The first fully integrated 2D CMOS imaging sensor with on-chip signal processing for applications in laser Doppler blood flow (LDBF) imaging has been designed and tested. To obtain a space efficient design over 64 × 64 pixels means that standard processing electronics used off-chip cannot be implemented. Therefore the analog signal processing at each pixel is a tailored design for LDBF signals with balanced optimization for signal-to-noise ratio and silicon area. This custom made sensor offers key advantages over conventional sensors, viz. the analog signal processing at the pixel level carries out signal normalization; the AC amplification in combination with an anti-aliasing filter allows analog-to-digital conversion with a low number of bits; low resource implementation of the digital processor enables on-chip processing and the data bottleneck that exists between the detector and processing electronics has been overcome. The sensor demonstrates good agreement with simulation at each design stage. The measured optical performance of the sensor is demonstrated using modulated light signals and in vivo blood flow experiments. Images showing blood flow changes with arterial occlusion and an inflammatory response to a histamine skin-prick demonstrate that the sensor array is capable of detecting blood flow signals from tissue.
References
[1]
Stern, M.D. In vivo evaluation of microcirculation by coherent light scattering. Nature 1975, 254, 56–58.
Clough, G.F.; Bennett, A.R.; Church, M.K. Effects of H1 antagonists on the cutaneous vascular response to histamine and bradykinin: A study using scanning laser Doppler imaging. Br. J. Dermatol. 1998, 138, 806–814.
[5]
Schiller, W.R.; Garren, R.L.; Bay, R.C.; Ruddell, M.H.; Holloway, G.A., Jr.; Mohty, A.; Luekens, C.A. Laser Doppler evaluation of burned hands predicts need for surgical grafting. J. Trauma—Inj. Infect. Crit. Care 1997, 43, 35–39.
[6]
Stucker, M.; Horstmann, I.; Nuchel, C.; Rochling, A.; Hoffmann, K.; Altmeyer, P. Blood flow compared in benign melanocytic naevi, malignant melanomas and basal cell carcinomas. Clin. Exp. Dermatol. 1999, 24, 107–111.
[7]
Speight, E.L.; Essex, T.J.H.; Farr, P.M. The study of plaques of psoriasis using a scanning laser-Doppler velocimeter. Br. J. Dermatol. 1993, 128, 519–524.
[8]
Foldvari, M.; Oguejiofor, C.; Wilson, T.; Afridi, S.; Kudel, T. Transcutaneous delivery of prostaglandin E1: In vitro and laser Doppler flowmetry study. J. Pharm. Sci. 1998, 87, 721–725.
[9]
Essex, T.J.; Byrne, P.O. A laser Doppler scanner for imaging blood flow in skin. J. Biomed. Eng. 1991, 13, 189–194.
[10]
Nilsson, G.E.; Wardell, K.; Linkoping, S. Imaging of Tissue Blood Flow by Coherent Light Scattering. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1989; pp. 9–12.
[11]
Bray, R.; Forrester, K.; Leonard, C.; McArthur, R.; Tulip, J.; Lindsay, R. Laser Doppler imaging of burn scars: A comparison of wavelength and scanning methods. Burns 2003, 29, 199–206.
[12]
Nguyen, H.C.; Hayes-Gill, B.R.; Morgan, S.P.; Zhu, Y.; Boggett, D.; Huang, X.; Potter, M. A field-programmable gate array based system for high frame rate laser Doppler blood flow imaging. J. Med. Eng. Technol. 2010, 34, 306–315.
[13]
Briers, J.D.; Webster, S. Laser speckle contrast analysis (LASCA): A non-scanning, full-field technique for monitoring capillary blood flow. J. Biomed. Opt. 1996, 1, 174–179.
Briers, J.D. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol. Meas. 2001, 4, 35–66.
[16]
Draijer, M.; Hondebrink, E.; Leeuwen, T.V.; Steenbergen, W. Review of laser speckle contrast techniques for visualizing tissue perfusion. Lasers Med. Sci. 2009, 24, 639–651.
[17]
Bonner, R.; Nossal, R. Model for laser Doppler measurements of blood flow in tissue. Appl. Opt. 1981, 20, 2097–2107.
[18]
Uranishi, R.; Nakase, H.; Sakaki, T.; Kempski, O.S. Evaluation of absolute cerebral blood flow by laser-Doppler scanning-comparison with hydrogen clearance. J. Vasc. Res. 1999, 36, 100–105.
[19]
Thompson, O.; Bakker, J.; Kloeze, C.; Hondebrink, E.; Steenbergen, W. Experimental Comparison of Perfusion Imaging Systems Using Multi-Exposure Laser Speckle, Single-Exposure Laser Speckle, and Full-Field Laser Doppler. Proceedings of SPIE 8222 in Dynamics and Fluctuations in Biomedical Photonics IX, 822204, San Francisco, CA, USA, 21 January 2012.
[20]
Donati, S.; Norgia, M. Self-mixing interferometry for biomedical signals sensing. IEEE J. Sel. Top. Quantum Electron. 2013, PP, doi:10.1109/JSTQE.2013.2270279.
[21]
Lim, Y.; Nikolic, M.; Bertling, K.; Kliese, R.; Rakic, A. Self-mixing imaging sensor using a monolithic VCSEL array with parallel readout. Opt. Express 2009, 17, 5517–5525.
[22]
Lim, Y.; Kliese, R.; Bertling, K.; Tanimizu, K.; Jacobs, P.; Rakic, A. Self-mixing flow sensor using a monolithic VCSEL array with parallel readout. Opt. Express 2010, 18, 11720–11727.
[23]
Serov, A.; Nieland, J.; Oosterbaan, S.; Mul, F.; Kranenburg, H.; Bekman, H.; Steenbergen, W. Integrated optoelectronic probe including a vertical cavity surface emitting laser for laser Doppler perfusion monitoring. IEEE Trans. Biomed. Eng. 2006, 56, 2067–2074.
[24]
Serov, A.; Lasser, T. High-speed laser Doppler perfusion imaging using an integrating CMOS image sensor. Opt. Express 2005, 13, 6416–6428.
[25]
Draijer, M.; Hondebrink, E.; Leeuwen, T.V.; Steenbergen, W. Twente optical perfusion camera: System overview and performance for video rate laser Doppler perfusion imaging. Opt. Express 2009, 17, 3211–3225.
[26]
Leutenegger, M.; Martin-Williams, E.; Harbi, P.; Thacher, T.; Raffoul, W.; André, M.; Lopez, A.; Lasser, P.; Lasser, T. Real-time full field laser Doppler imaging. Biomed. Opt. Express 2011, 2, 1470–1477.
[27]
Bourquin, S.; Seitz, P.; Salathé, R. Optical coherence topography based on a two-dimensional smart detector array. Opt. Lett. 2001, 26, 512–514.
[28]
Mitic, J.; Anhut, T.; Serov, A.; Lasser, T.; Bourquin, S. Real-Time Optically Sectioned Wide-Field Microscopy Employing Structured Light Illumination and a CMOS Detector. Proceedings of SPIE 4964 in Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing X, 41, San Jose, CA, USA, 25 January 2003.
[29]
Mead, C.A. Analog VLSI and Neural Systems; Addison-Wesley: Boston, MA, USA, 1989.
[30]
Pui, B.; Hayes-Gill, B.R.; Clark, M.; Somekh, M.; See, C.; Morgan, S.; Ng, A. Integration of a photodiode array and centroid processing on a single cmos chip for a real-time shack hartmann wavefront sensor. IEEE Sens. J. 2004, 4, 787–794.
[31]
Dmochowski, P.; Hayes-Gill, B.R.; Clark, M.; Crowe, J.; Somekh, M.; Morgan, S. Camera pixel for coherent detection of modulated light. Electron. Lett. 2004, 40, 1403–1404.
[32]
Gu, Q.; Hayes-Gill, B.; Morgan, S. Laser Doppler blood flow CMOS imaging sensor with analog on-chip processing. Appl. Opt. 2008, 47, 2061–2069.
