Multiparameter mapping of relaxation (R1, R2*), proton density and magnetization transfer saturation at 3 T: A multicenter dual‐vendor reproducibility and repeatability study

Abstract

Multicenter clinical and quantitative magnetic resonance imaging (qMRI) studies require a high degree of reproducibility across different sites and scanner manufacturers, as well as time points. We therefore implemented a multiparameter mapping (MPM) protocol based on vendor's product sequences and demonstrate its repeatability and reproducibility for whole‐brain coverage. Within ~20 min, four MPM metrics (magnetization transfer saturation [MT], proton density [PD], longitudinal [R1], and effective transverse [R2*] relaxation rates) were measured using an optimized 1 mm isotropic resolution protocol on six 3 T MRI scanners from two different vendors. The same five healthy participants underwent two scanning sessions, on the same scanner, at each site. MPM metrics were calculated using the hMRI‐toolbox. To account for different MT pulses used by each vendor, we linearly scaled the MT values to harmonize them across vendors. To determine longitudinal repeatability and inter‐site comparability, the intra‐site (i.e., scan‐rescan experiment) coefficient of variation (CoV), inter‐site CoV, and bias across sites were estimated. For MT, R1, and PD, the intra‐ and inter‐site CoV was between 4 and 10% across sites and scan time points for intracranial gray and white matter. A higher intra‐site CoV (16%) was observed in R2* maps. The inter‐site bias was below 5% for all parameters. In conclusion, the MPM protocol yielded reliable quantitative maps at high resolution with a short acquisition time. The high reproducibility of MPM metrics across sites and scan time points combined with its tissue microstructure sensitivity facilitates longitudinal multicenter imaging studies targeting microstructural changes, for example, as a quantitative MRI biomarker for interventional clinical trials.

Quantitative Multi-Parameter Mapping Optimized for the Clinical Routine

“…In line with previous reports (Weiskopf et al, 2013;Leutritz et al, 2020), R2 * had the lowest stability in the current study. Possible measures to improve the stability may be to correct for B0 inhomogeneities by adapting sequences as described by Baudrexel et al (2009) or by using the existing phase images acquired with the MPM protocol (Cohen-Adad et al, 2012).…”

“…Given the need for short acquisition times in the clinical setting, we tested which contrasts benefit from the additional scan time (∼2 min) required to acquire a B1+ map. Using the acquired B1+ maps increased the stability for PD and R1 with slight deviations in absolute R1 and MT values as expected, with higher deviations in R1 than MT (Callaghan et al, 2014;Leutritz et al, 2020). As expected, R2 * quantification is not affected by B1+ mapping (Tabelow et al, 2019).…”

“…Of note, intra-/inter-subject variability of all atlas regions were very comparable, suggesting that the optimized protocol is useful for both crosssectional and longitudinal clinical studies with similar sensitivity. The intra-subject CoV of all contrasts at 1.6 mm isotropic resolution are roughly 3 times smaller than the values reported by Weiskopf et al for their 20-min protocol with 1 mm isotropic resolution (Leutritz et al, 2020), even without Gibb's ringing correction. Therefore, in order to achieve the intra-subject CoV of our optimized 1.6 mm protocol, patients would have to be scanned for an estimated 3 2 = 9 times longer (∼3 h) using the 1 mm isotropic protocol by Weiskopf et al which is not feasible for clinical studies.…”

“…The optimized MPM protocol has excellent intra-subject variability both in tissue classes and individual atlas regions. The stability of our optimized protocol is 2-3 times higher than for widely used 1mm MPM protocols (Weiskopf et al, 2013;Callaghan et al, 2014;Grabher et al, 2015;Ziegler et al, 2018;Lommers et al, 2019;Leutritz et al, 2020;Taubert et al, 2020) and was achieved in less than half the acquisition time. Given the high effect sizes reported in former MPM studies (Grabher et al, 2015;Lommers et al, 2019), the optimized protocol is expected to have high sensitivity to detect subtle changes related to disease or treatment effects even at the single-subject level, making the current protocol a candidate for rare diseases and personalized medicine approaches.…”

“…Second, the explicit use of non-manufacturer sequences allowed for higher optimization than was possible in the current study and may explain some differences. Further, as recently highlighted (Leutritz et al, 2020), PD maps are calibrated to 69% in the white matter (Tabelow et al, 2019), which may have led to an underestimation of variability. The current study aimed to implement sequences for MPM that were fully certified for clinical use and based on manufacturer sequences, allowing for safe and immediate translation into clinical protocols (not just research centers).…”