Intrinsic Susceptibility MRI of Chemically-Induced Rat Mammary Tumours: Relationship to Histological Assessment of Hypoxia and Fibrosis

Intrinsic susceptibility MRI is being investigated to provide imaging biomarkers of tumour hypoxia. Deoxyhaemoglobin, which is paramagnetic, creates magnetic susceptibility perturbations, increasing the MRI transverse relaxation rate R2* of water in blood and in the tissue surrounding blood vessels. Gradient Recalled Echo (GRE) MRI methods are sensitive to R2* and thus to blood deoxyhaemoglobin levels. Deoxyhaemoglobin therefore acts as an intrinsic, blood oxygenation level dependent (BOLD) contrast agent. Changes in tumour R2* induced by carbogen (95% O2/5% CO2) breathing can be used to assess haemodynamic tumour vasculature . As the oxygenation of haemoglobin is proportional to the arterial blood paO2, and therefore in equilibrium with tissue pO2, measurements of tumour R2* should also provide a sensitive index of tissue oxygenation. A BOLD and DCE MRI study of human breast cancers revealed wide heterogeneity in tumour R2*, and that relatively slow R2* correlated with highest relative blood volume and grade, but not hypoxia. The presence of fibrosis in human breast cancer has been shown to correlate with high carbonic anhydrase IX expression, an intrinsic marker of hypoxia, and poor prognosis. It remains unclear how necrosis and fibrosis contribute to the overall R2* of tissue as a function of grade in breast cancer. In this study, we further investigate the relationship of R2* and carbogen-induced ΔR2* to histopathological status and hypoxia in a chemically-induced rat tumour model of breast cancer.