Revealing brain pathologies with multimodal visible light optical coherence microscopy and fluorescence imaging

Abstract. We present a multimodal visible light optical coherence microscopy (OCM) and fluorescence imaging (FI) setup. Specification and phantom measurements were performed to characterize the system. Two applications in neuroimaging were investigated. First, curcumin-stained brain slices of a mouse model of Alzheimer’s disease were examined. Amyloid-beta plaques were identified based on the fluorescence of curcumin, and coregistered morphological images of the brain tissue were provided by the OCM channel. Second, human brain tumor biopsies retrieved intraoperatively were imaged prior to conventional neuropathologic work-up. OCM revealed the three-dimensional structure of the brain parenchyma, and FI added the tumor tissue-specific contrast. Attenuation coefficients computed from the OCM data and the florescence intensity values were analyzed and showed a statistically significant difference for 5-aminolevulinic acid (5-ALA)-positive and -negative brain tissues. OCM findings correlated well with malignant hot spots within brain tumor biopsies upon histopathology. The combination of OCM and FI seems to be a promising optical imaging modality providing complementary contrast for applications in the field of neuroimaging.

[1]  Wolfgang Drexler,et al.  Optical coherence tomography: Technology and applications , 2013, 2013 Conference on Lasers & Electro-Optics Europe & International Quantum Electronics Conference CLEO EUROPE/IQEC.

[2]  Inga Kadish,et al.  Deposition of mouse amyloid β in human APP/PS1 double and single AD model transgenic mice , 2006, Neurobiology of Disease.

[3]  Yingtian Pan,et al.  Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model. , 2005, The Journal of urology.

[4]  Marco Augustin,et al.  Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline , 2019, Journal of Neuroscience Methods.

[5]  Marco Augustin,et al.  Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope , 2018, Neurophotonics.

[6]  Christoph K. Hitzenberger,et al.  White light polarization sensitive optical coherence tomography for sub-micron axial resolution and spectroscopic contrast in the murine retina , 2018, Biomedical optics express.

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

[8]  F. Bouwman,et al.  Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics , 2018, Acta Neuropathologica Communications.

[9]  Johannes F. de Boer,et al.  High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model. , 2018, Biomedical optics express.

[10]  Thilo Gambichler,et al.  Applications of optical coherence tomography in dermatology. , 2005, Journal of dermatological science.

[11]  Urs Utzinger,et al.  Ex vivo optical coherence tomography and laser induced fluorescence spectroscopy imaging of murine gastrointestinal tract , 2005, SPIE BiOS.

[12]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

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

[14]  Georg Widhalm,et al.  Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence. , 2014, Clinical neuropathology.

[15]  Sage C. Arbor,et al.  Amyloid-beta Alzheimer targets — protein processing, lipid rafts, and amyloid-beta pores , 2016, The Yale journal of biology and medicine.

[16]  Kwanghun Chung,et al.  Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems , 2015, Cell.

[17]  E. Lankenau,et al.  Imaging of human brain tumor tissue by near-infrared laser coherence tomography , 2009, Acta Neurochirurgica.

[18]  H. Lemij,et al.  Depth-resolved model-based reconstruction of attenuation coefficients in optical coherence tomography. , 2013, Biomedical optics express.

[19]  Elena V. Zagaynova,et al.  Quantitative nontumorous and tumorous human brain tissue assessment using microstructural co- and cross-polarized optical coherence tomography , 2019, Scientific Reports.

[20]  Nicolas Godbout,et al.  Dual-modality needle probe for combined fluorescence imaging and three-dimensional optical coherence tomography. , 2013, Optics letters.

[21]  Sadao Kaneko,et al.  Fluorescence-Guided Resection of Malignant Glioma with 5-ALA , 2016, Int. J. Biomed. Imaging.

[22]  D. Wilcock,et al.  Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain , 2006, Nature Protocols.

[23]  K. S. Yashin,et al.  Visual assessment criteria of microstructural ex vivo co-and cross-polarized optical coherence tomography images in gliomas , 2018, Photonics Europe.

[24]  Jennifer C. Waters,et al.  Accuracy and precision in quantitative fluorescence microscopy , 2009, The Journal of cell biology.

[25]  O. O. Ogedengbe,et al.  Basic Principles of Fluorescence Microscopy , 2013 .

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

[27]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[28]  Tomas Garzon-Muvdi,et al.  Intraoperative imaging techniques for glioma surgery. , 2017, Future oncology.

[29]  A. Schnitzler,et al.  Optical Coherence Tomography in Parkinsonian Syndromes , 2012, PloS one.

[30]  Myeong Jin Ju,et al.  Visible light sensorless adaptive optics for retinal structure and fluorescence imaging. , 2018, Optics letters.

[31]  Harry Moseley,et al.  Modelling fluorescence in clinical photodynamic therapy , 2012, Photochemical & Photobiological Sciences.

[32]  T. Lasser,et al.  Combined Optical Coherence and Fluorescence Microscopy to assess dynamics and specificity of pancreatic beta-cell tracers , 2015, Scientific Reports.

[33]  E. McVeigh,et al.  Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography , 2015, Science Translational Medicine.

[34]  Bruce J Tromberg,et al.  Combined multiphoton microscopy and optical coherence tomography using a 12-fs broadband source. , 2006, Journal of biomedical optics.

[35]  D. Borchelt,et al.  Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. , 2001, Biomolecular engineering.

[36]  J. Lalevée,et al.  Photoinduced curcumin derivative-coatings with antibacterial properties , 2015 .

[37]  D. Prayer,et al.  5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement , 2010, Cancer.

[38]  Shuliang Jiao,et al.  Simultaneous optical coherence tomography and lipofuscin autofluorescence imaging of the retina with a single broadband light source at 480nm. , 2014, Biomedical optics express.

[39]  Javier A. Jo,et al.  A dual-modality optical coherence tomography and fluorescence lifetime imaging microscopy system for simultaneous morphological and biochemical tissue characterization , 2010, Biomedical optics express.

[40]  W. Klunk,et al.  Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. , 2001, Life sciences.

[41]  Joanna L. Jankowsky,et al.  Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase , 2004 .

[42]  Hongki Yoo,et al.  Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography. , 2018, Biomedical optics express.

[43]  Daniel X. Hammer,et al.  Fluorescence-guided optical coherence tomography imaging for colon cancer screening: a preliminary mouse study , 2011, Biomedical optics express.

[44]  Shuliang Jiao,et al.  Visible-light optical coherence tomography-based multimodal retinal imaging for improvement of fluorescent intensity quantification. , 2016, Biomedical optics express.

[45]  S. A. Boppart,et al.  Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy , 2005, physics/0512161.

[46]  Xingde Li,et al.  Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection , 2017, Scientific Reports.

[47]  Ryan P. McNabb,et al.  Method for single illumination source combined optical coherence tomography and fluorescence imaging of fluorescently labeled ocular structures in transgenic mice. , 2016, Experimental eye research.

[48]  S. Gigan,et al.  Brain refractive index measured in vivo with high-NA defocus-corrected full-field OCT and consequences for two-photon microscopy. , 2011, Optics express.

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

[50]  A. Fercher,et al.  Submicrometer axial resolution optical coherence tomography. , 2002, Optics letters.

[51]  Shau Poh Chong,et al.  Ultrahigh resolution retinal imaging by visible light OCT with longitudinal achromatization. , 2018, Biomedical optics express.

[52]  P. Jannetta,et al.  Microneurosurgery: application of the binocular surgical microscope in brain tumors, intracranial aneurysms, spinal cord disease, and nerve reconstruction. , 1968, Clinical neurosurgery.

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

[54]  Walter J. Riker.  A Review of J , 2010 .

[55]  Herbert Stepp,et al.  5-Aminolevulinic Acid-derived Tumor Fluorescence: The Diagnostic Accuracy of Visible Fluorescence Qualities as Corroborated by Spectrometry and Histology and Postoperative Imaging , 2013, Neurosurgery.

[56]  Angelika Unterhuber,et al.  Optical coherence tomography today: speed, contrast, and multimodality , 2014, Journal of biomedical optics.

[57]  Theo Lasser,et al.  Visible spectrum extended-focus optical coherence microscopy for label-free sub-cellular tomography. , 2017, Biomedical optics express.

[58]  Michalina J Gora,et al.  Endoscopic optical coherence tomography: technologies and clinical applications [Invited]. , 2017, Biomedical optics express.

[59]  Christoph K. Hitzenberger,et al.  Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples , 2017, Biomedical optics express.

[60]  Hao F. Zhang,et al.  Visible-light optical coherence tomography: a review , 2017, Journal of biomedical optics.

[61]  Marina A. Sirotkina,et al.  Multimodal optical coherence tomography for in vivo imaging of brain tissue structure and microvascular network at glioblastoma , 2017, BiOS.

[62]  S. Bastacky,et al.  Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography. , 2003, Optics letters.

[63]  D. Basu,et al.  Optical Coherence Tomography Findings in Patients of Parkinson's Disease: An Indian Perspective , 2018, Annals of Indian Academy of Neurology.

[64]  S. Leenstra,et al.  Recent advances in the molecular understanding of glioblastoma , 2009 .

[65]  G. Cole,et al.  NSAID and Antioxidant Prevention of Alzheimer's Disease: Lessons from In Vitro and Animal Models , 2004, Annals of the New York Academy of Sciences.

[66]  R. Jain,et al.  Cancer imaging by optical coherence tomography: preclinical progress and clinical potential , 2012, Nature Reviews Cancer.

[67]  A Schweikard,et al.  Automatic scanning of large tissue areas in neurosurgery using optical coherence tomography , 2012, The international journal of medical robotics + computer assisted surgery : MRCAS.

[68]  Bernhard Baumann,et al.  Optical Coherence Tomography for Brain Imaging , 2019 .

[69]  A. Giese,et al.  Time‐domain and spectral‐domain optical coherence tomography in the analysis of brain tumor tissue , 2006, Lasers in surgery and medicine.

[70]  M. P. McDonald,et al.  Impaired spatial learning in the APPSwe + PSEN1ΔE9 bigenic mouse model of Alzheimer’s disease , 2007, Genes, brain, and behavior.

[71]  Andrew M. Rollins,et al.  Integrative Advances for OCT-Guided Ophthalmic Surgery and Intraoperative OCT: Microscope Integration, Surgical Instrumentation, and Heads-Up Display Surgeon Feedback , 2014, 2015 Conference on Lasers and Electro-Optics (CLEO).

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

[73]  Maristela L Onozato,et al.  High-resolution optical coherence tomography imaging of the living kidney , 2008, Laboratory Investigation.

[74]  B. Hyman,et al.  Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model , 2007, Journal of neurochemistry.

[75]  M. Colditz,et al.  Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 2: Theoretical, biochemical and practical aspects , 2012, Journal of Clinical Neuroscience.

[76]  Keith D. Paulsen,et al.  Quantitative, spectrally-resolved intraoperative fluorescence imaging , 2012, Scientific Reports.

[77]  Guido Gerig,et al.  User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability , 2006, NeuroImage.

[78]  A. Quiñones‐Hinojosa,et al.  Advances in Brain Tumor Surgery for Glioblastoma in Adults , 2017, Brain sciences.

[79]  J Mertz,et al.  Combined scanning optical coherence and two-photon-excited fluorescence microscopy. , 1999, Optics letters.

[80]  Shuai Yuan,et al.  Co-registered optical coherence tomography and fluorescence molecular imaging for simultaneous morphological and molecular imaging , 2008, LEOS 2008 - 21st Annual Meeting of the IEEE Lasers and Electro-Optics Society.