The effect of brain tumor angiogenesis on the in vivo relationship between the gradient-echo relaxation rate change (DeltaR2*) and contrast agent (MION) dose.

Abstract

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 (DeltaR2*) 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. The DeltaR2* 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 k(G) calculated and compared for the normal gray matter, normal white matter, tumor, and contralateral brain. The k(G) 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(G(Tumor) ) < k(G(Brain) ) 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 differences between tumor and normal brain tissue may be lessened when using gradient-echo susceptibility contrast agent methods.