학술논문

Toward a generalizable machine learning workflow for neurodegenerative disease staging with focus on neurofibrillary tangles
Document Type
article
Source
Acta Neuropathologica Communications. 11(1)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Neurosciences
Biological Sciences
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Aging
Alzheimer's Disease
Acquired Cognitive Impairment
Brain Disorders
Neurodegenerative
Dementia
Humans
Neurofibrillary Tangles
Neurodegenerative Diseases
tau Proteins
Workflow
Brain
Alzheimer Disease
Machine Learning
Neuropathology
Machine learning
Model-assisted-labeling
Alzheimer's disease
Neurofibrillary tangles
Braak NFT staging
Whole-slide-images
Alzheimer’s disease
Clinical Sciences
Biochemistry and cell biology
Language
Abstract
Machine learning (ML) has increasingly been used to assist and expand current practices in neuropathology. However, generating large imaging datasets with quality labels is challenging in fields which demand high levels of expertise. Further complicating matters is the often seen disagreement between experts in neuropathology-related tasks, both at the case level and at a more granular level. Neurofibrillary tangles (NFTs) are a hallmark pathological feature of Alzheimer disease, and are associated with disease progression which warrants further investigation and granular quantification at a scale not currently accessible in routine human assessment. In this work, we first provide a baseline of annotator/rater agreement for the tasks of Braak NFT staging between experts and NFT detection using both experts and novices in neuropathology. We use a whole-slide-image (WSI) cohort of neuropathology cases from Emory University Hospital immunohistochemically stained for Tau. We develop a workflow for gathering annotations of the early stage formation of NFTs (Pre-NFTs) and mature intracellular (iNFTs) and show ML models can be trained to learn annotator nuances for the task of NFT detection in WSIs. We utilize a model-assisted-labeling approach and demonstrate ML models can be used to aid in labeling large datasets efficiently. We also show these models can be used to extract case-level features, which predict Braak NFT stages comparable to expert human raters, and do so at scale. This study provides a generalizable workflow for various pathology and related fields, and also provides a technique for accomplishing a high-level neuropathology task with limited human annotations.