Synopsis
Myelin,
a thin layer of sheath-like cell, provides an important role in protecting
nerve axon and accelerating neural impulse transmission. Myelin water fraction
(MWF) mapping has been recently proposed for assessing myelin content in-vivo. One
quantitative MR method called mcDESPOT has shown promising results for
assessing myelin content. However, this method is lack of consideration of magnetization
transfer (MT) effect leading to the complication of interpretation for MWF
values. In this study, we proposed a method called mcRISE to account for MT effect
and investigate the feasibility of assessing myelin content with MT-insensitive
MWF as well as additional MT parameters.Introduction
Myelin,
a thin layer of sheath-like cell, provides an important role in protecting
nerve axon and accelerating neural impulse transmission. Recently a quantitative
MR method called multicomponent-driven equilibrium single-component observation
of T1 and T2 (mcDESPOT) has shown promising results for assessing myelin
content using rapid steady-state sequences (1). In this method, a
bicomponent water exchange system is used to characterize myelin water and
non-myelin water. Yet this simplified bicomponent model is practically useful, the
lack of consideration of interaction between non-aqueous macromolecular proton
and mobile water through magnetization transfer (MT) renders the complication
of interpretation for MWF values (2-4). Recent studies show that
the steady-state sequence signal could be strongly biased by MT under certain
imaging conditions (5,6). In our previous study, we
proposed a new method called multicomponent relaxation imaging using
steady-state signal evolution (mcRISE) in cartilage imaging to account for MT effect
while preserve the advantageous acquisition of mcDESPOT (7). In this study, we optimized
and applied the mcRISE method to the neural tissue and investigate the
feasibility of assessing myelin content with MT-insensitive MWF as well as
additional MT parameters.
Theory
In
mcRISE, a macromolecular proton pool in exchange with mcDESPOT water pools was
introduced to explicitly model MT exchange between macromolecular proton,
myelin and non-myelin water. A combined mcDESPOT and quantitative magnetization
transfer imaging (qMTI) (8) method is proposed to
resolve this three compartmental system. Simultaneous fitting for all
parameters of this system is not feasible.
Hence, an incremental fitting approach was introduced. First, the macromolecular
bound pool fraction
f and exchange
rate
k was estimated using balanced
steady-state free precession (bSSFP) based estimation of the MT parameters (8), where varying RF pulse
width (bSSFPv) was applied for exploring on-resonance MT effect. Then, these
values as fixed parameters were implemented in the full model fit with
additional varying flip angle spoiled gradient echo (SPGR) and bSSFP, which
involves the mutually exchanging slow and rapid relaxing water compartments and
the bound proton pool. The detailed processing pipeline is shown in Figure 1.
Methods
A
brain scan was performed on a healthy adult volunteer using a GE MR750 3.0T
scanner. The mcRISE parameters included: 1) SPGR scans with TR/TE=4.1/1.5ms over
a range of flip angles (α=3, 4, 5, 6, 7, 9, 13, 18°); 2) Two bSSFP scans with RF phase cycling on
(bSSFP
180) and off (bSSFP
0), with TR/TE=3.0/1.4ms over a
range of flip angles (α=2, 5, 10, 15, 20, 30, 40, 50°); 3) One bSSFPv scans
over a range of RF pulse width (T
RF) at T
RF/TR=0.27/2.5ms,
0.3/2.5ms, 0.4/2.6ms, 0.6/2.8ms, 0.8/3.0ms, 1.2/3.4ms, 1.6/3.8ms, 2/4.2ms and
α=35°. 4) Inversion recovery SPGR scan with TR/TE=4.1/1.5ms, TI=450ms, and
α=5°. All scans were performed in the sagittal plane with a 25.6cm field of
view, 128×128 matrix, 2mm thickness, one excitation.
Results & Discussion
mcRISE
was able
to simultaneously generate MWF
map and additional quantitative MT
f map
of the entire brain at 3.0T (Figure 2). The
spatial variations of the MWF and
f maps
within the brain tissue are consistent with the previous reported values from
multiple multicomponent T2 and quantitative MT studies (1,8). A significant reduced MWF
values is observed in the mcRISE method compared to mcDESPOT. A recent study
comparing the MWF between mcDESPOT and a multi-echo T2 decay method
demonstrated an overestimation of mcDESPOT MWF values in brain tissue, which was
largely attributed to MT effects (3). The MT-corrected MWF
values from mcRISE shows a better correspondence to reported multiecho T2 MWF
and our previous simulation results (7). In addition, a strong
correlation (
p<0.0001 in Pearson
test) between MWF and macromolecular proton fraction
f for both mcRISE and mcDESPOT is observed (Figure 3) which corresponds
well to one previous study comparing mcDESPOT MWF and
f obtained from traditional off-resonance MT method (9), indicating the strong
correlation between myelin content and macromolecular proton from qMT. Our
previous in-vivo qMT studies also show the primary source of qMT
f
comes from the myelin sheath (10). However, this correlation
is decreased for mcRISE (r
2=0.41)
as compared to
mcDESPOT (r
2=0.78), indicate that the MT
corrected MWF might preserve complimentary information from that of MT
measurements, although detailed studies comparing MWF and qMT parameters in
terms of sensitivity and specificity to myelin content and structure are still
required. In conclusion, mcRISE is capable of simultaneously estimating MT
corrected MWF and qMT parameters in whole brain, combination of which might
provide a new set of biomarkers for rapid and comprehensive assessing myelin
content and structure in multiple brain studies.
Acknowledgements
The
work was supported by NIH R01NS065034, NIH R01AR068373-01, and GE Healthcare.References
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