{"id":70285,"date":"2024-09-10T11:00:59","date_gmt":"2024-09-10T09:00:59","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=70285"},"modified":"2024-10-31T10:18:56","modified_gmt":"2024-10-31T09:18:56","slug":"follow-the-cellular-road","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/","title":{"rendered":"Follow the cellular road"},"content":{"rendered":"\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Summary    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">New research provides the proof of concept for a pioneering microscopy technique that can penetrate deep brain tissue.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Researchers enhanced the technology with artificial intelligence to enable it to track individual brain tumour cells migrating along a nerve fibre \u2018superhighway\u2019 known as the corpus callosum. They specifically targeted cancer cells related to glioblastomas, one of the deadliest brain cancers.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">The scientists believe that understanding early cancer cell \u2018traffic patterns\u2019 along the corpus callosum could help establish a biomarker for detecting glioblastomas earlier in patients, potentially leading to better diagnostic tools in the future.<\/span><\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Imagine building a traffic surveillance camera that could detect trouble-making cells speeding around in your brain before their cellular gang could commit \u2018crimes\u2019. Most importantly, this camera could catch some of the biggest interlopers of all \u2013 cancer cells.<\/p>\n\n\n\n<p>This \u2018surveillance camera\u2019 is no longer a figment of the imagination. Along the brain\u2019s biggest superhighway of nerve fibres that connects the brain\u2019s right and left hemispheres \u2013 the corpus callosum \u2013 travel cells that comprise one of the deadliest brain cancers, glioblastomas. Now, scientists have made this cellular detector a reality, introducing artificial intelligence to a state-of-the-art microscope. They can now visualise and track specific cells with unprecedented clarity in deep brain tissue, including along this superhighway.&nbsp;<\/p>\n\n\n\n<p>In a recent collaborative endeavour between EMBL and Heidelberg University, scientists are using this new technology to track glioblastoma tumour cells to better understand this deadly cancer and possibly detect it earlier, which could potentially lead to better diagnostic tools in the future.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>A deep tissue microscope is born<\/strong><\/h2>\n\n\n\n<p>In 2021, EMBL researchers \u2013 with collaborators from Germany, Austria, Argentina, China, France, the United States, India, and Jordan \u2013 <a href=\"https:\/\/www.embl.org\/news\/science\/new-microscopy-technique-makes-deep-in-vivo-brain-imaging-possible\/\">developed a new microscopy technique<\/a>. EMBL Group Leader Robert Prevedel and his research group worked with these diverse collaborators to address some of the challenges neuroscientists face in studying deep brain regions. Previously, diffuse brain tissue posed a problem for scientists when they tried to observe neurons and glial cells known as astrocytes and study how they communicate deep within the cortex. It also made it difficult to visualise neural cells in the hippocampus, another deep brain region responsible for spatial memory and navigation.&nbsp;<\/p>\n\n\n\n<p>The scientists based their new approach on state-of-the-art microscopy methods that could provide a wider and clearer aperture for viewing while also adjusting for the distortion that arises when light waves scatter in deep brain tissue. They envisioned many possible future applications in brain research.<\/p>\n\n\n\n<p>Now, in a study <a href=\"https:\/\/www.nature.com\/articles\/s41467-024-51432-4\">published in the journal <em>Nature Communications<\/em><\/a>, Prevedel has teamed up with neuroscientists, neurooncologists, and AI experts to take this microscope to the next level. The result is a microscope that can observe living neurons \u2013 and other kinds of brain cells \u2013 deep within the brain over a prolonged period of time.<\/p>\n\n\n\n<p>\u201cWe have now gone from taking a snapshot of cells in a mouse brain to zooming in on specific cells and being able to follow them for many hours or even days,\u201d Prevedel said. \u201cAlso, incorporating custom AI approaches has allowed us to distinguish different parts of the microenvironment of the cells, which is also very important to understand their behaviour in context.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Putting it to the test<\/strong><\/h2>\n\n\n\n<p>In 2021, Varun Venkataramani at the Neurology Clinic of the University Hospital Heidelberg read of this new approach to deep-tissue microscopy with great interest. His research focuses on human brain tumours \u2013 notably glioblastomas, which are prevalent, fast-growing, and intractable tumours. Venkataramani was learning more and more about neural mechanisms that determine how tumours originate, progress, and ultimately respond to or resist treatment. However, his microscopy approach at the time restricted imaging depth, limiting them mainly to the brain\u2019s grey matter.<\/p>\n\n\n\n<p>\u201cThe 2021 paper by Robert\u2019s group introduced a deep-tissue microscopy technique that I believed could extend our imaging capabilities to the white matter of the corpus callosum,\u201d Venkataramani said. White matter plays a role in communication between different grey matter areas of the brain and the rest of the body. \u201cThis could potentially reveal novel biological processes and offer insights into the behaviour of these tumours in a critical, yet understudied niche,\u201d he added.&nbsp;<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image  | vf-figure--align vf-figure--align-inline-end  size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"961\" height=\"961\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/Stackcomp.png\" alt=\"\" class=\"wp-image-70303\" style=\"width:381px;height:auto\" srcset=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/Stackcomp.png 961w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/Stackcomp-300x300.png 300w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/Stackcomp-150x150.png 150w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/Stackcomp-768x768.png 768w\" sizes=\"auto, (max-width: 961px) 100vw, 961px\" \/><figcaption class=\"vf-figure__caption\">A glioblastoma tumour cell (green) present in the white matter (blue) near a blood vessel (red), visualised via the novel three-photon microscopy workflow Deep3P. Credits: Stella Soyka\/Universit\u00e4tsklinikum Heidelberg, Marc Schubert\/Universit\u00e4tsklinikum Heidelberg, Robert Prevedel\/EMBL, Varun Venkataramani\/Universit\u00e4tsklinikum Heidelberg.<\/figcaption><\/figure>\n\n\n\n<p>Glioblastomas are primarily a white-matter disease. The new advanced imaging technique enabled Venkataramani\u2019s team to observe these tumour cells within their microenvironment in the white matter. This capability was crucial to understanding how tumour cells invade the densely myelinated (insulated) fibre \u2018lanes\u2019 of the corpus callosum superhighway and then adapt and spread throughout the brain. This process is also associated with glioblastomas\u2019 lethally invading critical brain structures.&nbsp;<\/p>\n\n\n\n<p>\u201cIt has been fascinating to observe tumour cell invasion in the corpus callosum in real-time,\u201d said Marc Schubert, one of the study\u2019s lead authors and medical student at Heidelberg University.&nbsp;<\/p>\n\n\n\n<p>\u201cAt this point, I think the most important aspect of this fundamental research is that it allows us to investigate these tumours in their most relevant microenvironmental niche for the first time,\u201d Venkataramani said. \u201cThese findings also help explain the current challenges in detecting glioblastoma cells at the tumour&#8217;s infiltrative edges using conventional MRI techniques, which are the standard in clinical imaging. As a neuroscientist, neurologist, and neurooncologist, I see potential for this technology to bridge the gap between laboratory research and clinical application, improving how we could diagnose and potentially treat brain tumours.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Artificial intelligence takes microscope to the next level<\/strong><\/h2>\n\n\n\n<p>An important feature of this latest collaboration was that the researchers incorporated an element of artificial intelligence.&nbsp;<\/p>\n\n\n\n<p>\u201cFrom a technical development point of view, the AI-based methods helped to \u2018denoise\u2019 our images, so the contrast now is much clearer,\u201d Prevedel said. \u201cThe AI can distinguish different structures inside the white matter, like myelinated fibres and blood vessels, which is important for a variety of reasons. AI was really instrumental in advancing the level of this microscope, so it can address these pressing medical questions.\u201d<\/p>\n\n\n\n<p>Anna Kreshuk\u2019s <a href=\"https:\/\/www.embl.org\/groups\/kreshuk\/\">research group<\/a> at EMBL Heidelberg provided this AI expertise. Kreshuk\u2019s group contributed to a customised workflow that helped distinguish blood vessel signals from the myelinated neural fibre ones, clarifying the tumour cells\u2019 microenvironment.<\/p>\n\n\n\n<p>Consequently, the researchers could identify a potential microscopic imaging biomarker linked to the structural properties of the white matter microenvironment. This innovative workflow sets the stage for potentially identifying imaging patterns for glioblastomas, so tumours could be detected earlier than they are currently.&nbsp;<\/p>\n\n\n\n<p>\u201cWe are looking forward to further customising this new approach towards more clinically practical needs in the future to maximise its potential,\u201d said Stella Soyka, one of the paper\u2019s lead authors and a medical resident in the Department of Neurology at Heidelberg University Clinic.<\/p>\n\n\n\n<p>\u201cIt\u2019s promising, but it\u2019s much too soon to apply it clinically without further development,\u201d Venkataramani said, explaining that the next steps will integrate further advanced imaging modalities, which can help build practical tools for standard clinical settings.<\/p>\n\n\n\n<p>\u201cWe are optimistic, particularly because of the robust interdisciplinary support from the Heidelberg-Mannheim Life Science Alliance network, which fosters collaboration across preclinical and clinical disciplines,\u201d he said.&nbsp; \u201cThis synergy is crucial for bringing these laboratory insights into clinical practice in the foreseeable future.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>An AI-enhanced advanced microscopy approach offers promise in better understanding glioblastomas, one of the deadliest brain cancers.<\/p>\n","protected":false},"author":100,"featured_media":70289,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591],"tags":[5620,4718,595,38,13926,43,598,859,79,592,653],"embl_taxonomy":[9796,19313,19357],"class_list":["post-70285","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","tag-adaptive-optics","tag-artificial-intelligence","tag-brain","tag-cancer","tag-health-life-science-alliance-heidelberg-mannheim","tag-heidelberg","tag-imaging","tag-microscope","tag-microscopy","tag-neuroscience","tag-tumour","embl_taxonomy-embl-heidelberg","embl_taxonomy-kreshuk-group","embl_taxonomy-prevedel-group"],"acf":{"vf_locked":false,"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>Scientists collaborate to customise top-of-the-line microscopy method with AI to better understand glioblastoma brain tumours<\/p>\n","related_links":[{"link_description":"Cell Biology and Biophysics Unit","link_url":"https:\/\/www.embl.org\/research\/units\/cell-biology-biophysics\/"},{"link_description":"Prevedel Group","link_url":"https:\/\/www.embl.org\/groups\/prevedel\/"},{"link_description":"New microscopy technique makes deep in vivo brain imaging possible\r\n","link_url":"https:\/\/www.embl.org\/news\/science\/new-microscopy-technique-makes-deep-in-vivo-brain-imaging-possible\/"}],"source_article":[{"publication_title":"Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis","publication_link":{"title":"","url":"https:\/\/www.nature.com\/articles\/s41467-024-51432-4","target":""},"publication_authors":"Schubert M.C., et al. ","publication_source":"Nature Communications","publication_date":"10 September 2024","publication_doi":"10.1038\/s41467-024-51432-4"}],"in_this_article":false,"press_contact":"EMBL Generic","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:\"f97d9bce-0a98-4250-ab74-de726b969114\";}","parents":[],"name":["Kreshuk Group"],"slug":"kreshuk-group","description":"What &gt; Cell biology and biophysics &gt; Kreshuk Group"},{"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"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Follow the cellular road | EMBL<\/title>\n<meta name=\"description\" content=\"An AI-enhanced advanced microscopy approach offers promise in better understanding glioblastomas, one of the deadliest brain cancers.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Follow the cellular road | EMBL\" \/>\n<meta property=\"og:description\" content=\"An AI-enhanced advanced microscopy approach offers promise in better understanding glioblastomas, one of the deadliest brain cancers.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2024-09-10T09:00:59+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-10-31T09:18:56+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/20240819_Prevedel_final_v2-scaled-e1725884283485.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Ivy Kupec\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Ivy Kupec\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/\"},\"author\":{\"name\":\"Ivy Kupec\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/427f2c9b624bc32ffa67d80414712274\"},\"headline\":\"Follow the cellular road\",\"datePublished\":\"2024-09-10T09:00:59+00:00\",\"dateModified\":\"2024-10-31T09:18:56+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/\"},\"wordCount\":1136,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/follow-the-cellular-road\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/09\/20240819_Prevedel_final_v2-scaled-e1725884283485.jpg\",\"keywords\":[\"adaptive optics\",\"artificial intelligence\",\"brain\",\"cancer\",\"Health + Life Science Alliance Heidelberg Mannheim\",\"heidelberg\",\"imaging\",\"microscope\",\"microscopy\",\"neuroscience\",\"tumour\"],\"articleSection\":[\"Science &amp; 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