The effect of brain tumor angiogenesis on the in vivo relationship between the gradient-echo relaxation rate change (δR2*) and contrast agent (MION) dose

Purpose: To determine in vivo if the susceptibility calibration factor for gradient-echo imaging (k_G), which characterizes the relationship between the tissue T2* relaxation rate change (ΔR2*) and tissue contrast agent concentration, is independent of tissue type and condition: in addition, to assess the consequences of such an assumption on the use of relative cerebral blood volume (rCBV) measurements as a direct index of tumor angiogenesis. Materials and Methods: The ΔR2* was measured as a function of monocrystalline iron oxide nanoparticles (MION) contrast agent dose in a rat brain tumor (9L gliosarcoma) model, the blood volume fraction independently measured, and kG calculated and compared for the normal gray matter, normal white matter, tumor, and contralateral brain. Results: The kG was found to be the same for gray and white matter (P = 0.53), but statistically different for tumor compared to contralateral brain (P = 0.005) with k_GTumor < k_GBrain Conclusion: The gradient-echo calibration factor, k_G, is the same for brain gray and white matter, but not the same for brain and tumor tissue. This difference may be attributed to the grossly different vascular morphology of tumors, dueto tumor angiogenesis, compared to normal brain and/or possibly differing blood rheological factors such as hematocrit. Consequently, the sensitivity to blood volume differ-ences between tumor and normal brain tissue may be lessened when using gradient-echo susceptibility contrast agent methods.