Imaging the Mouse Lung with Micro-CT

Wolfgang Recheis; Geoffrey McLennan; Alan F Ross

doi:10.1201/b14270-11

I. Introduction 136 II. Technical Principals and Overview of Micro-CT 137 A. Micro-CT Introduction 138 B. Micro-Focal Sources of X-ray Production 140 C. Filters 140 D. Some Detector Characteristics 143 E. Comments on Dose Exposure 145 F. Resolution of the Systems 146 G. Tomographic Reconstruction 147 H. Ring Artifact Reduction 148 I. Beam Hardening 149 J. Hounsfield Unit Calibration 151 K. Commercially Available Systems 151 III. Small Animal Lung Imaging 152 A. Optimized In Situ and In Vivo Mouse Lung Protocol 154 In Situ Scanning Protocols 154 In Vivo Scanning Protocols 156 B. Examination of Lung Tissue Samples from Larger Animals 156 C. Dynamic Imaging: Microfluoroscopy Coupled to Micro-CT 158 D. Conclusions 163 References 166 I. Introduction Computed tomography (CT) of the lung has made major advances in hardware and software over the last decade. The human lung can now be imaged rapidly and volumetrically, with digital information easily transported, stored, reviewed, and then both subjectively and objectively analyzed (1,2). Figure 6.1 depicts examples that span anatomic segmentation (3-8), automatic labeling (9), image based lung modeling (10,11), ventilation (12,13) and perfusion imaging (14,15), a morpho- metric correlation to in vivo imaging (16), and a large animal model of evolving lung inflammation. In large animal models, functional imaging demonstrates early changes in pathology (17). Our methods demonstrate that measures of both structure and function provide early signs of pathologic processes (2). Still, there remains a need to correlate pathologic phenotypes with genotypes and to pheno- type diversity at the alveolar/bronchiolar and arteriolar levels in vivo and in situ. It is our view that micro-CT will have a profound influence on the docu- mentation of anatomical and physiological phenotypic changes in many genetic mouse models. The mapping of the human genome, together with that of other animals and plants, is providing an enormous amount of new infor- mation, the full extent of which will still emerge over the next several decades. The mouse has become the prototypic animal model for the study of genetic based diseases. Frequently, however, abnormalities are noted within the animals, beyond the specifically induced biological defect or outside the tar- geted organ. Thus, the full phenotype of these animals may include a variety of unexpected anatomical and physiological abnormalities, in addition to biochemi- cal and genetic changes. Describing these abnormalities fully is critical to under- standing the complex interaction of different genetic influences. Although individual animals are relatively inexpensive, the cost of developing a model can be very significant. This expense is amplified when animals must be sacri- ficed and studied at multiple time points during growth or during the development of a disease. Determining such time points is somewhat arbitrary, and important information may not be recorded if complete observations are not made. Micro- CT scanning will allow numerous experiments in mouse models to be planned with greater precision. The cost of exploring the complex phenotypic expression of genetic changes will be reduced, and longitudinal studies will be greatly facili- tated by allowing a more complete and accurate description of events. As shown in Fig. 6.2, mouse imaging using conventional CT scanners lacks the spatial resolution needed. To maximize the potential of micro-CT to quantitatively evaluate the mouse lung, imaging protocols, reconstruction algorithms, and image analysis methods all must be established and specifically tailored to in vivo, in situ, and ex vivo imaging of lung tissue.

Imaging the Mouse Lung with Micro-CT

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