer from dementia are diagnosed. Even when a diagnosis is made, it may not be entered as a structured International Classification of Diseases (ICD) diagnosis code in a patient's charts. Information relevant to cognitive impairment (CI) is often found within electronic health records (EHR), but manual review of clinician notes by experts is both time consuming and often prone to errors. Automated mining of these notes presents an opportunity to label patients with cognitive impairment in EHR data. We developed natural language processing (NLP) tools to identify patients with cognitive impairment and demonstrate that linguistic context enhances performance for the cognitive impairment classification task. We fine-tuned our attention based deep learning model, which can learn from complex language structures, and substantially improved accuracy (0.93) relative to a baseline NLP model (0.84). Further, we show that deep learning NLP can successfully identify dementia patients without dementia-related ICD codes or medications.