Magnetic resonance imaging of the human locus coeruleus: A systematic review

Abstract

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies.

Higher rostral locus coeruleus integrity is associated with better memory performance in older adults

“…Repeated measurements of an independent younger adult sample further confirmed high reproducibility of the intensity assessment (see Supplemental results). However, as reported earlier for neuromelanin-sensitive sequences, our analyses do not capture the complete LC extent 47,66 leading to lower volume estimates than those obtained post-mortem studies 15 . In their histological analyses, Fernandes and colleagues describe a common, central LC zone which is shared across all subjects 14 .…”

“…We developed a semi-automatic procedure to extract individual LC ratios 47 , that is, a ratio score of peak LC MRI intensity relative to peak intensity in a dorsal pontine reference region, across the rostrocaudal extent of the nucleus (see Online methods and Figure 3a-c). The procedure evinced high reproducibility across multiple measurements (see Supplemental results) and was validated using both published LC maps (see Figure 3d) and manual intensity assessments (see Supplemental results).…”

“…For some participants, specific absorption rate (SAR) limits were exceeded, which precluded further scanning with the current set of parameters (cf. 47,64 ). To avoid data loss while maintaining contrast settings, for those participants the maximal number of TSE slices was reduced.…”

“…In noradrenergic cells, neuromelanin avidly chelates metals such as copper and iron and, as a compound, shows paramagnetic, T 1 -shortening effects 45 . Sasaki and colleagues developed a neuromelanin-sensitive Turbo Spin Echo (TSE) MRI sequence that visualizes the LC as an hyperintense area adjacent to the lateral floor of the fourth ventricle 46 (for a review of neuromelanin-sensitive MRI studies, see Liu and others 47 ). Keren To determine the importance of MRI-indexed, structural LC integrity for the maintenance of memory functioning in vivo, we assessed individual differences in learning and memory among younger and older adults with the Rey Auditory Verbal Learning Test (RAVLT), a validated neuropsychological measure of memory functioning.…”

Right-lateralized fronto-parietal network and phasic alertness in healthy aging

“…Second, our study lacks a direct link to the locus coeruleusnoradrenaline system as we did not include a specific readout. Neuromelanin-sensitive MRI sequences are a promising tool for quantifying locus coeruleus intergrity 59,60 . In addition, measuring pupil dilation would provide a window into locus coeruleus activity (for a review see 18 ).…”