Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model

Abstract

The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (CI), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI and E quantified with SE and DE protocols. Significant strong correlations (Pearson r > 0.7, p < 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model.

Accuracy and Precision of Iodine Quantification in Subtracted Micro-Computed Tomography: Effect of Reconstruction and Noise Removal Algorithms

“…First, the accuracy and precision of C I were evaluated with calibrated phantoms with a limited concentration range (0–3 mg I/ml). This C I range could be appropriate for tumor studies, since previous works have reported values of C I < 5 mg I/ml in several animal cancer models [ 1 , 11 , 14 , 15 ]. However, a wider range of C I should be evaluated to extend the understanding of the accuracy and precision of C I in several organs and tissues.…”

“…Image acquisition was performed with the micro-CT scanner of the trimodal PET/SPECT/CT Albira ARS preclinical system (Bruker, Spain). Micro-CT images were acquired with 45 kV, 0.8 mA, and 400 projections, according to a previously optimized imaging protocol for subtracted CE micro-CT imaging with this scanner [ 15 ]. This protocol involved the acquisition of two images: a pre-contrast image (i.e., the baseline image) and a second image after or during the administration of the contrast agent (i.e., the contrast-enhanced (CE) image).…”

“…The baseline image was then subtracted from the CE image to yield the subtracted CE image, which was then parameterized to units of C I with a calibration function to yield the subtracted C I image. The total radiation dose to water measured at the isocenter for this imaging protocol was 680 mGy [ 15 ].…”

“…Recently, one study has reported the evaluation of the bias of C I to compare the performance of two imaging detectors under two CE micro-CT imaging protocols [ 16 ]. To the best of our knowledge, no other studies have evaluated the accuracy or precision of C I in CE micro-CT. Additionally, current approaches in CE micro-CT involve the use of iterative reconstruction and noise removal algorithms that could have an impact on the accuracy and precision of C I [ 15 , 18 – 20 ]. The findings in CECT and the current approaches in CE micro-CT highlight the necessity to evaluate the impact of both conventional and novel approaches in CE micro-CT on the accuracy and precision of C I .…”