Ultra-high field ¹H magnetic resonance imaging approaches for acute hypoxia

Abstract

Background. Currently, radiation treatments are being optimised based on in vivo imaging of radioresistant, hypoxic tumour areas. This study aimed at detecting nicotinamide's reduction of acute hypoxia in a mouse tumour model by two clinically relevant magnetic resonance imaging (MRI) methods at ultra-high magnetic field strength. Material and methods. The C3H mammary carcinoma was grown to 200 mm³ in the right rear foot of CDF₁ mice. The mice were anaesthetised with ketamine and xylazine prior to imaging. A treatment group received nicotinamide intraperitoneally (i.p.) at the dose 1000 mg/kg, and a control group received saline. MRI was performed at 16.4 T with a spatial resolution of 0.156 × 0.156 × 0.5 mm³. The imaging protocol included BOLD imaging and two DCE-MRI scans. Initial area under the curve (IAUC) and the parameters from the extended Toft's model were estimated from the DCE-MRI data. Tumour median values of 1) T₂* mean, 2) T₂* standard deviation, 3) DCE-MRI parameters, and 4) DCE-MRI parameter differences between scans were compared between the treatment groups using Student's t-test (significance level p < 0.05). Results. Parametric maps showed intra- and inter-tumour heterogeneity. Blood volume was significantly larger in the nicotinamide-treated group, and also the blood volume difference between the two DCE-MRI scans was significantly larger in the treatment group. Conclusion. Higher blood volume and blood volume variation was observed by DCE-MRI in the treatment group. Other DCE-MRI parameters showed no significant differences, and the higher blood volume was not detected by BOLD MRI. The higher blood volume variation seen with DCE-MRI may be influenced by the drug effect reducing over time, and furthermore the anaesthesia may play an important role.

Acknowledgements

The authors would like to thank Inger Marie Horsman, Dorthe Grand, Pia Schjerbeck, Kristina Lystlund Lauridsen, and Mogens Jøns Johannsen for excellent technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work has been funded with support from The Danish Cancer Society, the METOXIA project no. 222741 under the 7th Research Framework Programme of the European Union, the Danish National Research Foundation (DNRF59), CIRRO – the Lundbeck Foundation Center for Interventional Research in Radiation Oncology, and the Danish Council for Strategic Research.