Multimodality imaging of glioma cells migration in organotypic brain slice culture (Conference Presentation)

Abstract

Glioblastoma is a primary malignant brain tumor characterized by highly migratory glioma cells capable of invading into surrounding healthy tissue. The mechanism and the physical paths by which glioma cells are capable of invading healthy brain are not well understood. Using human glioblastoma cell line U251 plated on healthy mouse brain slices, glioma cell migration behavior and dynamics are investigated by multimodality imaging. Polarization-sensitive optical coherence tomography (PS-OCT) is used to delineate nerve fiber tracts. PS-OCT is capable of generating depth-resolved images of reflectivity, phase retardance and optic axis orientation. Because of the birefringence property of myelin sheath, nerve fiber tracts as small as a few tens of micrometers can be resolved from phase retardance images. Swept field confocal imaging system is used to image U251 cells expressing GFP-actin and brain vasculature stained by Isolectin B4. Cell migration is acquired by time-lapse imaging and then correlated with brain vasculature and nerve fiber tracts after fine registration of the two modalities. We found out U251 cells preferentially adhere to and migrate along blood vessels. Our data do not suggest a strong correlation between U251 cell migration and white matter tracts distinguished by tissue birefringence. In addition, U251 cell motility is higher in gray matter compared with white matter. Finally, using higher temporal resolution and high magnification, we are able to observe short time-scale dynamic of U251 cells and the ability of U251 cells to exert forces as they deform blood vessels.