Optical coherence tomography for enhanced diagnostics and treatment monitoring

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1 Optical coherence tomography for enhanced diagnostics and treatment monitoring M.Yu. Kirillin 1, M.A. Shakhova 1,2, A.E. Meller 1,2, D.A. Sapunov 2, A.V. Shakhov 2, E.A. Sergeeva 1, P.D. Agrba 1,3, A.V. Khilov 1, D.A. Loginova 1,3, E.B. Kiseleva 1,2, and N.M. Shakhova 1 1 Institute of Applied Physics RAS, Nizhny Novgorod, Russia, 2 Nizhny Novgorod State Medical Academy, Russia 3 N.I. Lobachevsky State University of Nizhny Novgorod, Russia SFM 2017, Saratov, Russia, September, 2017

2 Outline Motivation Optical coherence tomography device OCT differential diagnostics of rhinitis OCT evaluation of the adrenaline test results OCT monitoring of pharynx cryotherapy OCT monitoring of pharynx antimicrobial photodynamic therapy (PDT) CP OCT monitoring of cosmetic PDT Conclusions

3 Motivation Requirement for novel diagnostic techniques Active introduction of OCT into clinical practice Subjectivism in evaluation of a diagnostic OCT image by a clinician Requirement for protocols of OCT application in clinical studies Requirement for numerical characterization of OCT-images in biological and medical studies Requirement for novel techniques for treatment monitoring and implementation of the principles of personalized medicine

4 OCT system OCT-1300U 1 mm - time-domain OCT - flexible en-face OCT-probe with angular scanning - central nm, - in-depth resolution (in air) 15 µm, - transversal resolution 30 µm, - frame acquisition rate: 8-10 fps V.M. Gelikonov et al, Laser Physics 13(5), (2003).

5 Diagnostics of chronic rhinitis Chronic rhinitis is the most frequent from all the pathologies of ENT organs Traditional diagnostic approaches provide low accuracy in differential diagnostics of chronic rhinitis Subjective evaluation of nasal mucosa state by a clinician in rhinoscopy may cause incorrect interpretation The timely treatment of chronic rhinitis may help in preventing complications in lungs, brain, and cardiovascular system Fast non-invasive diagnostic techniques are required OCT inspection in course of standard rhinoscopy

6 Typical OCT images of nasal mucosa in norm and with different pathologies epithelium relative norm vasomotor rhinitis allergic rhinitis subatrophy lamina propria epithelium Post mortem histologic images of nasal mucosa relative norm hypertrophy atrophy 1 mm lamina propria

7 Comparison of fitting parameters of the OCT images for differential diagnostics of rhinitis Histogram analysis Height Shift Width a1 a2 b2 c normal mucosa vasomotor rhinitis allergic rhinitis subatrophy b c1

8 Adrenaline test in diagnostics of rhinitis Adrenaline test is a traditional tool for differential diagnostics of rhinitis Adrenaline solution is topically applied on lower nasal concha mucosa Adrenaline induces vessel shrinkage and decrease in manifestation of edema. Currently tissue reaction to adrenaline test is evaluated visually at organ level in course of rhinoscopy. In case of vasomotor rhinitis a significant shrinkage of nasal concha is observed due to edema and vessel shrinkage. In case of hyperthrophic rhinitis accompanied by fibrosis of basal membrane the visual changes after adrenaline test are absent and the nasal concha size is preserved.

9 OCT evaluation of the results of adrenaline test relative norm functional changes (neurovegetative form) morphological changes (true hypertrophy) before test after test observed reaction vessel shrinkage (disappearance of a dark element) dramatic changes no changes

10 Diagnostics and treatment of chronic pharyngitis Chronic rhinitis is among the most frequent pathologies of ENT organs Traditional diagnostic approaches provide low accuracy in differential diagnostics of chronic pharyngitis Subjective evaluation of pharynx mucosa state by a clinician in pharyngoscopy may cause incorrect interpretation Fast non-invasive diagnostic techniques are required Correct choice of drug treatment requires knowledge the causative agent of the disease OCT inspection in course of standard pharyngoscopy PDT may produce wide-range antibacterial effect

11 OCT monitoring of pharynx cryotherapy before cryotherapy immediately after 4 days after cryotherapy in a month Cryotherapy contact application of liquid nitrogen T = ºС Tissue icing immediately after procedure Extensive edema (dark areas) and inflammation in 4 days Restoration of lamina propria (bright layer) in a month

12 Photodynamic therapy (PDT) before after Selective delivery of photosensitizer (PS) Illumination at PS absorption peak wavelength Photo-induced generation of singlet oxygen and free radicals Selective cytotoxic effect Suppression of pathologic processes and abnormal cells apoptosis

13 OCT monitoring of pharynx antimicrobial PDT before procedure after PS administration after the first PDT procedure before the second PDT procedure after the second PDT procedure 1 mm photosensitizer: Revixan Derma, Russia irradiation dose: 50 J/cm 662 nm 24 hours between PDT procedures PS acts as a clearing agent Decrease in edema manifestation Activation of lymph vessels and ducts

14 PDT in cosmetic applications before after Low-dose PDT Phototoxic effect induces collagen restoration Effective alternative to laser skin rejuvenation Collagen state can be non-invasively controlled by polarization-based optical techniques

15 Cross-polarization OCT (CP OCT) Mirror Probe SLD Polarizer 50/50 PM Splitter Lens Object V. Gelikonov, et al Fiber-Based OCT: From Optical Design to Clinical Applications Handbook of Photonics for Biomedical Science CRC Press, 2010.

16 CP OCT monitoring of cosmetic PDT Cosmetic PDT procedure: Revixan BEAUTY Photosensitizer: Revixan Derma Exposure time: 20 min Irradiation dose: 70 J/cm 662 nm Volunteer, female, 42 y.o. Skin location: frontal bone cross-polarization co-polarization before procedure PDT course start PDT course middle (1 month) PDT course end (2 months) after PDT course (4 months)

17 Evolution of integral depolarization factor in cosmetic PDT Integral depolarization factor frontal bone cheek II 0.05 IDF before procedure PDT course end PDT course start E. Kiseleva et al, Biomedical Optics Express, 6(4), (2015) t, days year after PDT course end

18 Conclusions OCT scoring based in histogram analysis allowed for differential diagnostics of rhinitis OCT monitoring of acute pharyngitis PDT allows for both detection of PS accumulation and tracing changes induced by PDT and follow up of tissue response to cryotherapy OCT evaluation provides additional accuracy to adrenaline test results CP OCT monitoring of skin rejuvenation PDT in combination with scoring allows to quantify anti-ageing PDT effect

19 Team Clinicians N. Shakhova M. Shakhova A. Meller D. Sapunov A. Shakhov Physicists M. Kirillin E. Sergeeva D. Loginova P. Agrba A. Khilov Biologist E. Kiseleva

20 Acknowledgements Russian Science Foundation (project ) REVIXAN Ltd. Dr. Ilya Turchin, PhD, Institute of Applied Physics RAS, Russia Dr. Sergey Gamayunov, MD, Republican clinical oncologic dispensary, Chuvash Republic, Russia

21 Topical problems of biophotonics: from optical bioimaging to clinical biophotonics Guest Editors: Special issue Submission deadline: December, 1st, 2017 Mikhail Kirillin Institute of Applied Physics RAS, Russia Kirill Larin University of Houston, USA Ilya Turchin Institute of Applied Physics RAS, Russia Valery Tuchin Saratov National Research State University, Russia National Research Tomsk University, Russia Institute of Precision Mechanics and Control RAS, Russia

22 Thank you for your attention! Questions?

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