Relaxivity of Ferumoxytol at 1.5 T and 3.0 T

Abstract

Objectives: The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T.

Materials and methods: Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated.

Results: A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol.

Conclusions: Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

Figure 1:

Setup of circulating water bath. Water was heated to 37°C in a first water bath in the control room using a revolving heater (A). A roller pump (B) was used to pump the heated water into a second water bath inside the MR scanner, which contained the ferumoxytol vials (C), and back into the first water bath. To monitor the actual water temperature inside the MR scanner, an MR compatible thermometer (D) was placed in the MR-control room and the tip of its fiberoptic probe was placed in the phantom-containing water bath inside the MR-scanner.

Figure 2:

There is a linear relationship of R1, R2 and R2* in saline and plasma and nonlinear relationship in blood with increasing ferumoxytol concentrations at 1.5T and 3.0T. The plots show (A:) the mean measured longitudinal relaxivity rates, R1, (B:) mean transverse relaxivity rates, R2, and (C:) mean transverse relaxivity rates from free induction decay, R2* with standard deviations (error bars) of different ferumoxytol concentrations in saline, plasma and whole blood at 37°C at 1.5T (left) and 3.0T (right). Note: most error bars are too small to be depicted by the plots.

Figure 3A:

The linear dependence with a slop of ~1 illustrates the independence of R2 from the field strength. The plot shows the measured mean R2 values at 1.5T and 3.0T at the six investigated ferumoxytol concentrations in saline, plasma and blood. 3B: The linear dependence with a slope of close to one illustrates that R2 and R2* values are almost identical at both field strengths with little to no refocusable spins in saline and plasma. The plot shows the measured mean R2 and R2* values at 1.5T and 3.0T at the six investigated ferumoxytol concentrations in saline and plasma. 3C: The linear dependence with a slop of ~1 illustrates the independence of R2* from the field strength. The plot shows the measured mean R2* values at 1.5T and 3.0T at the six investigated ferumoxytol concentrations in saline, plasma and blood.