Abstract
Fluorescence lifetime imaging (FLIM) is used for measuring material properties in a wide range of applications, including biology, medical imaging, chemistry, and material science. In frequency-domain FLIM (FD-FLIM), the object of interest is illuminated with a temporally modulated light source. The fluorescence lifetime is measured by computing the correlations of the emitted light with a demodulation function at the sensor. The signal-to-noise ratio (SNR) and the acquisition time of a FD-FLIM system is determined by the coding scheme (modulation and demodulation functions). In this article, we develop theory and algorithms for designing high-performance FD-FLIM coding schemes that can achieve high SNR and short acquisition time, given a fixed source power budget. Based on a geometric analysis of the image formation and noise model, we propose a novel surrogate objective for the performance of a given coding scheme. The surrogate objective is extremely fast to compute, and can be used to efficiently explore the entire space of coding schemes. Based on this objective, we design novel, high-performance coding schemes that achieve up to an order of magnitude shorter acquisition time as compared to existing approaches. We demonstrate the performance advantage of the proposed schemes in a variety of imaging conditions, using a modular hardware prototype that can implement various coding schemes.
Supplemental Material
Available for Download
Supplemental movie, appendix, image and software files for, Coding Scheme Optimization for Fast Fluorescence Lifetime Imaging
- Diego Airado-Rodríguez, Teresa Galeano-Díaz, Isabel Durán-Merás, and Jens Petter Wold. 2009. Usefulness of fluorescence excitation-emission matrices in combination with PARAFAC, as fingerprints of red wines. Journal of Agricultural and Food Chemistry 57, 5 (2009), 1711--172Google Scholar
Cross Ref
- Syed Abdullah Aljunid, Gleb Maslennikov, Yimin Wang, Hoang Lan Dao, Valerio Scarani, and Christian Kurtsiefer. 2013. Excitation of a single atom with exponentially rising light pulses. Physical Review Letters 111, 10 (2013), 103001.Google Scholar
Cross Ref
- Philippe I. H. Bastiaens and Anthony Squire. 1999. Fluorescence lifetime imaging microscopy: Spatial resolution of biochemical processes in the cell. Trends in Cell Biology 9, 2 (1999), 48--52.Google Scholar
Cross Ref
- Wolfgang Becker. 2014. The bh TCSPC Handbook. Becker 8 Hickl.Google Scholar
- Oscar Beijbom, Tali Treibitz, David I. Kline, Gal Eyal, Adi Khen, Benjamin Neal, Yossi Loya, B. Greg Mitchell, and David Kriegman. 2016. Improving automated annotation of benthic survey images using wide-band fluorescence. Scientific Reports 6 (2016), 23166.Google Scholar
Cross Ref
- Mikhail Y. Berezin and Samuel Achilefu. 2010. Fluorescence lifetime measurements and biological imaging. Chemical Reviews 110, 5 (2010), 2641--2684.Google Scholar
Cross Ref
- Ayush Bhandari, Christopher Barsi, and Ramesh Raskar. 2015a. Blind and reference-free fluorescence lifetime estimation via consumer time-of-flight sensors. Optica 2, 11 (Nov. 2015), 965--973.Google Scholar
Cross Ref
- Ayush Bhandari, Christopher Barsi, and Ramesh Raskar. 2015b. Blind and reference-free fluorescence lifetime estimation via consumer time-of-flight sensors. Optica 2, 11 (2015), 965--973.Google Scholar
Cross Ref
- Ayush Bhandari and Ramesh Raskar. 2016. Signal processing for time-of-flight imaging sensors: An introduction to inverse problems in computational 3-D imaging. IEEE Signal Processing Magazine 33, 5 (2016), 45--58.Google Scholar
Cross Ref
- M. J. Booth and T. Wilson. 2004. Low-cost, frequency-domain, fluorescence lifetime confocal microscopy. Journal of Microscopy 214, 1 (2004), 36--42.Google Scholar
Cross Ref
- A. Colasanti, A. Kisslinger, G. Fabbrocini, R. Liuzzi, M. Quarto, P. Riccio, G. Roberti, and F. Villani. 2000. MS-2 fibrosarcoma characterization by laser induced autofluorescence. Lasers in Surgery and Medicine 26, 5 (2000), 441--448.Google Scholar
Cross Ref
- Daniela Comelli, Cosimo D’Andrea, Gianluca Valentini, Rinaldo Cubeddu, Chiara Colombo, and Lucia Toniolo. 2004. Fluorescence lifetime imaging and spectroscopy as tools for nondestructive analysis of works of art. Applied Optics 43, 10 (2004), 2175--2183.Google Scholar
Cross Ref
- Kalyanmoy Deb, Amrit Pratap, Sameer Agarwal, and TAMT Meyarivan. 2002. A fast and elitist multiobjective genetic algorithm: NSGA-II. IEEE Transactions on Evolutionary Computation 6, 2 (2002), 182--197. Google Scholar
Digital Library
- Michelle A. Digman, Valeria R. Caiolfa, Moreno Zamai, and Enrico Gratton. 2008. The phasor approach to fluorescence lifetime imaging analysis. Biophysical Journal 94, 2 (2008), L14--L16.Google Scholar
Cross Ref
- L. A. Donaldson and K. Radotic. 2013. Fluorescence lifetime imaging of lignin autofluorescence in normal and compression wood. Journal of Microscopy 251, 2 (2013), 178--187.Google Scholar
Cross Ref
- Alan Elder, Simon Schlachter, and Clemens F. Kaminski. 2008. Theoretical investigation of the photon efficiency in frequency-domain fluorescence lifetime imaging microscopy. JOSA A 25, 2 (2008), 452--462.Google Scholar
Cross Ref
- Dan Elson, Jose Requejo-Isidro, Ian Munro, Fred Reavell, Jan Siegel, Klaus Suhling, Paul Tadrous, Richard Benninger, Peter Lanigan, James McGinty, et al. 2004. Time-domain fluorescence lifetime imaging applied to biological tissue. Photochemical 8 Photobiological Sciences 3, 8 (2004), 795--801.Google Scholar
- Alessandro Esposito, Hans Gerritsen, Thierry Oggier, Felix Lustenberger, and Fred S. Wouters. 2006. Innovating lifetime microscopy: A compact and simple tool for life sciences, screening, and diagnostics. Journal of Biomedical Optics 11, 3 (2006), 034016.Google Scholar
Cross Ref
- Alessandro Esposito, Hans C. Gerritsen, and Fred S. Wouters. 2007. Optimizing frequency-domain fluorescence lifetime sensing for high-throughput applications: Photon economy and acquisition speed. JOSA A 24, 10 (2007), 3261--3273.Google Scholar
Cross Ref
- A. Esposito, T. Oggier, H. C. Gerritsen, F. Lustenberger, and F. S. Wouters. 2005. All-solid-state lock-in imaging for wide-field fluorescence lifetime sensing. Optics Express 13, 24 (2005), 9812--9821.Google Scholar
Cross Ref
- Ying Fu, Antony Lam, Yasuyuki Matsushita, Imari Sato, and Yoichi Sato. 2014. Interreflection removal using fluorescence. In European Conference on Computer Vision. Springer, 203--217.Google Scholar
Cross Ref
- Mohit Gupta, Andreas Velten, Shree K. Nayar, and Eric Breitbach. 2018. What are optimal coding functions for time-of-flight imaging? ACM Transactions on Graphics (TOG) 37, 2 (2018), 13. Google Scholar
Digital Library
- Shuai Han, Yasuyuki Matsushita, Imari Sato, Takahiro Okabe, and Yoichi Sato. 2012. Camera spectral sensitivity estimation from a single image under unknown illumination by using fluorescence. In IEEE Conference on Computer Vision and Pattern Recognition (CVPR’12). IEEE, 805--812.Google Scholar
- Miles Hansard, Seungkyu Lee, Ouk Choi, and Radu Patrice Horaud. 2012. Time-of-Flight Cameras: Principles, Methods and Applications. Springer Science 8 Business Media. Google Scholar
Digital Library
- Samuel W. Hasinoff, Frédo Durand, and William T. Freeman. 2010. Noise-optimal capture for high dynamic range photography. In IEEE Conference on Computer Vision and Pattern Recognition (CVPR’10). IEEE, 553--560.Google Scholar
- Felix Heide, Matthias B. Hullin, James Gregson, and Wolfgang Heidrich. 2013. Low-budget transient imaging using photonic mixer devices. ACM Transactions on Graphics (ToG) 32, 4 (2013), 45.Google Scholar
Digital Library
- Felix Heide, Lei Xiao, Andreas Kolb, Matthias B. Hullin, and Wolfgang Heidrich. 2014. Imaging in scattering media using correlation image sensors and sparse convolutional coding. Optics Express 22, 21 (2014), 26338--26350.Google Scholar
Cross Ref
- J. Michael Hollas. 2004. Modern Spectroscopy. John Wiley 8 Sons.Google Scholar
- Matthias B. Hullin, Martin Fuchs, Ivo Ihrke, Hans-Peter Seidel, and Hendrik P. A. Lensch. 2008. Fluorescent immersion range scanning. ACM Transactions on Graphics 27, 3 (Aug. 2008), Article 87, 10 pages. Google Scholar
Digital Library
- Matthias B. Hullin, Johannes Hanika, Boris Ajdin, Hans-Peter Seidel, Jan Kautz, and Hendrik P. A. Lensch. 2010. Acquisition and analysis of bispectral bidirectional reflectance and reradiation distribution functions. ACM Transactions on Graphics 29, 4 (July 2010), Article 97, 7 pages. Google Scholar
Digital Library
- Moon S. Kim, Byoung-Kwan Cho, Alan M. Lefcourt, Yud-Ren Chen, and Sukwon Kang. 2008. Multispectral fluorescence lifetime imaging of feces-contaminated apples by time-resolved laser-induced fluorescence imaging system with tunable excitation wavelengths. Applied Optics 47, 10 (2008), 1608--1616.Google Scholar
Cross Ref
- Joseph R. Lakowicz. 2006. Principles of Fluorescence Spectroscopy. Springer.Google Scholar
- R. Lange. 2000. 3D Time of Flight Distance Measurement with Custom Solid State Image Sensors in CMOS, CCD Technology. https://books.google.com/books?id=upMuHwAACAAJGoogle Scholar
- Lea Lenhardt, Rasmus Bro, Ivana Zeković, Tatjana Dramićanin, and Miroslav D. Dramićanin. 2015. Fluorescence spectroscopy coupled with PARAFAC and PLS DA for characterization and classification of honey. Food Chemistry 175 (2015), 284--291.Google Scholar
Cross Ref
- Yuxiang Lin and Arthur F. Gmitro. 2010. Statistical analysis and optimization of frequency-domain fluorescence lifetime imaging microscopy using homodyne lock-in detection. JOSA A 27, 5 (2010), 1145--1155.Google Scholar
Cross Ref
- Douglas Magde, Gail E. Rojas, and Paul G. Seybold. 1999. Solvent dependence of the fluorescence lifetimes of xanthene dyes. Photochemistry and Photobiology 70, 5 (1999), 737--744.Google Scholar
Cross Ref
- John A. Nelder and Roger Mead. 1965. A simplex method for function minimization. The Computer Journal 7, 4 (1965), 308--313.Google Scholar
Cross Ref
- Austin Nevin, Daniela Comelli, Gianluca Valentini, Demetrios Anglos, Aviva Burnstock, Sharon Cather, and Rinaldo Cubeddu. 2007. Time-resolved fluorescence spectroscopy and imaging of proteinaceous binders used in paintings. Analytical and Bioanalytical Chemistry 388, 8 (2007), 1897--1905.Google Scholar
Cross Ref
- Lucio Pancheri, Nicola Massari, and David Stoppa. 2013. SPAD image sensor with analog counting pixel for time-resolved fluorescence detection. IEEE Transactions on Electron Devices 60, 10 (2013), 3442--3449.Google Scholar
Cross Ref
- Johan Philip and Kjell Carlsson. 2003. Theoretical investigation of the signal-to-noise ratio in fluorescence lifetime imaging. JOSA A 20, 2 (2003), 368--379.Google Scholar
Cross Ref
- Asima Pradhan, Prabir Pal, Gilles Durocher, Luc Villeneuve, Antonia Balassy, Féridoun Babai, Louis Gaboury, and Louise Blanchard. 1995. Steady state and time-resolved fluorescence properties of metastatic and non-metastatic malignant cells from different species. Journal of Photochemistry and Photobiology B: Biology 31, 3 (1995), 101--112.Google Scholar
Cross Ref
- J. Requejo-Isidro, J. McGinty, I. Munro, D. S. Elson, N. P. Galletly, M. J. Lever, M. A. A. Neil, G. W. H. Stamp, P. M. W. French, P. A. Kellett, et al. 2004. High-speed wide-field time-gated endoscopic fluorescence-lifetime imaging. Optics Letters 29, 19 (2004), 2249--2251.Google Scholar
Cross Ref
- Imari Sato, Takahiro Okabe, and Yoichi Sato. 2012. Bispectral photometric stereo based on fluorescence. In IEEE Conference on Computer Vision and Pattern Recognition (CVPR’12). IEEE, 270--277.Google Scholar
Cross Ref
- S. Schlachter, A. D. Elder, A. Esposito, G. S. Kaminski, J. H. Frank, L. K. Van Geest, and C. F. Kaminski. 2009. mhFLIM: Resolution of heterogeneous fluorescence decays in widefield lifetime microscopy. Optics Express 17, 3 (2009), 1557--1570.Google Scholar
Cross Ref
- L. K. Seah, U. S. Dinish, W. F. Phang, Z. X. Chao, and V. M. Murukeshan. 2005. Fluorescence optimisation and lifetime studies of fingerprints treated with magnetic powders. Forensic Science International 152, 2–3 (2005), 249--257.Google Scholar
Cross Ref
- L. K. Seah, P. Wang, V. M. Murukeshan, and Z. X. Chao. 2006. Application of fluorescence lifetime imaging (FLIM) in latent finger mark detection. Forensic Science International 160, 2–3 (2006), 109--114.Google Scholar
Cross Ref
- Nathan C. Shaner, Gerard G. Lambert, Andrew Chammas, Yuhui Ni, Paula J. Cranfill, Michelle A. Baird, Brittney R. Sell, John R. Allen, Richard N. Day, Maria Israelsson, et al. 2013. A bright monomeric green fluorescent protein derived from Branchiostoma lanceolatum. Nature Methods 10, 5 (2013), 407.Google Scholar
Cross Ref
- Wen Shi, Xiaohua Li, and Huimin Ma. 2014. Fluorescent probes and nanoparticles for intracellular sensing of pH values. Methods and Applications in Fluorescence 2, 4 (2014), 042001.Google Scholar
Cross Ref
- Ewa Sikorska, Tomasz Górecki, Igor V. Khmelinskii, Marek Sikorski, and Jacek Kozioł. 2005. Classification of edible oils using synchronous scanning fluorescence spectroscopy. Food Chemistry 89, 2 (2005), 217--225.Google Scholar
Cross Ref
- Shiwen Sun, Birgit Ungerböck, and Torsten Mayr. 2015. Imaging of oxygen in microreactors and microfluidic systems. Methods and Applications in Fluorescence 3, 3 (2015), 034002.Google Scholar
Cross Ref
- Virginia Torczon. 1997. On the convergence of pattern search algorithms. SIAM Journal on Optimization 7, 1 (1997), 1--25. Google Scholar
Digital Library
- Tali Treibitz, Zak Murez, B. Greg Mitchell, and David Kriegman. 2012. Shape from fluorescence. In European Conference on Computer Vision. Springer, 292--306. Google Scholar
Digital Library
- Andreas Velten, Thomas Willwacher, Otkrist Gupta, Ashok Veeraraghavan, Moungi G. Bawendi, and Ramesh Raskar. 2012. Recovering three-dimensional shape around a corner using ultrafast time-of-flight imaging. Nature Communications 3 (2012), 745.Google Scholar
Cross Ref
- Charles W. Wilkerson Jr., Peter M. Goodwin, W. Patrick Ambrose, John C. Martin, and Richard A. Keller. 1993. Detection and lifetime measurement of single molecules in flowing sample streams by laser-induced fluorescence. Applied Physics Letters 62, 17 (1993), 2030--2032.Google Scholar
Cross Ref
- Di Wu, Matthew O’Toole, Andreas Velten, Amit Agrawal, and Ramesh Raskar. 2012. Decomposing global light transport using time of flight imaging. In IEEE Conference on Computer Vision and Pattern Recognition (CVPR’12). IEEE, 366--373.Google Scholar
- Qiaole Zhao, Ian T. Young, and Jan Geert Sander De Jong. 2011. Photon budget analysis for fluorescence lifetime imaging microscopy. Journal of Biomedical Optics 16, 8 (2011), 086007.Google Scholar
Cross Ref
Index Terms
Coding Scheme Optimization for Fast Fluorescence Lifetime Imaging
Recommendations
Doppler time-of-flight imaging
Over the last few years, depth cameras have become increasingly popular for a range of applications, including human-computer interaction and gaming, augmented reality, machine vision, and medical imaging. Many of the commercially-available devices use ...
Embedded Fluorescence Lifetime Determination for High-Throughput, Low-Photon-Number Applications
Time-resolved fluorescence (TRF) analysis is considered to be among the primary research tools in biochemistry and biophysics. One application of this method is the investigation of biomolecular interactions with promising applications for biosensing. ...
Efficient FPGA implementation of homodyne-based time-of-flight range imaging
Time-of-flight range imaging systems illuminate a scene with an amplitude-modulated light source, the light is reflected from objects in the scene, and measurement of the phase of the modulation envelope is performed to determine the object's distance. ...





Comments