Journal Article

Characterization of an automated method to segment the human locus coeruleus

Gandhi, Rushali, Al‐Haddad, Rami, Chamoun, Mira, Pascoal, Tharick, Rosa‐Neto, Pedro, Sibahi, Ahmad, Therriault, Joseph, Tardif, Christine, Cassidy, Clifford M., Boutin‐Miller, Krysta

2023

Overview

Following the development of magnetic resonance imaging (MRI) methods to assay the integrity of catecholamine nuclei, including the locus coeruleus (LC), there has been an effort to develop automated methods that can accurately segment this small structure in an automated manner to promote its widespread use and overcome limitations of manual segmentation. Here we characterize an automated LC segmentation approach (referred to as the funnel‐tip [FT] method) in healthy individuals and individuals with LC degeneration in the context of Alzheimer's disease (AD, confirmed with tau‐PET imaging using [18F]MK6240). The first sample included n = 190 individuals across the AD spectrum from cognitively normal to moderate AD. LC signal assayed with FT segmentation showed excellent agreement with manual segmentation (intraclass correlation coefficient [ICC] = 0.91). Compared to other methods, the FT method showed numerically higher correlation to AD status (defined by presence of tau: Cohen's d = 0.64) and AD severity (Braak stage: Pearson R = −.35, cognitive function: R = .25). In a separate sample of n = 12 control participants, the FT method showed excellent scan–rescan reliability (ICC = 0.82). In another sample of n = 30 control participants, we found that the structure of the LC defined by FT segmentation approximated its expected shape as a contiguous line: <5% of LC voxels strayed >1 voxel (0.69 mm) from this line. The FT LC segmentation shows high agreement with manual segmentation and captures LC degeneration in AD. This practical method may facilitate larger research studies of the human LC‐norepinephrine system and has potential to support future use of neuromelanin‐sensitive MRI as a clinical biomarker. The automated segmentation (funnel tip [FT]) method showed good agreement to manual segmentation in measuring LC signal and LC localization. FT method showed numerically higher correlation to Alzheimer's disease severity measures compared to other segmentation approaches. FT method demonstrated a high scan–rescan reliability and provided a practical method to segment the LC along its full rostrocaudal extent.

• Publisher: John Wiley & Sons, Inc
• Subject: Aging / Alzheimer Disease - diagnostic imaging / Alzheimer Disease - pathology / Alzheimer's disease / automated / Automation / Biomarkers / Brain research / Catecholamine / Catecholamines / Cognitive ability / Correlation coefficient / Correlation coefficients / Degeneration / Dementia / Humans / Illnesses / Image segmentation / Loci / Locus coeruleus / Locus Coeruleus - diagnostic imaging / Magnetic resonance imaging / magnetic resonance imaging (MRI) / Magnetic Resonance Imaging - methods / Masks / Medical imaging / Neurodegenerative diseases / Neuroimaging / Norepinephrine / norepinephrine system / Positron emission / Positron emission tomography / Reproducibility of Results / Research ethics / segmentation / Tau protein