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Quantitative Myelin Mapping in Human Brain Using a Short TR Adiabatic Inversion Recovery Prepared Ultrashort Echo Time (STAIR-UTE) Sequence
Yajun Ma1, Hyungseok Jang1, Zhao Wei1, Zhenyu Cai1, Yanping Xue1, Eric Y Chang2, Jody Corey-Bloom1, and Jiang Du1
1UC San Diego, San Diego, CA, United States, 2VA health system, San Diego, CA, United States

Synopsis

To quantitatively image myelin on clinical scanners, we propose a Short TR Adiabatic Inversion Recovery prepared UTE (STAIR-UTE) sequence for in vivo brain imaging. With STAIR technique, long T2 tissues with a broad range of T1s can be sufficiently suppressed. Healthy volunteer has a higher myelin proton density in white matter than that in patient with multiple sclerosis.

Introduction

UTE sequences with echo times less than 50 µs can directly detect signals from myelin protons (1-4). However, over 90% of the UTE signal originates from long T2 water protons, even in myelin-rich white matter. Sufficient long T2 suppression is crucial for accurate quantitative myelin imaging. Adiabatic inversion recovery prepared UTE (IR-UTE) sequences have been proposed for imaging myelin (4-6). However, long T2 suppression is sensitive to the selection of TI in currently available IR-UTE techniques (3-7). A slight TI offset may cause significant long T2 contamination, leading to inaccurate short T2 myelin quantification. It is well-recognized that T1 relaxation may change with both age and pathology in the brain (8,9). This makes the corresponding TI determination more challenging. To address the aforementioned problems in quantitative myelin imaging, we propose a Short TR Adiabatic Inversion Recovery prepared UTE (STAIR-UTE) technique for more robust long T2 suppression regardless of T1 variations in white matter and which, therefore, provides more accurate quantitative myelin imaging.

Methods

Figure 1A shows features of the 3D STAIR-UTE sequence (10,11). Following an adiabatic IR pulse, Nsp separate k-space spokes with an identical time interval, τ, are used for fast data acquisition. Figure 1B shows the contrast mechanism of myelin imaging. The myelin magnetization recovers from zero, and pure myelin signals can be acquired at a specific TI when the long T2 components are nulled (12,13). Numerical simulation was performed to investigate the efficiency of long T2 suppression for the STAIR scheme with different TRs. The simulated T1 values of the long T2 components ranged from 20 to 2500 ms, which cover T1 values for both white matter and gray matter. The TIs were determined by Eq. [8] in Ma et al. (11) in order to minimize the average signals from the long T2 components with T1 values ranging from 500 to 1500 ms.

A myelin-D2O phantom was made by compounding myelin lipid powder with D2O in 1-mL syringes. A total of six myelin-D2O tubes with myelin concentrations of 0, 4, 8, 12, 16, and 20% weight/volume (w/v) were prepared. The myelin phantoms were simultaneously imaged in a homemade T/R birdcage coil using the STAIR-UTE sequence with the following parameters: FOV=10×10×6.4cm3, matrix=128×128×16, TR/TI=150/71ms, TE=32μs, Nsp=3, τ=5ms, FA=20°, bandwidth=62.kHz. T2* was also measured using the conventional 3D UTE sequence with TEs of 0.032, 0.2, 0.4, 0.8, and 2.2 ms.

In vivo brain imaging was performed on ten healthy volunteers (19-45 years of age) and ten patients with multiple sclerosis (MS) (35-70 years of age). Informed consent was obtained from all subjects in accordance with guidelines of the institutional review board. The sequence parameters are as follows: FOV=22×22×30 cm3, matrix=140×140×60, TR/TI=140/61ms, TE=3μs, Nsp=5, τ=3.2ms, FA=2°, bandwidth=125kHz, scan time=9.5 min. A rubber band with a short T2 (i.e., T2 around 0.3ms) was placed between each subject’s head and the coil to serve as a reference to calibrate the proton density of myelin using Eq. [9] in Ma et al. (11). Clinical T2-FlAIR sequence was used for comparison.

The signal intensities in both the normal-appearing white matter (NAWM) in MS patients and normal white matter (NWM) in volunteers were measured for comparison. ANOVA analysis was performed to evaluate the signal difference between lesion-containing and normal white matter.

Results and Discussion

The mean T2* value of the six myelin-D2O phantoms is 0.25±0.03ms. Figure 2 shows an excellent correlation (R2=0.98) between STAIR-UTE signal intensities and myelin concentrations for these six phantoms. The STAIR-UTE image from a healthy brain in Figure 3 with TE=32 μs shows a high signal intensity in the white matter region. Exponential fitting of the STAIR-UTE signals with different TEs demonstrates a short T2* of 0.22±0.01 ms. The measured short T2* value is very close to that of myelin-D2O phantoms (T2*=0.25±0.03 ms), demonstrating that STAIR technique allows sufficiently nulling of long T2 components in white matter.

Figure 4 shows morphological images and corresponding proton density maps from a healthy volunteer. Both T2-FLAIR and STAIR-UTE measures show significant differences in MS lesions between NWM of healthy volunteers and NAWM of MS patients (p<0.0001) (A, B, D, and E in Figure 5). This demonstrates the feasibility of the proposed STAIR-UTE in quantitatively detecting MS lesions. In addition, the STAIR-UTE measures show significant difference between NWM of healthy volunteers and NAWM of MS patients (p<0.0001, see Figure 5F). In contrast, there is no significant difference found in T2-FLAIR images between these two groups (p=0.21, see Figure 5C). Those results suggest that the proton density quantified by the STAIR-UTE technique may be a useful biomarker in differentiating the myelin content in MS lesions, NAWM, and NWM.

Conclusion

The 3D STAIR-UTE sequence with a short TR/TI combination provides robust suppression of long T2 components in white matter, allowing accurate volumetric mapping of myelin proton density in brain.

Acknowledgements

The authors acknowledge grant support from NIH (1R01NS092650) and VA Clinical Science and Rehabilitation R&D Awards (I01CX001388 and I01RX002604).

References

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Figures

Figure 1 The 3D STAIR-UTE sequence employs an adiabatic IR pulse to invert long T2 signals, followed by equally spaced multi-spoke (Nsp) UTE-Cones data acquisition (A). The long T2 signals are inverted by the IR pulse, while the magnetization of myelin is not inverted, but largely saturated, due to the fast T2 relaxation of myelin protons (A). B shows the simulation investigating the effect of TR on signal suppression of long T2 tissues with a wide range of T1s in STAIR-UTE imaging. The simulated signal curve is normalized by dividing the signal intensity of a tissue with T1=20 ms in each TR.

Figure 2 STAIR-UTE imaging of six myelin-D2O phantoms with myelin concentrations of 0, 4, 8, 12, 16, and 20% w/v (A). The signal intensities of these six phantoms show an excellent linear correlation with myelin concentrations (R2 = 0.98).

Figure 3 Representative STAIR-UTE brain images with TEs=0.032 (A) and 0.4 (B) for a healthy volunteer (29-year-old female) and an exponential fitting of mean signal intensity of an ROI (located in the green ellipse circle) in white matter demonstrating a short T2* of 0.22±0.01 ms (C).

Figure 4 The representative morphological images and corresponding myelin proton density maps in STAIR-UTE imaging for a healthy volunteer (36-year-old male).

Figure 5 Statistical analysis for quantitative proton density measures of white matter acquired with clinical T2-FLAIR (first row) and proposed 3D STAIR-UTE (second row) sequences, respectively. Both measures of T2-FLAIR and STAIR-UTE of MS lesions show significant differences compared between NWM in healthy volunteers (A and D) and NAWM in MS patients (B and E). The measured 3D STAIR-UTE proton density shows a significant difference between NWM in healthy volunteers and NAWM in MS patients (P<0.0001) (F), which is not observed in T2-FLAIR measurements (P = 0.21) (C)

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)
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