Myelin Water Imaging: Implementation and Development at 3.0T and Comparison to 1.5T Measurements Shannon H. Kolind, 1 * Burkhard Ma ¨dler, 1,2 Stefan Fischer, 2 David K.B. Li, 3 and Alex L. MacKay 1,3 Multicomponent T 2 relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). The goal of this study was to implement and develop the single-slice T 2 -imaging technique proposed by Poon and Henkelman. For refinement, scan parameters (gradi- ent crusher height and slew rate, bandwidth, echo spacing, matrix size, repetition time, and phase rewinding) were varied in water-based phantoms and in fixed and in vivo brain. Changes in the standard deviation of the residuals of the multiexponen- tial fit, MWF, T 2 , and peak width of the intra/extracellular water were monitored to determine which scan parameters mini- mized artifacts. Subsequently, we compared multicomponent T 2 measurements at 1.5T and 3.0T for 10 healthy volunteers, and investigated the differences in SNR, fit residuals, MWF, and T 2 and peak width of the intra/extracellular water, at higher mag- netic field. MWF maps were found to be qualitatively similar between field strengths. MWFs were found to be significantly higher at 3.0T than at 1.5T, but with a strongly significant cor- relation between measurements (R 2 > 0.92, P < 0.0005). The signal-to-noise ratio (SNR) was nearly double at 3.0T, but the standard deviation of residuals was increased in most cases. Magn Reson Med 62:106 –115, 2009. © 2009 Wiley-Liss, Inc. Key words: myelin; water; imaging; myelin water fraction It has long been a goal of MRI to obtain a quantitative measure of myelin in order to better understand the natu- ral development of the central nervous system (CNS) as well as to study an array of neurological diseases affecting myelin. While there are several MR techniques used to investigate myelin content or integrity, so far no MR mea- sure has been shown to relate explicitly to myelin content. For instance, while diffusion tensor imaging measures re- flect changes in myelination, they are affected by the de- gree of fiber tract orientational order and packing proper- ties of macroscopically large fiber bundles. Magnetization transfer measures are very sensitive to tissue damage due to myelin loss, but are highly influenced by other factors such as inflammation and axonal loss; and proton mag- netic resonance spectroscopy is capable of detecting active demyelination but is not able to assess intact myelin. A technique for studying myelin not yet in common usage but rapidly gaining in popularity is multicomponent T 2 relaxation, which is capable of resolving the various water reservoirs present within an image voxel based on the respective T 2 relaxation times of the water protons in dif- ferent microscopic environments (compartments). In nor- mal human white matter, the shortest T 2 component (20 ms) is attributed to water trapped between the mye- lin bilayers and an intermediate T 2 component (80 ms) is thought to arise from intra/extracellular (IE) water (1,2). The myelin water fraction (MWF) is the ratio of the short T 2 (or myelin water) signal to the total signal in the T 2 distribution. While multicomponent T 2 relaxation is still not a direct method of measuring myelin tissue, as it actually measures the water trapped between the myelin bilayers, it has been shown to be very highly correlated with histological measures of myelin in rats (3– 6), guinea pigs (7–9), and formalin-fixed human brains (10 –12). Other measures that can be extracted from multicompo- nent T 2 relaxation include the geometric mean T 2 (T  2 , analogous to the amplitude-weighted mean, but on a log- arithmic scale) and peak width of the IE peak. Changes in the size of the IE peak and its T  2 time indicate changes in the intra- and extracellular water environments, and con- sideration of both MWF and T  2 has been demonstrated to aid in distinguishing between demyelination and inflam- mation (5). The width of the IE peak provides information regarding the homogeneity of the intra- and extracellular environments (9). The total signal in the T 2 distribution is proportional to the total water content in the tissue and, if a water reference standard is included in the image, the total signal can be used to estimate the absolute water content (2). The approach most often used to collect multicompo- nent T 2 relaxation data was initially developed by Poon and Henkelman (13), and consists of a single-slice multie- cho pulse sequence, utilizing large gradient crushers of alternating polarity and composite RF block pulses. It is critical to achieve accurate 180° rotations (in the presence of inhomogeneous B 1 and B 0 fields), and to minimize any contribution from stimulated echoes and signal excited outside of the selected slice. Some further challenges in implementing this technique include the need for a high signal-to-noise ratio (SNR) and short echo spacing. In recent years a number of groups have published re- sults of myelin water imaging in vivo (1,14 –22); however, the majority of these studies were carried out at 1.5T. Higher field strength provides increased SNR, and it has been reported (23) that a high SNR (noise standard devia- 1 Department of Physics and Astronomy, University of British Columbia, Van- couver, Canada. 2 Philips Healthcare, Cleveland, Ohio, USA. 3 Department of Radiology, University of British Columbia, Vancouver, Can- ada. Grant sponsor: Canadian Institutes of Health Research; Grant sponsor: Killam Trusts; Grant sponsor: Natural Science and Engineering Research Council of Canada; Grant sponsor: Multiple Sclerosis Society of Canada. *Correspondence to: Shannon H. Kolind, UBC MRI Research Centre, Room M10, Purdy Pavilion / ECU, 2221 Wesbrook Mall, Vancouver, BC Canada, V6T 2B5. E-mail: skolind@physics.ubc.ca Received 13 August 2008; revised 20 November 2008; accepted 4 January 2009. DOI 10.1002/mrm.21966 Published online 7 April 2009 in Wiley InterScience (www.interscience. wiley.com). Magnetic Resonance in Medicine 62:106 –115 (2009) © 2009 Wiley-Liss, Inc. 106