Parameter estimation and confidence intervals for Xe-CT ventilation studies: a Monte Carlo approach

Abstract

Xenon-enhanced computed tomography (Xe-CT) is a technique for the noninvasive measurement of regional pulmonary ventilation from the washin and/or washout time constants of radiodense stable xenon gas, determined from serial computed tomography scans. Although the measurement itself is straightforward, there is a need for methods for the estimation of variability and confidence intervals so that the statistical significance of the information obtained may be evaluated, particularly since obtaining repeated measurements is often not practical. We present a Monte Carlo (MC) approach to determine the 95% confidence interval (CI) for any given measurement. This MC method was characterized in terms of its unbiasedness and coverage of the CI. In addition, 10 identical Xe-CT ventilation runs were performed in an anesthetized dog, and the time constant was determined for several regions of varying size in each run. The 95% CI, estimated from these repeated measurements as the mean +/- 2 x SE, compared favorably with the CI obtained by the MC approach. Finally, a simulation was performed to compare the performance of three imaging protocols in estimating model parameters.

Effect of low-xenon and krypton supplementation on signal/noise of regional CT-based ventilation measurements

“…Because data from multiple ROIs from the same images are correlated in an unknown way, traditional descriptive statistical measures may underestimate their variance (33). We estimated CIs about individual ROI parameter estimates using a Monte Carlo (MC) simulation, as previously described (33).…”

“…The 95% CI is determined by the time constant values at the 2.5th and 97.5th percentiles of the ordered results from the simulation. These CIs are conveniently expressed analogous as the CV (CV*), corresponding to one-half of the 95% CI/mean, to correct for differences in the means (33). Then increases in the CV* reflect wider CIs for individual measurements and indicate a loss of ability to detect regional differences.…”

“…Noise, modeled as a stochastic term in MC simulation, can be caused by multiple real sources: for example, lung motion during breathing, which can change the endexpiratory or end-inspiratory volume and lead to a change in tissue components in the ROIs; cardiac motion, which can have an influence on the lung tissue density by adjacent parenchymal motion or changes in pulmonary blood volume; and interscan variation in CT number in the ROI due to the measurement error within the scanner (23). Following Simon et al (33), we simulated a Gaussian-distributed noise component to add a stochastic term to the D 0 . The authors reported that noise was normally distributed (P ϭ 0.338) by performing the Shapiro-Wilks test for normality.…”

“…Stable (nonradioactive) Xe gas has a K-edge similar to that of iodine and is a potent X-ray attenuator, providing good contrast enhancement when used in conjunction with CT scanning (42). When imaged in a conventional CT scanner, lung attenuation varies linearly with the Xe concentration ([Xe]) in the air spaces (9), and the time course of Xe accumulation in the lung periphery during breathing, measured with serial CT images, is the basis for the Xe-CT measurement of regional ventilation (4,33).…”

Functional Imaging: CT and MRI

“…Little work had been done since the original description of this technique nearly twenty five years ago (97-100), although the FDA approval of Xe-MDCT for measurement of cerebral blood flow has met with moderate clinical acceptance (101). Recently, however, the application of Xe-MDCT for measurement of regional pulmonary ventilation has been updated, validated, and refined including extension of the technique to estimate regional perfusion and V/Q (28,(102)(103)(104)(105)(106)(107)(108)(109)(110)(111) In Figure 3, we demonstrate a typical Xenon wash-in wash-out attenuation curve in a sheep, along with a color coded image of regional ventilation. Scanning was accomplished through gated imaging (endexpiration) as a fixed concentration of Xenon gas was inspired during the wash-in phase and then room air was inspired during wash-out.…”