Nan-Hao Chen1,2, Li-Ping Chen3, Chia-Wei Hsu3, Chin-Hua Yang1,3,4, and Hsu-Hsia Peng1
1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, 2Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan, 3Department of Medical Imaging, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan, 4Department of Radiology, Taoyuan General Hospital, Taoyuan, Taiwan
Synopsis
Keywords: Brain Connectivity, Aging, Myelin co-variation network
Myelin co-variation networks was used to investigate the
myelinic alteration in brain degradation. However, a systematic investigation of
age-related co-variation networks of multiple myelin-related images remains deficient.
We aimed to investigate the age-related effect on myelin co-variation networks
in gray matter and white matter. Our results revealed that different
myelin-related indices presented different age-dependent evolution of
co-variation networks. The age-dependencies of strength of co-variation and
topological attributes were mostly in complex polynomial pattern. The
investigation of multiple age-related myelin co-variation networks might comprehend
the synchronous changes between brain regions and demonstrated its usefulness in
predicting the alteration of myelinic tissue.
Introduction
Apparent
Diffusion coefficient (ADC) map computed from diffusion weighted imaging (DWI) can
indirectly reflect the myelination in axon [1]. Fluid Attenuation
Inversion Recovery (FLAIR) images show the capability on evaluating the level
of myelin enrichment [2].
Myelin water fraction (MWF) is used to directly measure myelin water component in
myelin sheaths [3].
The apparent MWF (aMWF) has comparable image quality with conventional MWF
technique and benefits from the short acquisition and post-processing time [4]. The ratio of T1-weighted image to T2-weighted
image (T1w/T2w ratio) has been reported as an indicator of evaluating myelinic
contents with several confounding factors (e.g., axon density) [5,
6].
The synchronicity of myelinic changes in different brain regions, namely
myelin co-variation network, was used to investigate the myelinic alteration in
brain degradation [7, 8]. The elevated myelin
covariance was observed in the elderly brain, and the apparent vibrating
trajectory of topological attributes across the lifespan has been discussed [8]. However, a systematic
investigation of myelin co-variation networks of multiple myelin-related images
remains deficient. We aimed to investigate the myelin co-variation networks of different
myelin-related images and to explore the age-related effect on myelin
co-variation networks in gray matter (GM) and white matter (WM).Materials & Methods
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healthy volunteers were recruited (male/female=21/7, age=46±12 (28-72) y/o) and
sorted ascendingly by their ages. All MRI images were acquired in a
3-T system (Skyra, Siemens). The imaging protocol included DWI, T2-FLAIR, T1WI,
T2WI, and ViSTa [4] sequences. The scanning parameters
were listed in Figure 1a. aMWF is calculated by: aMWF(%)=(ViSTa/PDw)×0.55×100% [4]. The T1w/T2w ratio was processed with
bias correction and intensity standardization
[5]. T1WI of each participant
was registered on MCALT T1 template provided from Aging and Dementia Research
(ADIR) lab at Mayo Clinic [9].
Figure 1b illustrates the 4 and 6 regions
of interest (ROIs) selected in GM and WM of left and right hemispheres,
respectively. The ROI-based linear regressions were
performed to express the relationship between mean value of each myelin-related
index and age and sex. A Pearson correlation coefficient of the regressed mean
value of each myelin-related index between any two selected brain regions was
computed in every 5 volunteers with a sliding window of one-volunteer. The Pearson correlation coefficients were
transformed to z-score to form a 20-by-20 matrix, i.e., co-variation network (Figure
1c).
In addition to the strength of
co-variation, we computed topological attributes of networks, including characteristics
path length (Lp), global efficiency (Eg), clustering coefficient (Cp), and
local efficiency (Eloc) [10]. The
best-fitted models between age and strengths and attributes were determined by
Akaike Information Criterion (AIC) ranged from the 1st- to 8th-order polynomials [11]. Results
Figure 1d demonstrates the quantitative maps of ADC,
mFLAIR, aMWF, and T1w/T2w ratio in a 58-year-old female volunteer. In Figure 2,
the co-variation networks of 4 myelin-related indices were shown with an
age-interval of 4 years. Different myelin-related indices presented different
age-dependent evolution of co-variation networks. In Figure 3(a,d), the strength of co-variation
of ADC was monotonically increasing with age while that of T1w/T2w ratio was decreasing
with age. In mFLAIR (Figure 3b), the
association between the strength of co-variation and age was a 2nd-order
polynomial, whose lowest co-variation was at 51-year-old. In aMWF (Figure 3c), the
association between the strength of co-variation and age was expressed by a 4th-order
polynomial with two local maximums at 43-year-old and 61-year-old.
The Lp and Eg of ADC (Figure 4a)
presented a 4th-order polynomial age-trajectory, and those of T1w/T2w
ratio (Figure 4d) showed a 1st-order polynomial with age. In Figure
5(a,b), Cp and Eloc of ADC and mFLAIR associated with age in high order polynomial (4th- or 5th-order).
The Cp and Eloc of aMWF and T1w/T2w ratio revealed 3rd-order
polynomial age-trajectory, whose local maximum/minimum locate at similar age
(Figure 5(c,d)). aMWF presented similar age-trajectories in Lp, Cp, and Eloc. Discussion & Conclusion
In this study, we evaluated the myelin co-variation
networks of ADC, mFLAIR, aMWF, and T1w/T2w ratio and investigated their
age-dependency by topology analysis. The strength of co-variation in ADC and
T1w/T2w ratio increased and decreased with age, respectively; while that in
mFLAIR and aMWF was a more complex polynomial pattern. The age-dependency of topological
attributes, mostly in a high-order polynomial, was differential in each
myelin-related index. Lp, Cp and Eloc showed similar age-trajectory, especially
in aMWF.
Previous studies reported myelin
covariance networks of magnetization transfer ratio and T1w/T2w ratio to
present the modification of brain networks [7, 8].
Our results confirmed age-related effect on the strength and the topological
attributes of co-variation networks. Furthermore, the similar age-trajectory in
Lp, Cp, and Eloc implied that the network is alternatively working in an
integrated or segregated way and the homeostatic status appears in the observed
age range [12].
In
conclusion, a systematic investigation of co-variation networks from multiple
myelin-related indices could be helpful to comprehend the synchronous changes between
brain regions. The topological exploration of the age-related myelin co-variation
networks demonstrated its usefulness in predicting the alteration of myelinic
tissue. Acknowledgements
No acknowledgement found.References
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