Recent developments in genetic engineering, surgical and pharmacological modalities have led to a wide selection of mouse models of cardiovascular disease. For longitudinal monitoring of the mouse model under treatment, accurate quantification of heart function is mandatory. Cardiovascular magnetic resonance (CMR) has proven as excellent modality meeting the requirements of providing accurate functional information even for the small, fast-beating mouse heart ¹. Here especially the self-gating techniques show high potential for reproducible quantification of the cardiac function. Even though CMR has been applied to monitor changes in the cardiac function during early development ², assessment of its longitudinal reproducibility is limited. In this work adult mice were followed-up for 360 days to assess the long-term reproducibility of the technique and the functional cardiac parameters.Female wild type mice (C57/B6, n=5), 12 weeks old were included. The MR imaging protocol (Figure 1) comprised a multi-slab survey acquisition in axial, coronal, and sagittal orientation, followed by two long-axis cine scans in semi two-chamber (semi 2CH) and four-chamber (semi 4CH) geometry. The semi 2/4CH images were used to plan the subsequent stack of short axes orientations (SAX). The number of short axis slices was adopted to ensure full coverage of the ventricles in end-diastole. Final 2- and 4 chamber orientations were planned on the SAX data. All cine acquisitions were performed using a self-gating approach (intraGate^©, Bruper Biospin, Ettlingen, Germany), with subsequent acquisition of the gating and image data (Figure 2). All animals were followed over 360 days and scanned on d91, d93, d95, d151, d211, d451. On d91, d93, and d95, the entire protocol was performed twice within 2 hours with complete repositioning of the animals in the scanner. End diastolic volume (EDV), end systolic volume (ESV) and stroke volume (SV) were determined and LV ejection fraction (EF) and LV mass (LVM) were derived. All image analyses were done blinded using the freely available software Segment version 1.9.1. The data were used for assessing the (a) reproducibility of the proposed imaging approach, (b) the variability of the functional parameters within a group, and (c) the longitudinal changes of the functional parameters over 360 days.

a) Between the two subsequent measurements only insignificant differences were observed for all investigated parameters (EF = 1.33%, EDV = -1.17 ml, ESV = -1.00ml, SV = -0.17ml, and LVM = 1.40 mg). Linear correlation presented a highly significant (Pearson R = 0.979) linear correlation between the two measurements with a R² value of 0.96. The CoV resulted to values between 6.18 to 24.92, while largest values observed for ESV and SV. High reproducibility was obtained for EF, EDV and LVM.

b) Reproducibility was very good for the EF (CoV between 4.00% and 13.01%) and LVM (CoV between 3.01% and 9.36%), good for EDV (CoV between 8.59% and 17.06%) and SV (CoV between 9.70% and 18.29%), and moderate for ESV (CoV between 15.18% and 30.00%).

c) Longitudinal reproducibility was excellent (Figure 3 & Table 1) for the EF (CoV between 3.33% and 7.09%), good for LVM (CoV between 3.64% and 10.45%), EDV (CoV between 4.54% and 14.29%) and SV (CoV between 5.04% and 13.20%), and moderate for ESV (CoV between 9.67% and 23.74%). LVM showed a trend to increasing values with increasing age.

The self-gated CINE MRI technique proved very good reproducibility of the left ventricular functional parameters. Longitudinal follow-up did not reveal significant variations of the functional parameters over time, but a slight increase of the LVM after 360 days. In summary, self-gated MRI in combination with a strict animal positioning and scan planning protocol ensures reproducible assessment of LV functional parameters.