The emergence of digital pathology has enabled numerous quantitative analyses of histopathology structures. However, most pathology image analyses are limited to two-dimensional datasets, resulting in substantial information loss and incomplete interpretation. To address this, we have developed a complete framework for three-dimensional whole slide image analysis and demonstrated its efficacy on 3D vessel structure analysis with liver tissue sections. The proposed workflow includes components on image registration, vessel segmentation, vessel cross-section association, object interpolation, and volumetric rendering. For 3D vessel reconstruction, a cost function is formulated based on shape descriptors, spatial similarity and trajectory smoothness by taking into account four vessel association scenarios. An efficient entropy-based Relaxed Integer Programming (eRIP) method is proposed to identify the optimal inter-frame vessel associations. The reconstructed 3D vessels are both quantitatively and qualitatively validated. Evaluation results demonstrate high efficiency and accuracy of the proposed method, suggesting its promise to support further 3D vessel analysis with whole slide images.

A large number of cell-oriented cancer investigations require an effective and reliable cell segmentation method on three dimensional (3D) fluorescence microscopic images for quantitative analysis of cell biological properties. In this paper, we present a fully automated cell segmentation method that can detect cells from 3D fluorescence microscopic images. Enlightened by fluorescence imaging techniques, we regulated the image gradient field by gradient vector flow (GVF) with interpolated and smoothed data volume, and grouped voxels based on gradient modes identified by tracking GVF field. Adaptive thresholding was then applied to voxels associated with the same gradient mode where voxel intensities were enhanced by a multiscale cell filter. We applied the method to a large volume of 3D fluorescence imaging data of human brain tumor cells with (1) small cell false detection and missing rates for individual cells; and (2) trivial over and under segmentation incidences for clustered cells. Additionally, the concordance of cell morphometry structure between automated and manual segmentation was encouraging. These results suggest a promising 3D cell segmentation method applicable to cancer studies.

Recent advancements in systematic analysis of high resolution whole slide images have increase efficiency of diagnosis, prognosis and prediction of cancer and important diseases. Due to the enormous sizes and dimensions of whole slide images, the analysis requires extensive computing resources which are not commonly available. Images have to be tiled for processing due to computer memory limitations, which lead to inaccurate results due to the ignorance of boundary crossing objects. Thus, we propose a generic and highly scalable cloud-based image analysis framework for whole slide images. The framework enables parallelized integration of image analysis steps, such as segmentation and aggregation of micro-structures in a single pipeline, and generation of final objects manageable by databases. The core concept relies on the abstraction of objects in whole slide images as different classes of spatial geometries, which in turn can be handled as text based records in MapReduce. The framework applies an overlapping partitioning scheme on images, and provides parallelization of tiling and image segmentation based on MapReduce architecture. It further provides robust object normalization, graceful handling of boundary objects with an efficient spatial indexing based matching method to generate accurate

Three dimensional microscopy images present significant potential to enhance biomedical studies. This paper presents an automated method for quantitative analysis of 3D primary vessel structures with histology whole slide images. With registered microscopy images of liver tissue, we identify primary vessels with an improved variational level set framework at each 2D slide. We propose a Vessel Directed Fitting Energy (VDFE) to provide prior information on vessel wall probability in an energy minimization paradigm. We find the optimal vessel cross-section associations along the image sequence with a two-stage procedure. Vessel mappings are first found between each pair of adjacent slides with a similarity function for four association cases. These bi-slide vessel components are further linked by Bayesian Maximum A Posteriori (MAP) estimation where the posterior probability is modeled as a Markov chain. The efficacy of the proposed method is demonstrated with 54 whole slide microscopy images of sequential sections from a human liver.

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.