Dataset Information

Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.

ABSTRACT: Angiogenesis is a hallmark of cancer, and its noninvasive visualization and quantification are key factors for facilitating translational anticancer research. Using four tumor models characterized by different degrees of aggressiveness and angiogenesis, we show that the combination of functional in vivo and anatomical ex vivo X-ray micro-computed tomography (?CT) allows highly accurate quantification of relative blood volume (rBV) and highly detailed three-dimensional analysis of the vascular network in tumors. Depending on the tumor model, rBV values determined using in vivo ?CT ranged from 2.6% to 6.0%, and corresponds well with the values assessed using IHC. Using ultra-high-resolution ex vivo ?CT, blood vessels as small as 3.4 ?m and vessel branches up to the seventh order could be visualized, enabling a highly detailed and quantitative analysis of the three-dimensional micromorphology of tumor vessels. Microvascular parameters such as vessel size and vessel branching correlated very well with tumor aggressiveness and angiogenesis. In rapidly growing and highly angiogenic A431 tumors, the majority of vessels were small and branched only once or twice, whereas in slowly growing A549 tumors, the vessels were much larger and branched four to seven times. Thus, we consider that combining highly accurate functional with highly detailed anatomical ?CT is a useful tool for facilitating high-throughput, quantitative, and translational (anti-) angiogenesis and antiangiogenesis research.

SUBMITTER: Ehling J

PROVIDER: S-EPMC3920056 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.

Ehling Josef J Theek Benjamin B Gremse Felix F Baetke Sarah S Möckel Diana D Maynard Juliana J Ricketts Sally-Ann SA Grüll Holger H Neeman Michal M Knuechel Ruth R Lederle Wiltrud W Kiessling Fabian F Lammers Twan T

The American journal of pathology 20131118 2

Angiogenesis is a hallmark of cancer, and its noninvasive visualization and quantification are key factors for facilitating translational anticancer research. Using four tumor models characterized by different degrees of aggressiveness and angiogenesis, we show that the combination of functional in vivo and anatomical ex vivo X-ray micro-computed tomography (μCT) allows highly accurate quantification of relative blood volume (rBV) and highly detailed three-dimensional analysis of the vascular ne ...[more]

PMID: 24262753

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Project description:Micro-CT is widely used for small animal imaging in preclinical studies of cardiopulmonary disease, but further development is needed to improve spatial resolution, temporal resolution, and material contrast. We present a technique for visualizing the changing distribution of iodine in the cardiac cycle with dual source micro-CT.The approach entails a retrospectively gated dual energy scan with optimized filters and voltages, and a series of computational operations to reconstruct the data. Projection interpolation and five-dimensional bilateral filtration (three spatial dimensions + time + energy) are used to reduce noise and artifacts associated with retrospective gating. We reconstruct separate volumes corresponding to different cardiac phases and apply a linear transformation to decompose these volumes into components representing concentrations of water and iodine. Since the resulting material images are still compromised by noise, we improve their quality in an iterative process that minimizes the discrepancy between the original acquired projections and the projections predicted by the reconstructed volumes. The values in the voxels of each of the reconstructed volumes represent the coefficients of linear combinations of basis functions over time and energy. We have implemented the reconstruction algorithm on a graphics processing unit (GPU) with CUDA. We tested the utility of the technique in simulations and applied the technique in an in vivo scan of a C57BL∕6 mouse injected with blood pool contrast agent at a dose of 0.01 ml∕g body weight. Postreconstruction, at each cardiac phase in the iodine images, we segmented the left ventricle and computed its volume. Using the maximum and minimum volumes in the left ventricle, we calculated the stroke volume, the ejection fraction, and the cardiac output.Our proposed method produces five-dimensional volumetric images that distinguish different materials at different points in time, and can be used to segment regions containing iodinated blood and compute measures of cardiac function.We believe this combined spectral and temporal imaging technique will be useful for future studies of cardiopulmonary disease in small animals.

Project description:Photon-counting micro computed tomography (micro-CT) offers new potential in preclinical imaging, particularly in distinguishing materials. It becomes especially helpful when combined with contrast agents, enabling the differentiation of tumors from surrounding tissues. There are mainly two types of contrast agents in the market for micro-CT: small molecule-based and nanoparticle-based. However, despite their widespread use in liver tumor studies, there is a notable gap in research on the application of these commercially available agents for photon-counting micro-CT in breast and ovarian tumors. Herein, we explored the effectiveness of these agents in differentiating tumor xenografts from various origins (AU565, MDA-MB-231, and SKOV-3) in nude mice, using photon-counting micro-CT. Specifically, ISOVUE-370 (a small molecule-based agent) and Exitrone Nano 12000 (a nanoparticle-based agent) were investigated in this context. To improve tumor visualization, we proposed a novel color visualization method for photon-counting micro-CT, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Our in vivo experiments confirm its effectiveness, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggested that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 gives more comprehensive tumor enhancement but with a significant variance between scans due to its short blood half-time. This variability leads to high sensitivity to timing and individual differences among mice. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemistry. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor development and response to treatments.

Dataset Information

Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.

Publications

Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.

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