Time-resolved functional near-infrared spectroscopy

1. 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

2. e (cm-1 M-1) l1 l2 HHb O2Hb wavelength (nm) Principles of functional NIRS (fNIRS)

3. Lambert-Beer law Light attenuation in a clear medium L ma = e C I(0) I(L) z dz I = light intensity [W cm-2] ma = absorption coefficient [cm-1] L = source-detector distance = pathlength [cm]

4. turbid medium clear medium Light Propagation in Diffusive Media • Light scattering is greater than absorption •  Photons pathlength is not the geometrical source-detector distance •  Attenuation is dependent also on scattering

5. Modified Lambert-Beer Law 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

6. Intensity time Principles of Time-Resolved fNIRS r m’s , ma

7. Time-resolved fNIRS Effect of scattering Effect of absorption log10I log10I Slope changes m’s ma Slope do not change! time Time positiondo not change! time Time positionchanges

8. r Martelli et al. Perturbation model for light propagation through diffusive layered media Phys. Med. Biol.50 2159-2166 (2005) scalp/skull S0 m’s0 , ma0 m’s1 , ma1 S1 csf m’s2 , ma2 S2 Dma2 brain Semi-empirical approach: time-gate analysis I r time Steinbrink et al. Phys Med Biol 46:879-896 (2001) Del Bianco et al. Phys Med Biol 47:4131-4144 (2002) Motor task on human subject:- Time-gate analysis Head is not homogeneous!

9. baseline baseline task task recovery recovery • [ Nomura et al., Phys Med Biol 42:1009-1022 (1997) ] Motor task on human subject:- Time-gate & microscopic Lambert-Beer law

10. PoliMi multi-channel time-resolved fNIRS system- new set-up: S16-D64 PicoQuant PDL800 Piezojena F-SM19 OZOptics VISNIR5050 Microchip Technology dsPIC30F6014 Hamamatsu R5900-20-M4 Becker & Hickl, SPC-134, HRT-41, HAFC-26

11. System characterization:- detection section 4 anode PMT + high sensitivity: SS20 0.6%, SS25 6.0% @820 nm + large area (9x9 mm2 each quadrant) — temporal resolution (TTS 300 ps) 18 mm Fiber bundle + large NA (0.5) + home-made, low cost — seven 1-mm plastic fibers: not so flexible! — modal dispersion limits length to 1.5 m 3 mm  4 fiber bundles in each quadrant  total number of fiber bundles 64 … now limited to 16!!  See poster ME21 Contini et al. for details

12. 510 ps FWHM 520 ps FWHM System characterization:- Instrument response function (IRF) • 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

13. System characterization:- Linearity for absorption • Results for 690 nm, no major differences at 820 nm • Negligible coupling between ma and ms’ • Inter-channel dispersion (CV) < 9% • Integral non-linearity < 3%  See poster ME21 Contini et al. for details

14. @ 200K counts CV2004 - abs:  2% CV2006 - abs:  0.4% CV2006 - late gate:  0.1% System characterization:- Noise • Pifferi et al., “ ...The Medphot Protocol”, Applied Optics 44:2104-2114 (2005)

15. 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

16. baseline baseline task task recovery recovery 9 repetitions chan 1 solid phantom Motor task on human subject:- DHHb and DO2Hb

17. 15s task: 1 repetition 10s task : 1 repetition 5s task : 1 repetition Motor task on human subject:- DHHb and DO2Hb (single trials)

18. D1 D4 D7 D6 D9 S1 S2 S3 S4 2 cm D3 D2 D5 D8 D11 Motor task on human subject:- mapping DHHb and DO2Hb Protocol: 20 s baseline, 20 s task (finger tapping with right hand at 2Hz), 40 s recovery 4 repetitions, acquisition time 250 ms

19. task rest Time-resolved fNIRS of primate brain:- first results S1 D1 1 mm fiber 1 cm Optodes in direct contact with the dura Task: grasp food

20. Source: whitelight fiber laser Optics: photonic crystal devices Detection & Acquisition: IC SPAD Leon-Saval et al., “Multimode fiber devices with single-mode performance”, Optics Letters 30:2545-2527 (2005) Zappa et al., “Complete single-photon counting and timing module in a microchip” Optics Letters 30:1327-1329 (2005) Future Perspectives www.fianium.com

21. Time-Resolved fNIRS at Null Source-Detector Separation Improved contrast and resolution Torricelli et al. Phys Rev Lett 95, 078101 (2005)

22. “Future” Perspectives? "Pre-Crime" Image Thoughts of PreCogs (2054) Philip K. Dick, ”The Minority Report” (1956) Steven Spielberg, "Minority Report” (2002) Thanks to Turgut Durduran, Upenn