Normative Reference Values and Age-Related Variation in Advanced Diffusion MRI of the Pediatric Spinal Cord: DTI, DKI, and NODDI Metrics across Cervical and Thoracic Levels Using Hybrid Diffusion Imaging.

Authors

Zahra Sadeghi Adl, Devon Middleton, Laura Krisa, Sara Naghizadehkashani, Mahdi Alizadeh, Slimane Tounekti, Scott H Faro, Adam Flanders, Jürgen Finsterbusch, Julien Cohen-Adad, Feroze B Mohamed

Published in

AJNR. American journal of neuroradiology. Sep 09, 2026. Epub Sep 09, 2026.

Abstract

Normative diffusion values are essential for detecting microstructural abnormalities in the spinal cord. While diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide additional sensitivity beyond DTI, existing normative datasets are limited to adults with restricted cervical coverage. Pediatric spinal cord data remain scarce and predominantly DTI-based, leaving a gap in characterizing age-related microstructure. The purpose of this study was to establish a normative database of pediatric spinal cord diffusion metrics (DTI, DKI, NODDI) from C1-T12 using a clinically feasible Hybrid Diffusion Imaging (HYDI) protocol and to assess agreement between HYDI-derived and conventional DTI metrics.
One hundred typically developing children (mean age 12.07 ± 3.09 years), aged 6-17 years, underwent a 3T MRI scan including a T2-weighted, multi-shell, multiband, HYDI (b=0, 800, 2000 s/mm²) sequence covering C1-T12 and a validation subset, a single-shell DTI sequence covering C2-C5. Ten microstructural metrics were quantified for white matter (WM), gray matter (GM), and whole cord at each vertebral level. Multivariable regression modeled age and sex. Agreement between HYDI-derived and conventional DTI at C3 was evaluated using paired t-tests, Pearson correlation, and Bland-Altman analysis.
Normative C1-T12 vertebral diffusion values were established. WM-GM contrast was evident for FA, NDI, MD, and AD, with significant differences across most cervical and thoracic segments. All metrics demonstrated significant age dependence (p <.01) after adjustment for sex, with higher FA, kurtosis, ODI and NDI and lower diffusivity and fISO in older children. Sex effects were modest and did not remain significant after false-discovery-rate correction. Accelerated HYDI demonstrated minimal bias versus conventional DTI at C3 with moderate individual-level agreement (r = 0.35-0.43; ICC 0.34-0.39).
This study provides comprehensive normative reference values of pediatric spinal cord microstructure across C1-T12 and validates a time-efficient HYDI protocol for clinical translation.

PMID:
42716713
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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