Time-resolved functional near-infrared spectroscopy A.Torricelli, D.Contini, A.Pifferi, L.Spinelli and R.Cubeddu ULTRAS-CNR-INFM and IFN-CNR, Politecnico di Milano, Dipartimento di Fisica L.Craighero, L.Fadiga Faculty of Medicine – DBSTA, Section of Human Physiology, Università di Ferrara Trieste Workshop - “Tools to study language acquisition in early infancy”, May 5-8, 2006 Principles of functional NIRS (fNIRS) 1 10000 2 1 a1 HHb HHb O2 Hb O21Hb 2 2 O2 Hb O22Hb a HHb HHb ASSORBIMENTO (cm-1 M-1 ) (cm -1 M-1) 9000 8000 HbO 7000 6000 Hb HHb 5000 4000 3000 O2H b 2000 1000 0 600 700 800 900 1000 LUNGHEZZA D'ONDA (nm) wavelength (nm) a1 O22Hb a2 O21Hb HHb 1 2 2 1 HHb O2 Hb HHb O2 Hb 2 1 1 2 HHb a HHb a O Hb 1 2 2 1 2 O2 Hb HHb O Hb HHb 2 tHb HHb O2 Hb O2 Hb SO2 HHb O2 Hb Nome relatore A. Torricelli Lambert-Beer law Light attenuation in a clear medium L I L I 0 exp a L I(0) I(L) a = C I 0 a L CL A ln I L dz z I = light intensity [W cm-2] a = absorption coefficient [cm-1] L = source-detector distance = pathlength [cm] Nome relatore A. Torricelli Light Propagation in Diffusive Media clear medium turbid medium Light scattering is greater than absorption Photons pathlength is not the geometrical source-detector distance Attenuation is dependent also on scattering Nome relatore A. Torricelli Modified Lambert-Beer Law A CL B G B = Differential Pathlength Factor (DPF) [-] G = Signal loss due to scattering [-] L = source-detector distance [cm] L* = L B = effective pathlength [cm] Main problem: B (DPF) and G depend on wavelength, geometry, subject, ... Partial solution: Monitor changes, not absolute values A L B C Nome relatore A. Torricelli Principles of Time-Resolved fNIRS Intensity r ’s , a Nome relatore A. Torricelli time Time-resolved fNIRS Effect of scattering log10I Effect of absorption log10I Slope changes ’s Slope do not change! Time position changes time Nome relatore A. Torricelli a Time position do not change! time Motor task on human subject: - Time-gate analysis Head is not homogeneous! r a2 Martelli et al. Perturbation model for light propagation through diffusive layered media Phys. Med. Biol. 50 2159-2166 (2005) ’s0 , a0 S0 ’s1 , a1 S1 ’s2 , a2 S2 Semi-empirical approach: time-gate analysis r I time Steinbrink et al. Phys Med Biol 46:879-896 (2001) Del Bianco et al. Phys Med Biol 47:4131-4144 (2002) Nome relatore A. Torricelli scalp/skull csf brain Motor task on human subject: - Time-gate & microscopic Lambert-Beer law 0.10 690 nm 0.08 0.08 0.06 0.06 0.04 0.04 log(I/Io) log(I/Io) 0.10 0.02 0.00 -0.02 -0.04 baseline task baseline task recovery 0.02 0.00 -0.02 -0.04 recovery -0.06 -0.06 Early gate (0-750 ps) Late (2000-2750 ps) -0.08 -0.10 0 20 40 60 80 Early gate (0-750 ps) Late (2000-2750 ps) -0.08 -0.10 100 0 20 40 time (s) 0.10 0.06 0.04 0.02 690 nm 820 nm 0.00 -0.02 -0.08 -0.10 1000 1500 100 a a0 a -0.06 500 80 Rr , t; i ai vt ln R0 r , t; i -0.04 0 60 time (s) 0.08 max contrast 820 nm 2000 2500 i i i 1 a1 HHb HHb O2 Hb O21Hb 2 2 O2 Hb O22Hb a HHb HHb [ Nomura et al., Phys Med Biol 42:1009-1022 (1997) ] time-gate delay (ps) Nome relatore A. Torricelli PoliMi multi-channel time-resolved fNIRS system - new set-up: S16-D64 S1 PicoQuant PDL800 variable ND delay Piezojena F-SM19 690 nm Laser driver 50% variable ND 820 nm 2x2 fused splitter 50% TCSPC-2 4 ch router-2 TCSPC-3 4 ch router-3 TCSPC-4 4 ch router-4 R1 R2 R3 R4 clock S16 Microchip Technology dsPIC30F6014 4 ch router-1 2x4 fused splitter S9 CHIP TCSPC-1 1x9 fiber switch OZOptics VISNIR5050 sync clock 1x9 fiber switch S8 Hamamatsu R5900-20-M4 8 ch amp-1 8 ch amp-2 F1 4 anodes PMT-1 4 anodes PMT-2 4 anodes PMT-3 4 anodes PMT-4 Becker & Hickl, SPC-134, HRT-41, HAFC-26 Nome relatore A. Torricelli F16 System characterization: - detection section 4 anode PMT + high sensitivity: SS20 0.6%, SS25 6.0% @820 nm 18 mm + large area (9x9 mm2 each quadrant) — temporal resolution (TTS 300 ps) Fiber bundle + large NA (0.5) 3 mm + home-made, low cost — seven 1-mm plastic fibers: not so flexible! — modal dispersion limits length to 1.5 m 4 fiber bundles in each quadrant total number of fiber bundles 64 … now limited to 16!! See poster ME21 Contini et al. for details Nome relatore A. Torricelli System characterization: - Instrument response function (IRF) 510 ps FWHM 520 ps FWHM FWHM 500 ps 5 ms minimum acquisition time per single channel max injected power < 0.5 mW 8 MHz (2MHz/board) 106 ph/s per wavelength See poster ME21 Contini et al. for details Nome relatore A. Torricelli System characterization: - Linearity for absorption • Results for 690 nm, no major differences at 820 nm 0.6 A 0.5 B C D -1 Meas. absorption (cm ) -1 Meas. absorption (cm ) 0.6 0.4 0.3 0.2 0.1 8 0.5 7 0.4 6 5 0.3 4 0.2 3 2 0.1 1 0.0 0.0 0 0.1 0.2 0.3 0.4 0.5 True absorption (cm-1) 0 5 10 15 20 25 True scattering (cm-1) • Negligible coupling between a and s’ • Inter-channel dispersion (CV) < 9% • Integral non-linearity < 3% See poster ME21 Contini et al. for details Nome relatore A. Torricelli System characterization: - Noise 2004 - abs 2006 - abs 2006 - late gate 100.00% @ 200K counts CV (%) 10.00% CV2004 - abs: 2% 1.00% CV2006 - abs: 0.4% 0.10% CV2006 - late gate: 0.1% 0.01% 1.E+03 1.E+04 1.E+05 1.E+06 1.E+07 counts (ph) • Pifferi et al., “ ...The Medphot Protocol”, Applied Optics 44:2104-2114 (2005) Nome relatore A. Torricelli Motor task on human subject: - protocol Motor area for right hand identified by Transcranial Magnetic Stimulation (TMS) 2 cm S2 D2 2 cm S1 D1 volounteer solid phantom Protocol: 20 s baseline, 20 s task (finger tapping with right hand at 2Hz), 40 s recovery 9 repetitions, acquisition time 1s Nome relatore A. Torricelli Motor task on human subject: - HHb and O2Hb baseline 2.0 task recovery HHb O2Hb 1.5 1.0 contrast ( M) 1.5 contrast ( M) HHb O2Hb 2.0 chan 1 0.5 0.0 solid phantom 0.0 -1.0 -1.0 20 30 40 50 60 70 80 0 10 time (s) 20 30 40 50 60 70 time (s) HHb O2Hb 3.0 2.5 9 repetitions 2.0 contrast ( M) recovery 0.5 -0.5 10 task 1.0 -0.5 0 baseline 1.5 1.0 0.5 0.0 -0.5 -1.0 -1.5 0 80 160 240 320 400 480 time (s) Nome relatore A. Torricelli 560 640 720 80 Motor task on human subject: - HHb and O2Hb (single trials) 15s task: 1 repetition 1.0 HHb O2Hb 0.8 0.4 0.2 0.0 10s task : 1 repetition -0.2 -0.4 1.0 -0.6 HHb O2Hb 0.8 -0.8 0.6 0 20 40 time (s) 60 80 0.4 0.2 0.0 -0.2 5s task : 1 repetition -0.4 -0.6 1.0 -0.8 HHb O2Hb 0.8 -1.0 0 20 40 time (s) 60 80 0.6 contrast ( M) -1.0 contrast ( M) contrast ( M) 0.6 0.4 0.2 0.0 -0.2 -0.4 -0.6 -0.8 -1.0 0 20 40 time (s) Nome relatore A. Torricelli 60 80 Motor task on human subject: - mapping HHb and O2Hb D1 S1 D3 D4 S2 D2 D7 D6 S3 D5 D9 S4 D8 Nome relatore A. Torricelli 2 cm D11 Protocol: 20 s baseline, 20 s task (finger tapping with right hand at 2Hz), 40 s recovery 4 repetitions, acquisition time 250 ms Time-resolved fNIRS of primate brain: - first results HHb O2Hb 2.5 2.0 contrast ( M) 1.5 1.0 0.5 0.0 -0.5 -1.0 -1.5 task -2.0 rest -2.5 0 30 60 90 time (s) S1 D1 1 cm 1 mm fiber Optodes in direct contact with the dura Task: grasp food Nome relatore A. Torricelli 120 150 Future Perspectives Source: whitelight fiber laser Optics: photonic crystal devices www.fianium.com Detection & Acquisition: IC SPAD Zappa et al., “Complete single-photon counting and timing module in a microchip” Optics Letters 30:1327-1329 (2005) Nome relatore A. Torricelli Leon-Saval et al., “Multimode fiber devices with single-mode performance”, Optics Letters 30:2545-2527 (2005) Time-Resolved fNIRS at Null Source-Detector Separation Improved contrast and resolution Torricelli et al. Phys Rev Lett 95, 078101 (2005) Nome relatore A. Torricelli “Future” Perspectives? "Pre-Crime" Image Thoughts of PreCogs (2054) Philip K. Dick, ”The Minority Report” (1956) Steven Spielberg, "Minority Report” (2002) Nome relatore A. Torricelli Thanks to Turgut Durduran, Upenn