Abstract
BACKGROUND: Inflammation and metabolism exhibit a complex interplay, where inflammation influences metabolic pathways, and in turn, metabolism shapes the quality of immune responses. Here, glucose turnover is of special interest, as proinflammatory immune cells mainly utilize glycolysis to meet their energy needs. Noninvasive approaches to monitor both processes would help elucidate this interwoven relationship to identify new therapeutic targets and diagnostic opportunities. METHODS: For induction of defined inflammatory hotspots, LPS-doped Matrigel plugs were implanted into the neck of C57BL/6J mice. Subsequently, (1)H/(19)F magnetic resonance imaging (MRI) was used to track the recruitment of (19)F-loaded immune cells to the inflammatory focus and deuterium ((2)H) magnetic resonance spectroscopy (MRS) was used to monitor the metabolic fate of [6,6-(2)H(2)]glucose within the affected tissue. Histology and flow cytometry were used to validate the in vivo data. RESULTS: After plug implantation and intravenous administration of the (19)F-containing contrast agent, (1)H/(19)F MRI confirmed the infiltration of (19)F-labeled immune cells into LPS-doped plugs while no (19)F signal was observed in PBS-containing control plugs. Identification of the inflammatory focus was followed by i.p. bolus injection of deuterated glucose and continuous (2)H MRS. Inflammation-induced alterations in metabolic fluxes could be tracked with an excellent temporal resolution of 2 min up to approximately 60 min after injection and demonstrated a more anaerobic glucose utilization in the initial phase of immune cell recruitment. CONCLUSION: (1)H/(2)H/(19)F MRI/MRS was successfully employed for noninvasive monitoring of metabolic alterations in an inflammatory environment, paving the way for simultaneous in vivo registration of immunometabolic data in basic research and patients.