نهمین کنگره نقشه برداری مغز

نمایش مقاله

Title:

Diffusion MRI Microstructure in Autism Spectrum Disorder (NODDI, DKI, and Free-Water): Developmental Patterns and Clinical Correlates - A Systematic Review

Subject:

Autism and Brain Mapping

Presenter Author:
Name:	Mohammad Azizi

Author:
Name 1:	Mohammad Azizi - Corresponding - Presenter
Affiliation 1:	Department of Gynecology and Obstetrics, Maternal-Fetal and Neonatal Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Name 2:	Zeinab Sinaeifar
Affiliation 2:	Department of Gynecology and Obstetrics, Maternal-Fetal and Neonatal Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Abstract

Original Research

introduction :

Background: Diffusion MRI methods that extend beyond diffusion tensor imaging can better disentangle neurite architecture, tissue complexity, and extracellular water—biophysical features hypothesized to differ in autism spectrum disorder (ASD) and to vary across development. Neurite Orientation Dispersion and Density Imaging (NODDI) provides indices of neurite density (NDI), orientation dispersion (ODI), and an isotropic/free-water fraction (FISO/ISOVF). Diffusion Kurtosis Imaging (DKI) quantifies non-Gaussian diffusion (e.g., mean/axial/radial kurtosis), offering sensitivity to microstructural complexity in both white and gray matter. Free-water modeling explicitly estimates extracellular water and “free-water–corrected” diffusion metrics, potentially clarifying inconsistent findings from conventional diffusion measures. Objective: To systematically synthesize evidence on NODDI, DKI, and free-water approaches in ASD, with emphasis on developmental patterns and clinical correlates.

Methods:

A structured literature search of peer-reviewed human studies using NODDI, DKI, and/or free-water metrics in ASD was performed on 2 October 2025, supplemented by reference and citation tracking. Eligible studies included ASD participants with quantitative diffusion microstructure outcomes and/or symptom associations. Data were extracted on acquisition/modeling, sampled age range, regions analyzed, group differences, age-related effects, and associations with core ASD symptoms, social cognition, and sensory/behavioral phenotypes.

Results:

Evidence remains modest in volume and heterogeneous in acquisition, modeling choices, and analytic granularity, limiting quantitative pooling. Across NODDI studies, the most recurrent pattern is reduced neurite density in distributed cortico-cortical and callosal pathways and in frontal cortical regions, with several reports of elevated isotropic/free-water fraction in white matter—consistent with increased extracellular water load. DKI findings are more mixed by region and age but commonly indicate reduced kurtosis in cortical gray matter and altered callosal microstructure, broadly suggestive of reduced microstructural complexity or altered cytoarchitecture. Free-water studies more directly implicate elevated extracellular water in ASD and suggest atypical (often blunted or absent) age associations relative to neurotypical development, particularly in frontal interhemispheric systems. Across modalities, microstructural measures show clinically relevant associations with social-communication traits, repetitive behaviors, empathy-related measures, facial emotion recognition, and sensory responsivity, though effect localization and direction vary.

Conclusion:

Advanced diffusion microstructure models converge on ASD-related differences in neurite density/organization and extracellular water, with emerging evidence for atypical developmental trajectories. Future work should prioritize harmonized multi-shell protocols, rigorous control of partial-volume and motion effects, preregistered analytic plans, and longitudinal designs spanning childhood through older adulthood to clarify developmental mechanisms and strengthen links to clinically meaningful outcomes.

Keywords:

autism spectrum disorder; diffusion MRI; NODDI; diffusion kurtosis imaging; free-water imaging; neurodevelopment.