Age-related Magnetic Susceptibility in the Deep Gray Nuclei from 1 month to 6 Years: Comparison between Quantitative Susceptibility and R2* Mapping
Ning Ning1, Peng Wu2, Xianjun Li3, Yajie Hu3, Weishan Zhang1, Lei Zhang1, Sung-Min Gho4, Dong-Hyun Kim4, Hua Guo2, and Jian Yang1,3

1Department of Diagnostic Radiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China, People's Republic of, 2Department of Biomedical Engineering, Tsinghua University, Beijing, China, People's Republic of, 3Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China, People's Republic of, 4Department of Electrical and Electronic Engineering, Yonsei University, Seoul, Korea, Republic of

Synopsis

To observe the age-related susceptibility changes in the deep gray nuclei and assess the superiority of the quantitative susceptibility mapping(QSM) and effective transverse relaxation rate(R2*) for quantifying the iron deposits in children. 87 subjects(1M-6Y) were enrolled. The susceptibility in QSM and R2* values exhibited positive correlations with age and the reference iron concentrations calculated using an empirical equation. The correlation of the susceptibility with the iron is higher than the R2* with it. QSM may provide a more promising and reliable tool for assessment of iron content in children’s deep gray nuclei, even in the regions with lower iron content.

Purpose

Iron plays an important role in brain development and metabolism, so estimating the iron deposition may be important to assess neural development and diseases for children 1. The age-related susceptibility changes may provide valuable information regarding the iron deposition state of the human brain. The quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) are recognized as effective quantitative methods to measure the iron deposition in deep gray nuclei in adults 2. The purpose of this study is to observe the age-related susceptibility changes in the deep gray nuclei and assess the superiority of the two methods for quantifying the brain iron deposits in children.

Methods

87 young children (1M-6Y) without abnormalities in brain MR images were enrolled in this study and examined with informed consent from parents according to local ethics procedures. They were divided into 5 groups according to the age (1M-≤6M, >6M-≤1Y, >1Y-≤2Y, >2Y-≤3Y, and >3Y-≤6Y). A 3D gradient-echo sequence of enhanced T2* weighted angiography (ESWAN) was employed on a 3.0T MR system (GE Signa HDxt). TR=51ms, number of echoes=6, TE=6~60ms, FA=20°, slice/gap=2mm /0mm, NEX = 0.69, FOV=18×18cm2, matrix=256×256. For each subject, we performed a fitting of the data acquired at the 6 TEs to obtain a monoexponential signal decay curve (i.e. $$$S\left(t\right)=S0\times\exp^{-tR2*}$$$, where S=measured data, S0=multiplicative constant, t=echo time). QSM was obtained by the modified SHARP3 and LSQR method4. Regions of interest (ROIs) were outlined manually in caudate nucleus (CN), putamen (PUT), globus pallidus (GP) and thalamus (THA) (Fig 1). Susceptibility in splenium of the corpus callosum was taken as the reference. Same ROIs were used to for both QSM and R2* images. Susceptibility in QSM and R2* phase values were calculated and correlated with the ages and the reference iron concentrations. Note these reference values of iron concentrations were estimated from age using an empirical equation that was derived in an earlier postmortem study5.

Results

Representative QSM susceptibility maps and R2* maps with different age are shown in Fig 2. The susceptibility in QSM and R2* values of various deep gray nuclei exhibited significantly positive correlations with age especially in the GP (Fig. 3). The susceptibility and R2* values in 5 age groups are shown in Table. Both of the susceptibility and R2* values showed the strongly positive correlation with the iron content (P < 0.05) (Fig 4). The coefficient of correlation between the iron and the susceptibility is higher than the one with the R2* in each region.

Discussion

In brain, non-heme iron that presents sufficient concentration to affect MR contrast resides in ferritin or hemosiderin molecules, leading to susceptibility and R2* increase. R2* maps showed good contrast just between GP and surrounding tissues but very weak contrast between gray and white matter. In comparison, QSM showed not only good contrast between gray and white matter but also between iron-rich nuclei and surrounding tissues, which indicated QSM is more intuitive to reflect the susceptibility development of deep gray nuclei2. Both of the susceptibility and R2* values showed the strongly positive correlation with the iron content. The higher correlation with the iron in deep gray nuclei was found by QSM, although the correlation is similar in the GP. Thus, the susceptibility in QSM would be more sensitive and objective than R2* even in the regions with lower iron content. However, the R2* values have markedly higher positive correlation with the age than susceptibility of QSM, except in the GP with highest iron content. It may be interpreted that R2* value could be affected by iron and other age-related factors such as gradually decreased water content6 in the gray matter simultaneously.

Conclusion

It suggested that QSM may provide a more promising and reliable tool for assessment of iron content in children’s deep gray nuclei, even in the regions with lower iron content.

Acknowledgements

New Century Excellent Talent Support Plan from Ministry of Education of China (NCET-11-0438); the National Natural Science Foundation of China (81171317); the National Natural Science Foundation of China (81471631) from Dr. Jian Yang.

References

1. Morris CM. Any old iron? Brain. 2011; 134(Pt 4):924-927.

2. Li W, Wu B, Batrachenko A, et al. Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan. Hum Brain Mapp. 2014;35(6):2698-2713.

3. Schweser F, Deistung A, Lehr BW, et al. Quantitative imaging of intrinsic magnetic tissue properties using MRI signal phase: an approach to in vivo brain iron metabolism? Neuroimage. 2011;54(4):2789-2807.

4. Li W, Wu B, Liu C. Quantitative susceptibility mapping of human brain reflects spatial variation in tissue composition. Neuroimage. 2011;55(4):1645-1656.

5. Hallgren B, Sourander P. The effect of age on the non-haemin iron in the human brain. J Neurochem. 1958; 3: 41-51.

6. Lee J, Shmueli K, Kang BT, et al. The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain. Neuroimage. 2012;59(4):3967-3975.

Figures

Fig 1. Regions of interest (ROIs) in QSM. 1, 2 : caudate nucleus; 3, 4: putamen; 5, 6: globus pallidus; 7, 8: thalamus.

Fig 2. The changes of the QSM and R2* map according to the age (A:QSM, B:R2* map). Both QSM and R2* displayed the brighter intensity corresponding to more paramagnetic susceptibility. The QSM showed not only better contrast between gray and white matter but also between iron-rich nuclei and surrounding tissues.

Fig 3. Regional susceptibility(A) and R2* value(B) vs. age in deep gray nuclei. Both of the susceptibility and R2* values showed the positive correlation with the age in all gray nuclei (P < 0.0001). r is the coefficient of correlation. CN: caudate nucleus; PUT: putamen; GP: globus pallidus; THA: thalamus.

Table. The susceptibility in QSM and R2* values in the four deep gray nuclei in five periods (Mean±SD, n=87).

Fig 4. The susceptibility (upper) and R2* values (lower) vs. iron content in the five groups. Both of the susceptibility and R2* values showed the strongly positive correlation with the iron content (P < 0.05). r is the coefficient of correlation. CN: caudate nucleus; PUT: putamen; GP: globus pallidus.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0562