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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