Noninvasive Quantitative Assessment of Pulmonary Blood Flow with ¹⁸F-FDG PET

Abstract

Pulmonary blood flow (PBF) is a critical determinant of oxygenation during acute lung injury (ALI). PET/CT with 18 F-FDG allows the assessment of both lung aeration and neutrophil inflammation as well as an estimation of the regional fraction of blood (FB) if compartmental modeling is used to quantify 18 F-FDG pulmonary uptake. The aim of this study was to validate the use of FB to assess PBF, with PET and compartmental modeling of 15 O-H 2 O kinetics as a reference method, in both control animals and animals with ALI. For the purpose of studying a wide range of PBF values, supine and prone positions and various positive end-expiratory pressures (PEEPs) and tidal volumes (V T s) were selected. Methods: Pigs were randomized into 3 groups in which ALI was induced by HCl inhalation: pigs studied in the supine position with a low PEEP (5 6 3 [mean 6 SD] cm of H 2 O; n 5 9) or a high PEEP (12 6 1 cm of H 2 O; n 5 8) and pigs studied in the prone position with a low PEEP (6 6 3 cm of H 2 O; n 5 9). Also included were a control group that did not have ALI (n 5 6) and 2 additional groups (n 5 6 each) that had a high V T to maintain a transpulmonary pressure of greater than or equal to 35 cm of H 2 O and that either received HCl inhalation or did not receive HCl inhalation. PBF and FB were measured with PET and compartmental modeling of 15 O-H 2 O and 18 F-FDG kinetics in 10 lung regions along the anterior-to-posterior lung dimension, and both were expressed in each region as a fraction of their values in the whole lung. Results: PBF and FB were strongly correlated (R 2 5 0.9), with a slope of the regression line close to unity and a negligible intercept. The mean difference between PBF and FB was 0, and the 95% limits of agreement were 20.035 to 0.035. This good agreement between methods was obtained in both normal and injured lungs and under a wide range of V T , PEEP, and regional PBF values (7-71 mL/kg, 0-15 cm of H 2 O, and 24-603 mLÁ min 21 Á100 mL of lung 21 , respectively). Conclusion: FB assessed with 18 F-FDG is a good surrogate for PBF in both normal animals and animals with ALI. PET/CT has the potential to be used to study ventilation, perfusion, and lung inflammation with a single tracer.

Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary 18F-FDG Kinetics, Vascular Transit Times, and Perfusion

“…This discrepancy could be related to the underestimation of blood volume by Pouzot et al in consequence of their non-consideration of the delay, as shown in the current work, and supports the relevance of considering a delay for improved physiological description. Contrary to the suggestion of Pouzot et al that pulmonary transit times are homogeneous throughout the lungs, 26 regional pulmonary vascular delays in our study were highly heterogeneous, in agreement with numerous previous studies on the distributions of pulmonary capillary transit times. 3, 27, 40, 41 Overall, these findings suggest that while blood volume may be correlated with perfusion in most lung conditions, more accurate quantification of perfusion can be achieved by additionally accounting for regional transit times, according to Equation 4.…”

“…Fuld et al also observed the presence of a positive intercept of blood volume for zero flow using CT-based measurements of pulmonary blood flow and blood volume. 10 In contrast, Pouzot et al found a negligible intercept when comparing 18 F-FDG derived blood volume with 15 O-H 2 O perfusion, 26 which is inconsistent with that physiological principle of mean circulatory filling pressure. This discrepancy could be related to the underestimation of blood volume by Pouzot et al in consequence of their non-consideration of the delay, as shown in the current work, and supports the relevance of considering a delay for improved physiological description.…”

“…For example, the parameter blood volume (F B ), for which we found a small but systematic underestimation when the input function delay was ignored, was recently proposed by Pouzot et al as a useful surrogate for regional perfusion. 26 However, because their method only estimates relative and not absolute perfusion, and the F B values between the models were highly correlated (r=0.99), the incorporation of the input function delay in their approach may not afford any improvement in precision. Importantly, we found no major differences between models in the parameters K i , F e , and k 3 , which have been used in several studies to assess regional inflammatory cell activity.…”

“…4, 26, 33 We developed a modified version of this model (i.e., the delayed input function model; Fig. 1) wherein the local lung plasma concentration (C p [t]) is represented by a delayed version of the image-derived plasma function measured in the right heart (C RH [t-t delay ]) and calibrated with manual samples, as previously described.…”

“…6, 15, 18, 23, 31 Several analytical methods, including the Patlak analysis, 25 Sokoloff model, 36 and four-compartment model, 32 have been applied to quantify 18 F-FDG transport and trapping within lung tissue. Current techniques for defining the lung plasma input function that is required for these models include manual sampling of blood in the pulmonary artery 4 or systemic artery, 26 and imaging of a region-of-interest characterizing the right heart blood pool with calibration using manual samples. 33 …”