Adult brain aging investigated using BMC-mcDESPOT–based myelin water fraction imaging

Abstract

The relationship between regional brain myelination and aging has been the subject of intense study, with magnetic resonance imaging (MRI) perhaps the most effective modality for elucidating this. However, most of these studies have used nonspecific methods to probe myelin content, including diffusion tensor imaging, magnetization transfer ratio, and relaxation times. In the current study, we used the BMC-mcDESPOT analysis, a direct and specific method for imaging of myelin water fraction (MWF), a surrogate of myelin content. We investigated age-related differences in MWF in several brain regions in a large cohort of cognitively unimpaired participants, spanning a wide age range. Our results indicate a quadratic, inverted U-shape, relationship between MWF and age in all brain regions investigated, suggesting that myelination continues until middle age followed by decreases at older ages. We also observed that these agerelated differences vary across different brain regions, as expected. Our results provide evidence for nonlinear associations between age and myelin in a large sample of well characterized adults, using a direct myelin content imaging method.

The Myelin Water Fraction Serves as a Marker for Age-Related Myelin Alterations in the Cerebral White Matter – A Multiparametric MRI Aging Study

“…Noteworthy, some studies reported that in some brain regions (with emphasis on anterior brain areas), non-linear progressions of myelin proxies with age may be in closer agreements with histopathological findings of a preservation of myelin content during the first four decades of life, followed by a notable decrease of myelination in higher life decades, compared to linear trends (Peters, 2002;Lebel et al, 2012;Callaghan et al, 2014;Arshad et al, 2016). For instance, already in Flynn et al (2003) reported of protracted myelination in healthy individuals during the first decades of life, which reflects the statistical trends that have been reported in recent MWI studies (Arshad et al, 2016;Bouhrara et al, 2019). More extensive (longitudinal) imaging studies including higher subject numbers would be desirable to further validate these claims in terms of MWF estimates throughout different brain regions.…”

“…Accordingly, biomarkers sensitive for these specific developmental patterns of age-related myelin changes are of great interest for researchers studying aging. While many related imaging studies predominantly reported of linear declines of diffusion-based metrics (Bennett et al, 2010;Lebel et al, 2012;Billiet et al, 2015;Rathee et al, 2016), only very few studies found a correlation of MWF estimates with age (Billiet et al, 2015;Arshad et al, 2016;Faizy et al, 2018;Bouhrara et al, 2019). Histopathologically, normal brain-aging is marked by WM degeneration, including myelin pallor (Kemper, 1994), loss of myelinated nerve fibers (Bartzokis, 2004;Bartzokis et al, 2004) and malformation of myelin sheaths (Peters, 2002;Gunning-Dixon et al, 2009).…”

An atlas for human brain myelin content throughout the adult life span

“…Compared to the BMC-mcDESPOT results of Bouhrara et al, our MWF in WM ROIs shows much more variation between individual subject values 28 . This could reflect the increased myelin-specificity of our 3D multi-echo T 2 relaxation MWI method, which is less sensitive to magnetisation transfer or other effects that could explain the unusually high, homogeneous MWF provided by mcDESPOT and its derivative techniques 28 . Our results also show increased variation in the trajectory of MWF with age between regions, which may better reflect the heterochronous brain development trajectories expected from literature 33 .…”

“…The myelin-age relationship has also been studied using an alternative approach to MWI known as multicomponent-driven equilibrium single-component observation of T 1 and T 2 with Bayesian Monte Carlo analysis (BMC-mcDESPOT) 28 , which uses a more efficient steady state acquisition to provide a surrogate measure for the MWF 29 . Using a large sample and wide age range, Bouhrara et al (n = 106, range 22–94 years) found a quadratic association between myelin values and age 28 , similar to that found by Arshad et al and Papadaki et al 14 , 15 .…”

“…The myelin-age relationship has also been studied using an alternative approach to MWI known as multicomponent-driven equilibrium single-component observation of T 1 and T 2 with Bayesian Monte Carlo analysis (BMC-mcDESPOT) 28 , which uses a more efficient steady state acquisition to provide a surrogate measure for the MWF 29 . Using a large sample and wide age range, Bouhrara et al (n = 106, range 22–94 years) found a quadratic association between myelin values and age 28 , similar to that found by Arshad et al and Papadaki et al 14 , 15 . Although Bayesian Monte Carlo analysis improves the stability of mcDESPOT, which has been shown to provide biased myelin estimates with unpredictable fluctuations 30 , BMC-mcDESPOT values remain overestimated compared to the reference multi-echo T 2 relaxation method 31 and have not been validated with comparison to histological staining.…”