Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density

Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2012; 109(24):9605-10. DOI: 10.1073/pnas.1115107109
Source: PubMed


Magnetic resonance imaging has previously demonstrated its potential for indirectly mapping myelin density, either by relaxometric detection of myelin water or magnetization transfer. Here, we investigated whether myelin can be detected and possibly quantified directly. We identified the spectrum of myelin in the spinal cord in situ as well as in myelin lipids extracted via a sucrose gradient method, and investigated its spectral properties. High-resolution solution NMR spectroscopy showed the extract composition to be in agreement with myelin's known chemical make-up. The 400-MHz (1)H spectrum of the myelin extract, at 20 °C (room temperature) and 37 °C, consists of a narrow water resonance superimposed on a broad envelope shifted ∼3.5 ppm upfield, suggestive of long-chain methylene protons. Superimposed on this signal are narrow components resulting from functional groups matching the chemical shifts of the constituents making up myelin lipids. The spectrum could be modeled as a sum of super-Lorentzians with a T(2)* distribution covering a wide range of values (0.008-26 ms). Overall, there was a high degree of similarity between the spectral properties of extracted myelin lipids and those found in neural tissue. The normalized difference spectrum had the hallmarks of membrane proteins, not present in the myelin extract. Using 3D radially ramp-sampled proton MRI, with a combination of adiabatic inversion and echo subtraction, the feasibility of direct myelin imaging in situ is demonstrated. Last, the integrated signal from myelin suspensions is shown, both spectroscopically and by imaging, to scale with concentration, suggesting the potential for quantitative determination of myelin density.

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Available from: Cheng Li, Dec 17, 2013
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    • "Recently, a study proposed a possibility of imaging myelination by using asymmetric chemical exchange saturation transfer effect in the domain of Nuclear Overhauser Effects [32]. Another previous study directly measured extracted myelin in 1 H NMR system and reported that myelin exhibits main peak at 3.5 ppm upfield from water-resonance frequency due to the chemical shift [33]. From these results, it is anticipated that taking advantage of the chemical shift as well as the MT strength (rather than the MT strength alone) would be beneficial to image myelination. "
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    ABSTRACT: Magnetization transfer ratio (MTR) has been often used for imaging myelination. Despite its high sensitivity, the specificity of MTR to myelination is not high because tissues with no myelin such as muscle can also show high MTR. In this study, we propose a new magnetization transfer (MT) indicator, MT asymmetry (MTA), as a new method of myelin imaging. The experiments were performed on rat brain at 9.4 T. MTA revealed high signals in white matter and significantly low signals in gray matter and muscle, indicating that MTA has higher specificity than MTR. Demyelination and remyelination studies demonstrated that the sensitivity of MTA to myelination was as high as that of MTR. These experimental results indicate that MTA can be a good biomarker for imaging myelination. In addition, MTA images can be efficiently acquired with an interslice MTA method, which may accelerate clinical application of myelin imaging.
    01/2015; 2015(2):1-10. DOI:10.1155/2015/565391
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    • "Recently, several other new approaches that utilize magnetic susceptibility characteristics of myelin have been proposed to assess the integrity of myelin (Cohen-Adad et al., 2012; Duyn et al., 2007; Lee et al., 2010, 2011; Li et al., 2012; Liu, 2010; Miller et al., 2010; Wilhelm et al., 2012). These approaches, in conjunction with diffusion and MT imaging, may provide complementary information to ViSTa. "
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    ABSTRACT: White matter of the brain has been demonstrated to have multiple relaxation components. Among them, the short transverse relaxation time component (T2 < 40 ms; T2(⁎) < 25 ms at 3T) has been suggested to originate from myelin water whereas long transverse relaxation time components have been associated with axonal and/or interstitial water. In myelin water imaging, T2 or T2(⁎) signal decay is measured to estimate myelin water fraction based on T2 or T2(⁎) differences among the water components. This method has been demonstrated to be sensitive to demyelination in the brain but suffers from low SNR (R1.3) and image artifacts originating from ill-conditioned multi-exponential fitting. In this study, a novel approach that selectively acquires short transverse relaxation time signal is proposed. The method utilizes a double inversion RF pair to suppress a range of long T1 signal. This suppression leaves short T2(⁎) signal, which has been suggested to have short T1, as the primary source of the image. The experimental results confirms that after suppression of long T1 signals, the image is dominated by short T2(⁎) in the range of myelin water, allowing us to directly visualize the short transverse relaxation time component in the brain. Compared to conventional myelin water imaging, this new method of direct visualization of short relaxation time component (ViSTa) provides high quality images. When applied to multiple sclerosis patients, chronic lesions show significantly reduced signal intensity in ViSTa images suggesting sensitivity to demyelination.
    NeuroImage 06/2013; 83. DOI:10.1016/j.neuroimage.2013.06.047 · 6.36 Impact Factor
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    ABSTRACT: The current study investigates the whole brain myelin water content distribution applying a new approach that allows for the simultaneous mapping of total and relative myelin water content, T1 and T2* with full brain coverage and high resolution (1 × 1 × 2 mm3). The data was collected at two different sites in healthy controls to validate the independence of a specific setup. In addition, a group of patients with known white matter affections was investigated to compare two measures of myelin, i.e. relative and absolute myelin water content. Based on the first dataset, a quantitative myelin water content atlas was created which served as a control set for the other two datasets. Both control groups measured at different institutions yielded consistent results. However, distinct regions of reduced myelin water content were observed for the patient dataset, both on an individual basis and in a group-wise comparison. The comparison between the absolute and relative measurement of myelin water content in MS patients showed that the relative measurement, which is employed by many researchers, overestimates both disease volume and the corresponding reduction of myelin water content in white matter lesions. However, for normal appearing white matter, no difference between both approaches was detected. The results obtained in the current study demonstrate that absolute myelin water content can reliably be determined in a multicentre environment using standard MR sequences. The optimised protocol allows for a measurement of four quantitative parameters with full brain coverage in only 10 min. This might expedite a more widespread future use of quantitative MRI methods for clinical research and diagnosis.
    Clinical neuroimaging 10/2012; 1(1):121-30. DOI:10.1016/j.nicl.2012.09.013 · 2.53 Impact Factor
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