Miniaturized handheld confocal microscopy identifies focal brain invasion in a mouse model of aggressive meningioma

Brain Pathol. 2013 Jul;23(4):371-7. doi: 10.1111/bpa.12039. Epub 2013 Feb 28.

Abstract

Invasion of the brain parenchyma by a meningioma classified by histological criteria as World Health Organization (WHO) grade I meningioma, implies that the tumor has greater likelihood of recurrence and a biological behavior similar to the more aggressive WHO grade II meningiomas. It is therefore important to detect microscopic foci of brain invasion during surgery in order to maximize the resection and/or adapt imaging follow-up. In this study, we tested the sensitivity of two handheld confocal imaging devices to detect foci of brain invasion in two types of meningioma mouse models: in a genetically engineered mouse model and in a syngeneic xenograft model. Confocal imaging offered precise images of meningothelial and fibroblastic mouse meningiomas as well as malignant meningiomas, which corresponded exactly to the pathological findings. Imaging showed a sharp definition of the brain-tumor interface and enabled identification of embedded nerves and vessels. Importantly, in both mouse models used in this study, extension of tumor along Virchow-Robin spaces into adjacent brain was detected by imaging. In conclusion, this novel technique, following validation in clinical trials, may open new possibilities for use in operating rooms to influence both decision making during the surgery and planning for additional treatments.

MeSH terms

  • Acridine Orange
  • Animals
  • Brain / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Disease Models, Animal
  • Humans
  • Indocyanine Green
  • Meningeal Neoplasms / diagnosis*
  • Meningeal Neoplasms / genetics
  • Meningioma / classification
  • Meningioma / diagnosis*
  • Meningioma / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal / methods*
  • Neoplasm Recurrence, Local / pathology
  • Neurofibromatosis 2 / genetics

Substances

  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Acridine Orange
  • Indocyanine Green