Magnetic resonance imaging of in vitro glioma cell invasion

Abstract

Object An understanding of single glioma cell invasion has been limited by the static picture provided by histological studies. The ability to nondestructively assess cell invasion dynamically in a full 3D volume would improve the quality and quantity of information available from both in vivo and in vitro experiments. The purpose of this study was to observe glioma cell invasion in a 3D in vitro model using a microimaging protocol at 1.5 tesla and to assess the uptake of micron-sized particles of iron oxide (MPIO) and the consequent effects on cell function. Methods Rat C6 glioma cells were labeled with MPIO to a sufficient extent to allow single cell detection in vitro without significant effects on cell proliferation or plating efficiency. When placed on agar-coated plates, the cells formed stable multicellular tumor spheroids (MCTSs), which were embedded in collagen type I gel and serially visualized using magnetic resonance (MR) imaging and phase-contrast microscopy over 8 days. The MCTSs initially appeared as large susceptibility artifacts on MR images, but within 2 days, as cells moved away from the main MCTS, small discrete areas of signal loss, possibly due to single cells, could be observed and tracked. Conclusions Glioma cell invasion can be nondestructively observed using MR imaging. The sensitivity of MR imaging, along with its ability to represent full 3D volumes noninvasively over time, makes it ideal for longitudinal in vivo cell tracking studies.