Micro-Computed Tomography of the Lungs and Pulmonary-Vascular System

Abstract

Three-dimensional imaging of the intact lung and its vasculature is essential if the hierarchical and volumetric aspects of its structures and functions are to be quantitated. Although this is possible with clinical multislice helical CT scanners, the spatial resolution does not scale down adequately for small rodents for which cubic voxel dimensions of 50-100 m are required. Micro-computed tomography (micro-CT) provides the necessary spatial resolution of 3D images of the intact thoracic contents. Micro-CT can provide higher resolution so that basic micro-architectural structures, such as alveoli, can be individually visualized and quantitated. Dynamic events, such as the respiratory and cardiac cycles, can be imaged at multiple time points throughout a representative cycle by coordinating the scan sequence (i.e., gating) to the cycle phase of a sequence of cycles. Fusion of the micro-CT image data with other image data, such as micro-SPECT or histology, can enhance the information content beyond the mainly structural information provided by micro-CT. Conventional attenuation-based X-ray imaging can involve significant X-ray exposures at high spatial resolutions, and this could affect the phenotype (e.g., via interstitial fibrosis) and genotype (e.g., via mutation), so its use in longitudinal studies using micro-CT may be limited in some cases. However, because of recent developments in which the phase shift or refraction of X-rays rather than attenuation is used, the X-ray exposure may be significantly reduced.Keywords: microarchitecture; pulmonary hypertension; alveoli; airways Micro-computed tomography (micro-CT) is a rapidly developing imaging capability that has been described in detail elsewhere (1). This development is driven in large measure by the fact that because mice are rapidly becoming the experimental animals of choice for many research endeavors, there is motivation to scale clinical imaging capabilities down to the mouse level. There are several aspects to the scaling of the spatial and temporal resolution and volume scanned (2). One is to scale so as to generate a transaxial tomographic image equivalent to a clinical scan. Thus, with clinical multislice helical scanning, CT of the thorax generates 3D images that are approximately 300 to 400 mm in transverse diameter and are made up of voxels (a 3D picture-element or pixel) ‫ف‬ 1 mm 3 in volume. A "mini" CT scanner that is scaled to a proportional voxel resolution in a mouse (with a 20 mm thoracic diameter) would involve voxels ‫ف‬ 75 m in diameter. The mouse's lungs have a combined volume of about 1.3 cm 3 ; therefore, in the mouse a 3D volume of at least 2 cm 3 must be imaged to capture the entire lung. How- ever, the mouse heart and respiratory rate are much higher than in humans, so cardio-respiratory dynamic processes are much more difficult to image in mice than in humans (3) because the micro-CT scan durations are generally limited by the rate of X-ray production. If microscopic structures are to be imaged with micro-CT, image resolution...

Lung structure phenotype variation in inbred mouse strains revealed through in vivo micro-CT imaging

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High resolution tomographic imaging of the alveolar region of the mammalian lung

“…In contrast to TEM and SEM, Computed Tomography (CT) offers a nondestructive insight into the lung Relatively low resolution micro-Computed Tomography (µCT) enables the study of the major airways of swine [79], rat [136,137] or mice lung [115,138]. Ultrahigh resolution Synchrotron Radiation based X-ray Tomographic Microscopy (SRXTM) enables the study of the functional units of the pulmonary gas exchange area, the so-called acini with unmatched resolution and precision [19,139].…”

High-Resolution CT for Small-Animal Imaging Research

“…However, pulmonary micro-CT imaging in small animals has been challenging, due to the small size and rapid respiratory motion. As shown by Ritman (2005), a micro-CT voxel size on the order of 75 mm is required to provide anatomic resolution in the mouse comparable to that obtained in CT for humans. Nonetheless, micro-CT can be used successfully to study various lung disease models, such as emphysema and fibrosis.…”