The temporal distribution of photons produced when a short duration (a few picoseconds) pulse of light is transmitted through a highly scattering medium is known as the temporal point spread function (TPSF). After travelling through several centimetres of soft tissue, the TPSF will extend over several nanoseconds. Early technical validation studies, performed using laboratory picosecond lasers and a variety of sophisticated and expensive detector systems, such as streak cameras, were discussed in the 1997 review (Hebden et al. 1997). Since then, advances in time-correlated single-photon counting (TCSPC) hardware and pulsed laser diodes have significantly reduced the cost and complexity of time-resolved measurement, and facilitated the development of multi-detector systems. TCSPC involves correlating the arrival time of a detected photon with the sampling of a known variable analogue signal. The difference between samples resulting from a detected photon and that from an external reference (derived directly from the source) provides a measurement of the photon flight time. An example of this technology is the time-to-amplitude converter (TAC). The technique generally requires a photon-counting photomultiplier tube (PMT) detector. Maximising temporal resolution requires a PMT with a minimum transient time spread (TTS) of photoelectrons across the tube. PMTs with a TTS of 150-200 ps are available, but for a significantly shorter TTS (< 50 ps) it is necessary to employ a microchannel-plate PMT (for examples, see www.hamamatsu.com). To date, the application of time-resolved measurement to diffuse optical imaging has involved two distinct approaches:
- A transillumination technique in which sources and detectors are arranged on opposite sides of a slab of tissue. Typically a single source and detector, aligned along a common axis, are scanned in two dimensions across each surface, and a single projection image is produced directly. The approach was used in the first demonstration of 2D time-resolved imaging of tissue-like media by Hebden et al. (1991), and the slab imaging geometry has been adopted for several breast imaging systems (Ntziachristos et al. 1998, Grosenick et al. 1999, Pifferi et al. 2003), described in more detail in section 4.3. An array of sources or detectors is often used so that off-axis measurements are also available, which provides a degree of depth information sufficient for a 3D image reconstruction (Ntziachristos et al. 1998, Grosenick et al. 2004).
- A tomographic approach to imaging, which involves placing sources and detectors over the available surface of the tissue in order to sample multiple lines-of-sight across the entire volume either simultaneously or successively. Images are then reconstructed using techniques such as those described in section 3.
Early applications of time-domain measurements used time-gating to identify those photons which first emerge from the tissue, which are assumed to have travelled the shortest distance and therefore be least scattered. This approach is, however, limited by the number of available photons with sufficiently short flight-times. Experiments by Hebden and Delpy (1994) indicated that a degree of high resolution information is encoded into the shape of the TPSF, which can be extracted if the TPSF is measured sufficiently accurately. Time-gating techniques have also been developed which discriminate between late arrival photons which are predominantly affected by absorption, and early arrival photons which depend on both absorption and scatter (Grosenick et al. 2003). More recently, Selb et al. (2004) showed that time-gating can be used to provide additional depth resolution compared with CW measurements alone by rejecting light from superficial tissues.
Time-resolved measurements were first applied to clinical optical tomography by researchers at Stanford University (Benaron et al. 2000, Hintz et al. 2001), who developed an imaging system which was used to measure photon flight times between points on a newborn infants head (see section 4.2). However, since only a single solid state detector was used, transmitted light between each combination of source and detector position was recorded sequentially, resulting in scan times of between two and six hours. Much faster scan times are achievable by using multiple detectors, as demonstrated by the 32-channel time-resolved system developed at University College London (UCL) (Schmidt et al. 2000), and a 64-channel time-resolved imaging system built by Shimadzu Corporation in Japan (Eda et al. 1999).
The UCL system is based on TCSPC technology and a dual-wavelength fibre laser. The laser provides interlaced trains of picosecond pulses at 780 nm and 815 nm which are coupled to the surface of the subject via a 32-way optical fibre switch. Transmitted light is collected simultaneously by 32 detector fibre bundles, which deliver the light to four 8-anode microchannel-plate PMTs via 32 variable optical attenuators, which ensure that the intensity of detected light does not exceed the maximum photon counting rate of around 2.5 x 106 photons per second. The arrival time of each detected photon is measured with respect to a laser-generated reference signal, and TPSFs are accumulated.
References[]
- Benaron D A, S R Hintz, A Villringer, D A Boas, A Kleinschmidt, J Frahm, C Hirth, H Obrig, J C van Houten, E L Kermit, W-F Cheong, and D K Stevenson (2000), "Noninvasive functional imaging of human brain using light" J. Cerebr. Blood Flow Metab. 20 469-477.
- Eda H, I Oda, Y Ito, Y Wada, Y Oikawa, Y Tsunazawa, M Takada, Y Tsuchiya, Y Yamashita, M Oda, A Sassaroli, Y Yamada, and M Tamura (1999), "Multichannel time-resolved optical tomographic imaging system" Rev. Sci. Instrum. 70(9) 3595-3602.
- Grosenick D, K T Moesta, H Wabnitz, J Mucke, C Stroszczynski, Macdonald R, P M Schlag, and H Rinneberg (2003), "Time-domain optical mammography: initial clinical results on detection and characterization of breast tumors" Applied Optics 42(16) 3170-3186.
- Grosenick D, H Wabnitz, K T Moesta, J Mucke, M Möller, C Stroszczynski, J Stössel, B Wassermann, P M Schlag, and H Rinneberg (2004), "Concentration and oxygen saturation of haemoglobin of 50 breast tumours determined by time-domain optical mammography" Phys. Med. Biol. 49 1165-1181.
- Grosenick D, H Wabnitz, H H Rinneberg, K T Moesta, and P M Schlag (1999), "Development of a time-domain optical mammograph and first in vivo applications" Appl. Opt. 38 2927-2943.
- Hebden J C and D T Delpy (1994), "Enhanced time resolved imaging using a diffusion model of photon transport" Opt. Lett. 19 311-313.
- Hebden J C, R A Kruger, and K S Wong (1991), "Time resolved imaging through a highly scattering medium" Appl. Opt. 30 788-794.
- Hebden J C, S R Arridge, and D T Delpy (1997), "Optical imaging in medicine: I. Experimental techniques" Phys. Med. Biol. 42(5) 825-840.
- Hintz S R, D A Benaron, A M Siegel, A Zourabian, D K Stevenson, and D A Boas (2001), "Bedside functional imaging of the premature infant brain during passive motor activation" J. Perinat. Med. 29(4) 335-343.
- Ntziachristos V, X Ma, and B Chance (1998), "Time-correlated single photon counting imager for simultaneous magnetic resonance and near-infrared mammography" Rev. Sci. Instrum. 69(12) 4221-4233.
- Pifferi A, P Taroni, A Torricelli, F Messina, and R Cubeddu (2003), "Four-wavelength time-resolved optical mammography in the 680-980 nm range" Optics Letters 28(13) 1138-1140.
- Schmidt F E W, M E Fry, E M C Hillman, J C Hebden, and D T Delpy (2000), "A 32-channel time-resolved instrument for medical optical tomography" Rev. Sci. Instrum. 71(1) 256-265.
- Selb J, J J Stott, M A Franceschini, and D A Boas (2004), "Improvement of depth sensitivity to cerebral hemodynamics with a time domain system" OSA Biomedical Topical Meetings, Miami FC3.