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 spinecho 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 T1weighted 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 F 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.

High Field Magnetic Resonance Imaging Evaluation of Superparamagnetic Iron Oxide Nanoparticles in a Permanent Rat Myocardial Infarction

“…But the use of a T1 cine MR sequence made it possible the localization of the dyskinetic area of myocardium as at lower magnetic fields. 5,24,25 These results differ from previously published studies where quantifiable signal changes were observed in rats, 14,15 healthy volunteers 26,27 or in a model of myocardial infarction induced in pigs. 16 However, those studies were performed at lower magnetic fields whereas r1 relaxivity of the nanoparticles used in the present study was 36 mmol/L Ϫ1 ·s Ϫ1 at 0.5T and 12 mmol/ L Ϫ1 ·s Ϫ1 at 1.5T.…”

Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model

“…The contrast agent NC100150 Injection has been shown in human to induce both first-pass and steadystate changes in the signal intensity of the myocardium in healthy volunteers (25). A study by Tarlo et al (26) showed the possibility of determining myocardial blood flow quantitatively in pigs with this contrast agent.…”

Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging

“…Larger image intensity gradients at the endocardial border were expected to improve the capabilities of automated segmentation algorithms, reducing the uncertainty and need for manual editing [73].…”