No abstract

In vitro experiments on 15 white matter samples from five bovine brains were performed on a 1 H-NMR spectrometer at 24°C and 37°C. The average myelin water fractions (MWFs) were 10.9% and 11.8% for samples at 24°C and 37°C, respectively. The T 1 relaxation time at 37°C was found to be 830 ms, exhibiting monoexponential behavior. A four-pool model including intra/extracellular (IE) water, myelin water, nonmyelin tissue, and myelin tissue was proposed to simulate the NMR behavior of bovine white matter. A cross-relaxation correction was introduced to compensate for shifting of the measured data points and T 2 times over the duration of the Carr-Purcell-Meiboom-Gill (CPMG) measurement due to cross relaxation. This correction was found to be slight, providing evidence that MWFs measured using a multiecho technique are near physical values. At 24°C the cross-relaxation times between myelin tissue and myelin water, myelin water and IE water, and IE water and nonmyelin tissue were found to be approximately 227, 2064, and 402 ms, respectively. At 37°C these same cross-relaxation times were 158, 1021, and 170 ms, respectively. The exchange rate between myelin water and myelin was found to be 11.8 s -1 at 37°C, while the exchange rate between IE water and nonmyelin tissue was found to be 6.8 s -1 . These exchange rates are of similar magnitude, which indicates that the interaction between IE water and nonmyelin tissue cannot be ignored. Magn Reson Med 54:1072-1081, 2005.

Identification of remyelination is important in the evaluation of potential treatments of demyelinating diseases such as multiple sclerosis. Local injection of lysolecithin into the brain or spinal cord provides a murine model of demyelination with spontaneous remyelination. The aim of this study was to determine if quantitative, multicomponent T2 (qT2) analysis and magnetization transfer ratio (MTR), both indicative of myelin content, could detect changes in myelination, particularly remyelination, of the cervical spinal cord in mice treated with lysolecithin. We found that the myelin water fraction and geometric mean T2 value of the intra/extracellular water significantly decreased at 14 days then returned to control levels by 28 days after injury, corresponding to clearance of myelin debris and remyelination which was shown by eriochrome cyanine and oil red O staining of histological sections. The MTR was significantly decreased 14 days after lysolecithin injection, and remained low over the time course studied. Evidence of demyelination shown by both qT2 and MTR lagged behind the histological evidence of demyelination. Myelin water fraction increased with remyelination, however MTR remain lower after 28 days. The difference between qT2 and MTR may identify early remyelination.

Typical quantitative T 2 (qT 2 ) analysis involves creating T 2 distributions using a regularized algorithm from region-of-interest averaged decay data. This study uses qT 2 analysis of simulated and experimental decay signals to determine how (a) noise-type, (b) regularization, and (c) region-of-interest versus multivoxel analyses affect T 2 distributions. Our simulations indicate that regularization causes myelin water fraction and intra/extracellular water geometric mean T 2 underestimation that worsens as the signal-to-noise ratio decreases. The underestimation was greater for intra/extracellular water geometric mean T 2 measures using Rician noise. Simulations showed significant differences between myelin water fractions determined using region-of-interest and multivoxel approaches compared to the true value. The nonregularized voxel-based approach gave the most accurate measure of myelin water fraction and intra/extracellular water geometric mean T 2 for a given signal-to-noise ratio and noise type. Additionally, multivoxel analysis provides important information about the variability of the analysis. Results obtained from in vivo rat data were similar to our simulation results. In each case, a nonregularized, multivoxel analysis provided myelin water fractions significantly different from the regularized approaches and obtained the largest myelin water fraction. We conclude that quantitative T 2 analysis is best performed using a nonregularized, multivoxel approach.Magn Reson Med 63:212-217, 2010. © 2009 Wiley-Liss, Inc. Key words: T 2 relaxation; T 2 distribution; voxel-based analysis; white matter; rat T 2 decay measured by MRI is influenced by a number of factors, including diffusion, cross-relaxation, and compartmentalization of water within voxels. The resulting macroscopic signal is best described using a weighted combination of exponential decays (1), where the weights represent relative contributions of distinct water compartments to the measured T 2 decay. Using a multiecho acquisition to measure T 2 decays and fitting a weighted combination of exponential decays to the data is called quantitative T 2 (qT 2 ), which is sensitive to myelin content (2,3) and has uncovered previously undetected water environments in human brain pathology in vivo (4).

Texture analysis performed on routine clinical magnetic resonance images may be a potential measure of tissue integrity. Tissues with more severe myelin and axonal pathology are associated with greater texture heterogeneity.