Myelin water measurement in the spinal cord

Abstract

The desire to monitor the spatial-temporal characteristics of myelination in the spinal cord (SC), in the context of pathological change in demyelinating diseases or proposed neuroregenerative protocols, has led to an interest in noninvasive imagebased myelin measurement methods. We present one strategy: a magnetic resonance-based measure that capitalizes on the characteristics of T 2 relaxation of water compartmentalized within tissue. In this study, 32-echo relaxation studies for measuring the myelin water fraction (MWF) were applied in healthy control SC in vivo using a sagittal inversion recovery multiecho sequence, and findings were supported with supplemental studies in bovine SC samples in vitro. Mean human MWF varied according the level of the SC examined: cervical, thoracic, and lumbar MWF was found to be 21. The human spinal cord (SC) is a 0.5-m long cylindrical structure in the central nervous system (CNS) that occupies the upper two thirds of the vertebral canal, and serves as a liaison for impulses between the brain and the peripheral nerves. Transverse axial sections through the SC reveal a characteristic central "butterfly" distribution of gray matter (GM) within the surrounding white matter (WM) as depicted in Figure 1; the distinction between the two depends on the presence of myelin, a lipoprotein membrane that ensheathes axons and gives rise to the glistening white appearance of WM. Myelin's primary role of potentiating action potential propagation is well known; its importance in that respect is exemplified by the devastating pathologies of demyelinating diseases such as multiple sclerosis (MS).The motivation to explore a magnetic resonance marker of myelination in the SC is two-fold. The SC is often involved in the demyelinating pathology of MS and SC. Magnetic resonance imaging (MRI) has recently been recommended as a paraclinical test for MS (1,2). Meanwhile, demyelination has been suggested as a potential strategy toward creating a permissive extracellular environment for axonal regeneration after SC injury (3). In both cases, magnetic resonance markers of myelination in the SC are of interest in monitoring disease pathology and potential regenerative therapies. Myelin and T 2 RelaxationIndirect measurement of myelin is possible with MRI. T 2 relaxation aspires to resolve multiexponential T 2 decay data into its constituent exponential components, each of which is attributable to water protons within a distinct diffusion restricted relaxation environment in tissue. The T 2 component with the shortest relaxation time (ϳ20 ms) is believed to originate from water trapped within the bilayers of the myelin sheath (4,5); this "short" relaxation time is believed to arise due to the large interfacial contact area in the multilamellar myelin compartment. The fractional contribution of the signal from this short T 2 component relative to the total area under the T 2 distribution is called the myelin water fraction (MWF) (5). Magnetic resonance studies have amassed substantial evidence that the shor...

Rapid whole cerebrum myelin water imaging using a 3D GRASE sequence

“…First, higher field strength enables higher signal to noise which may result in an increase in measured MWF due to improved accuracy (Minty et al, 2009). Second, higher fields are associated with increased B 1 inhomogeneity which results in decay curves with stimulated echo artifacts.…”

“…For pulse sequences using multiple spin echoes, it has been demonstrated that increased noise leads to a decrease in measured MWF (Minty et al, 2009). The literature is currently in conflict about the nature of T 1 relaxation of water in white matter (Labadie et al, 2008(Labadie et al, , 2009).…”

Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI

“…Notably, myelin water fraction estimated from the short T2 relaxation of water trapped within myelin sheets is another measure that correlates with myelin content (Kozlowski et al, 2008;Laule et al, 2006). Despite several difficulties related to spinal cord motion and low SNR, this technique has been successfully applied in the human spinal cord at 1.5T (Minty et al, 2009).…”

Temporal phase correction of multiple echo T2 magnetic resonance images

“…Multiple echo fitting, using non-negative least squares (NNLS) [5], can be performed to determine the relative proportions of the micro-structural dependent T 2 times [6,7,8,9,10]. In some cases, such as healthy [3,4,11,12] and pathological [13,14,15,10,16] central nervous system tissue, different water environments with separate T 2 times are present within a given voxel, resulting in a decay curve from the voxel being the summation of exponential decays from each constituent T 2 time. Four regions are of particular interest: 1) one with a short T 2 time attributed to water trapped between myelin bilayers, called myelin water; 2) one with an intermediate T 2 time attributed to intra-and extracellular water; 3) one with a prolonged T 2 time longer than intra-and extracellular water, which has been noted in pathology [13,14] and in the corticospinal tract of healthy volunteers [13,17]; and 4) one with the longest T 2 time in the distribution, or near that of pure water, that is attributed to cerebrospinal fluid.…”