Related Experiment Video
Updated: Feb 5, 2026
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
White matter intercompartmental water exchange rates determined from detailed modeling of the myelin sheath
Peter van Gelderen1, Jeff H Duyn1
1Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological, Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
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.
Insights
Magnetization exchange (ME) in white matter is limited by proton exchange between semisolid (SS) and myelin water (MW) protons, not the myelin sheath itself. This finding impacts MRI interpretation by highlighting the short MW lifetime.
Area of Science:
- Neuroimaging
- Biophysics
- Magnetic Resonance Imaging
Background:
- Magnetization exchange (ME) between water and semisolid (SS) molecules in lipid bilayers is crucial for MRI signal generation and studying white matter pathology.
- Existing models often simplify white matter structure, neglecting the myelin sheath's complex multilayered composition of SS and myelin water (MW) layers.
Purpose of the Study:
- To investigate the impact of myelin's multicompartment structure on magnetization exchange (ME) in human brain white matter at 7 Tesla.
- To analyze ME data using a multilayer model that accounts for the alternating myelin SS and MW layers.
Main Methods:
- Utilized a multi-echo acquisition for T2*-based separation of myelin water (MW) from other water signals.
- Employed various preparation pulses to alter the state of SS and water pools.
- Analyzed the data by fitting it with a multilayer exchange model.
Main Results:
- Estimated the lifetime within a single MW layer at 260 µs, indicating a lipid bilayer permeability of 6.7 µm/s.
- Determined the magnetization lifetime of the aggregate MW to be 13 ms, which is shorter than previously reported values (40–140 ms).
Conclusions:
- Magnetization exchange (ME) between myelin SS and water protons is limited by the exchange process itself, not the myelin sheath.
- The relatively short MW lifetime necessitates accounting for it in ME contrast analysis.
- This finding influences the interpretation of tissue compartmentalization derived from MRI contrasts like T1- and diffusion-weighting.
Related Concept Videos
03:08Rate-Determining Steps
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...
02:49Classifying Matter by State
03:35Classifying Matter by Composition
According to its composition, the matter can be classified into two broad categories — pure substances and mixtures.
A pure substance is a form of matter that has a constant composition throughout with uniform properties. For example, any sample of sucrose has the same composition and same physical properties, such as melting point, color, and sweetness, regardless of the source from which it is isolated.
A mixture is composed of two or...
02:57Physical and Chemical Properties of Matter
02:59The Atomic Theory of Matter
01:20Determination of Michaelis Constant and Maximum Elimination Rate
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two...