Elucidating Microstructural Alterations in Neurodevelopmental Disorders: Application of Advanced Diffusion-Weighted...

Area of Science:

• Neuroimaging
• Neurodevelopmental Disorders
• Medical Physics

Background:

• Neurodevelopmental disorders (NDDs) significantly impair functioning, yet effective treatments remain limited.
• Understanding the underlying neurobiology is crucial for developing successful NDD treatments.
• A genetics-first approach using advanced imaging can reveal unique neural microstructural characteristics.

Purpose of the Study:

• To investigate advanced diffusion-weighted imaging (DWI) techniques for characterizing neural microstructure in neurofibromatosis type 1 (NF1) and Noonan syndrome (NS).
• To compare microstructural differences in subcortical regions and white matter tracts between children with NF1, NS, and typical development (TD).

Main Methods:

• Prospective study involving 88 children (31 NS, 25 NF1, 32 TD) using multi-shell DWI.
• Analysis included neurite orientation density and dispersion imaging (NODDI) and diffusion kurtosis imaging (DKI).
• Region-of-interest, tract-based analysis, ANCOVA, PCA, and LDA were employed for group comparisons.

Main Results:

• Significant differences in thalamic neurite density index (NDI), orientation dispersion index (ODI), and mean kurtosis (MK) between NF1 and NS.
• Reduced NDI in NF1 and NS compared to TD across all 39 white matter tracts.
• Multivariate analyses successfully distinguished between clinical groups, with LDA classifying NF1 with 97% accuracy based on subcortical region differences.

Conclusions:

• Advanced DWI techniques like NODDI and DKI can detect subtle neural microstructural alterations in NF1 and NS, differentiating them from typical development and each other.
• Specific differences were observed in subcortical regions and the middle cerebellar peduncle between NF1 and NS.
• These findings highlight the potential of advanced DWI in understanding NDD neurobiology and informing treatment strategies.