Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems

Background: Many translational MR biomarkers derive from measurements of the water proton longitudinal relaxation rate R ₁ , but evidence for between-site reproducibility of R ₁ in small-animal MRI is lacking. Objective: To assess R ₁ repeatability and multi-site reproducibility in phantoms for preclinical MRI. Methods: R ₁ was measured by saturation recovery in 2% agarose phantoms with five nickel chloride concentrations in 12 magnets at 5 field strengths in 11 centres on two different occasions within 1–13 days. R ₁ was analysed in three different regions of interest, giving 360 measurements in total. Root-mean-square repeatability and reproducibility coefficients of variation (CoV) were calculated. Propagation of reproducibility errors into 21 translational MR measurements and biomarkers was estimated. Relaxivities were calculated. Dynamic signal stability was also measured. Results: CoV for day-to-day repeatability (N = 180 regions of interest) was 2.34% and for between-centre reproducibility (N = 9 centres) was 1.43%. Mostly, these do not propagate to biologically significant between-centre error, although a few R ₁ -based MR biomarkers were found to be quite sensitive even to such small errors in R ₁ , notably in myocardial fibrosis, in white matter, and in oxygen-enhanced MRI. The relaxivity of aqueous Ni ²⁺ in 2% agarose varied between 0.66 s ⁻¹ mM ⁻¹ at 3 T and 0.94 s ⁻¹ mM ⁻¹ at 11.7T. Interpretation: While several factors affect the reproducibility of R ₁ -based MR biomarkers measured preclinically, between-centre propagation of errors arising from intrinsic equipment irreproducibility should in most cases be small. However, in a few specific cases exceptional efforts might be required to ensure R ₁ -reproducibility.