White matter intercompartmental water exchange rates determined from detailed modeling of the myelin sheath
Corresponding Author
Peter van Gelderen
Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
correspondence
Peter van Gelderen, NIH, Bld 10, Rm B1D724, 10 Center Drive MSC 1066, Bethesda MD 20892.
Email: [email protected]
Search for more papers by this authorJeff H Duyn
Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorCorresponding Author
Peter van Gelderen
Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
correspondence
Peter van Gelderen, NIH, Bld 10, Rm B1D724, 10 Center Drive MSC 1066, Bethesda MD 20892.
Email: [email protected]
Search for more papers by this authorJeff H Duyn
Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
Search for more papers by this authorAbstract
Purpose: Magnetization exchange (ME) between hydrogen protons of water and large molecules (semisolids [SS]) in lipid bilayers is an important factor in MRI signal generation and can be exploited to study white matter pathology. Current models used to quantify ME in white matter generally consider water to reside in 1 or 2 distinct compartments, ignoring the complexities of the myelin sheath’s multicompartment structure of alternating myelin SS and myelin water (MW) layers. Here, we investigated the effect of this by fitting ME data obtained from human brain at 7 T with a multilayer model of myelin.
Methods: A multi-echo acquisition for a T2*-based separation of MW from other water signals was combined with various preparation pulses to change the (relative) state of the SS and water pools and analyzed by fitting with a multilayer exchange model.
Results: The estimated lifetime within a single MW layer was 260 µs, corresponding to a lipid bilayer permeability of 6.7 µm/s. The magnetization lifetime of the aggregate of all MW was estimated at 13 ms, shorter than previously reported values in the range of 40 to 140 ms.
Conclusion: Contrary to expectations and previous reports, ME between protons in myelin SS and water is not limited by the myelin sheath but rather by the exchange between SS and water protons. The analysis of ME contrast should account for the relatively short MW lifetime and affects the interpretation of tissue compartmentalization from MRI contrasts such as T1- and diffusion-weighting.
Supporting Information
| Filename | Description |
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| mrm27398-sup-0001-Supinfo.docxapplication/docx, 2 MB | Supinfo DOCUMENT S1. Additional theory, results and error analysis. FIGURE S1. Example of MGRE three-compartment fitting, showing the real part of the complex data and fit. Legend: * = MGRE data from the corpus callosum divided by the CSF signal, brown= myelin water (MW), orange= axonal water, yellow= interstitial water, red= sum of axonal and interstitial water, forming the OW as used in the ML3 model, black= MW+OW= total water, + = residue plotted at 100x the scale (right hand axis). FIGURE S2. The Mz of the individual compartments in the ML3 model fitted to the MGRE data, immediately before the excitation. The different colors correspond to the five delay times, indicated in the lower row of plots. The horizontal axis is the index for the compartments. There are 15 SS compartments (0..14), plotted in the top row. There are 14 MW compartments (0..13), plus one OW compartment plotted as index 14 in the bottom row. FIGURE S3. Simulation of the evolution of MMWz,iover time (for i=1..N), for a starting condition of Mz,iMW=1 and Mz,iSS=MzOW=0 (for all i), and a hypothetical case without relaxation. For each value of N, the ML3 was fitted to the data and the resulting parameters used in the respective simulations. The colors correspond to the individual MW compartments . Averages of these curves shown in the bottom right plot. The decay time of these curves is what is calculated as the TMW. TABLE S1. Fitting results and calculated compartment lifetimes (τ) and pool (averaged) decay times (T), for five models used in this study, see text for details. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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