Myelin water imaging is a quantitative neuroimaging technique that provides the myelin water fraction (MWF), a metric highly specific to myelin content, and the intra-/extra-cellular T2 (IET2), which is related to water and iron content. We coupled high-resolution data from 100 adults with gold-standard methodology to create an optimized anatomical brain template and accompanying MWF and IET2 atlases. We then used the MWF atlas to characterize how myelin content relates to demographic factors. In most brain regions, myelin content followed a quadratic pattern of increase during the third decade of life, plateau at a maximum around the fifth decade, then decrease during later decades. The ranking of mean myelin content between brain regions remained consistent across age groups. These openly available normative atlases can facilitate evaluation of myelin imaging results on an individual basis and elucidate the distribution of myelin content between brain regions and in the context of aging.

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Investigating how hydrophobic molecules mix with phospholipid bilayers and how they affect membrane properties is commonplace in biophysics. Despite this, a molecular-level empirical description of a membrane model as simple as a phospholipid bilayer with long linear hydrophobic chains incorporated is still missing. Here, we present an unprecedented molecular characterization of the incorporation of two long n-alkanes, n-eicosane (C20) and n-triacontane (C30) with 20 and 30 carbons, respectively, in phosphatidylcholine (PC) bilayers using a combination of experimental techniques ( 2 H NMR, 31 P NMR, 1 H− 13 C dipolar recoupling solid-state NMR, X-ray scattering, and cryogenic electron microscopy) and atomistic molecular dynamics (MD) simulations. At low hydration, deuterated C20 and C30 yield 2 H NMR spectra evidencing anisotropic-motion, which demonstrates their miscibility in PC membranes up to a critical alkane-to-acyl-chain volume fraction, ϕ c . The acquired 2 H NMR spectra of C20 and C30 have notably different lineshapes. At low alkane volume fractions below ϕ c , CHARMM36 MD simulations predict such 2 H NMR spectra qualitatively and thus enable an atomistic-level interpretation of the spectra. Above ϕ c , the 2 H NMR lineshapes become characteristic of motions in the intermediate-regime that, together with the MD simulation results, suggest the onset of immiscibility between the alkane molecules and the acyl chains. For all the systems investigated, the phospholipid molecular structure is unperturbed by the presence of the alkanes. However, at conditions of excess hydration and at surprisingly low alkane fractions below ϕ c , a peak characteristic of isotropic motion is observed in both the 2 H spectra of the alkanes and 31 P spectra of the phospholipids, strongly indicating that the incorporation of the alkanes induces a reduction on the average radius of the lipid vesicles.

Abstract. Proton-detected local field (PDLF) NMR spectroscopy, using magic-angle spinning and dipolar recoupling, is presently the most powerful experimental technique to obtain atomistic structural information from small molecules undergoing anisotropic motion such as peptides, drugs, or lipids in model membranes. The accuracy of the measurements on complex systems is however compromised by the number of transients required and by the difficulty of fitting experimental data due to the omnipresent RF spatial inhomogeneity in NMR probes. Here, we present a new methodology to analyse R-type PDLF NMR experiments that brings a significant improvement of accuracy and that enables to address more complex systems. The new methodology consists of fitting the time-domain data with NMR simulations accounting for RF spatial inhomogeneity, making it possible (1) to use shorter experiments which enables to measure samples with lower material content and prevents RF-heating, (2) to measure smaller C–H bond order parameter magnitudes, |SCH|, and smaller variations of |SCH| upon perturbations of the system and (3) to determine |SCH| values with small differences from distinct sites having the same chemical shift. The increase in accuracy is demonstrated by comparison with 2H NMR quadrupolar echo experiments on mixtures of deuterated and non-deuterated dimyristoylphosphatidylcholine (DMPC). The methodology presented enables an unprecedented level of structural detail and will be highly useful for investigating complex membrane systems as illustrated with membranes composed of a brain lipid extract with many distinct lipid types.