Quantification Of Tumor Vascularity Research Articles

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis\u2014an animal experimental prospective cohort study

BackgroundThis study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads).ResultsIn both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p < 0.001], higher microvessel density (MVD) determined histologically after CD-31 staining [171.4 (± 18.9) as compared to 110.8 (± 11) vessels per mm2, p = 0.002], and higher perfusion as indicated by the number of beads [1.3 (± 0.1) as compared to 1.1 (± 0.04) beads per field of view, p = 0.001]. In [18F]FDG-PET/CT, co-transplanted tumors revealed significantly higher standardized uptake values [SUVmax, 2.8 (± 0.2) as compared to 1.1 (± 0.1), p < 0.001] and larger metabolic active volumes [2.4 (± 0.2) as compared to 0.4 (± 0.2) cm3, p < 0.001] than non-co-transplanted tumors. There were significant correlations for vascularization parameters derived from histology and [18F]FDG PET/CT [beads and SUVmax, r = 0.353, p = 0.005; CD-31 and SUVmax, r = 0.294, p = 0.036] as well as between CE-CT and [18F]FDG PET/CT [contrast enhancement and SUVmax, r = 0.63, p < 0.001; vital CT tumor volume and metabolic PET tumor volume, r = 0.919, p < 0.001].ConclusionsIn this study, a human xenograft tumor model with modifiable vascularization implementable for imaging, pharmacological, and radiation therapy studies was successfully established. Both [18F]FDG-PET/CT and CE-CT are capable to detect parameters closely connected to the degree of tumor vascularization, thus they can help to evaluate vascularization in tumors noninvasively. [18F]FDG-PET may be considered for characterization of tumors beyond pure glucose metabolism and have much greater contribution to diagnostics in oncology.

Evaluation of Vascularity, Blood Perfusion, and Oxygen Tension in Tumor Xenografts with Fluorescent Microscopy.

Histologic heterogeneity in glioblastoma (GBM) is highlighted by regional variability in vascular density. Areas of vascular hyperplasia are interspersed with avascular territories, in which necrosis is surrounded by a zone of hypoxic tumor cells expressing stem cell markers, a phenomenon known as pseudopalisading necrosis. This vascular heterogeneity suggests intratumoral oxygen gradients, which regulate cellular and metabolic adaptations in tumor cells. Quantification of tumor vascularity, blood perfusion and oxygenation is therefore critical. In this chapter, we describe three different methods, all of which involve microscopy to analyze these parameters in tumor xenografts. We present detailed protocols for analysis of tumor endothelium using endothelial markers, blood perfusion by systemic infusion of Evans Blue and oxygen tension by pimonidazole injection, followed by immunostaining.

Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases.

Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.

OC176: Three‐dimensional (3D) quantification of tumor vascularity as third step after B‐mode and power Doppler evaluation for detection of ovarian cancer

OC176: Three‐dimensional (3D) quantification of tumor vascularity as third step after B‐mode and power Doppler evaluation for detection of ovarian cancer

Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor.

To correlate the quantitated tumor vascularity of implanted murine tumors as depicted by contrast-enhanced sonography with estimates made with magnetic resonance imaging and with estimates of the percentage of viable (metabolically active) tumor as depicted by fluorodeoxyglucose autoradiography. Implanted tumors in 10 mice were imaged with contrast-enhanced sonography, magnetic resonance imaging, and fluorodeoxyglucose autoradiography. Tumor vascularity was estimated with each modality and compared with the percentage of viable tumor. Quantitated estimates of tumor vascularity with contrast-enhanced sonography closely correlated (r = 0.95) with estimates made by magnetic resonance imaging and with the percentage of viable tumor (r = 0.93) as depicted by fluorodeoxyglucose autoradiography. Contrast-enhanced sonography accurately depicts tumor vascularity in these implanted tumors. Tumor vascularity correlated with the amount of metabolically active tumor.

Sonographic depiction of tumor vascularity and flow: from in vivo models to clinical applications.

This review discusses and illustrates the sonographic depiction and quantification of tumor vascularity and flow using three-dimensional color Doppler sonography. The potential clinical applications mentioned here are based on work done with in vivo tumor models and as well as extensive clinical experience with this technique. Three-dimensional color Doppler sonography, as used with contrast agents and novel imaging techniques, has significant current and potential clinical application for detailed depiction of tumor vascularity and flow. This technique can provide important information concerning changes in tumor vascularity and flow related to various biologic, chemical, and radiation therapies as demonstrated in animals and a few human studies. Additional animal and human studies are needed for further refinement and eventual clinical application of this technique.

Quantification of Tumor Vascularity and Flow with Amplitude Color Doppler Sonography in an Experimental Model: Preliminary Results

Quantification of Tumor Vascularity and Flow with Amplitude Color Doppler Sonography in an Experimental Model: Preliminary Results

Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model: preliminary results.

This study was designed to evaluate a system to quantitate vascularity and tumor blood flow with amplitude (power) color Doppler sonography. The vascularity of nine transplanted murine tumors was determined with quantitated amplitude color Doppler sonography and compared to tumor vascularity estimated by histologic examination. The system used seemed to provide an accurate depiction of the vascularity of tumor vis-àa-vis histologic estimation of vessel density (r = 0.80). Time-activity curves showed greater flow in the experimental group injected with an exotoxin than in the group injected with saline solution. Vascular density quantification with amplitude color Doppler sonography also was more accurate when an intravascular agent (such as an exotoxin) was used than when saline infusions were given. This quantification scheme may allow the development of a system to assess the probability of malignancy and to monitor tumor response to treatment on the basis of the vascularity of the mass.