Spatiotemporal variations of magnetic susceptibility in the deep gray matter nuclei from 1 month to 6 years: A quantitative susceptibility mapping study

Abstract

Background Quantitative susceptibility mapping (QSM) is emerging as a technique that quantifies the paramagnetic nonheme iron in brain tissue. Brain iron quantification during early development provides insights into the underlying mechanism of brain maturation. Purpose To quantify the spatiotemporal variations of brain iron‐related magnetic susceptibility in deep gray matter nuclei during early development by using QSM. Study Type Retrospective. Subjects Eighty‐seven infants and children aged 1 month to 6 years. Field Strength/Sequence Enhanced T2*‐weighted angiography using a 3D gradient‐echo sequence at 3.0T. Assessment QSM was calculated by modified sophisticated harmonic artifact reduction for phase data and sparse linear equations and sparse least squares‐based algorithm. Means of susceptibility in deep gray matter nuclei (caudate nucleus, putamen, globus pallidus, thalamus) relative to that in splenium of corpus callosum were measured. Statistical Tests Relationships of mean susceptibility with age and referenced iron concentration were tested by Pearson correlation. Differences of mean susceptibility between the selected nuclei in each age group were compared by one‐way analysis of variance (ANOVA) and Fisher's Linear Significant Difference (LSD) test. Results Positive correlations of susceptibility with both referenced iron concentration and age were found (P < 0.0001); particularly, globus pallidus showed the highest correlation with age (correlation coefficient, 0.882; slope, 1.203; P < 0.001) and greatest susceptibility (P < 0.05) among the selected nuclei. Data Conclusion QSM allows the feasible quantification of iron deposition in deep gray matter nuclei in infants and young children, which exhibited gradual accumulation at different speeds. The fastest and highest iron accumulation was observed in the globus pallidus with increasing age during early development. Level of Evidence: 4 Technical Efficacy:Stage 2 J. Magn. Reson. Imaging 2018.

R2* and quantitative susceptibility mapping in deep gray matter of 498 healthy controls from 5 to 90 years

“…The present study offers a further advantage over previous literature by the inclusion of a greater number of subjects in middle ages of the lifespan which may mitigate extrapolation between young and older subjects. Although this study includes subjects as young as 5 years of age, this excludes critical years of early development marked by large changes in tissue susceptibility (Ning et al, 2019; Zhang et al, 2019) and iron accumulation (Hallgren & Sourander, 1958). Future work should strive to include large longitudinal cohorts spanning all ages to confirm cross‐sectional findings.…”

“…Putative age‐related changes of iron in deep gray matter during healthy development and aging have mostly been reported using only R2* (Aquino et al, 2009; Daugherty et al, 2019; Daugherty & Raz, 2016; Ghadery et al, 2015; Haacke et al, 2010; Hect et al, 2018; Larsen et al, 2020; Pirpamer et al, 2016) or only QSM (Acosta‐Cabronero, Betts, Cardenas‐Blanco, Yang, & Nestor, 2016; Bilgic, Pfefferbaum, Rohlfing, Sullivan, & Adalsteinsson, 2012; Carpenter et al, 2016; Darki et al, 2016; Gong, Wong, Hui, Chan, & Leung, 2015; Li et al, 2020; Ning et al, 2019; Persson et al, 2015; Zhang et al, 2019) in discrete age groups (only children or only adults, with two exceptions: R2* 1–80 years, n = 80—Aquino et al, 2009; QSM, 1–81 years, n = 191—Zhang et al, 2018). Only a limited number of studies have reported both QSM and R2* in deep gray matter of healthy populations, and include studies of infants (Zhang et al, 2019), adolescents (Peterson et al, 2019) or adults (Betts, Acosta‐Cabronero, Cardenas‐Blanco, Nestor, & Düzel, 2016).…”

Age-related magnetic susceptibility changes in deep grey matter and cerebral cortex of normal young and middle-aged adults depicted by whole brain analysis

“…A meta-analysis of 20 MRI studies that estimated iron content in the caudate nucleus, globus pallidus, putamen, red nucleus, and substantia nigra, documented the lowest age-related differences in globus pallidus although it was generally rich in iron in absolute value (11). Studies that included infants showed an exponential pattern with a steeply increasing iron concentration as well as magnetic susceptibility from birth and a plateau from the 3 rd decade onwards (13,14,16,(38)(39)(40). However, these studies did not aim at analyzing specifically the pallidal iron content trajectory during the adult lifespan.…”

Analysis of deep grey nuclei susceptibility in early childhood: a quantitative susceptibility mapping and R2* study at 3 Tesla

“…The relationship between brain iron content and aging has been the aim of several studies, ranging from the susceptibility in elderly to adolescents and also a few studies in children [8,10,11,27,[30][31][32][33][34][35]. If QSM was used in these studies, the mathematical methods of the QSM calculation were different.…”