Synopsis
Phase images have been a valuable source of contrast in applications such as venography and for depicting gray-white matter differences with high contrast in high field MR imaging. Phase differences evolve during typical TEs of 10 - 30ms in brain studies. It has been uncertain whether it would be possible to detect signal and obtain phase maps from ultrashort non-water protons in myelin which have typical mean T2s of 0.2 - 0.5 ms. In this study single and bicomponent T2* were measured in bovine myelin lipid, brain extract, and myelin basic proton and synthetic myelin and high quality phase maps were produced in each case.Introduction
In recent years magnetic resonance (MR) phase images have been shown to offer a new type of contrast for neuroimaging applications. Importantly, phase information requires no additional scanning time and is an inherent part of the MR image. Using gradient-echo phase images, contrast-to-noise ratios between gray and white matter can be improved 10-100 times over conventional magnitude images and in some instances can reveal structures that are not otherwise visible
1,2. Recently direct MR imaging of myelin protons has been performed using ultrashort echo time (UTE) techniques on NMR spectrometers and clinical MR scanners
3-5. However, evaluation of phase information using UTE sequences has been limited. This study aims to investigate direct phase imaging of myelin using UTE sequence on a clinical 3T scanner.
Materials
Four myelin phantoms were prepared for this study. The first one was a biologically derived bovine myelin lipid powder phantom (type-I bovine brain extract obtained from Signa-Aldrich Corp, St. Louis MO), which is an organophilic extract of predominantly myelin-related brain lipids
6. The second phantom was bovine brain extract powder combined with deionised D
2O to form a suspension with a solid-liquid mass ratio of 3:2, the expected value in physiological myelin. The third phantom was 90% purified (SDS-PAGE) bovine myelin basic protein (MBP) powder obtained from Sigma-Aldrich Corp. The fourth phantom was synthetic myelin lipid formulated to approximate the non-protein portion of biological myelin including cholesterol, galactocerebroside, phosphatidylcholine and sphingomyelin (all lipids from Sigma-Aldrich Corp). The powder was mixed with deionised D
2O to form a suspension with a solid-liquid mass ratio of 3:2, similar to the second phantom. The phantoms were imaged with a non-slice selective two-dimensional UTE (2D UTE) sequence with a minimal nominal TE of 8 μs using a GE 3T Signa TwinSpeed MR scanner (GE Healthcare Technologies, Milwaukee, MI). The 2D UTE sequence employed a short rectangular pulse (duration = 32 µs) for signal excitation, followed by 2D radial ramp sampling. Typical imaging parameters included a FOV of 4 cm, bandwidth of 62.5 kHz, flip angle = 10, TR = 100 ms, reconstruction matrix of 128×128, 403 projections, a series of TEs (TEs = 8 μs, 0.1, 0.2, 0.3, 0.4, 0.8, 1.5, 3, 5 ms), 40 seconds per image. A 1-inch solenoid coil was used for signal excitation and reception. Magnitude and phase images were generated for each UTE acquisition. The T
2* of myelin protons was fitted with both a single-component model and a bi-component model.
Results
Figure 1 shows selected UTE images of the bovine brain extract powder phantom. Myelin signal dropped to near zero at 0.4 ms. Single-component fitting of the UTE images suggests a short T2* of 167±7 µs. Phase images were generated with high contrast, demonstrating the feasibility of direct phase imaging of myelin protons using UTE sequences on a clinical 3T scanner.
Figure 2 shows selected UTE images of the bovine brain extract in D2O suspension. Myelin signal dropped at a slower rate than with the powder form, and the signal decay showed bi-component behavior with a short T2* component of 324±35 µs with a fraction of 28.4%, and a long T2* component of 982±48 µs with a fraction of 71.6%. Phase images can also be generated with high contrast.
Figure 3 shows both the magnitude and phase images of the myelin MBP powder phantom. Protons in MBP powder showed single-exponential decay behavior with a short T2* of 170±6 µs.
Figure 4 shows both the magnitude and phase images of the synthetic myelin powder in D2O suspension. The signal decay showed bi-component behavior with a short T2* component of 349±40 µs with a fraction of 26.1%, and a long T2* component of 3050±358 µs with a fraction of 73.9%. Again phase images were generated with high contrast.
Discussion and Conclusions
The preliminary results show that UTE sequences allow direct magnitude and phase imaging of protons in myelin lipid and myelin basic protein, both of which were previously undetectable with conventional clinical sequences on whole-body scanners. This technique may improve the sensitivity and specificity of diagnosis and therapeutic monitoring multiple sclerosis (MS), which is a disease that relatively specifically targets myelin. Many drugs have been designed to enhance remyelination
7, however, the lack of a robust biomarker for remylination has been problematic.
Acknowledgements
The authors acknowledge grant support from the NIH (1R01 NS092650) and Ningbo Jansen NMR Technology Co., Ltd.References
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