Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis

Kießling, Fabian; Greschus, Susanne; Lichy, Matthias P.; Bock, Michael; Fink, Christian; Vosseler, Silvia; Moll, Jens; Mueller, Margareta M.; Fusenig, Norbert E.; Traupe, Horst; Semmler, Willi

doi:10.1038/nm1101

Cited by 191 publications

(146 citation statements)

References 26 publications

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“…Ex vivo micro-CT angiography has been used to quantify vascular structure in whole tumors (6,7) but provides only a single measurement time point and detects structural information about the presence of vasculature, rather than functional information about how that vasculature was perfused in vivo. Contrastenhanced micro-CT angiography can be done in vivo with a rapid volume scanning system, but the resolution limit of the CT signal limits the size of detectable vessels; microvasculature smaller than 30-50 mm cannot be visualized (8).…”

mentioning

confidence: 99%

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Ungersma

Pacheco²,

et al. 2010

Magnetic Resonance in Med

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Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density. Here, this technique is validated with direct comparisons to ex vivo micro-CT angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and vessel density by two antiangiogenic therapeutics (anti-VEGF and anti-neuropilin-1) on an HM7 colorectal tumor model. Anti-VEGF reduced blood volume by 36 6 3% (P < 0.0001) and vessel density by 52 6 3% (P < 0.0001) at 48 h posttreatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18 6 6% (P < 0.05) and a reduction in vessel density of 33 6 5% (P < 0.05) at 48 h posttreatment.

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mentioning

confidence: 99%

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Ungersma

Pacheco²,

et al. 2010

Magnetic Resonance in Med

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“…Consequently, the reliability of repeated measurements for therapy monitoring is negatively affected by this shortcoming of conventional methods. Here, volume scanning offers improved comparability between consecutive examinations (33,34).…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects

Palmowski

Huppert

Ladewig

et al. 2008

Molecular Cancer Therapeutics

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Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric ''multitarget quantification'' and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and A v B 3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and A v B 3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and A v B 3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and A v B 3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.

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“…Last, but not least, FD technology has also been integrated in standard CT designs [50][51][52][53]. Respective efforts were labelled experimental and aimed at exploring so-called "volume CT" options.…”

Section: Fd-ct In Combination With Conventional Ct Gantriesmentioning

confidence: 99%

Flat-detector computed tomography (FD-CT)

2007

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Flat-panel detectors or, synonymously, flat detectors (FDs) have been developed for use in radiography and fluoroscopy with the defined goal to replace standard X-ray film, filmscreen combinations and image intensifiers by an advanced sensor system. FD technology in comparison to X-ray film and image intensifiers offers higher dynamic range, dose reduction, fast digital readout and the possibility for dynamic acquisitions of image series, yet keeping to a compact design. It appeared logical to employ FD designs also for computed tomography (CT) imaging. Respective efforts date back a few years only, but FD-CT has meanwhile become widely accepted for interventional and intraoperative imaging using C-arm systems. FD-CT provides a very efficient way of combining two-dimensional (2D) radiographic or fluoroscopic and 3D CT imaging. In addition, FD technology made its way into a number of dedicated CT scanner developments, such as scanners for the maxillo-facial region or for micro-CT applications. This review focuses on technical and performance issues of FD technology and its full range of applications for CT imaging. A comparison with standard clinical CT is of primary interest. It reveals that FD-CT provides higher spatial resolution, but encompasses a number of disadvantages, such as lower dose efficiency, smaller field of view and lower temporal resolution. FD-CT is not aimed at challenging standard clinical CT as regards to the typical diagnostic examinations; but it has already proven unique for a number of dedicated CT applications, offering distinct practical advantages, above all the availability of immediate CT imaging in the interventional suite or the operating room.

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Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis

Cited by 191 publications

References 26 publications

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects

Flat-detector computed tomography (FD-CT)

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