Person: Harris, Robert
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Harris
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Harris, Robert
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Publication Modeling \(^{18}F-FDG\) Kinetics during Acute Lung Injury: Experimental Data and Estimation Errors(Public Library of Science, 2012) Dittrich, A. Susanne; Winkler, Tilo; Wellman, Tyler James; de Prost, Nicolas; Musch, Guido; Harris, Robert; Vidal Melo, MarcosBackground: There 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 Findings Eleven 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 (k3), and volume of distribution (Fe) 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 (k5) and from (k6) 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 (k3 and Fe), 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 k5 and k5/k6, 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.Publication Ventilation Defect Formation in Healthy and Asthma Subjects Is Determined by Lung Inflation(Public Library of Science, 2012) Harris, Robert; Fujii-Rios, Hanae; Winkler, Tilo; Musch, Guido; Vidal Melo, Marcos; Venegas, JoseBackground: Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion. Objective: We studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma. Methods: Spirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous \(^{13}\)NN-saline positron emission tomography were measured before and after a challenge with nebulized methacholine. Vdefs were defined as regions with elevated residual 13NN after a period of washout. The average location, ventilation, volume, and fractional gas content of the Vdefs, relative to those of the rest of the lung, were calculated for both groups. Results: Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed Vdefs. These Vdefs tended to form in regions that, at baseline, had a lower degree of lung inflation and, in healthy subjects, tended to occur in more dependent locations than in subjects with asthma. Conclusion: The formation of Vdefs is determined by the state of inflation prior to bronchoconstriction.Publication Is the way to man's heart (and lung) through the abdomen?(BioMed Central, 2009) Owens, Robert Llewellyn; Harris, Robert; Malhotra, AtulIntra-abdominal hypertension is increasingly recognized to be both prevalent and clinically important in medical and surgical intensive care units. Intra-abdominal pressure (IAP) can impact organ function throughout the body, and it can also complicate standard measurements used in intensive care units. The article by Krebs and colleagues reports the effect of IAP on respiratory function, gas exchange and hemodynamic function. Their results show a relatively small effect of modestly elevated IAP on these variables in their patient population. However, their work raises several questions for clinicians and researchers regarding the pathophysiology and management of IAP.