title: First-pass myocardial perfusion imaging and equilibrium signal changes using the intravascular contrast agent NC100150 injection.
abstract: In this phase I clinical study, the new ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed AS, Oslo, Norway, a part of Nycomed Amersham), was assessed for first-pass magnetic resonance myocardial perfusion studies and its ability to produce equilibrium signal changes, as a possible indicator of myocardial blood volume. Data were acquired in 18 healthy male volunteers at 0.5 T and 1.5 T. At both field strengths, first-pass studies using T1-weighted sequences were acquired. Long TE spin-echo echoplanar imaging (EPI) was used at 0.5 T and short TE fast low-angle shot (FLASH) imaging at 1.5 T. With both sequences, T1 effects dominated the images for low doses, and time intensity curves potentially suitable for perfusion analysis were generated. At higher doses, T2 and T2* effects were observed. At 1.5 T, these predominantly affected the blood pool signal; however, at 0.5 T the myocardial signal was also involved, reflecting the relative T2 and T2* sensitivity of the spin-echo EPI sequence as a result of the long TE and long readout window, respectively. Equilibrium changes were assessed at both field strengths using T1-weighted FLASH sequences and in addition at 1.5 T using T2*-weighted gradient-echo EPI. With the T1-weighted images at both field strengths, signal changes were observed in all subjects; however, no dose-response relationship could be shown. With the T2*-weighted EPI there was significantly lower signal (P < 0.05) with the 3 and 4 mg/kg doses than with the 2 mg/kg dose. In conclusion, NC100150 Injection is useful for first-pass myocardial perfusion using T1-weighted sequences; however, low doses in combination with short TE sequences are required to minimize sensitivity to T2* effects. Equilibrium signal changes can also be induced in the myocardium. More work is required to optimize the imaging sequences and dose of NC100150 Injection for first-pass studies and also to determine whether the equilibrium signal changes can be used to measure myocardial blood volume changes in ischemic heart disease.
authors.affiliation: Magnetic Resonance Unit, Royal Brompton Hospital, London SW3 6NP, United Kingdom. j.panting@rbh.nthames.nhs.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Panting
authors.forename: A M
authors.initials: AM
authors.lastname: Taylor
authors.forename: P D
authors.initials: PD
authors.lastname: Gatehouse
authors.forename: J
authors.initials: J
authors.lastname: Keegan
authors.forename: G Z
authors.initials: GZ
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: McGill
authors.forename: J M
authors.initials: JM
authors.lastname: Francis
authors.forename: E D
authors.initials: ED
authors.lastname: Burman
authors.forename: D N
authors.initials: DN
authors.lastname: Firmin
authors.forename: D J
authors.initials: DJ
authors.lastname: Pennell
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003287:Contrast Media / Q000008:administration & dosage*; D003326:Coronary Circulation / Q000502:physiology*; D003911:Dextrans; D017352:Echo-Planar Imaging; D052203:Ferrosoferric Oxide; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage*; D058185:Magnetite Nanoparticles; D008297:Male; D010087:Oxides / Q000008:administration & dosage*
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide