The purpose of the study was to investigate the use of a dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) as a blood pool contrast agent for thoracic and abdominal MR angiography. Abdominal and thoracic MR angiography was performed in six healthy volunteers using two-dimensional and three-dimensional spoiled gradient echo (SPGR) sequences before and after intravenous administration of USPIO. Doses ranged from 1.1 to 2.6 mg Fe/kg. Flip angle was varied from 20 to 60 degrees. Subjective image quality, analysis of signal-to-noise ratio (SNR), and blood T1 relaxation times were measured. USPIO significantly lowered the T1 of blood (from 1,210 ms precontrast to 159 ms postcontrast at a dose of 2.6 mg Fe/kg) (P < .01). Image quality on coronal fast three-dimensional breath-hold SPGR images of the abdomen increased with increasing dose and was maximum at the highest dose, producing an aortic SNR of 9.6 compared to 1.8 precontrast. Axial two-dimensional time-of-flight (TOF) aortic SNR was reduced significantly from 13 on precontrast to 6 on the postcontrast images at the highest dose (P < .05) due to T2* shortening effects. There was little flip angle dependence on image quality. Due to the T1 shortening effect and long intravascular half-life, USPIO improved visualization of vascular anatomy using three-dimensional fast SPGR imaging. The echo time must be minimized to minimize signal loss from T2* shortening effects. The blood pool distribution of USPIO is useful for equilibrium-phase MR angiography.

The safety and magnetic resonance (MR) imaging potential of BMS 180549, a new superparamagnetic iron oxide contrast agent, were evaluated in a phase I, open-label, placebo-controlled study involving 41 healthy subjects. No clinically significant postdose changes in physical examination findings, vital signs, or electrocardiogram results were reported for any of the subjects evaluated. No clinically significant changes in clinical laboratory values were noted by the investigators. Fourteen adverse events considered not serious and considered possibly or definitely related to the drug were reported, three of which required minor treatment. Relaxation time measurements in plasma samples showed a strong, dose-dependent, and persistent decrease in T1 and T2 values. Significant changes in MR signal intensity of the blood pool and well-perfused organs (liver and spleen) were noted on both T1- and T2-weighted images. Changes in signal intensity of cervical lymph nodes were also observed at the higher doses and late postdose imaging times.

MR imaging with iron oxide can enable specific differentiation of metastatic and benign nodes in patients with head and neck cancer. This agent may potentially enhance the detection of metastatic lymph nodes and deserves further investigation.

These studies support the hypothesis that 3D MRA in the body will benefit from the use of intravascular contrast agents. Nevertheless, conventional MIP processing is unable to reveal the full advantage of the contrast improvement.