Affiliations: School of Chemistry, Physics and Mechanical Engineering and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), GPO Box 2434, Brisbane, Qld 4001, Australia
Corresponding author: Konstantin I. Momot, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology (QUT), GPO Box 2434, Brisbane, Qld 4001, Australia. Fax: +61 7 3138 9079; E-mail: [email protected].
Abstract: Background:Hydrogel-based cell cultures are excellent tools for studying physiological events occurring in the growth and proliferation of cells, including cancer cells. Diffusion magnetic resonance is a physical technique that has been widely used for the characterisation of biological systems as well as hydrogels. In this work, we applied diffusion magnetic resonance imaging (MRI) to hydrogel-based cultures of human ovarian cancer cells. Methods:Diffusion-weighted spin-echo MRI measurements were used to obtain spatially-resolved maps of apparent diffusivities for hydrogel samples with different compositions, cell loads and drug (Taxol) treatment regimes. The samples were then characterised using their diffusivity histograms, mean diffusivities and the respective standard deviations, and pairwise Mann–Whitney tests. The elastic moduli of the samples were determined using mechanical compression testing. Results:The mean apparent diffusivity of the hydrogels was sensitive to the polymer content, cell load and Taxol treatment. For a given sample composition, the mean apparent diffusivity and the elastic modulus of the hydrogels exhibited a negative correlation. Conclusions:Diffusivity of hydrogel-based cancer cell culture constructs is sensitive to both cell proliferation and Taxol treatment. This suggests that diffusion-weighted imaging is a promising technique for non-invasive monitoring of cancer cell growth in hydrogel-based, cellularly-sparse 3D cell cultures. The negative correlation between mean apparent diffusivity and elastic modulus suggests that the diffusion coefficient is indicative of the average density of the physical microenvironment within the hydrogel construct.
Keywords: Diffusion imaging, magnetic resonance imaging, hydrogels, cancer cell cultures, Taxol