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18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.

ABSTRACT: PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion.Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H2O; plateau pressure, 30 cm H2O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS+] group; n = 6) or not (lipopolysaccharide-negative group; n = 6). (18)F-FDG PET emission scans were then acquired. (18)F-FDG phosphorylation rate and distribution volume were calculated with a 4-compartment model. Lung tissue expression of inflammatory cytokines was measured using real-time quantitative reverse transcription polymerase chain reaction.(18)F-FDG uptake increased in LPS+ (P = 0.012) and in surfactant-depleted sheep (P < 0.001). These increases were topographically heterogeneous, predominantly in dependent lung regions, and without interaction between alveolar lavage and LPS. The increase of (18)F-FDG uptake in the LPS+ group was related both to increases in the (18)F-FDG phosphorylation rate (P < 0.05) and to distribution volume (P < 0.01). (18)F-FDG distribution volume increased with infiltrating neutrophils (P < 0.001) and phosphorylation rate with the regional expression of IL-1? (P = 0.026), IL-8 (P = 0.011), and IL-10 (P = 0.023).Noninvasive (18)F-FDG PET-derived parameters represent histologic and gene expression markers of early lung injury. Pulmonary metabolism assessed with (18)F-FDG PET depends on the mechanism of injury and appears to be additive for endotoxemia and surfactant depletion. (18)F-FDG PET may be a valuable imaging biomarker of early lung injury.

SUBMITTER: de Prost N

PROVIDER: S-EPMC4258066 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.

de Prost Nicolas N Feng Yan Y Wellman Tyler T Tucci Mauro R MR Costa Eduardo L EL Musch Guido G Winkler Tilo T Harris R Scott RS Venegas Jose G JG Chao Wei W Vidal Melo Marcos F MF

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20141006 11

<h4>Unlabelled</h4>PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion.<h4>Methods</h4>Twelve sheep underwent homogeneous unilateral surfactant ...[more]

PMID: 25286924

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Project description:BackgroundThere is increasing interest in Positron Emission Tomography (PET) of 2-deoxy-2-[18F]flouro-D-glucose ((18)F-FDG) to evaluate pulmonary inflammation during acute lung injury (ALI). We assessed the effect of extra-vascular lung water on estimates of (18)F-FDG-kinetics parameters in experimental and simulated data using the Patlak and Sokoloff methods, and our recently proposed four-compartment model.Methodology/principal findingsEleven sheep underwent unilateral lung lavage and 4 h mechanical ventilation. Five sheep received intravenous endotoxin (10 ng/kg/min). Dynamic (18)F-FDG PET was performed at the end of the 4 h period. (18)F-FDG net uptake rate (Ki), phosphorylation rate (k(3)), and volume of distribution (F(e)) were estimated in three isogravitational regions for each method. Simulations of normal and ALI (18)F-FDG-kinetics were conducted to study the dependence of estimated parameters on the transport rate constants to (k(5)) and from (k(6)) the extra-vascular extra-cellular compartment. The four-compartment model described 85.7% of the studied (18)F-FDG-kinetics better than the Sokoloff model. Relative to the four-compartment model the Sokoloff model exhibited a consistent positive bias in Ki (3.32 [1.30-5.65] 10(-4)/min, p<0.001) and showed inaccurate estimates of the parameters composing Ki (k(3) and F(e)), even when Ki was similar for those methods. In simulations, errors in estimates of Ki due to the extra-vascular extra-cellular compartment depended on both k(5) and k(5)/k(6), with errors for the Patlak and Sokoloff methods of 0.02 [-0.01-0.18] and 0.40 [0.18-0.60] 10(-3)/min for normal lungs and of -0.47 [-0.89-0.72] and 2.35 [0.85-3.68] 10(-3)/min in ALI.Conclusions/significance(18)F-FDG accumulation in lung extra-vascular fluid, which is commonly increased during lung injury, can result in substantial estimation errors using the traditional Patlak and Sokoloff methods. These errors depend on the extra-vascular extra-cellular compartment volume and its transport rates with other compartments. The four-compartment model provides more accurate quantification of (18)F-FDG-kinetics than those methods in the presence of increased extra-vascular fluid.

Project description:Positron emission tomography using 18F-Fluro-deoxy-glucose (18F-FDG) is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS) at a dose of 7.5 Gy, or whole body irradiated (WBI) with 4 or 7.5 Gy. Animals were imaged using 18F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for 18F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher 18F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow 18F-FDG uptake returned to sham levels. 18F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this interaction can be studied using non-invasive imaging modalities.

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18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.

Publications

18F-FDG kinetics parameters depend on the mechanism of injury in early experimental acute respiratory distress syndrome.

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