RESUMEN
BACKGROUND: Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores 11C-acetate PET as an imaging technique for detecting reactive astrogliosis. METHODS: Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and MCT1 expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis. RESULTS: Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with worse prognosis. CONCLUSION: Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.
RESUMEN
PURPOSE: A new positron emission tomography (PET) detector signal processing method, the charge signal transmission approach, is proposed for the development of a hybrid PET-magnetic resonance imaging (MRI). A number of experiments were performed to demonstrate that the Geiger-mode avalanche photodiode (GAPD) charge output could be transmitted to a preamplifier using a long cable without degrading the PET signal performance. METHODS: A PET module consisted of LYSO and a GAPD with a 4 x 4 array. The GAPD output was transmitted to the preamplifier through flexible flat cables. The effect of the cable length on the PET performance was examined using seven different lengths ranging from 10 to 300 cm outside and inside the 7 T animal MRI. Four parameters (rise time, fall time, amplitude, and area of the preamplifier output) were measured as a function of the cable length using a 10 GS/s oscilloscope and three parameters (photopeak position, energy resolution, and time resolution) were measured using a 100 MS/s DAQ unit. The effect of the cable length on the MR phantom images was investigated. In addition, the effect of the PET module configuration on its temperature stability was assessed by acquiring the energy and time spectra. RESULTS: There were no significant changes in the PET module performance as a function of the cable length, both outside and inside MRI. The performance changes in energy information, such as the amplitude, area, photopeak position, and energy resolution, were <3% with cable lengths ranging from 10 to 300 cm and the change in the time resolution was <6%. There were no obvious artifacts or changes in the line profile in the MR phantom images. Moreover, no manifest changes in the photopeak position and coincidence counting rate were observed in the PET modules employing the charge signal transmission approach, whereas considerable degradation of the PET module performance was observed in the voltage signal transmission approach. CONCLUSIONS: This study demonstrated that it is feasible to design a hybrid PET-MRI using the charge signal transmission approach, which is expected to have more advantages than other approaches.