The base-line level of signal enhancement present in normal mice following administration of Gd-DPTA was determined in uninfected animals. The mean percentage signal change measured in these mice was 7.105 ± 0.162% (Figs. 4B and 5). A similar level of enhancement was seen in animals scanned at 7 days -post-infection (7.6 ± 0.397%). However by day 14 post-infection the mean percentage signal change (15.269 ± 0.586%) had risen significantly compared to uninfected mice (p < 0.001, CI = 5.21, 10.93) and mice scanned at 7 days -post-infection (p < 0.001, CI = 5.179, 9.992). At this point the most prominent areas of signal enhancement were found in the ventricular and hypothalamic areas although more subtle changes could be seen throughout the parenchyma (Fig. 5). A significant (p < 0.001, CI = 6.881, 11.476) increase in barrier dysfunction of approximately 9% when compared to 14 days -post-infection was detected on day 21 post-infection (24.447 ± 0.968%). A further stepwise rise was apparent in animals scanned on day 28 post-infection (28.056 ± 0.766%). The mean percentage signal change measured at day 28 post-infection was significantly higher (p < 0.005) than in all earlier time-points (Fig.4B). Although the ventricular and hypothalamic regions exhibited the highest level of contrast infiltration, increased signal change was also evident in the striatum, cerebral cortex, thalamus, and pons (Fig. 5). Diffuse BBB impairment was therefore present throughout the brain parenchyma and not confined to specific regions, such as the circumventricular organs and ventricles, where barrier function is intrinsically weaker. Summary statistics for the percentage signal enhancement data are detailed in Supplementary Table 3.Fig. 5MRI percentage signal change maps. Percentage signal change maps (coloured), together with their respective T2 weighted scan images (grey), from an individual mouse, at each time-point studied are provided. In each case three slices, from the 20 measured in the procedure, are shown. The slices illustrated have been taken at similar levels in each mouse and cover the range of the scan. The colour bar represents the percentage signal change, with brighter colours corresponding to higher levels of change and therefore more severe BBB dysfunction. An increase in the intensity of the colours within the signal change maps can be clearly seen from day 14 post-infection and is most apparent in animals scanned on day 28 post-infection. Brain structures relevant to the images shown are described. LV, lateral ventricle; CTX, cerebral cortex; cing, cingulum; Str, striatum; aco,‘anterior commissure; ACB, nucleus accumbens; CP, Caudate putamen; V3, third ventricle; cc, corpus callosum; HPF, hippocampal formation; HY, hypothalamus; int, internal capsule; SC, superior colliculus; AQ, aqueduct (4th ventricle); pons, pons. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)