TrueBold by EU Research

New MR methods for functional imaging

Magnetic Resonance Imaging scanners have become an important tool in both medical diagnostics and research, yet current methods are not highly sensitive to the micro blood vessels around which neuronal activation typically occurs. We spoke to Professor Klaus Scheffler about his work in developing improved MR methods to detect neuronal activity in the brain. A technology developed in the ‘70s, Magnetic Resonance Imaging (MRI) scanners have since become an important diagnostic and research tool, providing anatomical images of the body from which Doctors can learn more about our organs and how they are affected by disease. As the Principal Investigator of the TrueBOLD project, Professor Klaus Scheffler now aims to develop improved magnetic resonance methods to

vessels with a diameter of between 5-10 micrometers,” says Professor Scheffler. This means the resulting signal or activation is much less easily confounded by vascular effects, so neuronal activation can be identified more clearly. While this is a significant attribute of the TrueFISP acquisition method, one disadvantage is that it is around 3-4 times slower in imaging acquisition speed than existing techniques, an issue which Professor Scheffler aims to address over the course of the project. “If the aim is to resolve rapid changes in the brain then this level of temporal resolution is a problem. That can be solved, and that’s what I will be working on intensively over the next few years,” he outlines. Neuronal processes take place over very short timescales and extremely rapid measurements are required to capture them, so this is an important aspect of Professor Scheffler’s research. “We want to develop a much more precise and higher spatially resolved method of mapping the working brain,” he says.

which has been oxygenated. “The oxygen in arterial blood goes to the nerve cells, where it is consumed. Then there is venous blood, which has a much lower oxygenation level,” explains Professor Scheffler. If a certain region of the brain needs to work more intensively, maybe because the individual is solving physics equations or focusing on another demanding task, then it will consume more oxygen; this is an important

We want to develop a much more precise and higher spatially resolved method of

mapping the working brain. detect neuronal activity in the brain. “Our focus is on functional imaging, to produce images showing which regions of the brain are working hardest at a particular point in time,” he explains. An image of the brain may allow researchers to see the different regions of the brain, but not necessarily which of those have been activated at a specific moment, an issue that Professor Scheffler is working to address. “I am trying to develop a new method that is more specific to neuronal activation than existing methods,” he says. These existing methods work primarily by detecting changes in water relaxation within a neurovascular network within the brain. There are essentially two sorts of blood in the brain, one of which is arterial blood,

consideration in Professor Scheffler’s research. “When a region of the brain has a task there is a local change in blood oxygenation level,” continues Professor Scheffler. “We cannot directly measure blood oxygenation, but we can measure a secondary effect on an MRI image, which can then be interpreted further.”

TrueFISP The current magnetic resonance methods are very sensitive to the larger draining veins in the brain, yet neuronal activation typically occurs near much smaller blood vessels, with diameters of between 5-10 micrometers. Researchers in the project have modified a fairly well-established

There are some significant technical challenges to deal with before this approach can be applied more widely in functional brain imaging, which is the wider goal over the long term. In particular, a very homogenous magnetic field is required in order to use this image acquisition method. “The field in conventional Magnetic Resonance systems is not really homogenous enough, that’s why we added dynamic shim arrays,” says Professor Scheffler. These dynamic shim arrays surround the brain, in order to make the field more homogenous and allow the application of the TrueBOLD technique, leading to a more distinct signal of neuronal activation. “For example, we want to make the red dots which indicate neural activation [see figure 1] more specific,” outlines Professor Scheffler. “If you have a more specific signal, more closely related to neural activation than vascular effects, then that opens up new possibilities in both radiology and neuroscience research.” A more detailed method of mapping the brain could in the long-term open up new avenues of investigation and help researchers build a deeper understanding of how it functions. While a lot of progress has been made in the neuroscience field over recent decades, there remains a lot to learn about the overall structure and function of the brain. “We don’t know whether certain paths work together and how different regions are controlled,” outlines Professor Scheffler. The project’s research holds important implications in these terms. “This is the only non-invasive method with such a high temporal and spatial resolution, and it is able to capture signals from the entire brain. We can put anybody into this scanner – it’s completely non-invasive – and look into their brain,” says Professor Scheffler. “This is about trying to answer very fundamental questions on how the brain functions.”

TrueBOLD Detecting brain activity with TrueFISP Project Objectives

TrueBOLD addresses the detection of neuronal activity in the human brain with magnetic resonance imaging based on an acquisition technique called TrueFISP or balanced SSFP at very high fields. Traditionally, blood oxygenation changes are detected with echo planar sequences (EPI) that are sensitive to the static spin dephasing around small and larger vessels filled with deoxygenated blood. EPI is not specific to a certain type of vessel architecture or size, it sometimes shows blurring and blooming around larger vessels, it shows significant spatial distortions and thus severe challenges in precise co-registration to submillimeter anatomical structures. The proposed detection of BOLD changes with pass-band balanced SSFP, TrueBOLD, in combination with localized and dynamic shim arrays and strategies to minimize physiological signal fluctuations has the potential to overcome these limitations.

Project Funding

German Research Foundation, DFG Reinhart Koselleck Project SCHE 658/12.

Contact Details

Project Coordinator, Prof. Dr. phil. nat. Klaus Scheffler, PhD MRC Department Max Planck Institute for Biological Cybernetics Department of Biomedical Magnetic Resonance Center for Integrative Neuroscience, CIN University of Tübingen Max-Planck-Ring 11 72076 Tuebingen, Germany T: +49 (0)7071 601-700/701 E: klaus.scheffler@tuebingen.mpg.de W: https://www.kyb.tuebingen.mpg. de/157539/dfg-reinhart-koselleck-project W: http://www.kyb.mpg.de/de/mr

Professor Klaus Scheffler, PhD

Klaus Scheffler is Director of the Biomedical Magnetic Resonance Department at the University of Tübingen, where he also works as a Professor of Neuroimaging and Magnetic Resonance Physics. He has a PhD in Biophysical Chemistry, and held research positions at several institutions in Europe and America before taking up his current role.

image acquisition technique called TrueFISP, mostly used for rapid cardiac imaging, which has been found to actually be better suited to imaging neuronal activation than existing methods. “The reason for this is that it is less sensitive to larger veins,” outlines Professor Scheffler. The goal here is to enable a more specific signal of neuronal activation, more easily distinguishable from vascular effects. “The new method essentially does not see the medium-sized vessels, it’s not sensitive to them. It’s more sensitive to the micro-

EU Research

Functional brain imaging