title: Investigating lipids as a source of chemical exchange-induced MRI frequency shifts.
abstract: While magnetic susceptibility is a major contributor to NMR resonance frequency variations in the human brain, a substantial contribution may come from the chemical exchange of protons between water and other molecules. Exchange-induced frequency shifts fehave been measured in tissue and protein solutions, but relatively lipid-rich white matter (WM) has a larger fethan gray matter, suggesting that lipids could contribute. Galactocerebrosides (GC) are a prime candidate as they are abundant in WM and susceptible to exchange. To investigate this, fewas measured in a model of WM lipid membranes in the form of multilamellar vesicles (MLVs), consisting of a 1:2 molar ratio of GC and phospholipids (POPC), and in MLVs with POPC only. Chemical shift imaging with 15% volume fraction of dioxane, an internal reference whose protons are assumed not to undergo chemical exchange, was used to remove susceptibility-induced frequency shifts in an attempt to measure fein MLVs at several lipid concentrations. Initial analysis of these measurements indicated a necessity to correct for small unexpected variations in dioxane concentration due to its effect on the water frequency shift. To achieve this, the actual dioxane concentration was inferred from spectral analysis and its additional contribution to fewas removed through separate experiments which showed that the water-dioxane frequency shift depended linearly on the dioxane concentration at low concentrations with a proportionality constant of -0.021 ± 0.002 ppb/mM in agreement with published experiments. Contrary to expectations and uncorrected results, for GC + POPC vesicles, the dependence of the corrected feon GC concentration was insignificant (0.023 ± 0.037 ppb/mM; r2= 0.085, p > 0.57), whereas for the POPC-only vesicles a small but significant linear increase with POPC concentration was found: 0.044 ± 0.008 ppb/mM (r2= 0.877, p < 0.01). These findings suggest that the exchange-induced contribution of lipids to frequency contrast in WM may be small. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
authors.affiliation: Department of Medical Physics & Biomedical Engineering, University College London, UK.|Advanced MRI Section, Laboratory of Functional & Molecular Imaging, National Institute of Neurological Disorders & Stroke, National Institutes of Health, USA.
authors.forename: K
authors.initials: K
authors.lastname: Shmueli
authors.affiliation: Laboratory of Functional & Molecular Imaging, National Institute of Neurological Disorders & Stroke, National Institutes of Health, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dodd
authors.affiliation: Advanced MRI Section, Laboratory of Functional & Molecular Imaging, National Institute of Neurological Disorders & Stroke, National Institutes of Health, USA.
authors.forename: P
authors.initials: P
authors.lastname: van Gelderen
authors.affiliation: Advanced MRI Section, Laboratory of Functional & Molecular Imaging, National Institute of Neurological Disorders & Stroke, National Institutes of Health, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Duyn
mesh_terms: D000818:Animals; D006801:Humans; D008055:Lipids / Q000032:analysis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000737:chemistry* / Q000000981:diagnostic imaging*
chemical_list: D008055:Lipids
keywords: chemical exchange; chemical shift imaging; dioxane; exchange-induced resonance frequency shifts; multilamellar lipid vesicles; phospholipids