Stopping the growth of blood vessels in tumours is a key target for glioblastoma therapies, and imaging methods are essential for initial diagnosis and monitoring the effects of treatments. While mapping vessels in tumours has proven a challenge, researchers have now developed a combined magnetic resonance imaging (MRI) and ultramicroscopy 'toolkit' to study vessel growth in glioma models in more detail than previously possible. Their study is to be published in the journal eLife.
"Gliomas are highly malignant brain tumours with poor prognosis," says Michael Breckwoldt, a physician-scientist and one of the lead authors of the paper from the University of Heidelberg.
"Many efforts have been made to develop therapies against the growth of blood vessels and therefore 'starve' tumours of their resources, but they are not entirely effective. Improved imaging techniques that faithfully show the vessel architecture, including their growth, structure and density, and the effects of treatments in a non-invasive way are therefore needed to inform the development of future clinical trials."
In their study in mice, the team combined an MRI approach in vivo with ultramicroscopy of ex vivo whole brains cleared for imaging.
The technique is based on T2*-weighted (T2*-w) MRI images, one of the basic pulse sequences in MRI, with high resolution to allow for substantially more detail than conventional T2*-w imaging. Pre- and post-contrast MR scans were performed to define the growth of vessels during glioma development in two different glioma models.
The team further mapped the development of vessels by dual-colour ultramicroscopy of whole, cleared brains. Using fluorescent labelling of microvessels, they collected complementary 3D MR and ultramicroscopy data sets (dubbed the 'MR-UM'), which could be compared side-by-side.
"MR-UM can be used as a platform for three-dimensional mapping of single vessels and detailed measurements of the growth of newly formed vessels over time," Dr. Breckwoldt explains.
"This provides a better understanding of the underlying mechanisms of existing treatment and could help identify novel targets for future drug development," adds Dr. Julia Bode, co-lead author from the German Cancer Research Centre.
The team 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 glioma models. They found that such treatments are insufficient to halt tumour growth in mice, which mirrors current human studies.
"Dual inhibitors of vessel growth are now being developed and our toolkit could also help assess their therapeutic effects in detail," says Bode.
The T2*-weighted imaging sequence and UM studies in ex vivo brains are at present only suitable for mapping tumour vessels in a preclinical setting. The team anticipates, however, that future studies using high-field clinical MR systems should enable possible translation of the MRI approach to the clinical arena. Furthermore, specimens taken for clinical diagnosis could be studied using ultramicroscopy, making the full MR-UM toolkit a potential player in a clinical setting.
eLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine -- from basic biological research to applied, translational, and clinical studies. All papers are selected by active scientists in the research community. Decisions and responses are agreed by the reviewers and consolidated by the Reviewing Editor into a single, clear set of instructions for authors, removing the need for laborious cycles of revision and allowing authors to publish their findings quickly. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org.
Emily Packer | EurekAlert!
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News