Endoluminal Biopsy for Vein of Galen Malformation

Andrew T Hale; Shanrun Liu; Fengyuan Huang; Yuwei Song; Michael R Crowley; David K Crossman; Caroline Caudill; Anastasia Arynchyna-Smith; Lindsey Chapman; Michael J Feldman; Benjamin W Saccomano; Brandon G Rocque; Curtis J Rozzelle; Jeffrey P Blount; James M Johnston; Zechen Chong; Jesse G Jones

doi:10.1227/neu.0000000000002986

Endoluminal Biopsy for Vein of Galen Malformation

Neurosurgery. 2024 May 15. doi: 10.1227/neu.0000000000002986. Online ahead of print.

Authors

Andrew T Hale¹, Shanrun Liu², Fengyuan Huang³, Yuwei Song³, Michael R Crowley³, David K Crossman³, Caroline Caudill⁴, Anastasia Arynchyna-Smith^{1

4}, Lindsey Chapman⁴, Michael J Feldman⁴, Benjamin W Saccomano¹, Brandon G Rocque^{1

4}, Curtis J Rozzelle^{1

4}, Jeffrey P Blount^{1

4}, James M Johnston^{1

4}, Zechen Chong³, Jesse G Jones^{1

4}

Affiliations

¹ Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
² Single Cell and Flow Cytometry Core, University of Alabama at Birmingham, Birmingham, Alabama, USA.
³ Heflin Genetics Center and Genetics Research Division, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Division of Pediatric Neurosurgery, Children's of Alabama, Birmingham, Alabama, USA.

PMID: 38747605
DOI: 10.1227/neu.0000000000002986

Abstract

Background and objectives: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance.

Methods: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations.

Results: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas.

Conclusion: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

Abstract

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