Visualizing flow in an intact CSF network using optical coherence tomography: implications for human congenital hydrocephalus

Authors

• Priya Date, Pediatric Genomics Discovery Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
• Pascal Ackermann, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
• Charuta Furey, Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
• Ina Berenice Fink, Department of Medical Informatics, Uniklinik RWTH Aachen, Pauwelsstr 30, 52074, Aachen, Germany.
• Stephan Jonas, Department of Informatics, Technical University of Munich, Munich, Germany.
• Mustafa K. Khokha, Pediatric Genomics Discovery Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
• Kristopher T. Kahle, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA. [email protected].
• Engin Deniz, Pediatric Genomics Discovery Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA. [email protected].

Document Type

Article

Abstract

Cerebrospinal fluid (CSF) flow in the brain ventricles is critical for brain development. Altered CSF flow dynamics have been implicated in congenital hydrocephalus (CH) characterized by the potentially lethal expansion of cerebral ventricles if not treated. CH is the most common neurosurgical indication in children effecting 1 per 1000 infants. Current treatment modalities are limited to antiquated brain surgery techniques, mostly because of our poor understanding of the CH pathophysiology. We lack model systems where the interplay between ependymal cilia, embryonic CSF flow dynamics and brain development can be analyzed in depth. This is in part due to the poor accessibility of the vertebrate ventricular system to in vivo investigation. Here, we show that the genetically tractable frog Xenopus tropicalis, paired with optical coherence tomography imaging, provides new insights into CSF flow dynamics and role of ciliary dysfunction in hydrocephalus pathogenesis. We can visualize CSF flow within the multi-chambered ventricular system and detect multiple distinct polarized CSF flow fields. Using CRISPR/Cas9 gene editing, we modeled human L1CAM and CRB2 mediated aqueductal stenosis. We propose that our high-throughput platform can prove invaluable for testing candidate human CH genes to understand CH pathophysiology.

Medical Subject Headings

Animals; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Carrier Proteins (genetics); Cerebral Ventricles (pathology); Cerebrospinal Fluid (diagnostic imaging); Cilia (pathology); Gene Editing (methods); Humans; Hydrocephalus (cerebrospinal fluid, diagnostic imaging, genetics, physiopathology); Hydrodynamics; Membrane Proteins (genetics); Neural Cell Adhesion Molecule L1 (genetics); Tomography, Optical Coherence (methods); Xenopus

Publication Date

4-17-2019

Publication Title

Scientific reports

E-ISSN

2045-2322

Volume

9

Issue

1

First Page

6196

PubMed ID

30996265

Digital Object Identifier (DOI)

10.1038/s41598-019-42549-4

Recommended Citation

Date, Priya; Ackermann, Pascal; Furey, Charuta; Fink, Ina Berenice; Jonas, Stephan; Khokha, Mustafa K.; Kahle, Kristopher T.; and Deniz, Engin, "Visualizing flow in an intact CSF network using optical coherence tomography: implications for human congenital hydrocephalus" (2019). Neurosurgery. 2415.
https://scholar.barrowneuro.org/neurosurgery/2415