Prospects on Time-Domain Diffuse Optical Tomography Based on Time-Correlated Single Photon Counting for Small Animal Imaging

This paper discusses instrumentation based on multiview parallel high temporal resolution (<50 ps) time-domain (TD) measurements for diffuse optical tomography (DOT) and a prospective view on the steps to undertake as regards such instrumentation to make TD-DOT a viable technology for small animal molecular imaging. TD measurements provide information-richest data, and we briefly review the interaction of light with biological tissues to provide an understanding of this. This data richness is yet to be exploited to its full potential to increase the spatial resolution of DOT imaging and to allow probing, via the fluorescence lifetime, tissue biochemical parameters, and processes that are otherwise not accessible in fluorescence DOT. TD data acquisition time is, however, the main factor that currently compromises the viability of TD-DOT. Current high temporal resolution TD-DOT scanners simply do not integrate sufficient detection channels. Based on our past experience in developing TD-DOT instrumentation, we review and discuss promising technologies to overcome this difficulty. These are single photon avalanche diode (SPAD) detectors and fully parallel highly integrated electronics for time-correlated single photon counting (TCSPC). We present experimental results obtained with such technologies demonstrating the feasibility of next-generation multiview TD-DOT therewith.

[1]  Andrew K. Dunn,et al.  A Time Domain Fluorescence Tomography System for Small Animal Imaging , 2008, IEEE Transactions on Medical Imaging.

[2]  Vincent Robichaud,et al.  Time-resolved fluorescence measurements for diffuse optical tomography using ultrafast time-correlated single photon counting , 2006, SPIE Optics East.

[3]  Molly L Flexman,et al.  Monitoring early tumor response to drug therapy with diffuse optical tomography. , 2012, Journal of biomedical optics.

[4]  R. Weissleder,et al.  Fluorescence molecular tomography resolves protease activity in vivo , 2002, Nature Medicine.

[5]  Y. Bérubé-Lauzière,et al.  Diffuse light propagation in biological media by a time-domain parabolic simplified spherical harmonics approximation with ray-divergence effects. , 2010, Applied optics.

[6]  Vasilis Ntziachristos,et al.  Free-space fluorescence molecular tomography utilizing 360° geometry projections , 2007 .

[7]  M. Ghioni,et al.  Single-photon avalanche diode with ultrafast pulse response free from slow tails , 1993, IEEE Electron Device Letters.

[9]  A. Gulinatti,et al.  Complete and Compact 32-Channel System for Time-Correlated Single-Photon Counting Measurements , 2013, IEEE Photonics Journal.

[10]  Andrea L. Lacaita,et al.  Double epitaxy improves single-photon avalanche diode performance , 1989 .

[11]  Daqing Piao,et al.  Alternative Transrectal Prostate Imaging: A Diffuse Optical Tomography Method , 2010, IEEE Journal of Selected Topics in Quantum Electronics.

[12]  Vincent Robichaud,et al.  Time-resolved non-contact fluorescence diffuse optical tomography measurements with ultra-fast time-correlated single photon counting avalanche photodiodes , 2007, European Conference on Biomedical Optics.

[13]  Scott C Davis,et al.  Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications. , 2010, Journal of photochemistry and photobiology. B, Biology.

[14]  Kevin Kalinsky,et al.  Optical biomarkers for breast cancer derived from dynamic diffuse optical tomography , 2013, Journal of biomedical optics.

[15]  Andrea L. Lacaita,et al.  20-ps timing resolution with single-photon avalanche diodes , 1989 .

[16]  S. Jacques,et al.  Angular dependence of HeNe laser light scattering by human dermis , 1988 .

[17]  Simon R. Arridge,et al.  Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate , 2006, NeuroImage.

[18]  A. Rehemtulla,et al.  Molecular Imaging , 2009, Methods in Molecular Biology.

[19]  Ming-Lun Gao,et al.  Current switch driver and current source designs for high-speed current-steering DAC , 2008, 2008 2nd International Conference on Anti-counterfeiting, Security and Identification.

[20]  Andreas H. Hielscher,et al.  Instrumentation for simultaneous magnetic resonance and optical tomographic imaging of the rodent brain , 2009, BiOS.

[21]  Angelo Gulinatti,et al.  Planar silicon SPADs with 200-μm diameter and 35-ps photon timing resolution , 2006, SPIE Optics East.

[22]  Y. Savaria,et al.  Design techniques for high speed current steering DACs , 2007, 2007 IEEE Northeast Workshop on Circuits and Systems.

[23]  Yves Bérubé-Lauzière,et al.  A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging. , 2012, The Review of scientific instruments.

[24]  M. Ghioni,et al.  Large-area avalanche diodes for picosecond time-correlated photon counting , 2005, Proceedings of 35th European Solid-State Device Research Conference, 2005. ESSDERC 2005..

[25]  Anthony J. Durkin,et al.  Modulated imaging: quantitative analysis and tomography of turbid media in the spatial-frequency domain. , 2005, Optics letters.

[26]  Srilekha Banerjee,et al.  Role of approximate phase functions in Monte Carlo simulation of light propagation in tissues , 2003 .

[27]  Miriam Leeser,et al.  The effect of temporal impulse response on experimental reduction of photon scatter in time-resolved diffuse optical tomography. , 2013, Physics in medicine and biology.

[28]  Timothy C Zhu,et al.  Reconstruction of in-vivo optical properties for human prostate using interstitial diffuse optical tomography. , 2009, Optics express.

[29]  Yujie Lu,et al.  A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography , 2012, Physics in medicine and biology.

[30]  Alberto Tosi,et al.  A High-Linearity, 17 ps Precision Time-to-Digital Converter Based on a Single-Stage Vernier Delay Loop Fine Interpolation , 2013, IEEE Transactions on Circuits and Systems I: Regular Papers.

[31]  Yuting Lin,et al.  Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system , 2010, Optics express.

[32]  Andreas H. Hielscher,et al.  Non-contact small animal fluorescence imaging system for simultaneous multi-directional angular-dependent data acquisition. , 2014, Biomedical optics express.

[33]  Alexander D. Klose,et al.  Radiative transfer of luminescence light in biological tissue , 2009 .

[34]  Hamid Dehghani,et al.  Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations. , 2009, Journal of the Optical Society of America. A, Optics, image science, and vision.

[35]  Y. Bérubé-Lauzière,et al.  Diffuse optical tomographic imaging of biological media by time-dependent parabolic SP(N) equations: a two-dimensional study. , 2012, Journal of biomedical optics.

[36]  C. Cottini,et al.  A NEW METHOD FOR ANALOG TO DIGITAL CONVERSION , 1963 .

[37]  F Panzeri,et al.  Custom single-photon avalanche diode with integrated front-end for parallel photon timing applications. , 2012, The Review of scientific instruments.

[38]  Huajiang Wei,et al.  Differential Diagnosis of Human Normal Bladder and Bladder Cancer Tissues by Utilizing Optical Properties of Tissues in vitro , 2006 .

[39]  Evaluation of a fast single-photon avalanche photodiode for measurement of early transmitted photons through diffusive media. , 2013, Optics letters.

[40]  D. Boas,et al.  Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging. , 2006, Applied optics.

[41]  B. Pogue,et al.  Comparison of imaging geometries for diffuse optical tomography of tissue. , 1999, Optics express.

[42]  S. Achilefu,et al.  In vivo fluorescence lifetime tomography. , 2009, Journal of biomedical optics.

[43]  John McGhee,et al.  Radiative transport in fluorescence-enhanced frequency domain photon migration. , 2006, Medical physics.

[44]  Mamadou Diop,et al.  Deconvolution method for recovering the photon time-of-flight distribution from time-resolved measurements. , 2012, Optics letters.

[45]  Angelo Gulinatti,et al.  Large-area low-jitter silicon single photon avalanche diodes , 2008, SPIE OPTO.

[46]  Soren D. Konecky,et al.  Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography. , 2009, Journal of biomedical optics.

[47]  Ivan Rech,et al.  Four Channel, 40 ps Resolution, Fully Integrated Time-to-Amplitude Converter for Time-Resolved Photon Counting , 2012, IEEE Journal of Solid-State Circuits.

[48]  E. Miller,et al.  Combined optical and X-ray tomosynthesis breast imaging. , 2011, Radiology.

[49]  B. Pogue,et al.  In vivo quantitative imaging of normal and cancerous breast tissue using broadband diffuse optical tomography. , 2010, Medical physics.

[50]  Xavier Intes,et al.  Wide-field fluorescence molecular tomography with compressive sensing based preconditioning. , 2015, Biomedical optics express.

[51]  Xavier Intes,et al.  Full-field time-resolved fluorescence tomography of small animals. , 2010, Optics letters.

[52]  Davide Contini,et al.  Brain functional imaging at small source-detector distances based on fast-gated single-photon avalanche diodes , 2009, BiOS.

[53]  Eva M. Sevick-Muraca,et al.  Experimental Comparison of Continuous-Wave and Frequency-Domain Fluorescence Tomography in a Commercial Multi-Modal Scanner , 2015, IEEE Transactions on Medical Imaging.

[54]  Experimental measurement of time-dependent photon scatter for diffuse optical tomography. , 2010, Journal of biomedical optics.

[55]  A. Goetzberger,et al.  Avalanche Effects in Silicon p—n Junctions. II. Structurally Perfect Junctions , 1963 .

[56]  Hamid Dehghani,et al.  A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging. , 2009, The Review of scientific instruments.

[57]  B. Vojnovic Advanced Time‐Correlated Single Photon Counting Techniques , 2006 .

[58]  Xavier Intes,et al.  Development of an optical imaging platform for functional imaging of small animals using wide-field excitation , 2010, Biomedical optics express.

[59]  Xavier Intes,et al.  Quantitative tomographic imaging of intermolecular FRET in small animals , 2012, Biomedical optics express.

[60]  Davide Contini,et al.  Fast-gated single-photon counting technique widens dynamic range and speeds up acquisition time in time-resolved measurements. , 2011, Optics express.

[61]  A Tosi,et al.  Non-contact time-resolved diffuse reflectance imaging at null source-detector separation. , 2012, Optics express.

[62]  Ivan Rech,et al.  Time-correlated single-photon counting system based on a monolithic time-to-amplitude converter , 2012 .

[63]  Yves Bérubé-Lauzière,et al.  A new deconvolution technique for time-domain signals in diffuse optical tomography without a priori information , 2009, European Conference on Biomedical Optics.

[64]  M. Gersbach,et al.  A 128 $\times$ 128 Single-Photon Image Sensor With Column-Level 10-Bit Time-to-Digital Converter Array , 2008, IEEE Journal of Solid-State Circuits.

[65]  M. Ghioni,et al.  Progress in Quenching Circuits for Single Photon Avalanche Diodes , 2010, IEEE Transactions on Nuclear Science.

[66]  I Rech,et al.  8-Channel acquisition system for Time-Correlated Single-Photon Counting. , 2013, The Review of scientific instruments.

[67]  A Gulinatti,et al.  Avalanche current read-out circuit for low jitter parallel photon timing. , 2013, Electronics letters.

[68]  Patrick Poulet,et al.  An instrument for small-animal imaging using time-resolved diffuse and fluorescence optical methods , 2006 .

[69]  R. Haitz,et al.  Model for the Electrical Behavior of a Microplasma , 1964 .

[70]  R. Fontaine,et al.  High precision time-to-amplitude converter for diffuse optical tomography applications , 2008, 2008 3rd International Conference on Design and Technology of Integrated Systems in Nanoscale Era.

[71]  Andreas H Hielscher,et al.  Optical tomographic imaging of small animals. , 2005, Current opinion in biotechnology.

[72]  M. Ghioni,et al.  Note: Fully integrated time-to-amplitude converter in Si-Ge technology. , 2010, The Review of scientific instruments.

[73]  Julien Pichette,et al.  Time-domain geometrical localization of point-like fluorescence inclusions in turbid media with early photon arrival times. , 2013, Applied optics.

[74]  V. Ntziachristos,et al.  Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons. , 2010, Optics letters.

[75]  Vasilis Ntziachristos,et al.  Time-resolved imaging of optical coefficients through murine chest cavities. , 2006, Journal of biomedical optics.

[76]  O Nalcioglu,et al.  A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging , 2011, Physics in medicine and biology.

[77]  Julien Pichette,et al.  Diffuse photon density wavefront speed as a contrast for tomographic imaging of heterogeneous diffusive media. , 2014, Optics letters.

[78]  D KloseAlexander,et al.  Light transport in biological tissue based on the simplified spherical harmonics equations , 2006 .

[79]  Massimo Ghioni,et al.  Avalanche detector with ultraclean response for time-resolved photon counting , 1998 .

[80]  R. Lecomte,et al.  (68)Ga/DOTA- and (64)Cu/NOTA-phthalocyanine conjugates as fluorescent/PET bimodal imaging probes. , 2013, Bioconjugate chemistry.

[81]  A. Lacaita,et al.  Physics and numerical simulation of single photon avalanche diodes , 1997 .

[82]  A. Lacaita,et al.  New silicon epitaxial avalanche diode for single-photon timing at room temperature , 1988 .

[83]  Jürgen Beuthan,et al.  Multipixel system for gigahertz frequency-domain optical imaging of finger joints. , 2008, The Review of scientific instruments.

[84]  S. Arridge Optical tomography in medical imaging , 1999 .

[85]  Imagerie de fluorescence et intrinsèque de milieux diffusants par temps d’arrivée des premiers photons , 2014 .

[86]  Angelo Gulinatti,et al.  35 ps time resolution at room temperature with large area single photon avalanche diodes , 2005 .

[87]  Hyewon Youn,et al.  In vivo Noninvasive Small Animal Molecular Imaging , 2012, Osong public health and research perspectives.

[88]  Edoardo Charbon,et al.  A 32×32 50ps resolution 10 bit time to digital converter array in 130nm CMOS for time correlated imaging , 2009, 2009 IEEE Custom Integrated Circuits Conference.

[89]  B. Paquette,et al.  Pre-irradiation of mouse mammary gland stimulates cancer cell migration and development of lung metastases , 2013, British Journal of Cancer.

[90]  Mahlega S. Hassanpour,et al.  Mapping distributed brain function and networks with diffuse optical tomography , 2014, Nature Photonics.

[91]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[92]  David Tyndall,et al.  A High-Throughput Time-Resolved Mini-Silicon Photomultiplier With Embedded Fluorescence Lifetime Estimation in 0.13 $\mu$m CMOS , 2012, IEEE Transactions on Biomedical Circuits and Systems.

[93]  Franco Zappa,et al.  A view on progress of silicon single-photon avalanche diodes and quenching circuits , 2006, SPIE Optics East.

[94]  Hamid Dehghani,et al.  Multi-modal molecular diffuse optical tomography system for small animal imaging , 2013, Measurement science & technology.

[95]  M. Ghioni,et al.  Monolithic Time-to-Amplitude converter for TCSPC applications with 45 ps time resolution , 2011, 2011 7th Conference on Ph.D. Research in Microelectronics and Electronics.

[96]  Edoardo Charbon,et al.  A 32x32-pixel array with in-pixel photon counting and arrival time measurement in the analog domain , 2009, 2009 Proceedings of ESSCIRC.

[97]  Axel Bergmann,et al.  Multi‐dimensional fluorescence lifetime and FRET measurements , 2007, Microscopy research and technique.

[98]  R. Haitz Mechanisms Contributing to the Noise Pulse Rate of Avalanche Diodes , 1965 .

[99]  M. Rudin,et al.  Validation of an XCT/fDOT System on Mice , 2012 .

[100]  Hyun K Kim,et al.  Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2: image classification , 2013, Journal of biomedical optics.

[101]  Sanjiv S Gambhir,et al.  A molecular imaging primer: modalities, imaging agents, and applications. , 2012, Physiological reviews.

[102]  Francesco Panzeri,et al.  SPAD array module for multi-dimensional photon timing applications , 2012 .

[103]  W. Brockherde,et al.  SPAD Smart Pixel for Time-of-Flight and Time-Correlated Single-Photon Counting Measurements , 2012, IEEE Photonics Journal.

[104]  Edward W. Larsen,et al.  Light transport in biological tissue based on the simplified spherical harmonics equations , 2006, J. Comput. Phys..

[105]  S. Rossitti Introduction to Functional Magnetic Resonance Imaging, Principles and Techniques , 2002 .

[106]  Scott C. Davis,et al.  Preclinical Whole-body Fluorescence Imaging: Review of Instruments, Methods and Applications , 2013 .

[107]  A. Lacaita,et al.  Avalanche photodiodes and quenching circuits for single-photon detection. , 1996, Applied optics.

[108]  V. Ntziachristos Fluorescence molecular imaging. , 2006, Annual review of biomedical engineering.

[109]  S. Cova,et al.  New silicon SPAD technology for enhanced red-sensitivity, high-resolution timing and system integration , 2012 .

[110]  P. Peltié,et al.  Noncontact fluorescence diffuse optical tomography of heterogeneous media. , 2007, Applied optics.

[111]  A. Bergmann,et al.  Multispectral fluorescence lifetime imaging by TCSPC , 2007, Microscopy research and technique.