Assessment of absolute blood volume in carcinoma by USPIO contrast-enhanced MRI

ObjectivesThe characterization of tumor vasculature is essential in studying tumor physiology. The aim of this study was to develop a new method — based on water proton MR density measurements, in combination with ultrasmall superparamagnetic iron oxide (USPIO) administration — to measure absolute blood volume (BV) in murine colon carcinoma.Materials and MethodsMRI experiments were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon carcinoma in six mice before and after administration of an USPIO blood-pool contrast agent. Density maps were obtained from the signal amplitude at TE=0 of the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO density maps to quantitatively yield absolute tumor BV maps. In a separate group of mice (n=6), the relative vascular area (RVA) of tumors was determined by immunohistochemistry.ResultsUltrasmall superparamagnetic iron oxide administration resulted in a small decrease in the water proton MR density. The BV averaged over the six tumors was 4.6±1.6%. The value of the RVA measured by immunohistochemical staining was equal to 3.9±2.2%.ConclusionsAfter administration of an USPIO blood-pool agent (T2 relaxivity > 100 mM−1 s−1), the blood water protons become MRI invisible, and pixel-by-pixel BV map can be obtained by subtracting the calculated post-USPIO density map from the pre-USPIO density map. The value of absolute BV obtained with this novel MR approach is in good agreement with the value of the relative vascular measured by immunohistochemical staining.