Experimental results on time-resolved reflectance diffuse optical tomography with fast-gated SPADs Agathe Puszka*a, Laura Di Sienob, Alberto Dalla Morab, Antonio Pifferib, Davide Continib, Gianluca Bosoc, Alberto Tosic, Anne Planat-Chrétiena, Lionel Hervéa, Anne Koeniga, Jean-Marc Dintena a CEA-LETI, Minatec Campus, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France; bPolitecnico di Milano, Dipartimento di Fisica, Piazza Leonardo da Vinci 32, Milano I-20133, Italy; cPolitecnico di Milano, Dipartimento di Elettronica, Informazione e Bioingegneria, Piazza Leonardo da Vinci 32 – I-20133 Milano, Italy. ABSTRACT We present experimental results of time-resolved reflectance diffuse optical tomography performed with fast-gated single-photon avalanche diodes (SPADs) and show an increased imaged depth range for a given acquisition time compared to the non gated mode. Keywords: Time-resolved imaging; Tomography; Image reconstruction techniques; Turbid media; Photon counting; Photodiodes. 1. INTRODUCTION In the context of analyzing biological tissue with near-infrared light, the possibility to realize optical probes with small interfiber distances to study deep layers with reflectance measurements is currently investigated. This specific geometry is relevant to probe organs whose access is anatomically restricted like the prostate1 for which a single fiber probe is useful2. But for organs like the breast3, the brain or the muscle4 it can also be preferred to other optodes configurations for other reasons: small probes are practical to handle for the medical practitioner and easy to position on the patient compared to rings of fibers for which a wrong placement causes errors on the obtained results. In the case of reflectance measurements at small interfiber distances, time-resolved techniques enable to reach high sensitivity to deep layers of the probed tissue by selecting late photons5. We have proposed an image reconstruction method for Diffuse Optical Tomography (DOT) based on the Mellin-Laplace transform (MLT) of Time-Point Spread Functions (TPSFs) which allows including the information of late photons in the reconstruction process6. We have shown that this method can be adapted to the dynamic range of the TPSF, and enables to detect and localize deeper absorbing inclusions in a diffusing medium for a higher dynamic range7. Recent developments with fast-gated single-photon avalanche diodes (SPADs) associated to a time-correlated singlephoton counting (TCSPC) setup have shown that it is possible to acquire TPSFs with a high dynamic range in limited acquisition time compared to the classical non gated mode8, in principle without any limit in the achievable dynamic range, in practice with the limitation due to the memory effect of the gated detector9. This technique has already been applied to turbid media for improving the contrast to deep absorbing inclusions in reflectance 10,11. We show here that it can be used to reconstruct images of the absorption coefficient in turbid media with DOT algorithms. In particular we demonstrate that the reconstructed depth range and depth localization accuracy of a single absorbing inclusion in a turbid medium are improved by using the fast-gated mode, for an interfiber distance of 15 mm. * agathe.puszka@cea.fr, Phone: +33 (0)4 38 78 14 46, Fax: + 33 (0)4 38 78 59 30. 2. EXPERIMENTS 2.1 Setup The setup is depicted in Figure 1. The source is a 4-wave mixing laser (Fianium, UK) providing picosecond pulses at 820 nm at 40 MHz. The laser beam is attenuated by a self-made variable optical attenuator (VOA) before being injected in the excitation fiber. Retro-diffused light is collected by an optical fiber coupled to a 100 µm diameter SPAD. The used SPAD detector and corresponding electronics were developed at the Dipartimento di Elettronica, Informazione e Bioingegneria of Politecnico di Milano12. The SPAD module is connected to a TCSPC board (SPC-130, Becker & Hickl GmbH). The tested probe features two couples of source and detector with the same interfiber distance of 15 mm (couples S1D2 and S2D1) aligned along the x axis (Figure 1). The experiment is performed in a liquid phantom with a movable solid diffusing and absorbing inclusion. The background is composed of Intralipid and black ink (µ a = 0.1 cm-1 and µs' = 10 cm-1 at 820 nm). The optical properties of the inclusion (cylinder of 8 mm diameter and 6 cm long made of resin, TiO 2 particles and black ink) are µ a = 0.6 cm-1 and µs' = 10 cm-1. This geometry consisting of a one-dimension probe and a cylindrical inclusion was chosen to mimic a two-dimension configuration, as the employed reconstruction algorithm is currently developed in 2D. The inclusion is placed in the liquid, perpendicular to the (x, z) plane and at the center of the 2 couples of source and detectors. During the experiment, it is only moved along the z axis at different depths values. The acquisition is successively done for each couple of source and detector. TCSPC SPAD sync. Delayer Laser λ = 820 nm 40 MHz Optical fiber delay Optical fiber S1 D1 D2 S2 y x z depth VOA 15 mm 15 mm Figure 1. Experimental setup and schematic view of the probe and phantom (2D cross section in plane (x, z)). 2.2 Protocol During gated acquisitions, the VOA is adapted for each temporal position of the gate in order to reach the allowed maximum count rate of 106 photons per second and therefore optimize the signal to noise ratio. We choose the temporal position of the different gates in order to obtain a smooth reconstitution of the full TPSF. 9 gates are used to acquire each TPSF (Figure 2) with a maximum power increase of around 2 decades between the first and the last gate. 1 second is acquired for each gate so the acquisition is 9 seconds in total for each couple of source and detector. For comparison purpose, we reproduce the same protocol with the non gated mode: the gate is positioned in order to acquire the full TPSF at once and we use an acquisition of 9 seconds per TPSF in order to compare the two modes for the same "photon counting time". 3. DATA ANALYSIS AND RECONSTRUCTION METHOD Each TPSF is built by pre-processing the 9 gated acquisitions (Figure 2). These TPSFs are then used as input for an iterative algorithm reconstructing µa nonlinearly in the 2D plane (x, z) orthogonal to the surface of the medium and including the line of excitation and detection points (2D see cross section shown in Figure 1). This algorithm is based on the Mellin-Laplace transform (MLT) of the TPSFs6,7. 4 4 10104 101022 4 10 104 10104 2 102 10 2 102 0 100 0 10 100 10 10 -2 0 -2 10 10-2 0 10100 gate 5 gate 6 gate 7 gate 8 gate 9 gate 1 gate 2 gate 3 gate 4 keep in analysis 10 10-2 16.276ns 00 16.3 16.3 16.276ns 00 DCR correction and rescaling 16.3 16.276ns Building the full diffusion curve Figure 2. Data pre-processing steps to build each TPSF from fast-gated acquisitions (couple S1D2). 4. RESULTS For a total acquisition time of 9 s per couple of source and detector, using the gated mode has enabled to recover the TPSFs with a dynamic range of more than 5 decades (Figure 3) compared to 3.5 decades with the non gated mode (not shown here). Figure 3 shows that the information on late photons is crucial to obtain contrast on the deepest inclusions. 102 Photon counts 104 reference 13 mm 19 mm 25 mm 101 102 b) 1.8 2.5 ns 3.1 3.6 ns 2.100 100 100 10-2 a) 0 2 Time 4 2.10-1 6 ns c) Figure 3. (a) Acquired signals after pre-processing for the reference and 3 depths of the inclusion (for S1D2), (b) zoom between 1.8 and 2.5 ns: the signal measured for the depth of 25 mm is overlapping the reference, (c) zoom between 3.1 and 3.6 ns: the signal measured for the depth of 25 mm is clearly below the reference signal in this time window. The reconstruction algorithm is based on the MLT defined as: f ( p , n ) M ( p , n ) f (t ) pn n! f (t )t n exp( pt )dt where 0 f(t) is the TPSF, p (in ns-1) a real positive and n a positive or null integer. A contrast is calculated as follows MLTwithout _ inclusion MLTwith _ inclusion Contrast 100 for each MLT order from the TPSFs with and without the inclusion in MLTwithout _ inclusion the medium. It provides information on the possibility to detect robustly an absorbing inclusion7. On Figure 4, we can see that the gated mode enables to reach higher values of contrast on orders of MLT > 10 (containing information on late photons) than with the non gated mode. For the depth of 2.5 cm in particular, the contrast with the gated mode reaches more than 15 % for some MLT orders whereas it is very noisy and inferior to 10% with the non gated acquisition. This analysis is consistent with the obtained reconstruction results shown in Figure 5. Whereas the obtained images for the most superficial inclusion (13 mm) are similar for gated and non-gated modes, the deepest inclusion at 25 mm is robustly detected and well localized with the gated mode, which is not the case for the non gated mode. 1.3 cm Contrast (%) 50 2.5 cm 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 Gated S1D2 S2D1 Non gated S1D2 S2D1 -10 5 10 15 20 25 30 -10 5 10 15 Figure 4. Contrast on MLT orders (for p = 3 and S2D1. ns-1) Non gated Gated 0.16 0 0.1 0 0 -20 0 20 30 -10 5 10 10 20 20 30 30 40 40 -20 0 20 Non gated 10 15 20 25 30 MLT order 13 mm 0 µa (cm-1) 0 25 for different depths of the inclusion for gated and non gated modes for S1D2 0 50 m 20 MLT order MLT order 0 0 1.9 cm 50 50 Gated 0.16 0.1 -20 25 mm 0 0 10 10 20 20 30 30 40 40 0 Non gated µa (cm-1) Gated 0 10 10 20 20 30 30 40 40 50 20 -20 0 µa (cm-1) 0.115 50 -20 0 20 50 0.1 -20 0 25 mm 0 20 Figure 5. Reconstruction results in plane (x, z) for the depths of 13 and 25 mm, with gated and non gated modes (red circle: real inclusion). 5. CONCLUSIONS We have shown that it is possible to exploit fast-gated measurements to build TPSFs that can be used by DOT algorithms. 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