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Lung diseases such as cancer substantially alter the mechanical properties of the organ with direct impact on the development, progression, diagnosis, and treatment response of diseases. Despite significant interest in the lung’s material properties, measuring the stiffness of intact lungs at sub-alveolar resolution has not been possible. Recently, we developed the crystal ribcage to image functioning lungs at optical resolution while controlling physiological parameters such as air pressure. Here, we introduce a data-driven, multiscale network model that takes images of the lung at different distending pressures, acquired via the crystal ribcage, and produces corresponding absolute stiffness maps. Following validation, we report absolute stiffness maps of the functioning lung at microscale resolution in health and disease. For representative images of a healthy lung and a lung with primary cancer, we find that while the lung exhibits significant stiffness heterogeneity at the microscale, primary tumors introduce even greater heterogeneity into the lung’s microenvironment. Additionally, we observe that while the healthy alveoli exhibit strain-stiffening of ∼1.75 times, the tumor’s stiffness increases by a factor of six across the range of measured transpulmonary pressures. While the tumor stiffness is 1.4 times the lung stiffness at a transpulmonary pressure of three cmH2O, the tumor’s mean stiffness is nearly five times greater than that of the surrounding tissue at a transpulmonary pressure of 18 cmH2O. Finally, we report that the variance in both strain and stiffness increases with transpulmonary pressure in both the healthy and cancerous lungs. Our new method allows quantitative assessment of disease-induced stiffness changes in the alveoli with implications for mechanotransduction.
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On the variability and dependence of human leg stiffness across strides during running and some consequences for the analysis of locomotion data
Typically, animal locomotion studies involve consecutive strides, which are frequently assumed to be independent with parameters that do not vary across strides. This assumption is often not tested. However, failing in particular to account for dependence across strides may cause an incorrect estimate of the uncertainty of the measurements and thereby lead to either missing (overestimating variance) or over-evaluating (underestimating variance) biological signals. In turn, this impacts replicability of the results because variability is accounted for differently across experiments. In this paper, we analyse the changes of a couple of measures of human leg stiffness across strides during running experiments, using a publicly available dataset. A major finding of this analysis is that the time series of these measurements of stiffness show autocorrelation even at large lags and so there is dependence between individual strides, even when separated by many intervening strides. Our results question the practice in biomechanics research of using each stride as an independent observation or of sub-selecting strides at small lags. Following the outcome of our analysis, we strongly recommend caution in doing so without first confirming the independence of the measurements across strides and without confirming that sub-selection does not produce spurious results.
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- PAR ID:
- 10447184
- Publisher / Repository:
- Royal Society Open Science
- Date Published:
- Journal Name:
- Royal Society Open Science
- Volume:
- 10
- Issue:
- 8
- ISSN:
- 2054-5703
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1098/rsos.230597
