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 extracellular matrix in the ovary is limited to histological methods. Magnetic resonance imaging (MRI) and two-photon microscopy (2PM) both enable dynamic visualisation and quantification of fibrosis by endogenous contrasts mechanisms: Magnetization Transfer (MT) MRI and Second Harmonic Generation (SHG) 2PM respectively.
Methods: Here we applied 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 heterogenous 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 stereomicroscope and SHG-2PM intravital microscopy of the collagen. Bi-modal 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
varian tumours in mice, on both macroscopic and microscopic levels.