Neuropathic pain (NPP) and neonatal hypoxic–ischaemic encephalopathy (HIE) both have a limited understanding of neurological damage onset and progression, hampering the development of novel treatments. This thesis evaluated the feasibility of preclinical positron emission tomography (PET) imaging for tracking time-dependent pathophysiological alterations in NPP and HIE animal models.

PET imaging using the 18-kDa translocator protein tracer [18F]F-DPA was conducted to evaluate gliosis-mediated inflammation in the spinal cord of a rat model of NPP. A new PET setup was used to assess brain oxygen metabolism in a rat model of HIE, in which 15O-labelled gases are inhaled spontaneously by rat neonates, enabling a quantitative assessment of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). The pathophysiological progression of HIE was longitudinally assessed by PET targeting inflammation ([18F]F-DPA), hypoxia ([18F]EF5), and uptake of the glucose analogue ([18F]FDG). [15O]O2 and [18F]FDG uptake levels within 48 h after hypoxic–ischaemic injury were further compared with the outcome of histological brain volume loss in a later phase.

[18F]F-DPA showed specific uptake in the inflamed spinal cord on ex vivo PET and autoradiography 7 days after injury in NPP rats. In vivo PET did not allow for visualisation of the inflammation site due to insufficient [18F]F-DPA uptake in the lesion and high background noise. The 15O-labelled gas PET setup detected temporal changes in CBF and CMRO2 associated with acute perfusion derangement within 48 h post-insult and tissue damage progression in HIE over 14 days along with maturation. On the injury day, transiently enhanced hypoxic and glucose uptake brain areas were detected, whereas inflammatory responses emerged 4 days post-injury and remained elevated until day 21. PET with [18F]FDG and [15O]O2 within 48 h post-insult showed predictive values for early recognition of damage severity. This thesis highlights the utility and limitations of preclinical PET techniques for the development of advanced diagnostic, prognostic, and therapeutic approaches for NPP and neonatal HIE.