Effects of orientational order and particle size on the NMR line positions of lipoproteins

Lounila, Juhani; Ala‐Korpela, Mika; Jokisaari, Jukka; Savolainen, Markku J.; Kesäniemi, Y. A.

doi:10.1103/physrevlett.72.4049

Cited by 93 publications

(109 citation statements)

References 10 publications

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“…The highly ordered lipid molecules within the myelin sheath form the most likely source of anisotropic magnetic susceptibility (18), since similar lipid structures have been shown to exhibit anisotropic magnetic properties (19,20). The lipids are packed together in bilayers, which spiral around the axon to form the myelin sheath.…”

Section: Resultsmentioning

confidence: 99%

Fiber orientation-dependent white matter contrast in gradient echo MRI

Wharton

Bowtell

2012

Proc. Natl. Acad. Sci. U.S.A.

296

611

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Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) and the contrast observed in magnitude and phase images acquired using gradient echo MRI. Understanding the origin of this link is of great interest because it could offer access to a new diagnostic tool for investigating tissue microstructure. Since it has been suggested that myelin is the dominant source of this contrast, creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the NMR signal is an essential step toward fully understanding WM contrast. In this study, we show by comparison of the results of simulations and experiments carried out on human subjects at 7T, that the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic magnetic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T 2 relaxation time and spin density relative to its surroundings, and also undergoes exchange. The accuracy and intrinsic simplicity of the hollow cylinder model provides a versatile framework for future exploitation of the effect of WM microstructure on gradient echo contrast in clinical MRI. G radient echo (GE) MRI is widely used in imaging the human brain, because both the phase and magnitude of the complex NMR signal measured with GE sequences can be used to create high-resolution images that show strong contrast between different types of brain tissue (1). Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) with respect to the magnetic field and the contrast observed in magnitude and phase images (2-6). Although the origin of this link is currently not fully understood, orientation-dependent contrast is of great interest because it could offer researchers access to a new diagnostic tool for investigating tissue microstructure using MRI.It has recently been suggested that the myelin sheaths that surround axons are the dominant source of WM contrast in GE MRI (7,8). Creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the magnitude and phase of the NMR signal is consequently an essential step toward fully understanding WM contrast and its relationship to fiber orientation. Such a model must incorporate two main features: (i) a representation of the microscopic spatial variation of resonant frequency, due to the myelin compartment-isotropic and anisotropic magnetic susceptibility effects (2, 9, 10) and chemical exchange of protons between water and macromolecules (11, 12), have been proposed as mechanisms through which myelin could perturb the resonant frequency in WM; (ii) a signal-weighting scheme to account for the reduced T 2 relaxation time constant of the myelin water relative to that of water found outs...

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Section: Resultsmentioning

confidence: 99%

Fiber orientation-dependent white matter contrast in gradient echo MRI

Wharton

Bowtell

2012

Proc. Natl. Acad. Sci. U.S.A.

296

611

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“…The terminal methyl groups on lipoproteinassociated lipids emit a characteristic NMR spectrum, which varies depending on the size of the lipoprotein particle, allowing NMR to estimate the different size LDL and other lipoprotein subfractions (9 ). A specific spectral region captures the NMR signal emitted by the total number of terminal methyl group protons of phospholipids, cholesterol, cholesteryl esters, and triglycerides of the different lipoprotein particle subclasses (10 ).…”

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confidence: 99%

Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices

Cole¹,

Contois²,

Csákó

et al. 2013

Clinical Chemistry

114

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BACKGROUND:The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P).CONTENT: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P.

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“…Unlike other methods for analyzing HDL particles, nuclear magnetic resonance (NMR) spectroscopy does not require a physical separation step because the protons (the nuclei of hydrogen atoms) within lipoprotein particles of different sizes have a natural magnetic distinctness arising from their unique physical structure (58 ). As a result, lipoprotein particles of different sizes in unfractionated plasma or serum give rise to distinguishable lipid NMR signals that have characteristically different frequencies (Fig.…”

Section: Hdl Particle Concentration Nuclear Magnetic Resonance Spectrmentioning

confidence: 99%

HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events

et al. 2011

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BACKGROUND A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk. CONTENT In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-β-1 HDL subclass that participates in macrophage cholesterol efflux. SUMMARY We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions.

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Effects of orientational order and particle size on the NMR line positions of lipoproteins

Cited by 93 publications

References 10 publications

Fiber orientation-dependent white matter contrast in gradient echo MRI

Fiber orientation-dependent white matter contrast in gradient echo MRI

Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices

HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events

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