Comparing the Inflammatory and Immunopathological Change of Brain in Hosts with Angiostrongylus Cantonensis Infection by Using nanoPET Imaging Technique

Angiostrongylus cantonensis that mainly parasitizes in rat heart and pulmonary artery causes human eosinophilic meningitis or meningoencephalitis. Many terrestrial or freshwater mollusks can become the Intermediate hosts for spreading this worm in Taiwan. It is still a very important zoonotic parasite to the local community. Young adult worm in brain of non-permissive host infected A. cantonensis induced eosinophils CSF. The cerebral pathogenesis is characterized by eosinophils infiltrate that induce significant inflammatory reactions in an attempt to eliminate the immature worms residing in the nervous system, but instead to result in severe tissue damage. Different species or strains of hosts will cause different levels of brain inflammation when infected by A. cantonensis. Various secreted inflammatory factors by microglia-derived eosinophils not only mediate protective immune responses but also contribute to the pathogenesis and pathophysiology associated with angiostrongyliasis syndromes. Most current researches related to the neuropathological changes of A. cantonensis infection usually just use the histopathological sections or morphological observation to detect indirectly, seldom monitor the live patterns by medical imaging techniques. Positron emission tomography (PET) is a functional medical imaging. Using different PET tracer, like 18F-FDG, can be observed in different pathological or physiological changes of patients. However, using 18F-FDG PET imaging in the pathogenesis-related research of parasitic infections is still lacking and worthy of further exploration. This study takes a hypothesis that A. cantonensis infection-induced inflammatory and immunomodulatory factors of microglia will impact the pathological changes of brain in non-permissive hosts, and could be analyzed in different brain areas by using in vivo 18F-FDG PET medicine imaging. This project expect to perform a three-year period, the first year will use a different number of A. cantonensis to infect non-permissive ICR mice and permissive SD rats, and then characterize the effects of inflammation to energy metabolism via nuclear medicine imaging as the goal, to explore varying degrees of inflammatory factors cause the changes of pathogenicity and pathophysiology in infection. The second year expect to infect different strains of mice with A. cantonensis and use nuclear medicine imaging to detect brain lesions caused by infection. We hope to analyze the inflammatory factors of different brain tissues of outbred and inbred mice, and explore their relationship with host genotype and the immunopathogenesis. The third year we will use infected A. cantonensis mice to quantitative the distributed uptake values in different brain areas, to build an evaluated imaging model of inflammatory responses on localized neuropathological damage. We will cooperate with the Nuclear Energy Institute and Chang Gung University to develop a cross disciplinary research combined with parasitology and nuclear medicine. Upon completion of this plan will help to develop the imaging analysis model of angiostrongyliasis that can apply to the clinical diagnosis and treatment of this important zoonotic infection in Taiwan.