PDF(Pubmed)
Abstract：
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.
摘要：
肺癌等肺部疾病会显著改变器官的机械特性，直接影响发育，programming,诊断,和疾病的治疗反应。尽管人们对肺的材料特性非常感兴趣，在肺泡下分辨率下测量完整肺的硬度是不可能的。最近,我们开发了晶体胸腔，以光学分辨率成像功能的肺，同时控制生理参数，如气压。这里,我们引入了数据驱动，在不同膨胀压力下拍摄肺部图像的多尺度网络模型，通过水晶胸腔获得，并生成相应的绝对刚度图。验证后，我们报告了健康和疾病中功能正常的肺的微观分辨率的绝对刚度图.对于健康肺和患有原发性癌症的肺的代表性图像，我们发现，虽然肺在微观尺度上表现出显著的硬度异质性，原发性肿瘤在肺的微环境中引入更大的异质性。此外,我们观察到，虽然健康的肺泡表现出75倍的应变硬化，在测量的经肺压力范围内，肿瘤的硬度增加了六倍。虽然在3cmH2O的经肺压力下，肿瘤硬度是肺硬度的1.4倍，在18cmH2O的经肺压力下，肿瘤的平均硬度几乎是周围组织的5倍。最后,我们报告说，在健康肺和癌性肺中，应变和僵硬度的变化都随着经肺压力的增加而增加。我们的新方法可以定量评估疾病引起的肺泡硬度变化，并对机械传导产生影响。
