Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies

Abstract

Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR- UTE sequences at different TEs. T2* values of ~110–330 μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS.

Towards quantification of myelin by solid-state MRI of the lipid matrix protons

“…Since transverse relaxation during excitation may be severe due to the relatively long slice-selective RF pulse, 2D IR-UTE detects only the portion of myelin protons with longer signal life-times. Such T 2 -selective excitation may also account for a longer apparent myelin T 2 * of ~300 µs measured by Sheth et al (Sheth et al, 2016). Again, because of the highly non-Lorentzian line shape of the myelin resonance, the concept of a single T 2 * value is not applicable.…”

“…2d). It is therefore not appropriate to characterize transverse relaxation of myelin in terms of a single time constant (even though measurements obtained using longer excitation pulses may suggest a mono-exponential decay (Sheth et al, 2016)). A mono-exponential appearance is merely the result of the inability of RF pulses longer than the signal lifetime to excite the shortest T 2 * components.…”

Susceptibility-Based Neuroimaging: Standard Methods, Clinical Applications, and Future Directions

“…[103] UTE methods have also shown promise in evaluating white matter via myelin selective imaging. [104, 105]…”

Modeling white matter microstructure

“…Unfortunately, measuring the signal directly from myelin is challenging due to the ultrashort myelin relaxation times (T2~10 ms), and because the signal from myelin gets lost in the strong water signal. Although some groups showed very promising results of direct myelin imaging in humans in vivo (Sheth et al, 2016), such techniques are very recent and further validation is required. Instead of detecting the myelin directly, researchers have developed strategies to retrieve quantitative metrics that correlate with absolute myelin content (or myelin volume fraction, MVF) from the water signal.…”

“…not perfectly correlated with conventional metrics) (Alexander et al, 2010;Zhang et al, 2012) that correlates with histology (Alexander et al, 2010;Barazany et al, 2009;Dula et al, 2010;Duval et al, 2015Duval et al, , 2016bOng and Wehrli, 2010;West et al, 2016b), and improves specificity in lesions (Kipp et al, 2016;Stikov et al, 2015a). More comprehensive models (Burcaw et al, 2015), as well as a new paradigm for measuring myelin (Sheth et al, 2016), should further improve the specificity of these metrics.…”