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

OBJECTIVES: The 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 METHODS: MRI 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. RESULTS: Ultrasmall 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%. CONCLUSIONS: After administration of an USPIO blood-pool agent (T(2) 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.