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!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering