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

Abstract

Purpose Aging is the most significant determinant for brain iron accumulation in the deep grey matter. Data on brain iron evolution during brain maturation in early childhood are limited. The purpose of this study was to investigate age-related iron deposition in the deep grey matter in children using quantitative susceptibility (QSM) and R2* mapping. Methods We evaluated brain MRI scans of 74 children (age 6–154 months, mean 40 months). A multi-echo gradient-echo sequence obtained at 3 Tesla was used for the QSM and R2* calculation. Susceptibility of the pallidum, head of caudate nucleus, and putamen was correlated with age and compared between sexes. Results Susceptibility changes in all three nuclei correlated with age (correlation coefficients for QSM/R2*: globus pallidus 0.955/0.882, caudate nucleus 0.76/0.65, and putamen 0.643/0.611). During the first 2 years, the R2* values increased more rapidly than the QSM values, indicating a combined effect of iron deposition and myelination, followed by a likely dominating effect of iron deposition. There was no significant gender difference. Conclusion QSM and R2* can monitor myelin maturation processes and iron accumulation in the deep grey nuclei of the brain in early life and may be a promising tool for the detection of deviations of this normal process. Susceptibility in the deep nuclei is almost similar early after birth and increases more quickly in the pallidum. The combined use of QSM and R2* analysis is beneficial.

Distinct brain iron profiles associated with logopenic progressive aphasia and posterior cortical atrophy

“…Additionally, substantia nigra is a major iron storage site, abundant in neuromelanin, which would suggest the dominant signal for QSM in this region would be iron ( Haining and Achat-Mendes 2017 ). Leading to the hypothesis that the contribution of myelin’s susceptibility would be minimal, and the dominant signal would remain paramagnetic, originating from iron ( Langkammer et al, 2012 , Chen et al, 2021 ), with the overall QSM signal at most being somewhat underestimated ( Habib et al, 2012 , Betts et al, 2016 , Raab et al, 2021 ).…”

Brain iron content and cognitive function in patients with β-thalassemia

“…Brain iron is primarily stored as non-heme iron, such as ferritin and hemosiderin, and is distributed unevenly in the brain, with higher concentrations in the basal ganglia, substantia nigra, and red nucleus; lower concentrations in the gray matter regions; and the lowest concentration in the white matter. 23 – 25 MRI quantifies the ferritin and hemosiderin signal, thus reflecting the brain iron deposition. Several MRI techniques have been used to quantify iron levels, including the transverse relaxation rate (R2, R2′, R2*), susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), as presented in Table 1 .…”

“…Also, it does not precisely detect the concentration of brain iron because ongoing myelination in the brain can increase the R2* value. 24 …”

“…The method with R2* reflects both brain iron and myelin content, meaning that changes in the myelin content of the brain in addition to iron would also increase the R2* value. Therefore, more studies combine R2* and QSM to quantitate brain iron content, 24 , 47 – 49 since these two methods provide complementary information, that is, iron increases both R2* and QSM, while myelin elevates R2* but decreases QSM.…”

“…32 32 patients with sickle cell disease; 15 patients with β-TM; 11 healthy controls Thalamus, caudate nucleus Raab et al24 74 healthy children Globus pallidus, caudate nucleus, putamenSWI Park et al 33 127 patients with Alzheimer disease; 127 healthy controls Motor cortex, sensory cortex, medial frontal cortex Xiong et al 34 17 patients with Parkinson disease; 10 healthy controls Substantia nigra, red nucleus, globus pallidus, thalamus, putamen, caudate nucleus, dentate nucleus Khattar et al 35 92 healthy adults Globus pallidus, red nucleus, putamen, caudate nucleus, amygdala, hippocampus, insula, substantia nigra QSM Thomas et al 36 100 patients with Parkinson disease; 37 healthy controls Prefrontal cortex, putamen, hippocampus, thalamus, caudate nucleus, substantia nigra Li et al 37 23 patients with type 2 diabetes; 25 healthy controls Right caudate nucleus, putamen, globus pallidus, frontal inferior triangular gyrus, and precentral gyrus Howard et al 38 67 healthy adults Right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices Chen et al 39 150 cognitively normal older adults Hippocampus, putamen, globus pallidus, caudate nucleus, entorhinal cortex, frontal cortex, temporal cortex β-TM, beta-thalassemia; QSM, quantitative susceptibility mapping; SWI, susceptibility-weighted imaging. journals.sagepub.com/home/tah…”