Visible spectrum extended-focus optical coherence microscopy for label-free sub-cellular tomography.

We present a novel extended-focus optical coherence microscope (OCM) attaining 0.7 μm axial and 0.4 μm lateral resolution maintained over a depth of 40 μm, while preserving the advantages of Fourier domain OCM. Our system uses an ultra-broad spectrum from a supercontinuum laser source. As the spectrum spans from near-infrared to visible wavelengths (240 nm in bandwidth), we call the system visOCM. The combination of such a broad spectrum with a high-NA objective creates an almost isotropic 3D submicron resolution. We analyze the imaging performance of visOCM on microbead samples and demonstrate its image quality on cell cultures and ex-vivo brain tissue of both healthy and alzheimeric mice. In addition to neuronal cell bodies, fibers and plaques, visOCM imaging of brain tissue reveals fine vascular structures and sub-cellular features through its high spatial resolution. Sub-cellular structures were also observed in live cells and were further revealed through a protocol traditionally used for OCT angiography.

[1]  Oliver Wirths,et al.  Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease , 2012, Neurobiology of Aging.

[2]  A. Fercher,et al.  Optical coherence tomography - principles and applications , 2003 .

[3]  L. Tian,et al.  3D intensity and phase imaging from light field measurements in an LED array microscope , 2015 .

[4]  Shau Poh Chong,et al.  Quantitative Microvascular Hemoglobin Mapping Using Visible Light Spectroscopic Optical Coherence Tomography References and Links , 2022 .

[5]  Olivier Thouvenin,et al.  Intracellular dynamics measurements with full field optical coherence tomography suggest hindering effect of actomyosin contractility on organelle transport. , 2016, Biomedical optics express.

[6]  A. Fercher,et al.  Performance of fourier domain vs. time domain optical coherence tomography. , 2003, Optics express.

[7]  Fabrice Harms,et al.  Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis. , 2016, Biomedical optics express.

[8]  Francisco E. Robles,et al.  Molecular imaging true-colour spectroscopic optical coherence tomography. , 2011, Nature photonics.

[9]  Maciej Wojtkowski,et al.  Extended-focus optical coherence microscopy for high-resolution imaging of the murine brain. , 2016, Biomedical optics express.

[10]  F. Del Bene,et al.  Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy , 2004, Science.

[11]  Ji Yi,et al.  Visible-light optical coherence tomography for retinal oximetry. , 2013, Optics letters.

[12]  J. Duker,et al.  Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. , 2004, Optics express.

[13]  J. C. Lodder,et al.  Volumetric Imaging and Quantification of Cytoarchitecture and Myeloarchitecture with Intrinsic Scattering Contrast References and Links , 2022 .

[14]  M. Gillette,et al.  Phase correlation imaging of unlabeled cell dynamics , 2016, Scientific Reports.

[15]  J. Fujimoto,et al.  Spectroscopic optical coherence tomography. , 2000 .

[16]  T. Lasser,et al.  Dark-field optical coherence microscopy , 2010, BiOS.

[17]  T. Weil,et al.  3D Time-lapse Imaging and Quantification of Mitochondrial Dynamics , 2017, Scientific Reports.

[18]  Russell M Taylor,et al.  Inverse-power-law behavior of cellular motility reveals stromal-epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy. , 2015, Optica.

[19]  Houssine Makhlouf,et al.  Simultaneous optically sectioned fluorescence and optical coherence microscopy with full-field illumination. , 2012, Optics letters.

[20]  S. D. Babacan,et al.  White-light diffraction tomography of unlabelled live cells , 2014, Nature Photonics.

[21]  David A Boas,et al.  Optical coherence tomography visualizes neurons in human entorhinal cortex , 2015, Neurophotonics.

[22]  Adolf Friedrich Fercher,et al.  Optical coherence tomography - development, principles, applications. , 2010, Zeitschrift fur medizinische Physik.

[23]  Xiongwei Zhu,et al.  High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer’s disease , 2016, Scientific Reports.

[24]  J. Duker,et al.  Visible Light Optical Coherence Correlation Spectroscopy References and Links , 2022 .

[25]  Christoph K. Hitzenberger,et al.  Visualization of neuritic plaques in Alzheimer’s disease by polarization-sensitive optical coherence microscopy , 2017, Scientific Reports.

[26]  Hans-Ulrich Dodt,et al.  Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy , 2015, PloS one.

[27]  B. Devaux,et al.  Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography☆ , 2013, NeuroImage: Clinical.

[28]  Hai Lin,et al.  Lessons Learned from Whole Exome Sequencing in Multiplex Families Affected by a Complex Genetic Disorder, Intracranial Aneurysm , 2015, PloS one.

[29]  V. Srinivasan,et al.  Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast , 2012, Optics express.

[30]  R. Leitgeb,et al.  Extended focus depth for Fourier domain optical coherence microscopy. , 2006, Optics letters.

[31]  C. Ayata,et al.  Quantitative Imaging of Cerebral Blood Flow Velocity and Intracellular Motility using Dynamic Light Scattering–Optical Coherence Tomography , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  Mathias Fink,et al.  Dynamic multimodal full-field optical coherence tomography and fluorescence structured illumination microscopy , 2017, Journal of biomedical optics.

[33]  David A Boas,et al.  Rapid volumetric angiography of cortical microvasculature with optical coherence tomography. , 2010, Optics letters.

[34]  M. Villiger,et al.  Label-Free Imaging of Cerebral β-Amyloidosis with Extended-Focus Optical Coherence Microscopy , 2012, The Journal of Neuroscience.

[35]  J. Extermann,et al.  Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging , 2016, Diabetologia.

[36]  Brett E. Bouma,et al.  Dual-modality fluorescence and full-field optical coherence microscopy for biomedical imaging applications , 2012, Biomedical optics express.