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!
'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS
New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
20.02.2018 | Life Sciences
20.02.2018 | Life Sciences
20.02.2018 | Physics and Astronomy