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 ...

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There is emerging evidence that chronic musculoskeletal pain is associated with anatomical and functional abnormalities in gray matter. However, little research has investigated the relationship between chronic musculoskeletal pain and white matter (WM). In this study, we used whole-brain tract-based spatial statistics, and region-of-interest analyses of diffusion tensor imaging (DTI) data to demonstrate that patients with chronic musculoskeletal pain exhibit several abnormal WM integrity as compared to healthy controls. Chronic musculoskeletal pain was associated with lower fractional anisotropy (FA) in the splenium of corpus callosum, and left cingulum adjacent to the hippocampus. Patients also had higher radial diffusivity (RD) in the splenium, right anterior and posterior limbs of internal capsule, external capsule, superior longitudinal fasciculus, and cerebral peduncle. Patterns of axial diffusivity (AD) varied: patients exhibited lower AD in the left cingulum adjacent to the hippocampus and higher AD bilaterally in the anterior limbs of internal capsule, and in the right cerebral peduncle. Several correlations between diffusion metrics and clinical variables were also significant at a p<0.01 level: FA in the left uncinate fasciculus correlated positively with Total Pain Experience and typical levels of pain severity. AD in the left anterior limb of internal capsule and left uncinate fasciculus were correlated with Total Pain Experience and typical pain level. Positive correlations were also found between AD in the right uncinate and both Total Pain Experience and Pain Catastrophizing. These results demonstrate that WM abnormalities play a role in chronic musculoskeletal pain; either as a cause, predisposing factor, consequence, or compensatory adaptation.