Bradley T. Hyman

Lin Tian, Sean I. Young, Jonathan Williams Ramirez et al. · harvard

Correlation of neuropathology with MRI has the potential to transfer microscopic signatures of pathology to invivo scans. Recently, a classical registration method has been proposed, to build these correlations from 3D reconstructed stacks of dissection photographs, which are routinely taken at brain banks. These photographs bypass the need for exvivo MRI, which is not widely accessible. However, this method requires a full stack of brain slabs and a reference mask (e.g., acquired with a surface scanner), which severely limits the applicability of the technique. Here we propose RefFree, a dissection photograph reconstruction method without external reference. RefFree is a learning approach that estimates the 3D coordinates in the atlas space for every pixel in every photograph; simple least-squares fitting can then be used to compute the 3D reconstruction. As a by-product, RefFree also produces an atlas-based segmentation of the reconstructed stack. RefFree is trained on synthetic photographs generated from digitally sliced 3D MRI data, with randomized appearance for enhanced generalization ability. Experiments on simulated and real data show that RefFree achieves performance comparable to the baseline method without an explicit reference while also enabling reconstruction of partial stacks. Our code is available at https://github.com/lintian-a/reffree.

Jonathan Williams Ramirez, Dina Zemlyanker, Lucas Deden-Binder et al.

Advances in image registration and machine learning have recently enabled volumetric analysis of postmortem brain tissue from conventional photographs of coronal slabs, which are routinely collected in brain banks and neuropathology laboratories worldwide. One caveat of this methodology is the requirement of segmentation of the tissue from photographs, which currently requires costly manual intervention. In this article, we present a deep learning model to automate this process. The automatic segmentation tool relies on a U-Net architecture that was trained with a combination of 1,414 manually segmented images of both fixed and fresh tissue, from specimens with varying diagnoses, photographed at two different sites. Automated model predictions on a subset of photographs not seen in training were analyzed to estimate performance compared to manual labels, including both inter- and intra-rater variability. Our model achieved a median Dice score over 0.98, mean surface distance under 0.4mm, and 95\% Hausdorff distance under 1.60mm, which approaches inter-/intra-rater levels. Our tool is publicly available at surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools.

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.