High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature

Abstract

Purpose:To evaluate high-resolution three-dimensional MR angiography (MRA) for the visualization and morphologic characterization of intratumoral vasculature. Materials and Methods:Two subcutaneous rodent tumor models (human skin carcinoma HaCaT-ras-A-5RT3 grown in nude mice and rat prostate carcinoma R3327-AT1 grown in Copenhagen rats) were examined with a clinical 1.5 T MR-system. For MRA a dedicated high-resolution threedimensional gradient echo pulse sequence with a voxel size of 166 ϫ 206 ϫ 320 m 3 was performed after injection of Gadomer-17. The image analysis included a correlation of intratumoral vessels with histology. Signal intensity measurements were performed in the vena cava, the tumor underlying muscle, and in various regions of the tumor. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated from this measurement.Results: High-resolution MRA allowed a clear distinction of intratumoral blood vessels. The mouse tumor model tended to be strongly vascularized with several intratumoral blood vessels clearly displayed by MRA. When correlated with histology, these intratumoral blood vessels had a size in the range of 300 to 400 m. In contrast, rat tumors had only sparse capillary intratumoral blood vessels that could only be demonstrated by histology. In both tumor models, dilated blood vessels were observed in the subcutaneous tissue near the tumor. In general, areas with a strong contrast enhancement correlated with viable, well vascularized tumor regions, whereas non-enhancing tumor areas correlated with tumor necrosis or hypoxic areas. Conclusion:High-resolution three-dimensional MRA allows the visualization of intratumoral vasculature in rodent models. With minimal hardware and software modifications, high-resolution MRA could be performed on a clinical 1.5 T MRI scanner. Morphologic characterization of intratumoral blood vessels could add important insights into the process of tumor angiogenesis.

Magnetic resonance angiography of collateral vessel growth in a rabbit femoral artery ligation model

“…Intravascular (i.e. blood pool) T 1 -shortening MR contrast agents might allow prolonged acquisition times and further improvements in spatial resolution (16,17). In addition, developments such as venous compression and parallel imaging techniques might prove to be useful for suppressing venous enhancement.…”

High-resolution 3D isotropic MR imaging of mouse flank tumours obtainedin vivowith solenoid RF micro-coil

“…MR angiography has been previously used to characterize intratumoural vasculature in mice (Fink et al 2003) and correlations made with histology (Graff et al 2005). Though, with a spatial resolution of 166 × 206 × 329 µm 3 , only larger vessels could be visualized.…”

Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications

“…administered diagnostic agents, ruling out the vast majority of applications for which nanodiagnostics are routinely employed in animal models. Among the applications for which nanodiagnostics, such as Gadomer-17 and Resovist, have been used in patients are the MR monitoring of (the perfusion of) tumor blood vessels and coronary arteries [38][39][40], the imaging of labelled stem cells [41] and the visualization of primary and/or metastatic liver lesions [42] (Figure 2G-L). A small number of additional clinical studies have focused on the use of Resovist-like iron oxide nanoparticles, such as Endorem and Sinerem, for monitoring neural stem cells [43], lymph node metastases [44], intranodally injected cancer vaccines [45], and macrophage activity in atherosclerosis [46].…”

“…from different types of sarcomas (R), thereby enabling patient preselection and (more) personalized nano-chemotherapeutic treatments. Images are adapted, with permission, from [30,[32][33][34][38][39][40][41][42][50][51][52]. Rationale for image-guided and personalized nanomedicine.…”