Preclinical Four-Dimensional Functional Lung Imaging and Quantification of Regional Airflow: A New Standard in Lung Function Evaluation in Murine Models

Regional variations in allergen‐induced airway inflammation correspond to changes in soluble guanylyl cyclase heme and expression of heme oxygenase‐1

“…Mouse lung tissue lysates generated from all the 14 segments of a mouse lung were run on SDS‐PAGE and western blotted with specific antibodies as depicted. (A) Lobar segmentation [adapted from Asosingh et al 7 …”

“…Studies can also aim to generate an algorithm using AI to list the distribution of specific molecular fingerprints of inflammation for lung segments in murine asthma models. Moreover, using murine asthma models, establishing a similar analysis of correlating molecular markers of inflammation in the various lung segments with lung ventilation data obtained from 4‐dimensional lung imaging scans 7 will lead to an enhanced understanding of the disease pathogenesis of asthma. This will also indicate which inflamed lung segments have the worst lung ventilation and thus can be effectively targeted for therapies 20 .…”

“…2,5 The molecular underpinnings associated with such inflammatory changes are incompletely understood, and studying these aspects would allow us to better understand the inherent drivers of these processes. Using translational models of mouse asthma, 6 it is possible to study the distribution of inflammation in all segments 7 of the asthma lungs with the ultimate aim to improve patient treatments and evaluate potential therapies.…”

“…However, sGC becomes dysfunctional in allergic asthma due to it becoming heme‐free on account of excess NO generated from iNOS upregulation during lung inflammation, which makes the epithelia lung hemoglobin (Hb) heme‐free, 19 thereby making it unable to scavenge this excess NO and in turn exposing the underlying smooth muscle sGC to excess NO, triggering its dysfunction 19,20 . In order to understand whether such a sGC dysfunction is associated with inflammation, which is either localized or globally distributed in an asthma lung, we resorted to connect the inflammatory regions to sGC dysfunction using lungs from murine models of asthma (ovalbumin [OVA] or complete Freund's adjuvant/house dust mite [CFA/HDM]) that underwent lobar segmentation into 14 lung segments 7 . The overall objective of the present study was to monitor the dynamics of inflammatory changes taking place in an asthmatic mouse lung and determine (i) the extent of localized inflammation, (ii) whether localized inflammatory regions can be correlated with sGC dysfunction by determining the heme status of the sGC in such areas of inflammation, (iii) whether such inflammatory areas can be tracked with molecular indicators of inflammation, and (iv) whether such regions in turn have increased iNOS activity since high NO levels have been shown to cause sGC dysfunction in asthma.…”

Findings on High Resolution Computed Tomography in Symptomatic Veterans with Deployment-Related Lung Disease

“…In conclusion, given the limitations of HRCT visual assessment for detection of DDLD observed in this cohort, along with cost and radiation dose, alternative approaches to diagnosis may be needed. Techniques such as quantitative image analysis of airway wall thickening and emphysema 37 and functional lung imaging for ventilation inhomogeneity 38 may be more sensitive than visual assessment of HRCT in detecting distal airways abnormalities. Other modalities such as lung clearance index testing, separately or in combination with quantitative image analysis, may enhance diagnostic sensitivity 39 and await further investigation.…”