Three‐pool model of white matter

Abstract

Purpose: To investigate the use of a three-pool relaxation model to measure myelin, myelinated-axon, and mixed water-pool fractions in white matter (WM) during myelination. Materials and Methods:MRI at 1.9 Tesla, and conventional spin-echo imaging were used to acquire T1 and T2 relaxation data in 15 normal children ranging in age from 3 months to 13 years 4 months. Three equations with three unknowns were solved to calculate three water-pool fractions for each child in a frontal association-fiber area and a frontal-parietal projection-fiber area. The temporal trend of the fractions was compared with a theoretical three-pool myelination model. Results:The myelin level in the projection-fiber area rose earlier than in the association-fiber area following the standard caudal-to-rostral trend. The temporal trend of the three-pool fractions followed that predicted by the theoretical myelination model in both brain areas. The myelinatedaxon and mixed pool sizes were significantly different in the two WM areas following early myelination, although their myelin pools were similar. T1 values correlated more highly with the myelinated-axon and mixed pool fractions than with the myelin pool fraction. Conclusion:The three-pool relaxation model provides measurements of water-pool fractions in WM that follow values predicted during myelination. MR IMAGES of the human brain provide excellent contrast between gray matter (GM) and white matter (WM) with a limiting spatial resolution of about 1 mL. Two mechanisms are largely responsible for this high contrast: spin-lattice (T1) and spin-spin (T2) relaxation. The microscopic environment of water in tissue determines the T1 and T2 relaxation times. A single volume element (voxel) in WM contains several distinct microscopic water environments (or water pools) separated by membranes that limit the exchange of water between them. For instance, in the genu of the corpus callosum (CC) there are approximately 100,000 individual axons with differing diameters and myelin content within a volume of 1 mm 3 (1). Interspersed among these axons are oligodendrocytes, other glial cells, extracellular fluid, and vessels. The interplay of within-pool relaxation times and between-pool exchange times of water for these biological pools determines the net relaxation properties in WM (2,3).T1-and T2-weighted images are commonly used for visual assessments of WM (4,5), while MRI relaxometry (calculating T1 and T2) is more appropriate when quantitative measures are desired (6). Several investigators have acquired age-related baseline values for T1 and T2 in normal children and adults (6 -9). MRI relaxometry has also been used to study myelin disorders, hypomyelination (7,10), and demyelination (11). While clinical MRI studies and MRI relaxometry are useful in myelin assessments, neither directly indicate myelin levels. Though changes in myelin content are known to produce changes in MR relaxation properties in WM (3,4,6,12), changes in net relaxation properties of WM arise from multiple water pools, not ...

Advances in white matter imaging: A review of in vivo magnetic resonance methodologies and their applicability to the study of development and aging

“…One study of young children who were born prematurely (mean age = 7) revealed longer T2 relaxation times in cerebral white matter compared to age-matched children who were born full-term (Abernethy et al, 2003). Another T2 Relaxometry study, which examined a small group of healthy children ages 3 months to 13 years, found that three-pool modeling revealed changes in myelin that corresponded very well to known patterns of myelination during development (Lancaster et al, 2003). Thus, both T2 Relaxometry and T2R may be useful methods for the study of myelin growth during important developmental periods such as adolescence and may also be applicable to the study of myelin changes during aging.…”

In vivo assessment of myelination by phase imaging at high magnetic field

“…A simple technique that would access the degree of myelination of white matter would be very useful in mature animal models of white matter injury such as multiple sclerosis and in immature animal models of white matter injury such as periventricular leukomalacia as well as in human studies. There are various methods available: one approach consists of quantification of myelin bond and free water fractions by a multiexponential analysis of the T 2 decay (Beaulieu et al, 1998;MacKay et al, 1994;Whittall and MacKay, 1989;Lancaster et al, 2003). This is generally performed using a CarrPurcell-Meiboom-Gill (CPMG) or a Turbo Spin-Echo sequences with multiple echo times (Beaulieu et al, 1998).…”

Improved myelin water quantification using spatially regularized non‐negative least squares algorithm

“…A technique that provides specific and sensitive information about the myelin content was developed based on an analysis of T 2 relaxation times (5,6). It has been reported that the T 2 spectrum of WM and several myelinated tissue samples consists of multiple components (7)(8)(9)(10)(11)(12)(13) and that the short component with T 2 between 10 ms and 50 ms corresponds to the water pool within the myelin sheath (2)(3)(4)(5)(6). Myelin content can therefore be quantitated using the fraction of this short T 2 component.…”