Quantitative MRI provides markers of intra-, inter-regional, and age-related differences in young adult cortical microstructure

Daniel Carey,Francesco Caprini,Micah Allen,Antoine Lutti,Nikolaus Weiskopf,Geraint Rees,Martina F Callaghan,Frederic Dick

doi:10.1016/j.neuroimage.2017.11.066

Abstract

Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18–39 years, N = 93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes – but increased tissue water content – when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure cross-sectionally, we found that parameters with sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5–1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre-central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter- and intra-cortical composition, which may be used as benchmarks in further studies.

Highlights

A core challenge for human neuroscience is the design of robust anatomical imaging methods that are sensitive to inter-regional differences in tissue properties, and to profiles of intra-cortical tissue change from the grey-white border to the pial surface in any one region
R1 and R2* exposed the heavily myelinated V1 extending across the calcarine sulcus (Sereno et al, 2013; Fracasso et al, 2016; Cohen-Adad et al, 2012); parameter magnetization transfer (MT) showed high values that were restricted to gyral banks flanking the calcarine sulcus (Fig. 1, parameter MT medial surface panels)
A possible source of this difference is the local contribution of myelin differences to macromolecular effects at gyri, versus the more anatomically diffuse effects of iron associated with oligodendrocyte cell bodies – contributing in part to the R1 signal, via R2* – found across sulci (e.g., Stüber et al, 2014; see 3.3, and discussion, 4.1)

Summary

Introduction

A core challenge for human neuroscience is the design of robust anatomical imaging methods that are sensitive to inter-regional differences in tissue properties, and to profiles of intra-cortical tissue change from the grey-white border to the pial surface in any one region. These are 1) the longitudinal relaxation rate, R1 1⁄4 1/T1 (sensitive to myelin, macromolecular content, iron and water); 2) the effective transverse relaxation rate, R2* 1⁄4 1/T2* (sensitive to susceptibility effects due to paramagnetic ions, most notably iron, myelin distribution and fibre orientation); 3) Magnetization Transfer (MT; sensitive to macromolecular content and bound water fraction); and 4) effective Proton Density (PD*; sensitive to free water content and residual R2* related effects) (Weiskopf et al, 2011; Callaghan et al, 2014a, 2014b; Lutti et al, 2014; Stüber et al, 2014; Fukunaga et al, 2010; Cohen-Adad et al, 2012; Mangeat et al, 2015; Lee et al, 2010, 2011; Bender and Klose, 2010; Denk et al, 2011) These methods allow quantitative measurement of inter- and intra-regional differences in tissue properties (e.g., Cohen-Adad et al, 2012, 2014; Govindarajan et al, 2015; Dinse et al, 2015; Marques et al, 2017) including age-related changes in subcortical fibre tract myelination (Yeatman et al, 2014), pathological changes in neurotrauma (Freund et al, 2013), maturation effects (Whitaker et al, 2016), and age-related tissue de-myelination (Callaghan et al, 2014a), whilst affording the means to do so in relation to functional ability (e.g., Gomez et al, 2017). We mapped a set of normative, cortical-depth-specific regional MPM values for young adults that can be used as reference values for future studies

Results

Discussion

Conclusion