Intra- and Inter-Frame Differential Doppler Optical Coherence Tomography

Spectrometer based optical coherence tomography suffers from fringe washout for fast flow, a drawback for flow visualization, which is of interest for both lable-free optical angiography and flow quantification. We presented a method, which can be used to contrast very fast flows, while maintaining relatively low A-scan rates. It is based on introducing a phase shift of during acquisition such that the interference fringes associated to moving sample structures are recovered depending on the axial velocity. This enables the use of slower line scan cameras for measuring the fast blood flows within the large vessels in the region of the optic nerve head, while keeping good sensitivity. Furthermore it can be used to contrast the fast moving structures by attenuating the static and slower moving tissue signals. A drawback is still the narrow velocity bandwidth, which is not optimal for providing optical angiography for the full vascular plexus. Nevertheless, it could be of value for following fast dynamic changes, as for example in optical elastography. We introduce different variants of this method, based on intra-frame phase switching, as well as between consecutive A-scans and B-scans, which are then pairwise summed. A phase shift of between summed scans is in fact equivalent to subtraction of both in general complex valued scans. Analyzing complex signal differences between successive B-scans allows in particular contrasting very slow flows of the capillary network. After setting the theoretical framework we show proof-of-principle measurements with a piezo mirror, as well as in vivo measurements of the human retina for the different intra-frame phase shifting schemes. We further show the capability to contrast the parafoveal capillary structure with the differential inter B-scan method and discuss its limitations. Improvement of the sensitivity might be achieved by increasing the number of B-scans to be used for calculating the signal differences, as well as by increasing the sampling density. Care must then be taken for in vivo imaging to keep the total measurement time still sufficiently small, typically a few seconds. The method may proof as a valuable diagnostic tool, as several retinal diseases will manifest at an early stage in capillary disorders.

1. Wojtkowski M., Leitgeb R., Kowalczyk A., Bajraszewski T., Fercher A.F. In vivo human retinal imaging by Fourier domain optical coherence tomography. J Biomed Opt 2002; 7(3); 457–463, http://dx.doi.org/10.1117/1.1482379.
2. Drexler W., Leitgeb R., Hitzenberger C.K. New developments in optical coherence tomography technology. In: Medical Retina. Holz F.G., Spaide R. (eds.). Springer Berlin Heidelberg; 2010; p. 201–216, http://dx.doi.org/10.1007/978-3-540-85540-8_17.
3. Leitgeb R., Hitzenberger C.K., Fercher A.F. Performance of fourier domain vs. time domain optical coherence tomography. Opt Express 2003; 11(8): 889–894, http://dx.doi.org/10.1364/OE.11.000889.
4. Wojtkowski M., Srinivasan V.J., Ko T.H., Fujimoto J.G., Kowalczyk A., Duker J.S. Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. Opt Express 2004; 12(11): 2404–2422, http://dx.doi.org/10.1364/OPEX.12.002404.
5. Leitgeb R.A., Drexler W., Unterhuber A., Hermann B., Bajraszewski T., Le T., Stingl A., Fercher A.F. Ultrahigh resolution Fourier domain optical coherence tomography. Opt Express 2004; 12(10): 2156–2165, http://dx.doi.org/10.1364/OPEX.12.002156.
6. Nassif N., Cense B., Park B.H., Yun S.H., Chen T.C., Bouma B.E., Tearney G.J., de Boer J.F. In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography. Opt Letters 2004; 29(5): 480–482, http://dx.doi.org/10.1364/OL.29.000480.
7. Leitgeb R.A., Werkmeister R.M., Blatter C., Schmetterer L. Doppler optical coherence tomography. Prog Retin Eye Res 2014; 41: 26–43, http://dx.doi.org/10.1016/j.preteyeres.2014.03.004.
8. Wang Y., Fawzi A.A., Varma R., Sadun A.A., Zhang X., Tan O., Izatt J.A., Huang D. Pilot study of optical coherence tomography measurement of retinal blood flow in retinal and optic nerve diseases. Invest Ophthalmol Vis Sci 2011; 52(2): 840–845, http://dx.doi.org/10.1167/iovs.10-5985.
9. Zhao Y., Chen Z., Saxer C., Xiang S., de Boer J.F., Nelson J.S. Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity. Opt Letters 2000; 25(2): 114–116, http://dx.doi.org/10.1364/ol.25.000114.
10. Leitgeb R.A., Schmetterer L., Drexler W., Fercher A.F., Zawadzki R.J., Bajraszewski T. Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Opt Express 2003; 11(23): 3116–3121, http://dx.doi.org/10.1364/oe.11.003116.
11. Yun S.H., Tearney G.J., de Boer J.F., Bouma B.E. Motion artifacts in optical coherence tomography with frequency-domain ranging. Opt Express 2004; 12(13): 2977–2998, http://dx.doi.org/10.1364/OPEX.12.002977.
12. Bachmann A.H., Villiger M.L., Blatter C., Lasser T., Leitgeb R.A. Resonant Doppler flow imaging and optical vivisection of retinal blood vessels. Opt Express 2007; 15(2): 408–422, http://dx.doi.org/10.1364/OE.15.000408.
13. Baumann B., Potsaid B., Kraus M.F., Liu J.J., Huang D., Hornegger J., Cable A.E., Duker J.S., Fujimoto J.G. Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT. Biomed Opt Express 2011; 2(6): 1539–1552, http://dx.doi.org/10.1364/BOE.2.001539.
14. Schmoll T., Leitgeb R.A. Heart-beat-phase-coherent Doppler optical coherence tomography for measuring pulsatile ocular blood flow. J Biophotonics 2013; 6(3): 275–282, http://dx.doi.org/10.1002/jbio.201200029.
15. Schmoll T., Kolbitsch C., Leitgeb R.A. Ultra-high-speed volumetric tomography of human retinal blood flow. Opt Express 2009; 17(5): 4166–4176, http://dx.doi.org/10.1364/OE.17.004166.
16. Singh A.S.G., Kolbitsch C., Schmoll T., Leitgeb R.A. Stable absolute flow estimation with Doppler OCT based on virtual circumpapillary scans. Biomed Opt Express 2010; 1(4): 1047–1059, http://dx.doi.org/10.1364/BOE.1.001047.
17. Fahraeus R., Lindqvist T. The viscosity of the blood in narrow capillary tubes. Am J Physiol 1931; 96: 562–568.
18. Moger J., Matcher S.J., Winlove C.P., Shore A. Measuring red blood cell flow dynamics in a glass capillary using Doppler optical coherence tomography and Doppler amplitude optical coherence tomography. J Biomed Opt 2004; 9(5): 982–994, http://dx.doi.org/10.1117/1.1781163.
19. Park B.H., Pierce M.C., Cense B., Yun S.-H., Mujat M., Tearney G.J., Bouma B.E., de Boer J.F. Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 µm. Opt Express 2005; 13(11): 3931–3944, http://dx.doi.org/10.1364/opex.13.003931.
20. Kolbitsch C., Schmoll T., Leitgeb R.A. Histogram-based filtering for quantitative 3D retinal angiography. J Biophotonics 2009; 2(6–7): 416–425, http://dx.doi.org/10.1002/jbio.200910026.
21. Singh A.S.G., Schmoll T., Leitgeb R.A. Segmentation of Doppler optical coherence tomography signatures using a support-vector machine. Biomed Opt Express 2011; 2(5): 1328–1339, http://dx.doi.org/10.1364/boe.2.001328.
22. Tao Y.K., Davis A.M., Izatt J.A. Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform. Opt Express 2008; 16(16): 12350–12361, http://dx.doi.org/10.1364/oe.16.012350.
23. An L., Wang R. K. In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical microangiography. Opt Express 2008; 16(15): 11438–1145, http://dx.doi.org/10.1364/oe.16.011438.
24. Yang V.X.D., Gordon M.L., Qi B., Pekar J., Lo S., Seng-Yue E., Mok A., Wilson B.C., Vitkin I.A. High speed, wide velocity dynamic range Doppler optical coherence tomography (Part I): system design, signal processing, and performance. Opt Express 2003 11(7): 794–809, http://dx.doi.org/10.1364/oe.11.000794.
25. Grulkowski I., Gorczynska I., Szkulmowski M., Szlag D., Szkulmowska A., Leitgeb R.A., Kowalczyk A., Wojtkowski M. Scanning protocols dedicated to smart velocity ranging in spectral OCT. Opt Express 2009; 17(26): 23736–23754, http://dx.doi.org/10.1364/OE.17.023736.
26. Braaf B., Vermeer K.A., Vienola K.V., de Boer J.F. Angiography of the retina and the choroid with phase-resolved OCT using interval-optimized backstitched B-scans. Opt Express 2012; 20(18): 20516–20534, http://dx.doi.org/10.1364/OE.20.020516.
27. Zotter S., Pircher M., Torzicky T., Bonesi M., Götzinger E., Leitgeb R.A., Hitzenberger C.K. Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography. Opt Express 2011; 19(2): 1217–1227, http://dx.doi.org/10.1364/OE.19.001217.
28. Blatter C., Grajciar B., Eigenwillig C.M., Wieser W., Biedermann B.R., Huber R., Leitgeb R.A. Extended focus high-speed swept source OCT with self-reconstructive illumination. Opt Express 2011; 19(13): 12141–12155, http://dx.doi.org/10.1364/OE.19.012141.
29. Mariampillai A., Leung M.K.K., Jarvi M., Standish B.A., Lee K., Wilson B.C., Vitkin A., Yang V.X.D. Optimized speckle variance OCT imaging of microvasculature. Opt Lett 2010; 35(8): 1257–1259, http://dx.doi.org/10.1364/OL.35.001257.
30. Mariampillai A., Standish B.A., Moriyama E.H., Khurana M., Munce N.R., Leung M.K.K., Jiang J., Cable A., Wilson B.C., Vitkin I.A., Yang V.X.D. Speckle variance detection of microvasculature using swept-source optical coherence tomography. Opt Lett 2008; 33(13): 1530–1532, http://dx.doi.org/10.1364/ol.33.001530.
31. An L., Qin J., Wang R.K. Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds. Opt Express 2010; 18(8): 8220–8228, http://dx.doi.org/10.1364/OE.18.008220.
32. Lee J., Wu W., Jiang J.Y., Zhu B., Boas D.A. Dynamic light scattering optical coherence tomography. Opt Express 2012; 20(20): 22262–22277, http://dx.doi.org/10.1364/OE.20.022262.

Tilman Schmoll, Ioana R. Ivascu, Amardeep S. G. Singh, Cedric Blatter, Rainer A. Leitgeb Intra- and Inter-Frame Differential Doppler Optical Coherence Tomography. Sovremennye tehnologii v medicine 2015; 7(1): 34, https://doi.org/10.17691/stm2015.7.1.05