INTRODUCTION:

Parkinson’s disease is characterized by a depletion of catecholaminergic neurons in mid-brain nuclei, including the substantial nigra (SN) and the locus coeruleus (LC). Our previous work and a few other MRI studies have investigated the neuromelanin changes in SN and LC caused by such neurodegenerative diseases. However, very few have revealed the physiological changes during human development and normal ageing. To address this question, we aim to noninvasively inspect these changes of SN and LC across a wide range of age in healthy subjects using neuromelanin-sensitive MRI for the first time.

METHODS:

Subjects: Forty-three healthy subjects aged from 6.5 to 78 years old (mean age ± SD, 32.4 ± 20.4, 22 male, 21 female) underwent neuromelanin-sensitive T1-weighted image sequence using the following parameters on a 3T GE scanner: TR: 38.4ms; TE: 3ms; slice thickness: 2mm with 2mm gap. 3.25min scanning time was used to collect 30 image slices. Image Analysis: A Matlab based semi-automated method was used to count the suprathreshold hyperintense voxels in bilateral SNs in three consecutive slices. Two standard deviations from the average intensity extracted from the three background ROIs (at midbrain tegmentum and cerebral peduncles) were chosen given the lack of neuromelanin in young children. In addition, we calculated the contrast ratio by dividing the mean intensity of the four voxels neighbouring the voxel with maximum intensity in bilateral LC by the average signal of the background ROIs at pons in four consecutive slices. SN suprathreshold voxel counts and LC contrast ratio were correlated, respectively with age. Polynomial regression analysis alpha level of 0.05 was performed for statistical significance.

RESULTS:

Polynomial regression analysis with quadratic curve fitting showed that the contrast ratio of the LC increased to the age of 45 to 55 years and gradually and significantly decreased in elderly normal subjects for all three slices. Similarly, the above-threshold voxels count was significantly correlated with age.

DISCUSSION:

This result provided corroborative evidence to the ex-vivo histological study based on post-mortem brain specimen, suggesting that neuromelanin deposited within the cells in an age-dependent manner and is scarce at birth with incremental accumulation as age increases. Moreover, it was consistent with and expand the previous MRI findings of LC, which did not include children and teenagers. Further, the gradual drop in both SN and LC may indicate a good correlation with age-related neurodegenerative pathology in neuromelanin content within these two nuclei.

CONCLUSION:

As best of our knowledge, this is the first study to investigate the physiological changes of SN and LC in healthy subjects across human development and aging using MRI. The suprathreshold hyperintense voxel counts as well as the signal intensity showed a reversed U-shape with age, suggesting that neuromelanin-sensitive imaging can be used as an indicator for quantitatively measure age-related changes. This may also be helpful to reflect the abnormalities due to diseases involved neuromelanin-contained neurons.

Acknowledgements

Parkinson's UK for funding

References

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