Quantifying iron-oxide nanoparticles at high concentration based on longitudinal relaxation using a three-dimensional SWIFT Look-Locker sequence

Abstract

Purpose: Iron-oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2 * mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2 * because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look-Locker method to map T1 of IONPs in high concentrations.

Methods: T1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look-Locker method and with inversion recovery spectroscopy. Precisions of Look-Locker and variable flip angle (VFA) methods were compared in simulations.

Results: The measured R1 (=1/T1 ) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look-Locker method is also much less sensitive to B1 inhomogeneity than the VFA method.

Conclusion: SWIFT Look-Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy.

Keywords: Look-Locker; SWIFT; T1 mapping; iron-oxide nanoparticles; magnetic hyperthermia; positive contrast.

Figure 1

Example of the Look-Locker acquisition scheme for fast 3D radial T₁ mapping. Totally, N_vs (=2 in fig.1) view sets with N_v (=24 in fig.1) views in each set were acquired. Each predefined time window (with N_bin views) along the recovery curve was sampled with N_bin*N_vs (=8*2 in fig.1) unique views. To reconstruct an image from a given time point along the recovery curve, all the projections acquired during that time window are used. The outer extents of k-space, which are undersampled, were filled in with data from all other time windows (in black). The center part of k-space were filled only with data acquired in the given time window (in red, blue and green separately). The view order for each recovery curve was preset to make the total views for single time window in a Halton distribution. N_v/N_bin (=3 in fig.1) images were reconstructed.

Figure 2

Error analysis of VFA method and Look-Locker method with flip angle deviating from 0.8 to 1.2 of the real value.

Figure 3

(a) Images of gradient echo and SWIFT in the presence of high IONP concentrations. The SWIFT images are normal SWIFT images acquired at TR = 2.6 ms and bandwidth = 125 kHz with matched resolution with GRE (matrix = 256×256×256). (b) Concentration for different tubes. (c) The SNR plots. GRE sequence reaches the noise floor at 9 mM; The SNR for SWIFT sequence at 15° remains well above the IONP-free water signal intensity even at 53.6 mM.

Figure 4

(a), (b) & (c) Examples of the T₁ recovery curves are plotted with the resulting fits. τ is the recovery time. The symbols are the average voxel values from images and the solid lines are the fittings from the non-linear least squares algorithm. (d) SWIFT T₁ map of agar with high IONP concentrations as illustrated in fig. 3b.

Figure 5

Example images of the SWIFT Look-Locker method along the recovery curves. First column is for shorter recovery curve with total recovery time = 1151 ms. Second column is for longer recovery curve with total recovery time = 4596 ms. The numbers on the images show the number of the time window the images belong to.

Figure 6

R₁ (1/ T₁) is plotted versus the concentration of iron to determine if T₁ could be used as a measurement for determining IONP concentration. The data shows that the R₁ and the concentration have a linear relationship.