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.