Abstract
The locus coeruleus (LC) is a brainstem nucleus involved in important cognitive functions. Recent developments in neuroimaging methods and scanning protocols have made it possible to visualize the human LC in vivo by utilizing a T1-weighted turbo spin echo (TSE) scan. Despite its frequent use and its application as a biomarker for tracking the progress of monoaminergic-related neurodegenerative diseases, no study to date has investigated the reproducibility and inter-observer variability of LC identification using this TSE scan sequence. In this paper, we aim to quantify the test–retest reliability of LC imaging by assessing stability of the TSE contrast of the LC across two independent scan sessions and by quantifying the intra- and inter-rater reliability of the TSE scan. Additionally, we created a probabilistic LC atlas which can facilitate the spatial localization of the LC in standardized (MNI) space. Seventeen healthy volunteers participated in two scanning sessions with a mean intersession interval of 2.8 months. We found that for intra-rater reliability the mean Dice coefficient ranged between 0.65 and 0.74, and inter-rater reliability ranged between 0.54 and 0.64, showing moderate reproducibility. The mean LC contrast was 13.9% (SD 3.8) and showed scan–rescan stability (ROI approach: ICC = 0.63; maximum intensity approach: ICC = 0.53). We conclude that localization and segmentation of the LC in vivo are a challenging but reliable enterprise although clinical or longitudinal studies should be carried out carefully.
Highlights
Recent developments in neuroimaging methods and scanning protocols have made possible what had been challenging for many years: the visualization of the human brainstem nucleus locus coeruleus (LC) in vivo
The visualization of the LC has been made possible by the adaptation of a T1-weighted turbo spin echo (TSE) scan sequence for 3-T MRI, which is thought to be sensitive to neuromelanin (Keren et al 2015; Sasaki et al 2006)
The most important findings of this study are threefold: First, there was a moderate scan–rescan reliability of the TSE scan in visualizing the LC; second, the LC volume estimated with the TSE scan appears to be smaller than volumes reported in ex vivo studies; and third, we observed a lateralization effect in terms of LC volume and intensity
Summary
Recent developments in neuroimaging methods and scanning protocols have made possible what had been challenging for many years: the visualization of the human brainstem nucleus locus coeruleus (LC) in vivo. Given that LC dysfunction plays an important role in cognitive and neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease (Grudzien et al 2007; Mravec et al 2014), multiple system atrophy, and monoamine-related psychiatric disorders such as depression (Ressler and Nemeroff 1999; Schramm, McDonald and Limbird 2001) and schizophrenia (van Kammen and Kelley 1991), it has been suggested that TSE scans may be used as a diagnostic tool for tracking the progression of these disorders (Matsuura et al 2013; Ohtsuka et al 2013; Sasaki et al 2006, 2008; Takahashi et al 2015), as a biomarker for the efficacy of attention-related pharmaceutical treatments (Keren et al 2009) or as a biomarker for differential diagnosis of parkinsonian disorders (e.g., differentiate Parkinson’s disease from multiple system atrophy) (Matsuura et al 2013) This requires a reliable and robust scan protocol that allows delineation of the LC in a reproducible manner across different time points and by different raters/clinicians. To date no study has investigated the reproducibility and inter-observer variability of the LC masks identified using the TSE scan sequence
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