Segmentation of Pulmonary Vascular Trees from Thoracic 3D CT Images

This paper describes an algorithm for extracting pulmonary vascular trees (arteries plus veins) from three-dimensional (3D) thoracic computed tomographic (CT) images. The algorithm integrates tube enhancement filter and traversal approaches which are based on eigenvalues and eigenvectors of a Hessian matrix to extract thin peripheral segments as well as thick vessels close to the lung hilum. The resultant algorithm was applied to a simulation data set and 44 scans from 22 human subjects imaged via multidetector-row CT (MDCT) during breath holds at 85% and 20% of their vital capacity. A quantitative validation was performed with more than 1000 manually identified points selected from inside the vessel segments to assess true positives (TPs) and 1000 points randomly placed outside of the vessels to evaluate false positives (FPs) in each case. On average, for both the high and low volume lung images, 99% of the points was properly marked as vessel and 1% of the points were assessed as FPs. Our hybrid segmentation algorithm provides a highly reliable method of segmenting the combined pulmonary venous and arterial trees which in turn will serve as a critical starting point for further quantitative analysis tasks and aid in our overall goal of establishing a normative atlas of the human lung

Development of lung tissue phantoms for bioluminescent imaging

White nylon material was chosen to make cylindrical tissue phantoms for development of bioluminescence tomography techniques. A low-level light source, delivered through an optic fiber of core diameter 200 μm, was placed at different locations on one phantom surface. The light travels through the phantom, reaches the external surface, and is captured by a liquid nitrogen-cooled CCD camera. The scattering, absorption, and anisotropy parameters of the phantom are obtained by matching the measured light transmission profiles to the profiles generated by the TracePro software. The perturbation analysis, with the homogeneous phantoms, demonstrated that the imaging system is sufficiently sensitive to capture intensity change of higher than 0.5nW/cm2 or a location shift of the light source of more than 200 microns. It is observed that the system can distinguish two point light sources with separation of about 2 mm. The perturbation analysis is also performed with the heterogeneous phantom. Based on our data, we conclude that there is inherent tomographic information in bioluminescent measures taken on the external surface of the mouse, which suggests the feasibility of bioluminescence tomography for biomedical research using the small animals, especially the mice

In vivo tomographic imaging based on bioluminescence

The most important task for bioluminescence imaging is to identify the emission source from the captured bioluminescent signal on the surface of a small tested animal. Quantitative information on the source location, geometry and intensity serves for in-vivo monitoring of infectious diseases, tumor growth, metastases in the small animal. In this paper, we present a point-spread function-based method for reconstructing the internal bioluminescent source from the surface light output flux signal. The method is evaluated for sensing the internal emission sources in nylon phantoms and within a live mouse. The surface bioluminescent signal is taken with a highly sensitive CCD camera. The results show the feasibility and efficiency of the proposed point-spread function-based method

Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease

Development of lung tissue phantoms for bioluminescent imaging

White nylon material was chosen to make cylindrical tissue phantoms for development of bioluminescence tomography techniques. A low-level light source, delivered through an optic fiber of core diameter 200 μm, was placed at different locations on one phantom surface. The light travels through the phantom, reaches the external surface, and is captured by a liquid nitrogen-cooled CCD camera. The scattering, absorption, and anisotropy parameters of the phantom are obtained by matching the measured light transmission profiles to the profiles generated by the TracePro software. The perturbation analysis, with the homogeneous phantoms, demonstrated that the imaging system is sufficiently sensitive to capture intensity change of higher than 0.5nW/cm2 or a location shift of the light source of more than 200 microns. It is observed that the system can distinguish two point light sources with separation of about 2 mm. The perturbation analysis is also performed with the heterogeneous phantom. Based on our data, we conclude that there is inherent tomographic information in bioluminescent measures taken on the external surface of the mouse, which suggests the feasibility of bioluminescence tomography for biomedical research using the small animals, especially the mice

CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury

Background: Chronic inflammation is the driver of liver injury and results in progressive fibrosis and eventual cirrhosis with consequences including both liver failure and liver cancer. We have previously described increased expression of the highly multifunctional glycoprotein CD147 in liver injury. This work describes a novel role of CD147 in liver inflammation and the importance of leukocyte aggregates in determining the extent of liver injury. Methods: Non-diseased, progressive injury, and cirrhotic liver from humans and mice were examined using a mAb targeting CD147. Inflammatory cell subsets were assessed by multiparameter flow cytometry. Results: In liver injury, we observe abundant, intrahepatic leukocyte clusters defined as ≥5 adjacent CD45+ cells which we have termed “leukocyte aggregates”. We have shown that these leukocyte aggregates have a significant effect in determining the extent of liver injury. If CD147 is blocked in vivo, these leukocyte aggregates diminish in size and number, together with a marked significant reduction in liver injury including fibrosis. This is accompanied by no change in overall intrahepatic leukocyte numbers. Further, blocking of aggregation formation occurs prior to an appreciable increase in inflammatory markers or fibrosis. Additionally, there were no observed, “off-target” or unpredicted effects in targeting CD147. Conclusion: CD147 mediates leukocyte aggregation which is associated with the development of liver injury. This is not a secondary effect, but a cause of injury as aggregate formation proceeds other markers of injury. Leukocyte aggregation has been previously described in inflammation dating back over many decades. Here we demonstrate that leukocyte aggregates determine the extent of liver injury

In vivo tomographic imaging based on bioluminescence

The most important task for bioluminescence imaging is to identify the emission source from the captured bioluminescent signal on the surface of a small tested animal. Quantitative information on the source location, geometry and intensity serves for in-vivo monitoring of infectious diseases, tumor growth, metastases in the small animal. In this paper, we present a point-spread function-based method for reconstructing the internal bioluminescent source from the surface light output flux signal. The method is evaluated for sensing the internal emission sources in nylon phantoms and within a live mouse. The surface bioluminescent signal is taken with a highly sensitive CCD camera. The results show the feasibility and efficiency of the proposed point-spread function-based method