Background

Previous works have demonstrated that iron tends to accumulate in deep brain nuclei during aging. However, in some structures (e.g. thalamus), this trend has been disputed.

Objectives

The main objective of this study was to quantify age-related changes in regional brain magnetic susceptibilities in healthy subjects.

Methods

Brain MRI was performed in 103 healthy individuals (62 females and 41 males) aged between 21 and 56 years. MRI was performed on a 3T scanner and included 3D MPRAGE T1-weighted images in sagittal plane, susceptibility weighted images (3D flow-compensated multi-echo GRE scan) for quantitative susceptibility mapping (QSM). QSM images were calculated using QSMbox package in MATLAB and co-registered with 3D MPRAGE in order to perform skull stripping (FSL BET), multi-atlas segmentation (MRICloud), and extraction of mean bulk magnetic susceptibility.

Results

Mean susceptibility (ppm) values ranged between 0.00 in total white matter and 0.95 in the substantia nigra. We found no significant differences between genders in magnetic susceptibilities in any of the examined structures. There was a positive correlation between age and magnetic susceptibility in the putamen (r=0.6443, p<0.0001), external globus pallidus (r= 0.5085, p<0.0001), red nucleus (r= 0.5015, p<0.0001), caudate (r=0.4525, p<0.0001), cerebral and cerebellar cortex (r= 0.4246, p<0.0001), substantia nigra (r=0.4060, p<0.0001), subthalamic nucleus (r= 0.3611, p=0.0002), internal globus pallidus (r= 0.2749, p=0.0049), and pulvinar (r= 0.2292, p=0.0199). Negative correlation was found in white matter (r= - 0.2792, p=0.0043) and thalamus (r= - 0.1947, p=0.0488).

Conclusions

We report evolution of regional brain magnetic susceptibilities in healthy subjects during aging. The results of this study define normal brain susceptibility values for age groups between 20 and 60 years; they may be used for iron level estimation in deep grey matter and as additional biomarkers of neurodegenerative diseases and multiple sclerosis. Our results suggest that iron content in external globus pallidus increases with aging, a finding that has previously been disputed. We demonstrate a positive age-related susceptibility increase in pulvinar while the opposite, i.e. gradual susceptibility decrease, was observed in other thalamic nuclei emphasising the necessity of separate analysis of these thalamic subregions. Gender does not relevantly impact susceptibility variations in brain tissue. The results of this study define normal brain iron levels which may be used as biomarkers of neurodegenerative and neuroinflammatory changes.

This study was supported by the Czech Ministry of Health grant (NV18-08-00062, 15-25602A, and RVO VFN64165), by the Charles University in Prague grant (PROGRES Q27) and by Roche company.

Background

Previous works have demonstrated that iron tends to accumulate in deep brain nuclei during aging. However, in some structures (e.g. thalamus), this trend has been disputed.

Objectives

The main objective of this study was to quantify age-related changes in regional brain magnetic susceptibilities in healthy subjects.

Methods

Brain MRI was performed in 103 healthy individuals (62 females and 41 males) aged between 21 and 56 years. MRI was performed on a 3T scanner and included 3D MPRAGE T1-weighted images in sagittal plane, susceptibility weighted images (3D flow-compensated multi-echo GRE scan) for quantitative susceptibility mapping (QSM). QSM images were calculated using QSMbox package in MATLAB and co-registered with 3D MPRAGE in order to perform skull stripping (FSL BET), multi-atlas segmentation (MRICloud), and extraction of mean bulk magnetic susceptibility.

Results

Mean susceptibility (ppm) values ranged between 0.00 in total white matter and 0.95 in the substantia nigra. We found no significant differences between genders in magnetic susceptibilities in any of the examined structures. There was a positive correlation between age and magnetic susceptibility in the putamen (r=0.6443, p<0.0001), external globus pallidus (r= 0.5085, p<0.0001), red nucleus (r= 0.5015, p<0.0001), caudate (r=0.4525, p<0.0001), cerebral and cerebellar cortex (r= 0.4246, p<0.0001), substantia nigra (r=0.4060, p<0.0001), subthalamic nucleus (r= 0.3611, p=0.0002), internal globus pallidus (r= 0.2749, p=0.0049), and pulvinar (r= 0.2292, p=0.0199). Negative correlation was found in white matter (r= - 0.2792, p=0.0043) and thalamus (r= - 0.1947, p=0.0488).

Conclusions

We report evolution of regional brain magnetic susceptibilities in healthy subjects during aging. The results of this study define normal brain susceptibility values for age groups between 20 and 60 years; they may be used for iron level estimation in deep grey matter and as additional biomarkers of neurodegenerative diseases and multiple sclerosis. Our results suggest that iron content in external globus pallidus increases with aging, a finding that has previously been disputed. We demonstrate a positive age-related susceptibility increase in pulvinar while the opposite, i.e. gradual susceptibility decrease, was observed in other thalamic nuclei emphasising the necessity of separate analysis of these thalamic subregions. Gender does not relevantly impact susceptibility variations in brain tissue. The results of this study define normal brain iron levels which may be used as biomarkers of neurodegenerative and neuroinflammatory changes.

This study was supported by the Czech Ministry of Health grant (NV18-08-00062, 15-25602A, and RVO VFN64165), by the Charles University in Prague grant (PROGRES Q27) and by Roche company.