Longitudinal characterization of tumor vascular adaptation using superfine magnetic resonance angiography

This study aimed to establish a noninvasive magnetic resonance angiography (MRA) framework for monitoring tumor vascular adaptation longitudinally using the intravascular supramolecular contrast agent 8-arm PEG-FGd₃. (1) Unlike conventional Gd-chelates, which predominantly enhanced tumor tissue because of contrast extravasation, 8-arm PEG-FGd₃ provided high-contrast delineation of tumor-feeding vessels and microvascular architecture, visualizing tumor vessels as small as 190 μm. (2) This is the first instance of defining neovascularization patterns in superfine MRA images. (3) The longitudinal atlas of tumor vessels varied over time. In the fast-growing stage, both tumor doubling time and vessel doubling time were positive, vessels initiated neovascularization processes such as vessel co-option-like appearance, sprouting-like appearance, and elongation-tortuosity-like change. In the slow-growing stage, vessel doubling time turned negative, vessels became more structured, with continued elongation-tortuosity. Vessel remodeling followed vascular disruption rapidly. In the shrinkage stage, vessel loss preceded tumor shrinkage. (4) Seven days post-ligation, there were more vessels than the second day. ANG2 also showed a increasing tendency during this period, while VEGF was decreasing but still higher than that in the tumor without ligation, although there was no significant difference.