Assessment of iron deposition and white matter maturation in infant brains by using enhanced T2 star weighted angiography (ESWAN): R2* versus phase values

Abstract

Background and purpose: Iron deposition and white matter (WM) maturation are very important for brain development in infants. It has been reported that the R2* and phase values originating from the gradient-echo sequence could both reflect the iron and myelination. The aim of this study was to investigate age-related changes of R2* and phase value, and compare their performances for monitoring iron deposition and WM maturation in infant brains.

Methods: 56 infants were examined by enhanced T2 star weighted angiography (ESWAN) and diffusion tensor imaging in the 1.5T MRI system. The R2* and phase values were measured from the deep gray nuclei and WM. Fractional anisotropy (FA) values were measured only in the WM regions. Correlation analyses were performed to explore the relation among the two parameters (R2* and phase values) and postmenstrual age (PMA), previously published iron concentrations as well as FA values.

Results: We found significantly positive correlations between the R2* values and PMA in both of the gray nuclei and WM. Moreover, R2* values had a positive correlation with the iron reference concentrations in the deep gray nuclei and the FA in the WM. However, phase values only had the positive correlation with PMA and FA in the internal capsule, and no significant correlation with PMA and iron content in the deep gray nuclei.

Conclusions: Compared with the phase values, R2* may be a preferable method to estimate the iron deposition and WM maturation in infant brains.

Figure 1. Regions of interest (ROIs) in phase images.

ROIs placement is illustrated on images from an infant brain(postmenstrual age = 90 w)(A) 1, 2 : caudate nucleus; 3, 4: putamen; 5, 6: globus pallidus; 7, 8: thalamus. (B) 9, 10: red nucleus; 11, 12: substantia nigra. (C) 13, 14: anterior limb of the internal capsule; 15, 16: posterior limb of the internal capsule. (D) 17, 18: genu of the corpus callosum; 19, 20: splenium of the corpus callosum.

Figure 2. Bland-Altman plots showing inter-observer variability of measurements.

(A) Upper: for R2* values, (B) middle: for phase values, and (C) lower: for FA values. CN: caudate nucleus; ALIC: anterior limb of the internal capsule; PLIC: posterior limb of the internal capsule; L: left; R: right.

Figure 3. Regional R2* value vs. postmenstrual age in deep gray nuclei.

Pearson correlation analysis showed a positive correlation between the R2* values and postmenstrual age in gray nuclei (P<0.001). r is the coefficient of correlation. CN: caudate nucleus; PUT: putamen; GP: globus pallidus; THA: thalamus; RN: red nucleus; SN: substantia nigra.

Figure 4. Regional phase value vs. postmenstrual age in deep gray nuclei.

Pearson correlation analysis showed no significant correlation between the phase values and postmenstrual age in gray nuclei (P>0.05). The P values of the linear correlation in different regions are shown. CN: caudate nucleus; PUT: putamen; GP: globus pallidus; THA: thalamus; RN: red nucleus; SN: substantia nigra.

Figure 5. R2* and phase values vs. iron concentration calculated by equations in CN, PUT and GP.

(A) Upper: R2* vs. iron concentration, and (B) lower: phase vs. iron concentration. Pearson correlation analysis showed a strongly positive correlation between the R2* values and the iron concentrations (P<0.001). r is the coefficient of correlation. As for phase values, no correlations with the iron concentrations were found (P>0.05). CN: caudate nucleus; PUT: putamen; GP: globus pallidus.

Figure 6. Regional R2* value vs. postmenstrual age in the white matter regions.

Pearson correlation analysis showed a positive correlation between the R2* values and postmenstrual age in the white matter regions (P<0.001). r is the coefficient of correlation. ALIC: anterior limb of the internal capsule; PLIC: posterior limb of the internal capsule; GCC: genu of the corpus callosum; SCC: splenium of the corpus callosum.

Figure 7. Regional phase value vs. postmenstrual age in the white matter regions.

Pearson correlation analysis showed a positive correlation between the phase values and postmenstrual age in ALIC and PLIC (P<0.001). r is the coefficient of correlation. As for phase values in GCC and SCC, no correlations with postmenstrual age were found (P>0.05). ALIC: anterior limb of the internal capsule; PLIC: posterior limb of the internal capsule; GCC: genu of the corpus callosum; SCC: splenium of the corpus callosum.

Figure 8. R2* and phase values vs. FA values in the white matter regions.

(A) Upper: R2* vs. FA values, and (B) lower: phase vs. FA values. Pearson correlation analysis showed a positive correlation between the R2* values and FA values in the white matter regions (P<0.01), and between phase values and FA values in ALIC and PLIC (P<0.05). r is the coefficient of correlation. As for phase values, no correlations with FA values in GCC and SCC were found (P>0.05). FA: fractional anisotropy; ALIC: anterior limb of the internal capsule; PLIC: posterior limb of the internal capsule; GCC: genu of the corpus callosum; SCC: splenium of the corpus callosum.