Miaomiao Wang1, Yao Ge1, Xianjun Li1, Congcong Liu1, and Jian Yang1
1the first affiliated hospital of Xi'an Jiaotong university, Xi'an, China
Synopsis
MR elastography is a promising approach for describing
biomechanical properties. Some studies investigated stiffness of subcortical
gray matter (SGM), which are critical for cognitive. However, they have not
been explored in infants. MRE has some limitations in application of infants, and
this study aims to measure SGM stiffness in preterm and term infants using virtual
MRE. Our study suggested that virtual shear stiffness of SGM were similar
between the preterm at term equivalent and the term, and GP is the stiffest
region. This finding suggested that virtual MRE is a sensitive method to characterize
the SMG maturity in infants.
Introduction
Changes in tissue composition and cellular
architecture have been associated with neurological development and disease,
and these in turn can affect biomechanical properties[1].
Natural biological factors such as growth and aging, can affect underlying
tissue biomechanics in different brain regions[2]. With the development of
MR elastography, it was a promising approach for describing brain
stiffness, and has great potential to reflect pathology in tissue
microstructures[3].
Since the subcortical gray matter (SGM) structures are critical for cognitive
performance, executive function and skill learning[4],
previous study have investigated their stiffness using MR elastography (MRE) in youth and adults[5].
However, the SGM stiffness has not been explored in infants. Because of MRE
lacks in image resolution, relies on dedicated hardware and software, and adds
to examination time, it has limitations in the application of neonates and
infants[6].
Recently, Le Bihan et.al proposed a novel method that based
on a clinically available diffusion MRI sequences, known as virtual MRE
(vMRE), is attractive for evaluation of brain development[6].
Thus, this study aims to measure the stiffness of SGM structures in preterm and
term infants using vMRE. Methods
The local institutional review board approved this
study and all the written informed consents were obtained from parents of infants.
Subjects
Preterm infants scanned at term equivalent age and term infants without any
MRI abnormality were included. Subjects with obvious
imaging artifacts were excluded. MRI Protocols All MR examinations
were performed using a 3T scanner (Signa HDxt, GE Healthcare, Milwaukee,
Wisconsin) with an 8-channel head coil. The parameters of DKI sequence were as
follows: b values =0, 50, 200, 500, 1000, 2000, 2500 s/mm2; 18
gradient directions per nonzero b value; repetition time/echo time=11000/91.7
ms; slice thickness =4 mm; field of view=180×180 mm2; acquisition
matrix=128×128. Data and statistical analysis DKI images of the lower
b-value (Slow, b value=200 s/mm2) and those of the higher b-value
(Shigh, b value=1000 s/mm2) were used to estimate the virtual shear
stiffness[6, 7]: virtual shear
stiffness = a·ln (Slow/Shigh) + b. The scaling (a) and the shift (b) factors
were separately set to −9.8 and 14 according to the previous calibration
studies[6, 7]. DKI-derived FA and MK
maps were also calculated. All individual images were firstly registered to the
group mean image, and then registered to the JHU neonatal brain atlas using a
combination of linear and nonlinear methods[8]. Finally, thalamus,
putamen, globus pallidus (GP) and caudate nucleus of each hemisphere were
selected for comparison according to the atlas (Figure 1). The values of bilateral ROIs were averaged for further
analysis. Wilcoxon signed-rank tests were used to assess
between-group differences in demographicsand parameters. Wilcoxon
paired tests were used for the differences of mentioned values among SGM structures
in each group. All statistical analysis was performed by using SPSS 19.0 (SPSS,
Chicago, IL, USA); P<0.05 was
considered as statistically significant difference. In multiple comparisons,
P<0.008 (0.05/6) was considered
statistically significant after the Bonferroni correction.Results
A total of 12 preterm and 11 term infants were
enrolled (Table 1). No significant diļ¬erences
were found in virtual shear stiffness, FA and MK between groups (P>0.05). There is a significant
difference in virtual shear stiffness among SMG structures in both groups, in
which the GP is the stiffest region and caudate nucleus is the softest (P<0.008, Figure1). The GP and thalamus demonstrate relatively higher FA and
MK values compared with other regions, the caudate nucleus and putamen show the
relatively lower FA and MK, respectively (P<0.008,
Figure2).Discussion
This study suggested that the virtual shear
stiffness of SGM were similar between the preterm at term equivalent age and
the term, and GP is the stiffest region at this period. This reflects that preterm
infants could catch up term infants in stiffness in the SGM regions. GP as the
stiffest region among the SGM structures in both groups, which may be related
to the maturity. The higher FA and MK of GP were further confirmed this, and it
is consistent with previous study[9]. More importantly,
FA and MK could not distinguish between GP and thalamus, while vMRE results
showed that the virtual shear stiffness of GP was higher than thalamus. It is
possible that GP has early neuronal development and synaptic connections[10]. Since this method
for quantitative evaluation of brain stiffness is an exploratory study based on
the diffusion and DKI-based sequences proposed by Le Bihan et.al[6], its relationship
with the real stiffness value needs further exploration.Conclusion
Compared with conventional DKI-derived parameters, virtual
MRE is a sensitive method to characterize the maturity of SMG structures. It may
have broad prospects in detecting protentional injury in infants.Acknowledgements
This study was supported by the National Natural
Science Foundation of China (No. 82101815, 81971581, 81771810, 81471631 and
51706178), and the Clinical Research Award of the First Affiliated Hospital of
Xi’an Jiaotong University (No. XJTU1AF-CRF-2015-004).References
[1] Murphy MC, Huston
J, 3rd, Ehman RL. MR elastography of the brain and its application in
neurological diseases [J]. NeuroImage, 2019, 187(176-83.
[2] Arani
A, Murphy MC, Glaser KJ, et al. Measuring the effects of aging and sex on
regional brain stiffness with MR elastography in healthy older adults [J].
NeuroImage, 2015, 111(59-64.
[3] Riek
K, Millward JM, Hamann I, et al. Magnetic resonance elastography reveals
altered brain viscoelasticity in experimental autoimmune encephalomyelitis [J].
NeuroImage Clinical, 2012, 1(1): 81-90.
[4] Laforce
R, Jr., Doyon J. Distinct contribution of the striatum and cerebellum to motor
learning [J]. Brain and cognition, 2001, 45(2): 189-211.
[5] Hiscox
LV, Johnson CL, Barnhill E, et al. Magnetic resonance elastography (MRE) of the
human brain: technique, findings and clinical applications [J]. Physics in medicine
and biology, 2016, 61(24): R401-r37.
[6] Le
Bihan D, Ichikawa S, Motosugi U. Diffusion and Intravoxel Incoherent Motion MR
Imaging-based Virtual Elastography: A Hypothesis-generating Study in the Liver
[J]. Radiology, 2017, 285(2): 609-19.
[7] Lagerstrand
K, Gaedes N, Eriksson S, et al. Virtual magnetic resonance elastography has the
feasibility to evaluate preoperative pituitary adenoma consistency [J].
Pituitary, 2021, 24(4): 530-41.
[8] Oishi
K, Mori S, Donohue PK, et al. Multi-contrast human neonatal brain atlas:
application to normal neonate development analysis [J]. NeuroImage, 2011,
56(1): 8-20.
[9] Paydar
A, Fieremans E, Nwankwo JI, et al. Diffusional kurtosis imaging of the
developing brain [J]. AJNR American journal of neuroradiology, 2014, 35(4):
808-14.
[10] Ouyang
M, Dubois J, Yu Q, et al. Delineation of early brain development from fetuses
to infants with diffusion MRI and beyond [J]. NeuroImage, 2019, 185(836-50.