Evaluation of a Cerebral-Blood-Volume (CBV) pharmaco-MRI (phMRI) assay utilizing low (0.1mg/70kg) and high (0.2mg/70kg) dose buprenorphine infusion and a novel USPIO contrast agent (Ferumoxytol) in healthy human subjects

We present results from a clinical trial of pharmaco-MRI (phMRI) employing cerebral blood volume (CBV) imaging using ferumoxytol (Rienso/Feraheme, AMAG) as a blood pool contrast agent. The study examined the pharmacodynamic effects of two single doses of buprenorphine (0.2mg/70kg and 0.1mg/70kg administered intravenously). We found that contrast-enhanced CBV phMRI signals are more sensitive reporters of pharmacodynamic effects than conventional blood oxygen level dependent (BOLD) phMRI. In particular, higher sensitivity of CBV phMRI compared to BOLD allows for elucidation of PD responses at lower doses of buprenorphine, which has practical implications for similar phMRI studies with centrally acting drugs.