Kim Annink

62 Chapter 3 Figure 5: Median ADC values in the vermis (A), cerebellar hemispheres (B) and DN (C) in in- fants with no, mild, moderate and severe cytotoxic edema based on H&E stained slices. DISCUSSION This study showed that infants with HIE had lower ADC values in the vermis and DN compared to controls, but not in the cerebellar hemispheres. ADC values in the vermis were correlated with the number of normal PCs in the vermis, furthermore there were no correlations between ADC values and histology measures. The lower ADC values in the vermis and DN imply that it is possible to detect hypoxic injury in these structures with ADC maps. There were two patients with clear abnormalities on both the DWI and ADC map, so when cytotoxic edema is very severe, the ADC map will detect this. However, in the hemispheres there were no differences between the HIE group and controls; although in case of severe HIE severe cytotoxic edema in the hemispheres is to be expected (9). We hypothesize that only parts of the hemispheres show diffusion restriction and that by measuring the whole hemisphere, this effect is leveled out. There was an excellent interrater reliability for ADC measurements. This shows that ADC measurements can be reproduced and that the measurements are reliable. As expected, PC injury was found in the neonates with HIE during autopsy. PCs fire action potentials at high frequencies of ~100 Hz, and can even achieve frequencies up to 500 Hz when triggered by climbing fibers (29). This high firing rate combined with a large membrane surface sums up to an extraordinary high metabolic demand of PCs and high vulnerability for hypoxic-ischemic injury (30). In addition, the early and high susceptibility of cerebellar PCs for hypoxic-ischemia, as evidenced by the present study, can be explained by their decreased ability to minimize excitotoxic glutamate release in the acute hypoxic-ischemic state (26,31).