In this study, we performed a quantitative analysis to compare regional characteristics of lung functions between the SP and PP by using image registration applied to matched pairs of inspiratory and expiratory CT scans. We derived functional CT metrics by quantifying lung deformation and computed the regional tissue deformation and mechanics on a lobar basis. This study visualized that PP induced more uniform contributions of regional lung ventilation on RRAVC maps and a shift of 3D s* toward anterior regions on the 3D motionography. We calculated the ratio of functional measures in each lobe and found that the PP minimized the lobar differences in lung functions.
In several previous studies, researchers attempted to develop a hypothesis of homogeneous ventilation in the PP by using density-based CT analysis. Studies with standard CT volumetry showed that the vertical gradient CT density was attenuated when patients with ARDS were in PP [10, 26], and the cephalocaudal gradient was reduced in experimental animal models . These results indicate that the PP induces a more uniform distribution of gas and tissue by reducing anteroposterior and cephalocaudal gradients. Other studies showed that the volume of overinflated lung mass decreased, whereas the volume of nonaerated or poorly aerated lung mass increased in the PP, which suggests that lung recruitment and homogeneity were enhanced in the PP [15, 25]. In this study, we computed tissue fractions (TFIN and TFEX) rather than the CT density-based volumetry to quantify the regional homogeneity.
The present study demonstrates that, in the PP, TFIN and TFEX were increased in the right middle lobe but decreased in the lower lobes in the PP (P < 0.05; Table 1). In addition, UM/L ratios of TFIN and TFEX were all near unity in the PP, and were significantly greater than those in the SP (P < 1.0 ⋅ 10− 7). These findings corroborate the previous results from density-based CT volumetry studies with regard to homogeneity in the PP. This improvement in ventilatory homogeneity in ARDS leads to a decrease in the shunt fraction [5, 6], and in approximately 70% of patients, ventilation-perfusion mismatching and oxygenation were markedly improved in the PP [5, 6]. However, improvement in oxygenation in the PP does not fully explain the decreased mortality of ARDS . Thus, the survival benefit observed with the PP is assumed to be more related to a protective effect against VALI [12, 31]. Indeed, recent data indicate that the paradigm of ARDS management has shifted from improving gas exchange to minimizing VALI and ensuring lung protection .
ARDS is characterized by a massive loss of lung aeration for tidal ventilation, which predominates in dorsal regions in the SP . Hence, the mechanical distortion and regional overdistension caused by tidal ventilation develop in “ventral aerated lungs” in the SP, which is the most important determinant of VALI . The PP has been reported to delay and attenuate the progression of VALI in animal studies [16, 31], and a CT volumetric study in patients with ARDS also revealed that PP was an effective lung protective strategy that could possibly alleviate VALI . However, these studies did not provide evidence of CT metrics with regard to reduced strain in the PP. A more recent experimental study with inspiratory and expiratory CT scans revealed that the PP alleviated lung injury by minimizing the patterns with suboptimal aeration and large tidal swings (termed “unstable inflation”) . The investigators employed parametric response maps, which have an advantage of spatial localization compared with simple density maps, and can depict regional heterogeneity. However, simple density difference measures are confounded by the effect of the baseline inflation of the target lung region. Therefore, we used the functional CT metrics of regional ventilation and tissue mechanics including s*, J, and RRAVC, which enable us to detect additional heterogeneity of lung strain and stress over CT density map [18, 36].
Our results showed that UM/L and U/ML ratios of RRAVC and J were all near unity in the PP and significantly higher in the PP than in the SP (Ps < 0.001; Table 2). Moreover, the regional displacement gradient was reduced and shifted toward the anterior regions in the PP (Fig. 3). Because the loss of lung aeration is distributed mainly in the dorsal and caudal lungs in the SP [37, 38], these results together suggest that regional differences in strain between lung regions are reduced in the PP. Given that it is a crucial step to decrease lung strain in ARDS to prevent VALI, the PP could be an effective strategy of recruiting nonaerated lung and preventing overinflation. Nonetheless, the PP has been shown to be effective and is recommended in only severe ARDS [8, 39]. It is speculated that the PP benefits more hypoxemic patients with ARDS, who have more severe and heterogeneous lung injury and greater ventilation–perfusion mismatch. However, with increasing understanding of the heterogeneous pathophysiology of ARDS, identifying patients who will most benefit from the PP remains elusive . Recently, lung morphology, assessed by CT images, has been suggested as a predictor of benefit from the PP, which indicates that focal ARDS is more likely to respond to the PP than is diffuse ARDS [15, 40]. Of note was that a lobar analysis in our study showed a trend for RRAVC and J to increase in the right middle and upper lobes and to decrease in the lower lobes in the PP (Table 3). Moreover, our study included the 3D motionography and mapping of the regional lung homogeneity and strain. In the real-life clinical practice for ARDS, lung morphology assessments are not readily available and frequently misclassified , and so the visual information provided in this study could serve as a surrogate to apply personalized PP therapy in patients with focal or patchy ARDS.
Interestingly, according to a recent study of patients with coronavirus 2019 (COVID-19) associated ARDS, alternating body position between the SP and PP increased lung recruitability; while in a majority of patients, the lungs were poorly recruitable with high positive end-expiratory pressure . Of hospitalized patients with COVID-19 pneumonia, 17–41% develop ARDS[42–44], and the majority of COVID-19 deaths occur among the patients with ARDS. In COVID-19 associated ARDS, lung mechanics are relatively preserved compared to severe hypoxemia  and CT findings show bilateral and multilobar ground glass opacity with subsegmental consolidative opacities . In this context, our 3D regional ventilation map and motionography in healthy subjects might be helpful to guide the decision to apply PP in patients with COVID-19 associated ARDS.
This study had some limitations that need to be considered. First, a comparison of CT measures between the SP and PP was performed mostly in different subjects. Thus, intersubject variability may have affected CT measures. However, we included only subjects with normal lungs. In addition, the distributions of specific volume change and density have been demonstrated to be more homogeneous in healthy subjects than in patients with lung disease . Second, this quantitative analysis was in healthy subjects with normal lungs, not in patients with ARDS. Unlike healthy lungs, ARDS presents severe and heterogeneous lung injury, and the extent of lung inhomogeneities is increased with the severity of ARDS . Hence, the effect of CT metrics extracted from homogeneous normal lungs could be different in heterogeneous ARDS with impaired lung mechanics. Indeed, the PP is known to be effective only in severe ARDS, and identifying patients who would most benefit from the PP remains a clinical challenge . Therefore, further research into the comparison of these regional ventilation and lung mechanics between the SP and PP in ARDS is warranted.