Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T

Abstract

Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems.

Methods: Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues.

Results: Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T).

Conclusion: Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement.

Trial registration: ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.

Keywords: Cardiac; Inflammation; MRI; USPIO.

Figures

Fig. 1

MRI protocol

Fig. 2

Myocardial R2* pre- and post-USPIO administration at 1.5 and 3 T. Following administration, USPIO was detected by an increase in R2* at 24 h in the myocardium at both 1.5 and 3 T. (**** = p < 0.0001, ** = p < 0.01)

Fig. 3

Tissue R2* pre- and post-USPIO administration at 1.5 and 3 T. Following administration, USPIO was detected by an increase in R2*, 24 h after administration in skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and kidney, liver, spleen, blood and bone at 3 T. (**** = p < 0.0001, *** = p < 0.001, ** = p < 0.01, * = p < 0.05)

Fig. 4

Body-mass Index vs Panmyocardial R2* change at 1.5 and 3 T. Body-mass index correlates with panmyocardial R2* change pre- and post-USPIO

Fig. 5

Inferior Blooming artifact. Example illustrating the challenge in assessing whether the inferior myocardial signal attenuation seen arrowed on the T2* colourmap (a, scale 0-60 ms) is true or caused by artifact. Drawing a region of interest (b) and examining the decay curve (c) along with visualising individual echos (d1-8) helps determine that this is a ‘blooming artifact’ from outside the heart is seen to influence echos 4-8. These can be manually removed, forming a new decay curve (e) with improvement in curve fitting (R2 value), although with fewer fitting points

Fig. 6

Example of high and low T2* values. Regions of Interest with excessively low or high T2* value (pre-contrast blood pool, a, and post USPIO bone marrow, b, respectively) can often be difficult to generate an accurate T2* decay curve. Imaging with tissue-spcific echo times will help generate more accurate T2* decay curves