Study on the Developmnt and Application of Nuclear Medical Assessment Model for Brain Inflammation by Angiostrongylus Cantonesis Infection

Angiostrongylus cantonensis infects the heart and pulmonary artery of rats, and also a mainly cause of human eosinophilic meningitis or meningoencephalitis in Southeast Asia, Pacific islands and Far East. The cerebral pathogenesis is characterized by eosinophils infiltrate that induce inflammatory reactions in an attempt to eliminate the worms residing in the nervous system, but instead to result in severe tissue damage. Various secreted inflammatory factors by microglia-derived eosinophils not only mediate protective immunity but also contribute to the pathogenesis of hypereosinophilic syndromes. Most studies relating to the neuropathological variability of A. cantonensis infection just use histopathological or morphological examination indirectly, and seldom employ medical imaging techniques to monitor the live patterns. 18F-FDG, a Positron emission tomography (PET) tracer, is used to observe the pathological changes in the regions of rapid cell energy consumption. A large number of eosinophils rapidly are recruited to brain inflammatory regions, and quickly absorb glucose as energy source after activation, these characteristics of A. cantonensis infection so that the use of 18F-FDG/PET imaging for detecting may be feasible. This study takes a hypothesis that induced inflammatory factors of microglia have an impact on recruiting eosinophils accumulation within some brain regions of the hosts with A. cantonensis infection. These pathological changes could be assessed by in vivo 18F-FDG PET/CT imaging and this evaluation model could be used further for analyzing the effects of albendazole treatment. This project is expected to be carried out over a three-year period. In the first year, we will quantitatively measure the uptake values of different brain regions of infected A. cantonensis BALB/c mice, to build an 18F-FDG /PET imaging evaluated model for detecting neuropathological lesions caused by eosinophils-inflammation. The inflammatory factors of mice will also be detected to confirm their relationship with radioactivity values by employing histopathology and molecular biology in brain lesions. In the second year, we expect to further verify our 18F-FDG/PET imaging evaluated model by using A. cantonensis infection with susceptible BALB/c mice and resistant C57BL/6 mice. Through using PET to analyze different degrees of the pathogenesis of infection, follow-up characterization will be informative in revealing the effects of angiostrongyliasis on different brain areas. In addition, the association between the inflammatory factors and 18F-FDG /PET findings will be addressed, with the results also verified by histopathological and molecular biological analysis. In the third year, we will apply the 18F-FDG/PET imaging evaluated model to assess the effects of albendazole treatment on the brain lesions of BALB/c mice infected with A. cantonensis. In order to determine the pathological changes in the brains of the treated mice, the histopathological and molecular biological analysis will also be employed as the evaluated markers. We will work with the Nuclear Energy Institute and Chang Gung University to develop a cross-disciplinary research project combining parasitology and nuclear medicine. Upon completion of this plan, we will develop an effective 18F-FDG/PET imaging evaluated model for angiostrongyliasis that can be applied to the clinical diagnosis and treatment monitoring of this important zoonotic infection in Taiwan.