Using the dynamic scanning data, pulmonary vascular leakiness was assessed by LI, which is the exponential equilibration coefficient of Ga-circulating transferrin between the intravas-cular and pulmonary interstitial compartments. Our deliberate choice of Ga as a leak marker, instead of mIn-transferrin used in our earlier study, was our intent to examine nearly simultaneously the relationship between pulmonary Ga uptake and vascular leakiness. In addition, Raijmakers et al had reported the successful in vivo use of transferrin labeling with Ga to study changes in pulmonary vascular leakiness. The yield of protein-bound Ga in plasma using the trichlolacetate method was > 98%.
Time activity curves were determined by a computer system for region of interests (ROIs) with a 5 X 5 pixel size, including the heart, the upper, middle and lower lung fields, bilaterally, and the left shoulder for background. The maximum counts obtained from the lung and heart ROIs were approximately 7,500 counts per minute and 15,000 counts per minute, respectively (Fig 1).
In Figure 2, left, the shaded area between the curves represents the accumulation of Ga in the pulmonary interstitium. L(t) represents the external gamma count for Ga in the total lung, and V(t) represents the amount in the pulmonary vasculature. The slopes of L(t) and V(t) were calculated by the external gamma counts in the lung and heart ROIs, respectively, between time 7 min and time 30 min. The decay of the gamma counts in the heart ROI corresponds to the loss of Ga from the pulmonary plasma compartment. The gamma decay in the lung ROI corresponds to the same loss but is lessened by the accumulation of Ga in the pulmonary interstitium. Figure 2, right, shows the increasing concentration of Ga in the pulmonary interstitium (bottom line), which is derived from the shaded area in the left panel, assuming that the interstitial volume/plasma volume ratio is 1.0, according to the data of Staub. This concentration is expressed relative to the plasma concentration of Ga (upper line). The plasma concentration minus the interstitial concentration represents the concentration gradient across the pulmonary endothelium (dashed line). The decay of this curve expresses the equilibration rate between lung interstitial Ga and lung plasma Ga. The exponential equilibration coefficient of this curve was calculated as LI. LI was calculated for the ROIs of each lung, and the average LI was calculated from these six ROIs as representative data for each individual.
Quantitative Assessment of Pulmonary Ga Uptake
Pulmonary Ga uptake was expressed as a gallium index, calculated according to the method described by Wesselius et al Gallium index was determined using the static images obtained 48 h after Ga injection and ROI analysis. By adjusting the liver image, the ROIs used for LI estimation were superimposed on the static images. The liver ROI was set at the middle of the right lobe, and the background ROI was set at the left shoulder. The mean gallium index was calculated as representative data for each study participant. The gallium index for each lung ROI (six ROIs for each patient) was calculated by the formula:
Data were expressed as mean ± SEM. Student’s t test was used for between-groups comparisons. Correlation between leak index and gallium index was examined by simple regression test. A p value < 0.05 was considered significant.
Figure 1. External gamma counts data in the heart and lung ROIs from a patient with IP. The difference in slope of time decay curve in lung vs heart ROI after Ga citrate injection is due to the accumulation of Ga in lung interstitium. CPM = counts per minute.
Figure 2. Schematic presentation of the vascular permeability assessment. L(t) = external gamma count for Ga in the total lung; V(t) = amount in the pulmonary vasculature.