Original Research First-Pass Contrast-Enhanced Magnetic Resonance Angiography in Humans Using Ferumoxytol, a Novel Ultrasmall Superparamagnetic Iron Oxide (USPIO)-Based Blood Pool Agent Wei Li, MD, 1 * Sean Tutton, MD, 1 Anthony T. Vu, PhD, 2 Linda Pierchala, BS, 1 Belinda S.Y. Li, PhD, 3 Jerome M. Lewis, PhD, 4 Pottumarthi V. Prasad, PhD, 1 and Robert R. Edelman, MD 1 Purpose: To evaluate the feasibility of first-pass contrast- enhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. Materials and Methods: First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy vol- unteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The ex- amined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 mol Fe/kg (n = 9), or 35.8 mol Fe/kg (n = 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 mol Fe/mL was diluted by either four-fold (134.3 mol Fe/mL) or eight-fold (67.1 mol Fe/ mL) for first-pass MRA. Results: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhance- ment, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be ob- tained by subtraction of arterial phase images from equilib- rium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. Conclusion: Our preliminary experience supports the feasi- bility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with in- jection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam. Key Words: magnetic resonance imaging; blood pool con- trast agent; intravascular contrast agent; ferumoxytol; contrast-enhanced MR angiography; first pass J. Magn. Reson. Imaging 2005;21:46 –52. © 2004 Wiley-Liss, Inc. CONTRAST-ENHANCED magnetic resonance angiogra- phy (MRA) is typically performed using extracellular gadolinium chelates, with data acquired during the first pass of the agent through the target vasculature (1,2). Although of great clinical utility, these MRA studies suffer from certain limitations. The limitations include a short time window for data acquisition and soft tissue enhancement that masks blood vessels on maximum intensity projection images. Consequently, there is con- siderable interest in the use of blood pool (also called intravascular) agents for contrast-enhanced MRA. Var- ious blood pool agents have been tested, including ga- dolinium-based and ultrasmall superparamagnetic iron oxide (USPIO)-based agents (3–9). Compared with extracellular agents, blood pool agents provide a much longer time window for data acquisition, so that data can be repeatedly acquired over a period of minutes to hours with little loss of intravascular signal intensity. Moreover, true blood pool agents produce only minimal soft tissue enhancement. These features allow for ex- tensive signal averaging to improve the intravascular signal-to-noise ratio (SNR) and thereby permit images with much higher spatial resolution to be obtained than would be feasible using extracellular agents (10 –19). However, equilibrium images acquired over many min- utes show both arterial and venous contrast enhance- ment, which complicates the interpretation of the vas- culature (14). It would be ideal to have a contrast agent that can be used for both first-pass and equilibrium MRA in a sin- gle exam. Several blood pool agents, both gadolinium- based and iron oxide-based, are currently being inves- tigated for first-pass MRA in experimental and clinical studies (20 –27). Recently, another blood pool agent, 1 Department of Radiology, Evanston Northwestern Healthcare and Northwestern University’s Feinberg School of Medicine, Evanston, Illi- nois. 2 MR PSD/Applications Engineering, GE Healthcare, Waukesha, Wis- consin. 3 Applied Science Laboratory Central, GE Healthcare, c/o Department of Radiology, Evanston Northwestern Healthcare, Evanston Illinois. 4 Advanced Magnetics, Inc., Cambridge, Massachusetts. Present address for Dr. Li: Department of Radiology/CAI, Walgreen Building, Suite G507, Evanston, IL, 60201. *Address reprint requests to: W.L., MRI Research, Department of Ra- diology, Rm 5108, Evanston Hospital, 2650 Ridge Ave., Evanston, IL 60201. E-mail: lwei@enh.org Received April 8, 2004; Accepted September 8, 2004. DOI 10.1002/jmri.20235 Published online in Wiley InterScience (www.interscience.wiley.com). JOURNAL OF MAGNETIC RESONANCE IMAGING 21:46 –52 (2005) © 2004 Wiley-Liss, Inc. 46