Relaxometry of brain: Why white matter appears bright in MRI

Abstract

The remarkable success of magnetic resonance imaging of adult brain relates to the unusually large ratio of the longitudinal relaxation rates 1/T1 of white and gray matter, approximately 2:1 at physiological temperature and traditional imaging fields. Several investigators have conjectured that myelin is the source of the greater 1/T1 of white matter without, however, suggesting details of the molecular mechanisms responsible. From measurements of the magnetic field dependence of 1/T1 (NMRD profiles) of adult and neonatal gray and white matter at 5 and 35 degrees C, we find a thermally activated contribution to the NMRD profile of adult white matter that is not present in the profiles of either adult gray or neonatal gray and white matter. We attribute this contribution to myelin and develop a quantitative model that accounts for the unique relaxation behavior of myelinated white matter. We find that myelin water, 15% of the total, has a relatively short T1 that arises from an unexpectedly large interaction with myelin lipid; when cast in terms of an interaction over the entire myelin bilipid-water interface, it is sevenfold greater than the analogous protein-water interfacial interaction. Its magnitude remains to be accounted for, but cholesterol, known to alter the relaxation rates of lipid protons, may play an important role. The contribution of myelin to 1/T1 at physiological temperatures is attributed to thermally activated transmembrane diffusion of water and, hence, more rapid mixing of axonal and the rapidly relaxing myelin water molecules.

Characterizing healthy and diseased white matter using quantitative magnetization transfer and multicomponent T2 relaxometry: A unified view via a four‐pool model

“…Assuming a membrane permeability of 10 m/sec (35,36), the reported water exchange rate in bovine WM (17) corresponds to a median number of 50 myelin wrappings, which falls within the range of counts reported in histology (37). In this model, the nondirectional exchange rate R D is proportional to the membrane permeability and inversely proportional to the number and spacing of the myelin lamellae.…”

“…A model considering the layered structure of myelin has been proposed to estimate the rate of water exchange between myelin and IE compartments (35), which can be extended to a population of myelinated axons. Assuming a membrane permeability of 10 m/sec (35,36), the reported water exchange rate in bovine WM (17) corresponds to a median number of 50 myelin wrappings, which falls within the range of counts reported in histology (37).…”

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

“…2 Whereas immobilized myelin macromolecules accelerate the transverse relaxation of affected water protons (T 2 < 15 ms), the myelin water comprises only a small volume fraction (<15%) in WM, 2,21 and its exchange with other compartments is slow. 12 Accordingly, WM/GM contrast is not much observed in T 2 maps of the human brain 2 because the T 2 is similar of the non-myelin water in WM and the water in GM. 2,21 With regard to macromolecules, only lipids play a significant role in WM/GM MR imaging contrast because there is no substantial difference in WM/ GM concentration in proteins, carbohydrates, or nucleotides.…”

“…11 In the human brain, T 1 relaxation of water protons is accelerated by close contact to macromolecular protons, e.g., at myelin sheaths, 12 so that the intensity is higher of white matter (WM) than gray matter (GM) in T 1 -weighted (T 1 W) MR imaging (Fig. 1a).…”

Nuclear magnetic relaxation induced by exchange-mediated orientational randomization: Longitudinal relaxation dispersion for a dipole-coupled spin-1/2 pair

“…The spin-1/2 pair may then be identified with either the two protons in a water molecule or with a labile macromolecular proton and another (labile or nonlabile) proton. In the past, such data have been interpreted [15][16][17] with semi-phenomenological models involving dubious assumptions about the relaxation-inducing motions. 18,19 Previous water 1 H MRD studies of biopolymer gels from this laboratory 19,20 made use of a nonrigorous extension of the multi-spin Solomon equations to conditions outside the motional-narrowing regime.…”