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

Abstract

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.

Prediction of Ovarian Follicular Dominance by MRI Phenotyping of Hormonally Induced Vascular Remodeling

“…In this study, we focused on functional vascular changes that characterize early stages of DF selection. We utilized DCE-MRI for the three-dimensional non-invasive visualization of the mouse ovarian vasculature combined with high-resolution imaging performed using an MRI-compatible ovarian window reported by us previously recently ( 40 , 43 , 44 ). The window spatially holds the ovary to reduce motion and allows a smaller field of view.…”

Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders

“…Based on this, due to the poor clinical translatability of in vivo microscopy, various (pre)clinical efforts are currently ongoing to correlate SHG-based microscopy features with MRI and histology features (Fig. 8c; image 7-9) [309].…”

“…Color-coding: the analysis of manuscripts described in section 4.2 reveal the frequency in which each organ and imaging modality are investigated and used for the detection of fibrosis in cancer; light red = low frequency; red = medium frequency; dark red = high frequency. All images were adapted with permission [300,302,303,309,312,314].…”

Modelling the Functions of Polo-Like Kinases in Mice and Their Applications as Cancer Targets with a Special Focus on Ovarian Cancer

“…This technique allows in vivo tracking of cells over a long time. Additionally, magnet resonance imaging (MRI) can be used to track cancer cells in mouse models [ 317 , 318 ]. Xenograft models, however, often have the disadvantage of an immune-deficient setting not being able to consider (micro)-environmental tumor interactions.…”