A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain

Mahmoud Mostapha, Sun Hyung Kim, Alan C. Evans, Stephen R. Dager, Annette M. Estes, Robert C. McKinstry, Kelly N. Botteron, Guido Gerig, Stephen M. Pizer, Robert T. Schultz, Heather C. Hazlett, Joseph Piven, Jessica B. Girault, Mark D. Shen, Martin A. Styner

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed processing framework combines probabilistic brain tissue segmentation, cortical surface reconstruction, and streamline-based local EA-CSF quantification. The quantitative analysis of local EA-CSF was applied to a dataset of typically developing infants with longitudinal MRI scans from 6 to 24 months of age. There was a high degree of consistency in the spatial patterns of local EA-CSF across age using the proposed methods. Statistical analysis of local EA-CSF revealed several novel findings: several regions of the cerebral cortex showed reductions in EA-CSF from 6 to 24 months of age, and specific regions showed higher local EA-CSF in males compared to females. These age-, sex-, and anatomically-specific patterns of local EA-CSF would not have been observed if only a global EA-CSF measure were utilized. The proposed methods are integrated into a freely available, open-source, cross-platform, user-friendly software tool, allowing neuroimaging labs to quantify local extra-axial CSF in their neuroimaging studies to investigate its role in typical and atypical brain development.

Original languageEnglish
Article number561556
JournalFrontiers in Neuroscience
StatePublished - Oct 2 2020


  • EA-CSF
  • Laplacian PDE
  • autism
  • brain development
  • extra-axial cerebrospinal fluid
  • neurodevelopmental disorders
  • structural MRI
  • surface analysis


Dive into the research topics of 'A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain'. Together they form a unique fingerprint.

Cite this