Bimodal magnetic resonance and optical imaging of extracellular matrix remodelling by orthotopic ovarian tumours

BACKGROUND: The extracellular matrix modulates the development of ovarian tumours. Currently, evaluation of the extracellular matrix in the ovary is limited to histological methods. Both magnetic resonance imaging (MRI) and two-photon microscopy (2PM) enable dynamic visualisation and quantification of fibrosis by endogenous contrast mechanisms: magnetisation transfer (MT) MRI and second-harmonic generation (SHG) 2PM, respectively. METHODS: Here, we applied the MT-MRI protocol for longitudinal imaging of the stroma in orthotopic human ovarian cancer ES-2 xenograft model in CD1 athymic nude mice, and for orthotopically implanted ovarian PDX using a MR-compatible imaging window chamber implanted into NSG mice. RESULTS: We observed differences between ECM deposition in ovarian and skin lesions, and heterogeneous collagen distribution in ES-2 lesions. An MR-compatible imaging window chamber enabled visual matching between T2 MRI maps of orthotopically implanted PDX grafts and anatomical images of their microenvironment acquired with a stereomicroscope and SHG–2PM intravital microscopy of the collagen. Bimodal MRI/2PM imaging allowed us to quantify the fibrosis within the same compartments, and demonstrated the consistent results across the modalities. CONCLUSIONS: This work demonstrates a novel approach for measuring the stromal biomarkers in orthotopic ovarian tumours in mice, on both macroscopic and microscopic levels.