Imaging Toolkit Helps Identify Brain Tumor Drug Targets

A combined magnetic resonance imaging (MRI) and ultramicroscopy (UM) toolkit could help study vessel growth as an aid in glioblastoma therapies, according to a new study.

Researchers at the University of Heidelberg, (Germany), University Medical Center Göttingen (Germany), and other institutions have developed a method to study neoangiogenesis in two glioma models that is based on in vivo MRI and correlative ex-vivo UM of cleared whole brains. The technique is based on T2*-weighted MRI—one of the basic pulse sequences in MRI—with high resolution to allow for substantially more detail than conventional imaging.

First, the researchers performed pre- and post-contrast MRI scans to define the growth of vessels during glioma development in two different mouse models. The researchers then mapped the development of the vessels by dual-color UM of the whole, cleared brains via fluorescent labelling, which helped resolve typical features of neoangiogenesis and tumor cell invasion with a spatial resolution of ~5 µm. The three dimensional (3D) MRI and complimentary UM data sets—dubbed MR-UM—were then compared side-by-side.

The researchers also used the toolkit to assess the effects of existing anti-vascular endothelial growth factor (anti-VEGF) treatments or radiation therapy on the vessel compartment within the two glioma models. They found that such treatments are insufficient to halt tumor growth in mice, which mirrors current human studies. According to the researchers, MR-UM could provide a better understanding of the underlying mechanisms of existing treatment, and could help identify novel targets for future drug development. The study was published on February 3, 2016, in the journal eLife.

“Gliomas are highly malignant brain tumors with poor prognosis. Many efforts have been made to develop therapies against the growth of blood vessels and therefore 'starve' tumors of their resources, but they are not entirely effective,” said lead author Michael Breckwoldt, PhD, of the University of Heidelberg. “Improved imaging techniques that faithfully show the vessel architecture, including their growth, structure and density, and the effects of treatments in a noninvasive way are therefore needed to inform the development of future clinical trials.”

Neoangiogenesis is a pivotal therapeutic target in glioblastoma, since blood helps transport oxygen, nutrients, hormones, and waste products quickly and efficiently around the body. As tumors are made up of particularly active cells, their growth heavily depends on numerous blood vessels, in such that a fundamental hallmark of tumor progression is that nearby blood vessels form more quickly. Tumor blood vessels also differ in structure from their normal counterparts, for reasons that need to be investigated in more detail.

Related Links:
University of Heidelberg
University Medical Center Göttingen