A framework for 3D vessel analysis using whole slide images of liver tissue sections

Three-dimensional (3D) high resolution microscopic images have high potential for improving the understanding of both normal and disease processes where structural changes or spatial relationship of disease features are significant. In this paper, we develop a complete framework applicable to 3D pathology analytical imaging, with an application to whole slide images of sequential liver slices for 3D vessel structure analysis. The analysis workflow consists of image registration, segmentation, vessel cross-section association, interpolation, and volumetric rendering. To identify biologically-meaningful correspondence across adjacent slides, we formulate a similarity function for four association cases. The optimal solution is then obtained by constrained Integer Programming. We quantitatively and qualitatively compare our vessel reconstruction results with human annotations. Validation results indicate a satisfactory concordance as measured both by region-based and distance-based metrics. These results demonstrate a promising 3D vessel analysis framework for whole slide images of liver tissue sections

Histological 3D reconstruction and in vivo lineage tracing of the human endometrium

Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher‐order primates. The current consensus postulates endometrial glands to have a single‐tubular architecture, where multi‐potential stem cells reside in the blind‐ending glandular‐bases. Utilising fixed samples from patients, we have studied the three‐dimensional (3D) micro‐architecture of the human endometrium. We demonstrate that some non‐branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated by in vivo lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem‐cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar‐less regenerative potential of the human endometrium

Histological 3D reconstruction and in vivo lineage tracing of the human endometrium

Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher‐order primates. The current consensus postulates endometrial glands to have a single‐tubular architecture, where multi‐potential stem cells reside in the blind‐ending glandular‐bases. Utilising fixed samples from patients, we have studied the three‐dimensional (3D) micro‐architecture of the human endometrium. We demonstrate that some non‐branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated by in vivo lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem‐cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar‐less regenerative potential of the human endometrium

Automated quantification of steatosis: agreement with stereological point counting

Background: Steatosis is routinely assessed histologically in clinical practice and research. Automated image analysis can reduce the effort of quantifying steatosis. Since reproducibility is essential for practical use, we have evaluated different analysis methods in terms of their agreement with stereological point counting (SPC) performed by a hepatologist. Methods: The evaluation was based on a large and representative data set of 970 histological images from human patients with different liver diseases. Three of the evaluated methods were built on previously published approaches. One method incorporated a new approach to improve the robustness to image variability. Results: The new method showed the strongest agreement with the expert. At 20× resolution, it reproduced steatosis area fractions with a mean absolute error of 0.011 for absent or mild steatosis and 0.036 for moderate or severe steatosis. At 10× resolution, it was more accurate than and twice as fast as all other methods at 20× resolution. When compared with SPC performed by two additional human observers, its error was substantially lower than one and only slightly above the other observer. Conclusions: The results suggest that the new method can be a suitable automated replacement for SPC. Before further improvements can be verified, it is necessary to thoroughly assess the variability of SPC between human observers

Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit