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A correction to the article "New Imaging Approaches for Understanding Lung Cancer Response to Treatment" that was published in the September 2008 issue is presented.

The change in alveolar size and number during the full breathing cycle in mammals remains unanswered, yet these descriptors are fundamental for understanding alveolar-based diseases and for improving ventilator management. Genetic and environmental mouse models are used increasingly to evaluate the evolution of disease in the peripheral lung; however, little is known regarding alveolar structure and function in the fresh, intact lung. Therefore, we have developed an optical confocal process to evaluate alveolar dynamics in the fresh intact mouse lung and as an initial experiment, have evaluated mouse alveolar dynamics during a single respiratory cycle immediately after passive lung deflation. We observe that alveoli become smaller and more numerous at the end of inspiration, and propose that this is direct evidence for alveolar recruitment in the mouse lung. The findings reported support a new hypothesis that requires recruitable secondary (daughter) alveoli to inflate via primary (mother) alveoli rather than from a conducting airway.

Three-dimensional, structural and functional digital image databases have many applications in education, research, and clinical medicine. However, to date, apart from cryosectioning, there have been no reliable means to obtain whole-organ, spatially conserving histology. Our aim was to generate a system capable of acquiring high-resolution images, featuring microscopic detail that could still be spatially correlated to the whole organ. To fulfill these objectives required the construction of a system physically capable of creating very fine whole-organ sections and collecting high-magnification and resolution digital images. We therefore designed a large image microscope array (LIMA) to serially section and image entire unembedded organs while maintaining the structural integrity of the tissue. The LIMA consists of several integrated components: a novel large-blade vibrating microtome, a 1.3 megapixel peltier cooled charge-coupled device camera, a high-magnification microscope, and a three axis gantry above the microtome. A custom control program was developed to automate the entire sectioning and automated raster-scan imaging sequence. The system is capable of sectioning unembedded soft tissue down to a thickness of 40 microm at specimen dimensions of 200 x 300 mm to a total depth of 350 mm. The LIMA system has been tested on fixed lung from sheep and mice, resulting in large high-quality image data sets, with minimal distinguishable disturbance in the delicate alveolar structures., (Copyright 2007 Wiley-Liss, Inc.)

Pulmonary emphysema is usually the result of chronic exposure to cigarette smoke in at risk individuals. To investigate the hypothesis that lung damage in emphysema results from coincident weakening in the structural properties of the tissue and increased mechanical forces--as one explanation of the continued development of pulmonary emphysema after smoking cessation--we developed a three dimensional, geometric dodecahedron-based acinar model. Using the model numerical analysis of the stress distribution in normal conditions could be compared with those resulting in emphysematous conditions. Finite element analysis was used to evaluate the model at a number of lung inflation levels, using quasi-static loading of the alveolar pressure. When internal alveolar pressure was increased along with the adjustment of the material properties to represent a weakening of one wall in the acinus, increased stress resulted at the perimeters of the weakened area. In particular this increased stress was localized at the junction points of the internal alveolar septa. It was also found that under the proposed simulated emphysematous conditions, a significant disruption in the stress distribution within the acinus model occurred at low, rather than high, lung volumes. This is supportive of the physiological observation that destruction of the diseased tissue can occur under less stress than those existing in the normal state.

Respiratory research with mice using micro-computed tomography (micro-CT) has been predominantly hindered by the limited resolution and signal-to-noise ratio (SNR) as a result of respiratory motion artefacts. In this study, we develop a novel technique for capturing the lung microstructure in vivo using micro-CT, through a computer-controlled intermittent iso-pressure breath hold (IIBH), to reduce respiratory motion, increasing resolution and SNR of reconstructed images. We compare four gating techniques, i.e. no gating, late expiratory (LE) gating, late inspiratory (LI) gating and finally intermittent iso-pressure breath hold (IIBH) gating. Quantitatively, we compare several common image analysis methods used to extract valuable physiologic and anatomic information from the respiratory system, and show that the IIBH technique produces the most representative and repeatable results.