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Abstract Tissue micro‐morphological abnormalities and interrelated quantitative data can provide immediate evidences for tumorigenesis and metastasis in microenvironment. However, the multiscale three‐dimensional nondestructive pathological visualization, measurement, and quantitative analysis are still a challenging for the medical imaging and diagnosis. In this work, we employed the synchrotron‐based X‐ray phase‐contrast tomography (SR‐PCT) combined with phase‐and‐attenuation duality phase retrieval to reconstruct and extract the volumetric inner‐structural characteristics of tumors in digesting system, helpful for tumor typing and statistic calculation of different tumor specimens. On the basis of the feature set including eight types of tumor micro‐lesions presented by our SR‐PCT reconstruction with high density resolution, the AlexNet‐based deep convolutional neural network model was trained and obtained the 94.21% of average accuracy of auto‐classification for the eight types of tumors in digesting system. The micro‐pathomophological relationship of liver tumor angiogenesis and progression were revealed by quantitatively analyzing the microscopic changes of texture and grayscale features screened by a machine learning method of area under curve and principal component analysis. The results showed the specific path and clinical manifestations of tumor evolution and indicated that these progressions of tumor lesions rely on its inflammation microenvironment. Hence, this high phase‐contrast 3D pathological characteristics and automatic analysis methods exhibited excellent recognizable and classifiable for micro tumor lesions.

The primary goal of this study was to evaluate the feasibility of using anti-vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated poly(lactic-co-glycolic acid) (PLGA) microspheres as an x-ray phase contrast agent to assess the VEGFR2 expression in cell cultures. The cell lines, mouse LLC (Lewis lung carcinoma) and HUVEC (human umbilical vein endothelial cell), were selected for cell adhesion studies. The bound PLGA microspheres were found to better adhere to LLC cells or HUVECs than unbound ones. Absorption and phase contrast images of PLGA microspheres were acquired and compared in vitro. Phase contrast imaging (PCI) greatly improves the detection of the microspheres as compared to absorption contrast imaging. The cells incubated with PLGA microspheres were imaged by PCI, which provided clear 3D visualization of the beads, indicating the feasibility of using PLGA microspheres as a contrast agent for phase contrast CT. In addition, the microspheres could be clearly distinguished from the wall of the vessel on phase contrast CT images. Therefore, the approach holds promise for assessing the VEGFR2 expression on endothelial cells of tumor-associated vessels. We conclude that PLGA microsphere-based PCI of the VEGFR2 expression might be a novel, promising biomarker for future studies of tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Computed tomography combined with angiography has recently been developed to visualize three-dimensional (3D) vascular structure in experimental and clinical studies. However, there remain difficulties in using conventional x-ray angiography to detect small vessels with a diameter less than 200 µm. This study attempted to develop a novel method for visualizing the micro-angioarchitecture of rat spinal cord. Herein, synchrotron radiationbased x-ray in-line phase contrast computed tomography (IL-XPCT) was used to obtain 3D micro-vessel structure without angiography. The digital phase contrast images were compared with conventional histological sections. Our results clearly demonstrated that the resolution limit of the spatial blood supply network in the normal rat thoracic cord appeared to be as small as ∼10 µm. The rendered images were consistent with that obtained from histomorphology sections. In summary, IL-XPCT is a potential tool to investigate the 3D neurovascular morphology of the rat spinal cord without the use of contrast agents, and it could help to evaluate the validity of the pro- or anti-angiogenesis therapeutic strategies on microvasculature repair or regeneration. [ABSTRACT FROM AUTHOR]