Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of 3D CEUS Images: Role of Liposomes and Microbubbles

Abstract

This Chapter (The contents of this chapter build upon the paper: F. Molinari, K. M. Meiburger, P. Giustetto, S. Rizzitelli, C. Boffa, M. Castano, and E. Terreno, “Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High Resolution 3D Contrast-Enhanced Ultrasound Images: Role of Liposomes and Microbubbles”, In: Technology in Cancer Research and Treatment, 13(6):541–550, 2014) opens the second section of this work, which is based on emphasizing quantitative imaging techniques for the assessment of architectural parameters of vasculature that can be extracted from 3D volumes. Using contrast-enhanced ultrasound (CEUS) imaging, it was demonstrated how the characterization and description of the vascular network of a cancer lesion in mouse models can be effectively determined using both traditional microbubbles and liposomes. Eight mice were administered both microbubbles and liposomes and 3D CEUS volumes were acquired. Vascular architectural descriptors were calculated after a skeletonization technique was applied. The accurate characterization and description of the vascular network of a cancer lesion is of critical importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1, 2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3D contrast-enhanced images of the tumor lesions were acquired pre-contrast, after the injection of microbubbles, and after the injection of liposomes. The 3D representation of the vascular architecture in these three conditions was obtained with a previously developed reconstruction and characterization image processing technique,. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2D curvature measure, the number of vascular flexes of the vessels, and the 3D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic ”(i.e. therapeutic $+$ diagnostic) ultrasound probes.