1.Institute of Pharmacology and Toxicology & Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich, Zurich, Switzerland
2.Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland
3.Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland
4.Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
5.Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Vienna, Austria
Daniel Razansky (daniel.razansky@uzh.ch)
Published:31 December 2024,
Published Online:11 November 2024,
Received:15 March 2024,
Revised:04 September 2024,
Accepted:18 September 2024
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Glandorf, L. et al. Bessel beam optical coherence microscopy enables multiscale assessment of cerebrovascular network morphology and function. Light: Science & Applications, 13, 3210-3223 (2024).
Glandorf, L. et al. Bessel beam optical coherence microscopy enables multiscale assessment of cerebrovascular network morphology and function. Light: Science & Applications, 13, 3210-3223 (2024). DOI: 10.1038/s41377-024-01649-1.
Understanding the morphology and function of large-scale cerebrovascular networks is crucial for studying brain health and disease. However
reconciling the demands for imaging on a broad scale with the precision of high-resolution volumetric microscopy has been a persistent challenge. In this study
we introduce Bessel beam optical coherence microscopy with an extended focus to capture the full cortical vascular hierarchy in mice over 1000 × 1000 × 360 μm
3
field-of-view at capillary level resolution. The post-processing pipeline leverages a supervised deep learning approach for precise 3D segmentation of high-resolution angiograms
hence permitting reliable examination of microvascular structures at multiple spatial scales. Coupled with high-sensitivity Doppler optical coherence tomography
our method enables the computation of both axial and transverse blood velocity components as well as vessel-specific blood flow direction
facilitating a detailed assessment of morpho-functional characteristics across all vessel dimensions. Through graph-based analysis
we deliver insights into vascular connectivity
all the way from individual capillaries to broader network interactions
a task traditionally challenging for in vivo studies. The new imaging and analysis framework extends the frontiers of research into cerebrovascular function and neurovascular pathologies.
Blinder, P. et al. The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow.Nat. Neurosci.16, 889–897 (2013)..
Meyer, E. P. et al. Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease.Proc. Natl Acad. Sci. USA105, 3587–3592 (2008)..
El Amki, M. et al. Neutrophils obstructing brain capillaries are a major cause of no-reflow in ischemic stroke.Cell Rep.33, 108260 (2020)..
Quintana, D. D. et al. The cerebral angiome: high resolution MicroCT imaging of the whole brain cerebrovasculature in female and male mice.NeuroImage202, 116109 (2019)..
Todorov, M. I. et al. Machine learning analysis of whole mouse brain vasculature.Nat. Methods17, 442–449 (2020)..
Daulatzai, M. A. Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease.J. Neurosci. Res.95, 943–972 (2017)..
Walek, K. W. et al. Near-lifespan longitudinal tracking of brain microvascular morphology, topology, and flow in male mice.Nat. Commun.14, 2982 (2023)..
Binder, N. F. et al. Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.Neuron112, 1456–1472. e6 (2024)..
Xiao, S. et al. High-throughput deep tissue two-photon microscopy at kilohertz frame rates.Optica10, 763–769 (2023)..
Fan, J. L. et al. High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics.Nat. Commun.11, 6020 (2020)..
Postnov, D. D. et al. Dynamic light scattering imaging.Sci. Adv.6, eabc4628 (2020)..
Razansky, D., Klohs, J.&Ni, R. Q. Multi-scale optoacoustic molecular imaging of brain diseases.Eur. J. Nucl. Med. Mol. Imaging48, 4152–4170 (2021)..
Yao, J. J. et al. High-speed label-free functional photoacoustic microscopy of mouse brain in action.Nat. Methods12, 407–410 (2015)..
Errico, C. et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging.Nature527, 499–502 (2015)..
Deán-Ben, X. L. et al. Deep optoacoustic localization microangiography of ischemic stroke in mice.Nat. Commun.14, 3584 (2023)..
Zhou, Q. Y. et al. Depth-resolved localization microangiography in the NIR-Ⅱ window.Adv. Sci.10, 2204782 (2023)..
Marchand, P. J. et al. Validation of red blood cell flux and velocity estimations based on optical coherence tomography intensity fluctuations.Sci. Rep.10, 19584 (2020)..
Spaide, R. F. et al. Optical coherence tomography angiography.Prog. Retin. Eye Res.64, 1–55 (2018)..
Srinivasan, V. J. et al. Micro-heterogeneity of flow in a mouse model of chronic cerebral hypoperfusion revealed by longitudinal Doppler optical coherence tomography and angiography.J. Cereb. Blood Flow. Metab.35, 1552–1560 (2015)..
Leitgeb, R. A. et al. Doppler optical coherence tomography.Prog. Retin. Eye Res.41, 26–43 (2014)..
Tang, J. B. et al. Capillary red blood cell velocimetry by phase-resolved optical coherence tomography.Opt. Lett.42, 3976–3979 (2017)..
Lee, J. et al. Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography.J. Cereb. Blood Flow Metab.33, 819–825 (2013)..
Wang, R. K. et al. Optical coherence tomography angiography-based capillary velocimetry.J. Biomed. Opt.22, 066008 (2017)..
Marchand, P. J. et al. Imaging of cortical structures and microvasculature using extended-focus optical coherence tomography at 1.3 μm.Opt. Lett.43, 1782–1785 (2018)..
Leitgeb, R. A. et al. Extended focus depth for Fourier domain optical coherence microscopy.Opt. Lett.31, 2450–2452 (2006)..
Blatter, C. et al. Extended focus high-speed swept source OCT with self-reconstructive illumination.Opt. Express19, 12141–12155 (2011)..
Villiger, M., Pache, C.&Lasser, T. Dark-field optical coherence microscopy.Opt. Lett.35, 3489–3491 (2010)..
Schmid, F. et al. Depth-dependent flow and pressure characteristics in cortical microvascular networks.PLoS Comput. Biol.13, e1005392 (2017)..
Pan, Y. T. et al. Ultrasensitive detection of 3D cerebral microvascular network dynamics in vivo.NeuroImage103, 492–501 (2014)..
Merkle, C. W. et al. Dynamic Contrast Optical Coherence Tomography reveals laminar microvascular hemodynamics in the mouse neocortex in vivo.NeuroImage202, 116067 (2019)..
Zhu, J. et al. Visibility of microvessels in Optical Coherence Tomography angiography depends on angular orientation.J. Biophoton.13, e202000090 (2020)..
Szkulmowski, M. et al. Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography.Opt. Express16, 6008–6025 (2008)..
Bouwens, A. et al. Quantitative lateral and axial flow imaging with optical coherence microscopy and tomography.Opt. Express21, 17711–17729 (2013)..
Ren, H. W. et al. Imaging and quantifying transverse flow velocity with the Doppler bandwidth in a phase-resolved functional optical coherence tomography.Opt. Lett.27, 409–411 (2002)..
Srinivasan, V. J. et al. Quantitative cerebral blood flow with Optical Coherence Tomography.Opt. Express18, 2477–2494 (2010)..
Blatter, C. et al. In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography.Sci. Rep.6, 29035 (2016)..
Hwang, Y. et al. Retinal blood flow speed quantification at the capillary level using temporal autocorrelation fitting OCTA.Biomed. Opt. Express14, 2658–2677 (2023)..
Tang, J. B. et al. Normalized field autocorrelation function-based optical coherence tomography three-dimensional angiography.J. Biomed. Opt.24, 036005 (2019)..
Fahrbach, F. O., Simon, P.&Rohrbach, A. Microscopy with self-reconstructing beams.Nat. Photon.4, 780–785 (2010)..
Wittmann, B. et al. Simulation-based segmentation of blood vessels in cerebral 3D OCTA images. Print athttps://arxiv.org/abs/2403.07116https://arxiv.org/abs/2403.07116(2024).
Çiçek, Ö. et al. 3D U-Net: learning dense volumetric segmentation from sparse annotation.Proceedings of the 19th International Conference Medical Image Computing and Computer-Assisted Intervention. p. 424–432 (Springer, 2016).
Ronneberger, O., Fischer, P.&Brox, T. U-Net: convolutional networks for biomedical image segmentation.Proceedings of the 18th International Conference Medical Image Computing and Computer-Assisted Intervention. p. 234–241 (Springer, 2015).
Isensee, F. et al. nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation.Nat. Methods18, 203–211 (2021)..
Schneider, M. et al. Tissue metabolism driven arterial tree generation.Med. Image Anal.16, 1397–1414 (2012)..
Drees, D. et al. Scalable robust graph and feature extraction for arbitrary vessel networks in large volumetric datasets.BMC Bioinform.22, 346 (2021)..
Stefan, S.&Lee, J. Deep learning toolbox for automated enhancement, segmentation, and graphing of cortical optical coherence tomography microangiograms.Biomed. Opt. Express11, 7325–7342 (2020)..
Schrandt, C. J. et al. Chronic monitoring of vascular progression after ischemic stroke using multiexposure speckle imaging and two-photon fluorescence microscopy.J. Cereb. Blood Flow. Metab.35, 933–942 (2015)..
Pian, Q. et al. Cortical microvascular blood flow velocity mapping by combining dynamic light scattering optical coherence tomography and two-photon microscopy.J. Biomed. Opt.28, 076003 (2023)..
Tomsits, P. et al. Medetomidine/midazolam/fentanyl narcosis alters cardiac autonomic tone leading to conduction disorders and arrhythmias in mice.Lab Anim.52, 85–92 (2023)..
Przybylski, A. et al. Gpufit: an open-source toolkit for GPU-accelerated curve fitting.Sci. Rep.7, 15722 (2017)..
Hormel, T. T., Huang, D.&Jia, Y. L. Artifacts and artifact removal in optical coherence tomographic angiography.Quant. Imaging Med. Surg.11, 1120–1133 (2021)..
Sudre, C. H. et al. Generalised dice overlap as a deep learning loss function for highly unbalanced segmentations.Proceedings of the Third International Workshop. p. 240–248 (Springer, 2017).
Drew, P. J. et al. Rapid determination of particle velocity from space-time images using the Radon transform.J. Comput. Neurosci.29, 5–11 (2010)..
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