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.
Richard Baumgartner 1 , Arie Struyk 2 , Jeff Evelhoch 2 , Cynthia Gargano 2 , Francheska Colon Gonzalez 2 , Haiying Liu 1 , Ruben Declercq 3 , Hans Verheyden 3 , Ingeborg Heirman 3 , Hans De Pla 4 , Griet Van Lancker 4 , Sofie Van den Abeele 4 , Adelheid Hollebosch 4 , Brant Delafontaine 4 , Luc Van Bortel 4 , Rik Achten 4 , Patricia Clement 4 , Pieter Vandemaele 4 , Dai Feng 1 , and Sofia Apreleva 1
Merck and Co, Rahway, New Jersey, United
and Co, Pennsylvania, United States,
and Co, Belgium,
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.
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