The Effects of Physiological and Methodological Determinants on 18

Introduction: In this study, the influence of physiological determinants on 18F-fluoro- d -glucose ( 18 F-FDG) brain uptake was evaluated in a mouse model of Alzheimer disease. Materials and Methods: TASTPM (Tg) and age-matched C57BL/6 J (WT) mice were fasted for 10 hours, while another group was fasted for 20 hours to evaluate the effect of fasting duration. The effect of repeatedly scanning was evaluated by scanning Tg and WT mice at days 1, 4, and 7. Brain 18 F-FDG uptake was evaluated in the thalamus being the most indicative region. Finally, the cerebellum was tested as a reference region for the relative standard uptake value (rSUV). Results: When correcting the brain uptake for glucose, the effect of different fasting durations was attenuated and the anticipated hypometabolism in Tg mice was demonstrated. Also, with repeated scanning, the brain uptake values within a group and the hypometabolism of the Tg mice only remained stable over time when glucose correction was applied. Finally, hypometabolism was also observed in the cerebellum, yielding artificially higher rSUV values for Tg mice. Conclusion: Corrections for blood glucose levels have to be applied when semiquantifying 18 F-FDG brain uptake in mouse models for AD. Potential reference regions for normalization should be thoroughly investigated to ensure that they are not pathologically affected also by afferent connections

Neuroinflammation: From target selection to preclinical and clinical studies

Inflammation is a highly dynamic and complex adaptive process to preserve and restore tissue homeostasis in neurological disorders and often serves as a prognostic marker for disease outcome. The underlying cellular and factorial heterogeneity represents an opportunity in the development of disease-modifying therapies. Molecular imaging of neuroinflammation (NI) may support the characterization of key aspects of the dynamic interplay of various inducers, sensors, transducers, and effectors of the multifactorial inflammatory response in vivo in animal models and patients. The characterization of the NI response by molecular imaging will (i) support early diagnosis and disease follow-up, (ii) guide (stereotactic) biopsy sampling, (iii) highlight the dynamic changes during disease pathogenesis in a noninvasive manner, (iv) help monitoring existing therapies, (v) support the development of novel NI-modifying therapies, and (vi) aid stratification of patients, according to their individual NI profile. This book chapter will review the basic principles of NI, recent developments and applications of novel molecular imaging targets, key considerations for the selection and development of imaging targets, as well as examples of successful clinical translation of NI imaging