Validation of the X-ray microtomography in the assessment of duodenal morphometry and surface area in celiac disease.

Background: Duodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas. Methods: Endoscopic biopsies from 58 individuals were utilized for the micro-CT imaging, selecting histological changes ranging from normal to severely damaged mucosa. The imaging protocol was optimized for practicability and resolution. The Bland-Altman method was applied to test intra- and interobserver variations in the blinded measurements. Results: The 3D micro-CT reconstructions enabled easy and precise digital cutting with optimal orientation and computer-assisted measurement of the surface area. Intraobserver analysis of morphological measurements showed a mean difference of 0.011 with limits of agreement (LA) from -0.397 to 0.375 and a standard deviation (SD) of 0.197. The corresponding figures for interobserver analysis were 0.080, from -0.719 to 0.537 and 0.320, respectively. The intraclass correlation coefficients (ICC) for the intraobserver and interobserver variations were 0.981 and 0.954, respectively. Intraobserver surface area analysis yielded a mean difference of 0.010, LA from -0.764 to 0.785 and an SD of 0.395, and an interobserver analysis mean difference of 0.028, LA from -0.642 to 0.698 and SD of 0.342. The respective ICCs for the intra- and interobserver variations were 0.963 and 0.972. Conclusions: Micro-CT showed excellent accuracy and reproducibility in the evaluation of mucosal morphometry and surface areas. The improved sensitivity for histological changes is a powerful tool for the diagnosis of celiac disease and for clinical and pharmacological studies.

X-ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area.

The often poorly orientated small-bowel mucosal biopsies taken for the diagnostics of celiac disease and other intestinal disorders are prone to misinterpretation. Furthermore, conventional histopathology has suboptimal sensitivity for early histopathological changes observed in short-term challenge studies. X-ray microtomography (micro-CT) is a promising new method for accurate imaging of human-derived biological samples. Here, we report that micro-CT could be utilized to create virtual reconstructions of endoscopically obtained intestinal biopsies. The formed digital 3D images enabled selection of always optimal cutting angles for accurate measurement of the mucosal damage and revealed diagnostic lesions in cases interpreted as normal with conventional histomorphometry. We also demonstrate that computer-assisted point cloud analysis can be used to calculate biologically meaningful surface areas of the biopsies in different stages of mucosal damage with excellent replicability and correlation with other disease parameters. We expect the improved diagnostic accuracy and capability to measure the surface areas to provide a powerful tool for the diagnostics of intestinal diseases and for future clinical and pharmaceutical trials.