The brain discovered thanks to ultrasound microscopy – Sciences et Avenir

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Ultrasound to reveal all the secrets of the brain. Researchers from the Physics for Medicine research unit at the School of Physics and Industrial Chemistry in Paris have found a way to see the brain with unprecedented precision, thanks to ultrasound. Their technique, presented in the journal Nature Methods on August 4, 2022, exposes the entire brain at the micron scale in near real time, in a non-invasive and non-ionizing manner. Sciences et Avenir interviewed the team’s director, Mickael Tanter, to learn more about this method, which is sure to revolutionize the study of the brain and the diseases that affect it. Sciences et Avenir: What techniques are currently used to look at the brain? Mickael Tanter: There are two types of techniques for reading brain activity: those that directly see the electrical currents propagating between neurons, such as electroencephalography, and those that see this activity indirectly, using neurovascular coupling , that is, the fact that the activity increases locally when the neurons of a certain region are activated, because they need to be fed to work. The first are techniques that allow direct access to the signal of the neurons, but they do not have a good spatial resolution: we have a good signal, but we do not know exactly which area it comes from. The seconds allow better spatial resolution of neuronal activity by observing activity in the blood vessels that feed them. The most well-known method is magnetic resonance imaging (functional MRI), which analyzes the change in local oxygenation, a marker of increased blood flow and therefore the activity of neurons in that area. But there is another technique, less expensive and less cumbersome than magnetic resonance imaging, on which we are working and which allows us to see cerebral blood flow very precisely: functional ultrasound. Ultrasound to reveal all the secrets of the brain. Researchers at the Physics for Medicine research unit in Paris (Inserm, ESPCI Paris-PSL, CNRS) have found a way to see the brain with incredible precision, thanks to ultrasound. Their technique, presented in the journal Nature Methods on August 4, 2022, exposes the entire brain at the micron scale in near real time, in a non-invasive and non-ionizing manner. Sciences et Avenir interviewed the team’s director, Mickael Tanter, to learn more about this method, which is sure to revolutionize the study of the brain and the diseases that affect it. Sciences et Avenir: What techniques are currently used to look at the brain? Mickael Tanter: There are two types of techniques for reading brain activity: those that directly see the electrical currents propagating between neurons, such as electroencephalography, and those that see this activity indirectly, using neurovascular coupling , that is, the fact that the activity increases locally when the neurons of a certain region are activated, because they need to be fed to work. The first are techniques that allow direct access to the signal of the neurons, but they do not have a good spatial resolution: we have a good signal, but we do not know exactly which area it comes from. The seconds allow better spatial resolution of neuronal activity by observing activity in the blood vessels that feed them. The most well-known method is magnetic resonance imaging (functional MRI), which analyzes the change in local oxygenation, a marker of increased blood flow and therefore the activity of neurons in that area. But there is another technique, less expensive and less cumbersome than magnetic resonance imaging, on which we are working and which allows us to see cerebral blood flow very precisely: functional ultrasound. How long have you been working on this ultrasound technique? We started developing this technique about ten years ago, when our lab showed that ultrasound could pick up even the small blood vessels in the brain and see when they changed in diameter (indicating increased blood flow and thus a activation of the neurons in this area) with a spatial resolution of the order of one millimeter with several images per second In 2015 we improved this technique by adding gas bubbles to the blood flow: these bubbles of 2-3 microns in diameter are visible with ultrasound, since this gas is much less dense than the liquid surrounding it in the bloodstream and much more compressible. These bubbles are therefore hyperreflective for ultrasound and we can locate them when they pass through the vascular network, which allows us to make a very detailed map of the blood flow and the vessels Thanks to these bubbles we have been able to increase the resolution of 30 to 30. 40 times more than with ultrasound alone. For the first time, we were able to see the cerebrovascular network at the micron scale deep in the brain, unlike microscopes that only see the surface. So you already had excellent spatial resolution. So what is the improvement announced in your last post? In fact, this technique allowed us to see even the smallest blood vessels, but it takes time for bubbles to reach these capillaries, so it took 20-30 seconds to image the entire vascular network. In other words, we had very good spatial resolution, but no temporal resolution. So we couldn’t see a rapidly changing phenomenon. We have now managed to solve this problem by grouping the signals from several stimulations. For example, we tickle a rat’s whiskers 20 times instead of just once and add the signal from all these stimulations, second by second (first second of the first experiment plus first second of the second experiment, etc.). Suddenly, instead of having the image of one second, we have the equivalent of 30 seconds, and this is the case for the entire duration of the stimulation. It allows a temporal resolution of one second on the scale of one micron. Thanks to this improvement, we were able to see, for the first time, how blood flow changes in very small vessels when neurons are stimulated. Thus, we can perform neuroimaging at the scale of the whole brain in a dynamic manner down to the micron scale. Now we can see exactly how small blood vessels will change in diameter throughout the brain – a complete map of brain activity at a microscopic scale, in a completely non-invasive way. Is this brain map three-dimensional? For now, this is 2D imaging, but we know that we will be able to make 3D images of the brain by increasing the number of sensors used (thousands versus hundreds today). We’ve already done it in mice, so we know we can do it in humans too. How useful could your technique be at a clinical level? In the clinic, this technique will contribute a lot, for example to better study the neurovascular coupling, the basis of all our brain activity. We may have a formidable neural network, but it doesn’t work if the neurons aren’t well fed. This is also what we see with neurodegenerative diseases, where there are alterations in the cerebral vascular system. Diseases usually start in the small blood vessels before they develop and affect the larger vessels. The growth of cancerous tumors begins, for example, with the appearance of small vessels – let’s talk about angiogenesis – that will nourish the tumor and allow it to grow. Diabetes is also a disease that affects the small vessels. With current brain imaging techniques (CT angiography or magnetic resonance imaging), we see vessels larger than a tenth of a millimeter in diameter, but we are blind to the smallest vessels (between a few microns and ten thousand limit), so we see the disease when it is already in an advanced phase. With our functional ultrasound microscopy technique, which is also non-ionizing, we will be able to see the microvessels and we will be able to observe on a microscopic scale how the alteration of the neurovascular coupling can progressively degenerate into neurodegenerative disease. The more we start to see smaller and smaller vessels, the more we go back in time on the disease.
#brain #discovered #ultrasound #microscopy #Sciences #Avenir

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