3884

Quantitative susceptibility mapping of early myelination in the posterior limb of internal capsule in neonates

Brian Ma¹, Lara Bartels^1,2, Christian Kames^1,2, Yuting Zhang³, Alexander Weber^1,4, and Alexander Rauscher^1,2,4,5
¹UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ²Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ³Department of Radiology, Children's Hospital of Chongqing Medical University, Chongqing, China, ⁴Division of Neurology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada, ⁵Department of Radiology, University of British Columbia, Vancouver, BC, Canada

Synopsis

We performed quantitative susceptibility mapping (QSM) of the posterior limb of internal capsule (PLIC) in human neonates. As the PLIC is one of the earliest structures to myelinate, it is clearly visible as a hypointense structure on QSM. This work investigates the potential as a marker for brain health in neonates. There were no significant differences in magnetic susceptibility of the PLIC between healthy controls, injured preterm, and injured term neonates.

Introduction

Myelination of human brains begins during the second trimester of gestation in some brain regions but the majority of myelin is built after birth, with rapid myelination until 2 years of age, after which it slows but continues into late adulthood.^1,2Prenatal injuries and premature birth can lead to injury to immature white matter, and consequently, hypomyelination in white matter tracts.³ Impaired myelination of the posterior limb of internal capsule (PLIC) is considered to be indicative of developmental delay in newborns,⁴ being one of the abnormalities observed on magnetic resonance imaging (MRI) scans of preterm neonates at term-equivalent age linked to significantly premature birth,⁵ along with term infants diagnosed with hypoxic-ischemic encephalopathy.⁶ Disruptions of the myelination process is linked to abnormal neurodevelopment, such as deficits in cognitive and motor function.⁷ Quantitative susceptibility mapping is based on gradient-echo MR and was shown to be sensitive to changes in myelin content.⁸ Here we investigated QSM in the PLIC of neonates.

Methods

Data were acquired on a 3T system (Achieva; Philips Healthcare) at term equivalent age in 14 preterm infants with a clinical history of perinatal asphyxia and mild to moderate HIE (Mean gestational age at birth = 33.6 ± 2.1 weeks; at scan = 38.8 ± 2.9 weeks), 9 term infants with a clinical history of perinatal asphyxia and moderate HIE (Mean gestational age at birth = 39.0 ± 1.0 weeks; at scan = 41.0 ± 1.0 weeks), and 7 healthy controls (Mean gestational age at birth = 39.3 ± 0.7 weeks; at scan = 41.2 ± 1.0 weeks). Neonates were classified into mild and moderate injury groups based on the clinical classification of HIE, including the clinical symptoms and signs, such as seizures and inhibited primitive reflexes, among others.⁹ The QSM scan was a 5-echo 3D gradient echo scan (TR = 30 ms, TE1 = 4.5 ms, echo spacing = 5.5 ms, flip angle = 17°, FOV = 196 x 154 x 103 mm³, acquired voxel size = 0.5 x 0.5 x 1 mm³, reconstructed voxel size = 0.5 x 0.5 x 0.5 mm³).¹⁰ Diffusion tensor data were also acquired for anatomical identification of the PLIC. 2D T1-weighted scans were acquired as per clinical protocol.

QSM was computed using a 2-step dipole inversion algorithm¹¹ after Laplacian unwrapping and background removal using V-SHARP.^12,13 The last three echoes were averaged for the final quantitative susceptibility map used to measure susceptibility values (χ). Diffusion data were processed using FSL’s DTIFIT.¹⁴ FA maps were registered into susceptibility weighted imaging (SWI) space using FSL’s FLIRT.^15,16 Regions of interest were manually drawn in FSLview¹⁷ using the FA map that was registered into SWI space. The researcher was blinded to patient condition when drawing masks of the PLIC to avoid bias, masks were drawn based on anatomical references.¹⁸

Statistical analysis was performed using R 4.0.3 (2020; https://www.r-project.org/). The relationship between susceptibility value (χ) and condition (healthy control, preterm injury, and term injury) was investigated using a 1-way ANOVA. Shapiro-Wilks normality test revealed no deviations from normality within groups.¹⁹

Results

The PLIC was present as a hyperintense area on the T1-weighted scans of all subjects and as hypointense areas on QSM. The mean susceptibility value (χ) of the PLIC in healthy controls, injured preterm, and injury term neonates was -0.0058 (SD, 0.0021) ppm, -0.0077 (SD, 0.0041) ppm, and -0.0050 (SD, 0.0032) ppm, respectively. One-way ANOVA analysis revealed that the condition (healthy control, preterm injury, and term injury) did not make a significant difference among groups (p = 0.18, see Figure 2). A weak, positive correlation was found between gestational age at birth and magnetic susceptibility (χ) of the PLIC (Fig. 3: r = 0.33, N = 31), but this relationship was not significant (p = 0.07, see Figure 3).

Discussion

We quantified the degree of myelination of the PLIC in injured term and preterm neonates and healthy term controls using magnetic susceptibility measurements from QSM. It has been shown that abnormal signal intensity in the PLIC, namely in T1 and T2-weighted scans, can be an accurate predictor of neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy.⁶ Thus, the quantification of the degree of myelination in the PLIC using QSM could serve as a marker for neonatal brain health. No significant differences in the mean magnetic susceptibility of the PLIC were found between the three cohorts. A weak, but non-significant positive correlation between gestational age at birth and magnetic susceptibility was also found (Fig. 3). These findings may be due to a mixed effect of a possible earlier onset of postnatal myelination in preterm neonates,²⁰ and hypomyelination secondary to perinatal insults.³

Conclusion

In injured preterm, injured term, and healthy term neonates, the PLIC can be clearly identified on QSM as a structure that is myelinated at birth. However, no significant differences in magnetic susceptibility were measured between these cohorts. In this work the susceptibility of the PLIC obtained using a conventional QSM sequence does not appear to be a good marker of injury in this cohort of neonates. Given the clear visibility of the PLIC in QSM, an adjusted acquisition that is more appropriate for the newborn brain is a promising avenue for future studies.

Acknowledgements

UBC Vancouver is located on the traditional, ancestral, and unceded territory of the Musqueam people.

We acknowledge the support of the Natural Sciences and Engineering Research Council of Canada, (Grant/Award Number 016-05371), the Canadian Institutes of Health Research, (Grant Number RN382474-418628), the National MS Society (RG-1507-05301). A.R. is supported by Canada Research Chairs (950-230363). B.M. was supported by an NSERC Undergraduate Student Research Award.

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Figures

Figure 1. Sample axial images from one healthy control patient, red arrows indicate the PLIC: A) T1-weighted, myelinated PLIC shows hyperintensity; B) In the color coded FA map, the PLIC shows clear anisotropy (blue); C) Quantitative susceptibility map showing little tissue contrast, except for the localized hypointensities at the region of the PLIC.

Figure 2. Boxplot of mean susceptibility values of PLIC region by group. Points are the ROI measurements from each individual subject.

Figure 3. Scatterplot showing relationship between magnetic susceptibility values of the PLIC in individual subjects and their gestation age at birth. Pearson’s r = 0.33, N = 31.

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)

3884

DOI: https://doi.org/10.58530/2022/3884