Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis

摘要

Blood vessels are the body’s highways that allow blood to transport oxygen, nutrients, hormones and waste products quickly and efficiently around the body. Tumors are made up of particularly active cells and so their growth heavily depends on blood vessels. Indeed, a fundamental hallmark of tumor progression is for nearby blood vessels to form more quickly. Tumor blood vessels also differ in structure from their normal counterparts for reasons that need to be investigated in more detail. Compounds that block the formation of blood vessels have been developed for treating highly malignant brain tumors called gliomas. However, although many of these compounds show promising effects in preclinical trials, clinical trials on humans have been less successful. Having the ability to image the blood vessels in high detail during preclinical trials would help to reveal how treatments that inhibit blood vessel formation work and how tumors might develop resistance to these drugs. However, studying tumor blood vessels remains a challenge due to technical restrictions techniques that are able to capture how the vessels change over time are unable to show individual cells in much detail, and vice versa. Magnetic resonance imaging is a versatile tool that can monitor how the blood vessel system of a tumor changes over time in living animals. On the other hand, ultramicroscopy is able to determine the structure of single cells of a particular type. By combining these techniques, Breckwoldt, Bode et al. have now developed a imaging platform that allows the formation of tumor blood vessels to be precisely mapped in the setting of a preclinical study. It also enables detailed investigations into how the structure of the blood vessels is altered by treatments that aim to inhibit the formation and growth of new vessels. Using this approach on mice with gliomas, Breckwoldt, Bode et al. demonstrated that drugs that inhibit the formation of the blood vessels that supply tumors also cause the blood vessels to take on a more normal structure. Furthermore, treating the mice with a single inhibitory drug was unable to stop tumor growth, mirroring the situation in humans. Currently, new inhibitors are being developed, offering the possibility of combined treatments that may be more effective than using a single drug on its own. The imaging platform developed by Breckwoldt, Bode et al. will allow the therapeutic effects obtained by these new treatments to be analyzed in detail during preclinical studies.