Development and validation of a controlled heating apparatus for long-term MRI of 3D microfluidic tumor models

Abstract

Conventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and in vivo MRI is limited by regulatory approval of long-term anesthesia use. Microfluidic tumor models (MTMs) offer a cost-effective, reproducible, and high throughput platform for bridging cell and animal models. Yet, MRI of microfluidic devices is challenging, due to small fluid volumes generating low sensitivity. For the first time, an MRI of MTMs was performed at low field strength (1 T) using conventional imaging equipment without microcoils. To enable longitudinal MRI, we developed (1) CHAMP-3 (controlled heating apparatus for microfluidics and portability) which heats MTMs during MRI scans and (2) an MRI-compatible temperature monitoring system. CHAMP-3 maintained chip surface temperature at ~37°C and the media inside at ~35.5°C. Enhanced T₁-weighted MRI contrast was achieved in 3D MTMs with free manganese (Mn²⁺) solutions and Mn²⁺ labeled tumor cells.