SummaryThe safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction.

The objective of this study was to investigate non-invasive imaging methods to update the used regression equation for stationary tested boars. A total of 94 boars were examined. 20 boars were dissected to provide the reference LMP. Performance data (PD) from right carcasses were available from all groups. The left carcasses were studied by MRI & DXA. Based on the reference LMP and the MRI & DXA data, regression equations for LMP were developed. The estimates for LMP based on MRI & DXA data were used to calculate new regression equations for entire male carcass halves based on linear PD. Further 33 PD sets served as independent sample, which was included in a Monte Carlo simulation for imputing the missing reference LMPs (n=74) and discussing the accuracy of the results. The LMP regression equation based on the combined MRI & DXA data is as accurate as the former regression equation, but needs only three instead of seven variables.

SummarySafety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes, among others, the pathological examination of the injection site in frequent intervals. This examination requires a selected killing of animals in frequent intervals. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible local reactions after vaccination in vivo. Sixty-four pigs were divided into four experimental groups (n = 16); two groups consisting of 12-week-old pigs and two of 6-month-old pigs at vaccination day. The pigs were vaccinated with four licensed products (each group receiving one vaccine) and examined up to 6 times using MRI during a period of 5 weeks. The MR images were evaluated semi-automatically, comparing the volumes of altered signal intensities on the vaccination side (VS) with the volumes of the signal intensities on the control side (CS). A paired t-test was used to identify significant differences (p < 0.05) between VS and CS. The results show that MRI allows a 3D-quantification of the extent of local reactions in vivo by scanning the same live animals at several time points after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be applied to reduce animal numbers used for safety testing purposes.