Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

Abstract

Purpose: To investigate age-related changes in the locus ceruleus (LC) in healthy subjects using neuromelanin magnetic resonance (MR) imaging at 3 Tesla.Methods: We examined 64 healthy volunteers (aged 23 to 80 years) using neuromelaninsensitive T 1 -weighted images and measured the contrast of areas of high signal intensity corresponding to the LC.Results: A pair of punctate areas of high signal intensity that represented neuromelanin within the noradrenergic neurons of the LC was easily recognized in all subjects. The contrast ratio of the LC to the adjacent pontine tegmentum increased to the age of 40 to 59 years and gradually and signiˆcantly decreased in elderly subjects. This correlates well with pathologically proven age-related changes in neuromelanin content within the LC.Conclusion: Age-related variance should be considered when determining the existence of abnormalities in the LC.

Neuromelanin-Sensitive MRI

“…By using multidirectional images, we could visualize the three-dimensional distributions of the SNc, and observed distributions were closely correlated with those described in neuroanatomic textbooks (Figure 3). Neuromelanin-sensitive MRI also visualizes bilateral areas of rod-shaped high signal intensity within the pontine tegmentum, immediately anterolateral to the fourth ventricle floor at the level of the upper pons (Figures 2 and 3) [2,3]. The location was identical to that of the LC in the gross specimen, suggesting that the high-signal spots reflect the neuromelanin in the noradrenergic neurons of the LC.…”

“…The neuronal number and intraneuronal neuromelanin content of the SNc and LC change substantially with age [27,28]. Our preliminary study showed a significant age-dependent variance in the signal intensity of the LC [3]; this variance should be considered while evaluating signal alteration. The iron concentration in the SNc neurons, which strongly influences the T1-shortening effects of neuromelanin [13], is increased in normal subjects with aging and in PD patients [28,29].…”

“…However, these nuclei have remained invisible on magnetic resonance imaging (MRI), and the neuromelanin-generated contrast has hardly been studied. Recently, we proposed a new MRI technique that can depict the neuromelanin-related contrast generated by these nuclei and demonstrate pathologic changes occurring in some degenerative and psychiatric diseases [2][3][4][5]. In this review, we introduce the basics, the imaging technique, and clinical applications of neuromelanin-sensitive MRI.…”

Monoamine neurons in the human brain stem: anatomy, magnetic resonance imaging findings, and clinical implications

“…On neuromelanin-sensitive MR axial images, it is identified as a spotty high signal intensity area in the upper pontine tegmentum [17,20] (Fig. 3).…”

Mechanisms underlying memory enhancement in humans

“…In a new set of experiments, the same authors have recently demonstrated a positive correlation between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC by simultaneously recording pupilometry and fMRI both at rest and during performance of a two-stimulus oddball task (Murphy, O'Connell, O'Sullivan, Robertson, & Balsters, 2014). LC was localized via both neuromelaninsensitive structural imaging (Shibata et al, 2006) and a previously published LC atlas (Keren, Lozar, Harris, Morgan, & Eckert, 2009). This relationship was present with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise (Glover, Li & Ress, 2000).…”