{"id":41768,"date":"2021-09-30T17:00:00","date_gmt":"2021-09-30T15:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=41768"},"modified":"2024-08-16T15:37:33","modified_gmt":"2024-08-16T13:37:33","slug":"new-microscopy-technique-makes-deep-in-vivo-brain-imaging-possible","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/new-microscopy-technique-makes-deep-in-vivo-brain-imaging-possible\/","title":{"rendered":"New microscopy technique makes deep in vivo brain imaging possible"},"content":{"rendered":"\n<p>A pioneering technique developed by the <a href=\"https:\/\/www.embl.org\/groups\/prevedel\/\">Prevedel Group<\/a> at EMBL allows neuroscientists to observe live neurons deep inside the brain \u2013 or any other cell hidden within an opaque tissue. The technique is based on two state-of-the-art microscopy methods, three-photon microscopy and adaptive optics. The paper reporting on this advancement was published on 30th September 2021 in <em>Nature Method<\/em>s.<\/p>\n\n\n\n<p>Until the development of the new technique, it was challenging for neuroscientists to observe astrocytes generating calcium waves in deep layers of the cortex, or to visualise any other neural cells in the hippocampus, a region deep in the brain that is responsible for spatial memory and navigation. The phenomenon takes place regularly in the brains of all live mammals. By developing the new technique, Lina Streich from the Prevedel Group and her collaborators were able to capture the fine details of these versatile cells at unprecedented high resolution. The international team included researchers from Germany, Austria, Argentina, China, France, the USA, India, and Jordan.<\/p>\n\n\n\n<p>In the neurosciences, brain tissues are observed mostly in small model organisms or in <em>ex vivo<\/em> samples that need to be sliced up to be observed \u2013 both of which represent non-physiological conditions. Normal brain cell activity takes place only in live animals, but the \u201cmouse brain is a highly scattering tissue,\u201d said Robert Prevedel. \u201cIn these brains, light cannot be focused very easily, because it interacts with the cellular components. This limits how deep you can generate a crisp image, and it makes it very difficult to focus on small structures deep inside the brain with traditional techniques.\u201d<\/p>\n\n\n\n<p>Thanks to Streich, a former PhD student in the lab who worked for more than four years to overcome this problem, scientists can now peer further into tissues.<\/p>\n\n\n\n<p>\u201cWith traditional fluorescence brain microscopy techniques, two photons are absorbed by the fluorescence molecule each time, and you can make sure that the excitement caused by the radiation is confined to a small volume,\u201d explained Prevedel, a physicist by training. \u201cBut the further the photons travel, the more likely they are lost due to scattering.\u201d One way to overcome this is to increase the wavelength of the exciting photons towards the infrared, which ensures enough radiation energy to be absorbed by the fluorophore. In addition, using three photons instead of two allows to obtain crisper images deep inside the brain. But another challenge remains: making sure that the photons are focused, so that the whole image is not blurry.<\/p>\n\n\n\n<p>This is where the second technique used by Streich and her team is important. Adaptive optics is used regularly in astronomy \u2013 and indeed it was crucial for Roger Penrose, Reinhard Genzel and Andrea Ghez to obtain the Nobel Prize in Physics in 2020 for their discovery of black holes. Astrophysicists use deformable, computer-controlled mirrors to correct in real time for the distortion in the light wave front caused by atmospheric turbulence. In Prevedel\u2019s lab, the distortion is caused by the scattering in homogeneous tissue, but the principle and the technology are very similar. \u201cWe also use an actively controlled deformable mirror, which is capable of optimising the wave fronts to allow the light to converge and focus even deep inside the brain,\u201d explained Prevedel. \u201cWe developed a custom approach to make it fast enough to use on live cells in the brain,\u201d added Streich. To reduce the invasiveness of the technique, the team also minimised the number of measurements needed to achieve high-quality images.<\/p>\n\n\n\n<p>\u201cThis is the first time these techniques have been combined,\u201d said Streich, \u201cand thanks to them, we were able to show the deepest <em>in vivo<\/em> images of live neurons at high resolution.\u201d The scientists, who worked in collaboration with colleagues from EMBL Rome and the University of Heidelberg, even visualised the dendrites and axons that connect the neurons in the hippocampus, while leaving the brain completely intact.<\/p>\n\n\n\n<p>\u201cThis is a leap towards developing more advanced non-invasive techniques to study live tissues,\u201d Streich said. Although the technique was developed for use on a mouse brain, it is easily applicable to any opaque tissue. \u201cBesides the obvious advantage of being able to study biological tissues without the need to sacrifice the animals or to remove overlaying tissue, this new technique opens the way to study an animal longitudinally, that is, from the onset of a disease to the end. This will give scientists a powerful instrument to better understand how diseases develop in tissues and organs.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Scientists in EMBL\u2019s Prevedel Group have developed a pioneering microscopy technique that allows researchers to observe cells hidden within opaque tissues, such as live neurons embedded deep in the brain.<\/p>\n","protected":false},"author":105,"featured_media":42816,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[5620,527,595,3664,598,79,615,592,464],"embl_taxonomy":[9796,19357,19093],"class_list":["post-41768","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-adaptive-optics","tag-biological-imaging","tag-brain","tag-hippocampus","tag-imaging","tag-microscopy","tag-neuron","tag-neuroscience","tag-prevedel","embl_taxonomy-embl-heidelberg","embl_taxonomy-prevedel-group","embl_taxonomy-robert-prevedel"],"acf":{"featured":true,"show_featured_image":false,"article_intro":"<p>This advancement will allow scientists to capture the fine details of neurons at unprecedented high resolution<\/p>\n","related_links":false,"source_article":[{"publication_title":"High-resolution structural and functional deep brain imaging using adaptive optics three-photon microscopy","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41592-021-01257-6","target":""},"publication_authors":"Streich L, et al. ","publication_source":"Nature","publication_date":"September, 2021","publication_doi":"10.1038\/s41592-021-01257-6"}],"in_this_article":false,"press_contact":"None","field_target_display":"","vf_locked":false,"field_article_language":{"value":"english","label":"English"},"article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"ab46b6d4-71d8-49f8-b2f4-b326d4c8ea4e\";}","parents":[],"name":["EMBL Heidelberg"],"slug":"embl-heidelberg","description":"Where &gt; All EMBL sites &gt; EMBL Heidelberg"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"64999cc4-9a7c-4fea-8339-0e2acc990e08\";i:2;s:36:\"22615b4a-0ac4-4141-8574-199436bb4913\";}","parents":[],"name":["Prevedel Group"],"slug":"prevedel-group","description":"What &gt; Cell biology and biophysics &gt; Prevedel Group"},{"uuid":"a:2:{i:0;s:36:\"4428d1fd-441a-4d6d-a1c5-5dcf5665f213\";i:1;s:36:\"a42830ba-69f4-40ca-8727-80195960e834\";}","parents":[],"name":["Robert Prevedel"],"slug":"robert-prevedel","description":"Who &gt; Robert Prevedel"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>New microscopy technique makes deep in vivo brain imaging possible | EMBL<\/title>\n<meta name=\"description\" content=\"Scientists in Prevedel Group have developed a new technique that allows researchers to observe cells hidden within opaque tissues. 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