TY - JOUR
T1 - Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis
AU - Schubert, Marc Cicero
AU - Soyka, Stella Judith
AU - Tamimi, Amr
AU - Maus, Emanuel
AU - Schroers, Julian
AU - Wißmann, Niklas
AU - Reyhan, Ekin
AU - Tetzlaff, Svenja Kristin
AU - Yang, Yvonne
AU - Denninger, Robert
AU - Peretzke, Robin
AU - Beretta, Carlo
AU - Drumm, Michael
AU - Heuer, Alina
AU - Buchert, Verena
AU - Steffens, Alicia
AU - Walshon, Jordain
AU - McCortney, Kathleen
AU - Heiland, Sabine
AU - Bendszus, Martin
AU - Neher, Peter
AU - Golebiewska, Anna
AU - Wick, Wolfgang
AU - Winkler, Frank
AU - Breckwoldt, Michael O.
AU - Kreshuk, Anna
AU - Kuner, Thomas
AU - Horbinski, Craig
AU - Kurz, Felix Tobias
AU - Prevedel, Robert
AU - Venkataramani, Varun
N1 - Grants and funding :
DFG: VE1373/2-1/Deutsche Forschungsgemeinschaft (German Research Foundation)
DFG: SFB 1389/Deutsche Forschungsgemeinschaft (German Research Foundation)
DFG: BR 6153/1-1/Deutsche Forschungsgemeinschaft (German Research Foundation)
507778602/Deutsche Forschungsgemeinschaft (German Research Foundation)
951991, Brainiaqs/European Commission (EC)
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9/10
Y1 - 2024/9/10
N2 - Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.
AB - Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.
UR - http://www.scopus.com/inward/record.url?scp=85203458734&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/39256378/
U2 - 10.1038/s41467-024-51432-4
DO - 10.1038/s41467-024-51432-4
M3 - Article
C2 - 39256378
AN - SCOPUS:85203458734
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7383
ER -