MultiexponentialT₂, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord

Abstract

Quantitative MRI measures of multiexponential T 2 relaxation and magnetization transfer were acquired from six samples of excised and fixed rat spinal cord and compared with quantitative histology. MRI and histology data were analyzed from six white matter tracts, each of which possessed unique microanatomic characteristics (axon diameter and myelin thickness, in particular) but a relatively constant volume fraction of myelin. The results indicated that multiexponential T 2 relaxation characteristics varied substantially with variation of microanatomy, while the magnetization transfer characteristics remained close to constant. The most-often-cited multiexponential T 2 relaxation metric, myelin water fraction, varied by almost a factor of 2 between two regions with myelin volume fractions that differed by only % 12%. Based on the quantitative histology, the proposed explanation for this variation was intercompartmental water exchange, which caused the underestimation of myelin water fraction and T 2 values and is, presumably, a greater factor in white matter regions where axons are small and myelin is thin. In contrast to the multiexponential T 2 relaxation observations, magnetization transfer metrics were relatively constant across white matter tracts and concluded to be relatively insensitive to intercompartmental water exchange. Magn Reson Med 63:902-909, 2010. V C 2010 Wiley-Liss, Inc.Key words: MRI; multiexponential T 2 ; magnetization transfer; histology; myelin Multiexponential T 2 (MET 2 ) and quantitative magnetization transfer (qMT) have been proposed as potential MRI-derived reporters of myelin content in white matter (WM) and nerve. With MET 2 , the relative size of shortlived T 2 component (typically, T 2 ¼ 8-50 ms, depending on the amplitude of static field) has been defined as the myelin water fraction (MWF) and interpreted as a direct measure of myelin content (1,2). Similarly, in WM, the macromolecular protons that exchange magnetization with water protons are thought to be substantially constituents of myelin (3,4). That is, the qMT measure of this macromolecular pool size relative to the total water signal, sometimes called the pool-size-ratio (PSR) (5), is believed to be a measure of relative myelin content. While both MWF and PSR have been found to correlate with myelin content when comparing normal myelinated tissue with demyelinated or dysmyelinated tissue (6-11 and many others), the exact relationship between these measures and myelin content is not well understood.The interpretation of MWF as a measure of myelin content is predicated on the assumption of slow exchange between myelin water and water in the intraand interaxonal spaces, referred to herein as other water. If the rate of exchange between myelin water and other water is dependent upon the dimensions of these compartments (i.e., axon diameter [AxD], myelin thickness [MyTh], interaxonal distance), then the slow exchange model may be more suitable in some myelinated tissues than others. For example, peripheral nerve tends to have...

Axon Diameters and Myelin Content Modulate Microscopic Fractional Anisotropy at Short Diffusion Times in Fixed Rat Spinal Cord

“…Our most striking findings in this study, perhaps, is that µFA DODE showed an extremely high, and statistically significant, negative correlation with axon diameters reported by Dula et al [75] and Harkins et al [98] for the different tracts ( Table 3). This observation lends further credence to the explanation above: the finite parallel length scale probed by DODE makes the measurement strongly dependent on the perpendicular restriction, which in this case is reflected through axon sizes.…”

“…Extracellular space contributions again cannot be neglected here, but for coherently aligned systems the arguments are similar as one could potentially treat the space between densely packed axons as potentially even more restricted than the intra-axonal space itself [45]. It is also worth mentioning that MWF extracted from multiexponential T 2 measurements, as performed in this study, have been shown in the past to reflect microstructural metrics such as axon size and myelin thickness very faithfully in white matter [67,75,97].…”

“…Figures 8A,B plot mean µFA and FA against the axon diameters reported in Dula et al [75] for the different spinal cord tracts. These data, along with the values tabulated in Table 3, demonstrate that µFA DODE exhibits very strong anticorrelation with axon diameters (Spearman's ρ = −0.96, p = 0.0028).…”

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents

“…For example, if the tissue of interest has a low T2 relaxation time before contrast administration (e.g., liver), resolving the concentration of the two agents may be problematic due to excessive T2 decay. In addition, in vivo studies may be impacted by multiple factors including partial volume effects, flow effect, and magnetization transfer and/or chemical exchange that may benefit from multi-exponential relaxation models instead of the simple mono-exponential models used here 44,45 . Despite these challenges, DC-MRF offers a unique opportunity to expand the portfolio of in vivo contrast-enhanced MRI applications.…”

Modeling white matter microstructure

“…Although MWF mapping was particularly noisy when it was first introduced (MacKay et al, 1994), relatively good quality MWF maps can now be obtained rapidly (Deoni et al, 2008;Oh et al, 2013;Prasloski et al, 2012). qMT generates maps with similar noise level as MWF (depending on acquisition time), but with particularly small contrast in the white matter (Dula et al, 2010;Levesque et al, 2010). Proton density maps are highly detailed with relatively good quality and correlate with qMT and MWF (Mezer et al, 2013).…”