Direct IR-UTE imaging of myelin in healthy volunteers: the effect of T1 variation
Rong Luo1, Soorena Azam ZAnganeh1, Hongda Shao1, Jun Chen1, Graeme Bydder1, and Jiang Du1

1Radiology, University of California, San Diego, San Diego, CA, United States

Synopsis

MS is a disease that relatively specifically affects myelin which is invisible with conventional sequences. Adiabatic inversion recovery prepared ultrashort echo time (IR-UTE) sequences have been proposed to directly image myelin protons and suppress the long T2 water signal by adiabatic inversion and signal nulling. However, water signal contamination is a major challenge. T1 variation in long T2 white matter, and thus imperfect choice of TI is a potential source of error in direct myelin imaging. We aimed to investigate the T1 variation in long T2 white matter in volunteers, and the effects of this on IR-UTE imaging of myelin.

Introduction

Multiple sclerosis is a disease that relatively specifically affects myelin, a lamellar membranous structure consisting of alternating protein and lipid layers 1. Myelin has an ultrashort T2* and is not detected with conventional clinical fast spin echo or gradient echo sequences 2-4. In recent years adiabatic inversion recovery prepared ultrashort echo time (IR-UTE) sequences with nominal TEs as short as 8 µs have been proposed to directly image myelin protons and suppress the long T2 water signal by adiabatic inversion and signal nulling 5. However, water signal contamination is a major challenge, especially considering the much lower signal from myelin relative to that from water in white matter of the brain. T1 variation in long T2 white matter, and thus imperfect choice of the time to null (TI) is a potential source of error in direct myelin imaging. In this study, we aimed to investigate the T1 variation for long T2 white matter in healthy volunteers, and the effects of this on IR-UTE imaging of myelin using a clinical 3T scanner.

Method

In total 12 healthy volunteers (1 female, 11 male, ages 27-71) were recruited for this study with IRB approval before the MR scan. A 2D IR-UTE sequence was used for direct imaging of myelin protons, with long T2 water protons being suppressed by adiabatic inversion and signal nulling, as well as by subtraction of the 2nd echo image from the first one (Figure 1). TI plays a critical role in selective imaging of myelin as shown in Figure 1. The T1s of long T2 white matter (WML) and gray matter (GML) were measured with a clinical IR-FSE sequence (TR = 6500 ms, TI = 50, 200, 400, 600, 1000, 1500, 2000 ms). The T2* of myelin was measured with two sets of dual echo IR-UTE sequences (TR = 1500 ms, TE = 0.01/2.2; 0.3/4.4 ms). Other imaging parameters included a flip angle of 60o, a bandwidth of 125 kHz, a field of view of 24 cm, a slice thickness of 5 mm, reconstruction matrix of 192×192, projection of 101, scan time of 5 min. The T2* measurements were repeated five times with TI variations of ±5 ms and ±10 ms around the optimal value. T1 was measured with standard inversion recovery imaging with T1 and inversion efficiency as the two fitting parameters. T2* was quantified using a mono-exponential decay model.

Results

Figure 2 shows T1 fitting for two volunteers. The female volunteer had a 9.4% longer T1 of WML than the male volunteer. Figure 3 shows T1 values for WML and GML of 12 volunteers. As indicated there is a variation in T1 from 803-894 ms for WML and 1360-1510 ms for GML. These T1 values are largely consistent with the literature. Figure 4 shows IR-UTE imaging of two volunteers as well as T2* fitting at two TIs. A short T2* of around 0.35 ms was demonstrated at the optimal TI. However, T2* increased by more than 100% with even a 10 ms increase in TI, suggesting significant long T2 water signal contamination. The optimal TI differs between the two volunteers (410 ms vs 422 ms) highlighting the importance of accurate T1 measurement of the long T2 component in white matter of the brain in order to achieve selective myelin imaging.

Discussion and Conclusion

Myelin imaging with the IR-UTE sequence depends on accurate assessment of the T1 of the long T2 component in white matter of the brain. Significant long T2 water signal contamination is introduced in myelin imaging when an inaccurate TI is chosen, as indicated by the more than doubled T2* values obtained with only a 10 ms increase in TI. Accurate T1 measurement for long T2 white matter is necessary for myelin imaging in healthy volunteers and MS patients. This can be achieved with the IR-FSE sequence in a clinical set.

Remyelination-enhancing therapies for MS patients are not yet a reality 6. Preclinical research has identified multiple targets affecting remyelination in animal model of MS 7-9. Many drugs have been designed to enhance remyelination 6, however, the lack of a robust biomarker for remylination highlights the importance of this study. The optimized IR-UTE sequence may allow direct imaging and monitoring of demyelination and remyelination in vivo, thus improving the diagnosis, management and therapeutic monitoring of MS patients.

Acknowledgements

The authors acknowledge grant support from the NIH (1R01 NS092650).

References

1. van der Knaap MS, Valk J. Magnetic resonance of myelination and myelin disorders, eds Heilmann U, Mennecke-Buhler D (Springer, Berlin), 2005; pp 1-19.

2. Waldman A, Rees JH, Brock CS, Robson MD, Gatehouse PD, Bydder GM. MRI of the brain with ultra-short echo time pulse sequences. Neuroradiology 2003; 45: 887-892.

3. Horch RA, Gore JC, Does MD. Origins of the ultrashort T2 1H NMR signals in myelinated nerve: a direct measure of myelin content? Magn Reson Med 2011; 66: 24-31.

4. Wilhelm MJ, Ong HH, Wehrli SL, Li C, Tsai PH, Hackney DB, et al. Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density. Proc Natl Acad Sci USA 2012; 109: 9605-9610.

5. Du J, Ma G, Li S, Carl M, Szeverenyi NM, VandenBerg S, et al. Ultrashort TE echo time (UTE) magnetic resonance imaging of the short T2 components in white matter of the brain using a clinical 3T scanner. NeuroImage 2013; 87: 32-41.

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9. Pirko I, Ciric B, Gamez J, Bieber AJ, Warrington AE, Johnson AJ, et al. A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virus-induced murine model of MS. FASEB J 2004; 18: 1577-1579.

Figures

Figure 1. The IR-UTE sequence (A) and myelin imaging contrast mechanism (B). An adiabatic IR pulse is used to invert the long T2 WM (WML). Myelin is largely saturated, recovered during TI and detected by subsequent UTE acquisition (B). Inaccurate TI leads to negative or positive WML signal contamination (B).

Figure 2. T1 of WML measured with IR-FSE imaging of two volunteers: 42 years old male (A) and 40 years old female (B), with T1 values of 811±19 ms and 887±28 ms, respectively.

Figure 3. T1 for WML (A) and GML (B) of 12 healthy volunteers at 3T. T1 ranges from 803-894 ms for WML and 1360-1510 ms for GML.

Figure 4. IR-UTE imaging of two volunteers with TEs of 8µs (A,F) and 2.2ms (B,G), the subtraction images (C,H) and T2* fitting with an optimal TI of 410ms (D) and 422 ms (I). With only 10 ms increase in TI, T2* values more than doubled for both volunteers (E,J).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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