Colin Magdamo

Benjamin Billot, Colin Magdamo, You Cheng et al.

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 is robust enough to cope with the high variability in clinical acquisitions (MR contrasts, resolutions, orientations, artefacts, subject populations). Here we present SynthSeg+, an AI segmentation suite that enables, for the first time, robust analysis of heterogeneous clinical datasets. 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.

Karthik Gopinath, Douglas N. Greve, Colin Magdamo et al.

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.

Jesper Duemose Nielsen, Karthik Gopinath, Andrew Hoopes et al.

Surface-based cortical analysis is valuable for a variety of neuroimaging tasks, such as spatial normalization, parcellation, and gray matter (GM) thickness estimation. However, most tools for estimating cortical surfaces work exclusively on scans with at least 1 mm isotropic resolution and are tuned to a specific magnetic resonance (MR) contrast, often T1-weighted (T1w). This precludes application using most clinical MR scans, which are very heterogeneous in terms of contrast and resolution. Here, we use synthetic domain-randomized data to train the first neural network for explicit estimation of cortical surfaces from scans of any contrast and resolution, without retraining. Our method deforms a template mesh to the white matter (WM) surface, which guarantees topological correctness. This mesh is further deformed to estimate the GM surface. We compare our method to recon-all-clinical (RAC), an implicit surface reconstruction method which is currently the only other tool capable of processing heterogeneous clinical MR scans, on ADNI and a large clinical dataset (n=1,332). We show a approximately 50 % reduction in cortical thickness error (from 0.50 to 0.24 mm) with respect to RAC and better recovery of the aging-related cortical thinning patterns detected by FreeSurfer on high-resolution T1w scans. Our method enables fast and accurate surface reconstruction of clinical scans, allowing studies (1) with sample sizes far beyond what is feasible in a research setting, and (2) of clinical populations that are difficult to enroll in research studies. The code is publicly available at https://github.com/simnibs/brainnet.

Yu Leng, Yingnan He, Colin Magdamo et al.

Identifying cognitive impairment within electronic health records (EHRs) is crucial not only for timely diagnoses but also for facilitating research. Information about cognitive impairment often exists within unstructured clinician notes in EHRs, but manual chart reviews are both time-consuming and error-prone. To address this issue, our study evaluates an automated approach using zero-shot GPT-4o to determine stage of cognitive impairment in two different tasks. First, we evaluated the ability of GPT-4o to determine the global Clinical Dementia Rating (CDR) on specialist notes from 769 patients who visited the memory clinic at Massachusetts General Hospital (MGH), and achieved a weighted kappa score of 0.83. Second, we assessed GPT-4o's ability to differentiate between normal cognition, mild cognitive impairment (MCI), and dementia on all notes in a 3-year window from 860 Medicare patients. GPT-4o attained a weighted kappa score of 0.91 in comparison to specialist chart reviews and 0.96 on cases that the clinical adjudicators rated with high confidence. Our findings demonstrate GPT-4o's potential as a scalable chart review tool for creating research datasets and assisting diagnosis in clinical settings in the future.

Matthew West, Colin Magdamo, Lily Cheng et al.

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.

Karthik Gopinath, Douglas N. Greve, Sudeshna Das et al.

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

Tanish Tyagi, Colin G. Magdamo, Ayush Noori et al.

Dementia related cognitive impairment (CI) is a neurodegenerative disorder, affecting over 55 million people worldwide and growing rapidly at the rate of one new case every 3 seconds. 75% cases go undiagnosed globally with up to 90% in low-and-middle-income countries, leading to an estimated annual worldwide cost of USD 1.3 trillion, forecasted to reach 2.8 trillion by 2030. With no cure, a recurring failure of clinical trials, and a lack of early diagnosis, the mortality rate is 100%. Information in electronic health records (EHR) can provide vital clues for early detection of CI, but a manual review by experts is tedious and error prone. Several computational methods have been proposed, however, they lack an enhanced understanding of the linguistic context in complex language structures of EHR. Therefore, I propose a novel and more accurate framework, NeuraHealth, to identify patients who had no earlier diagnosis. In NeuraHealth, using patient EHR from Mass General Brigham BioBank, I fine-tuned a bi-directional attention-based deep learning natural language processing model to classify sequences. The sequence predictions were used to generate structured features as input for a patient level regularized logistic regression model. This two-step framework creates high dimensionality, outperforming all existing state-of-the-art computational methods as well as clinical methods. Further, I integrate the models into a real-world product, a web app, to create an automated EHR screening pipeline for scalable and high-speed discovery of undetected CI in EHR, making early diagnosis viable in medical facilities and in regions with scarce health services.

Tanish Tyagi, Colin G. Magdamo, Ayush Noori et al.

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.

Zhuoqiao Hong, Colin G. Magdamo, Yi-han Sheu et al.

Dementia is under-recognized in the community, under-diagnosed by healthcare professionals, and under-coded in claims data. Information on cognitive dysfunction, however, is often found in unstructured clinician notes within medical records but manual review by experts is time consuming and often prone to errors. Automated mining of these notes presents a potential opportunity to label patients with cognitive concerns who could benefit from an evaluation or be referred to specialist care. In order to identify patients with cognitive concerns in electronic medical records, we applied natural language processing (NLP) algorithms and compared model performance to a baseline model that used structured diagnosis codes and medication data only. An attention-based deep learning model outperformed the baseline model and other simpler models.