Fast multislice mapping of the myelin water fraction using multicompartment analysis of T decay at 3T: A preliminary postmortem study

Abstract

Quantitative mapping of the myelin water content can provide significant insight into the pathophysiology of several white matter diseases, such as multiple sclerosis and leukoencephalopathies, and can potentially become a useful clinical tool for early diagnosis of these diseases. In this study, multicompartment analysis of T* 2 decay (MCAT2*) was used for the quantitative mapping of myelin water fraction (MWF). T* 2 decay of each voxel at multiple slice locations was acquired in fixed human brains using a multigradient-echo (MGRE) pulse sequence with alternating readout gradient polarities. Compared to prior techniques using Carr-Purcell-Meiboom-Gill (CPMG) acquisition, the MGRE acquisition approach has: 1) a very short first echo time (Ϸ2 ms) and echo-spacing (Ϸ1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal; 2) a low RF duty cycle, which is especially important for achieving acceptable specific absorption rate (SAR) levels at high field strengths. Multicompartment analysis was then applied to the T* 2 decay in each pixel using a 3-pool model of white matter to detect the signal arising from the myelin water, myelinated axonal water, and mixed water While conventional MRI methods are sensitive to the various pathologies affecting white matter in the central nervous system, it provides relatively nonspecific information about the nature of the underlying pathology. One approach developed based on multicompartment analysis of T 2 decay provides quantitative measurements of myelin water fraction (MWF) (1). Quantitative mapping of the MWF is a direct indicator of the integrity of the myelin sheath and can provide valuable insights into the pathology of focal and diffuse white matter (WM) diseases, such as in multiple sclerosis (MS).One technique for quantitative in vivo mapping of the MWF was presented by MacKay et al. (2). In this technique the time course of T 2 decay was acquired using a 32-echo single-slice Carr-Purcell-Meiboom-Gill (CPMG) sequence with composite 90°x-180°y-90°x refocusing pulses (3) and big crusher gradients around the refocusing pulses (4). A nonnegative least squares (NNLS) algorithm was used to estimate the MWF from the short T 2 decay compartment (5). This technique has very successfully demonstrated the merit of quantitative MWF measurement in the study of MS (6). However, there are some limitations associated with this technique. First, it is difficult to further shorten the first echo time (TE1) and echo spacing (ES) with this pulse sequence, since the durations of the nonselective refocusing pulses and the crusher gradients (4) substantially increase the minimum TE1 and ES. With the TE1 and ES values typically used, the myelin water signal is effectively detected only in the first 2-3 measurements (i.e., first 2-3 echoes), leading to compromised accuracy in estimating the MWF using multicompartment analysis. For example, the myelin water signal with a T 2 of 15 ms is reduced to 51% at the first echo, 26% at the seco...

3D high spectral and spatial resolution imaging of ex vivo mouse brain

“…High-resolution proton spectra associated with each image voxel in a 3D volume were acquired using a multigradient echo pulse sequence (echo-planar spectroscopic imaging, EPSI). 25,26 This is consistent with the approach of multiple groups; 23,27 these researchers analyzed multigradient echo data in the temporal domain (i.e., the free induction decay or FID). Their results suggest subtle resonance frequency variations due to microstructural compartmentalization.…”

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

“…PET ligands targeting the 18 kDa translocator protein, which is upregulated with inflammation, detect neuroinflammation in human diseases including multiple sclerosis and in animal models, but the effectiveness of these PET markers remains to be seen (Banati et al, 2000;Papadopoulos et al, 2006;Chauveau et al, 2009Chauveau et al, , 2011Abourbeh et al, 2012;Xie et al, 2012). Promising advances in imaging myelination have been reported including myelin water imaging (MacKay et al, 1994;Du et al, 2007;Laule et al, 2008;Hwang et al, 2010;Prasloski et al, 2012), magnetization transfer (Inglese et al, 2003;Schmierer et al, 2004Schmierer et al, , 2007aDortch et al, 2011;Stikov et al, 2011;Underhill et al, 2011), optical imaging (Wang et al, 2011a) and myelin-specific PET markers (Wang et al, 2009;Wu et al, 2013). For specifically identifying axon injury and loss, reduced NAA content measured by magnetic resonance spectroscopy (MRS) has been used (De Stefano et al, 1999;Aboul-Enein et al, 2010;Wood et al, 2012).…”

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

“…Due to specific absorption rate (SAR) (especially at high fields) and timing constraints, the T 2 decay curve is often not fully sampled for an accurate quantification. Recently, it has been shown that myelin water fraction can also be measured using a multi-exponential analysis of the T 2 * decay in multislice multiple echo gradient echo sequence (Du et al, 2007;Hwang et al, 2010). The resulting myelin water fractions are highly dependent on the constraints introduced on the multi-exponential fitting procedure (Hwang et al, 2010) and suffer from significant inaccuracies in regions close to air-tissue interfaces.…”