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Background: Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. 18F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using in vivo18F-FDG PET imaging. Methodology/Findings: Non-permissive host ICR mice and permissive host SD rats were infected with A. cantonensis, and the effects of the resulting inflammation on 18F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of 18F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-γ and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that 18F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain. Conclusions: An in vivo18F-FDG/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of A. cantonensis-infected mice and rats. Author summary: Angiostrongylus cantonensis infection in humans can cause brain inflammation, and there is currently no effective diagnostic method to clarify the pathological changes in the brain. Current diagnostic methods include CSF detection and eosinophilia immune examination after lumbar puncture, but these protocols are risky and may produce false-positive responses. Non-invasive medical imaging techniques might allow for the circumvention of these problems. The effective use of 18F-FDG PET imaging as a diagnostic tool for parasitic infections has been reported. In this study, we hypothesize that the A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils have an impact on the localized pathological changes in the brains of non-permissive hosts. These changes can be analyzed using live in vivo18F -FDG PET medical imaging. A. Cantonensis was infected in non-permissive ICR mice and permissive SD rats, after which the effects of the resulting inflammation on energy metabolism were characterized via nuclear medicine imaging. We also quantitatively measured the distributed uptake values of different brain regions, to build an evaluated imaging model of localized neuropathological damages caused by eosinophil-inflammation. Through the completion of this study, we intend to develop a specific radiological medical imaging analysis model of angiostrongyliasis for important endemic zoonotic parasitic diseases. We are trying to develop a cross-disciplinary research project combining parasitology and nuclear medicine and to establish an imaging model for analyzing angiostrongyliasis that can be applied to clinical evaluation and prognosis. [ABSTRACT FROM AUTHOR]