Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy

Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor molecular function in living animals using specific fluorescent probes. However, macroscopic imaging methods such as FMT generally exhibit low anatomical details. To overcome this, we report a quantitative technique to image both structure and function by combining FMT and magnetic resonance (MR) imaging. We show that FMT-MR imaging can produce three-dimensional, multimodal images of living mouse brains allowing for serial monitoring of tumor morphology and protease activity. Combined FMT-MR tumor imaging provides a unique in vivo diagnostic parameter, protease activity concentration (PAC), which reflects histological changes in tumors and is significantly altered by systemic chemotherapy. Alterations in this diagnostic parameter are detectable early after chemotherapy and correlate with subsequent tumor growth, predicting tumor response to chemotherapy. Our results reveal that combined FMT-MR imaging of fluorescent molecular probes could be valuable for brain tumor drug development and other neurological and somatic imaging applications.