Time-resolved functional near-infrared spectroscopy A.Torricelli, D.Contini, A.Pifferi, L.Spinelli...

Time-resolved functional near-infrared spectroscopyA.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.FadigaFaculty of Medicine – DBSTA, Section of Human Physiology, Università di Ferrara

Trieste Workshop - “Tools to study language acquisition in early infancy”, May 5-8, 2006

Nome relatoreA. Torricelli

2

2

22

1

2

11

2

2

HbOHHba

HbOHHba

HbOHHb

HbOHHb

1

2

22

2

1

2112

1

2

22

2

1

1

2

22

2

1

2

HbOHHbHbOHHb

HHbaHHba

HbOHHbHbOHHb

HbOaHbOa

HbO

HHb

Principles of functional NIRS (fNIRS)

HbOHHb

HbOSO

HbOHHbtHb

2

22

2

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

600 700 800 900 1000

LUNGHEZZA D'ONDA (nm)

AS

SO

RB

IME

NT

O (

cm-1

M-1

)

HbO

Hb

O2Hb

HHb

1 2

wavelength (nm)

(c

m-1

M-1

)


Lambert-Beer law

z

L

I(0) I(L)

Light attenuation in a clear medium

LILI a exp0

dz

I = light intensity [W cm-2]

a = absorption coefficient [cm-1]

L = source-detector distance = pathlength [cm]

a = C

CLLLI

IA a

0ln


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

clear medium turbid medium


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]

GBCLA

CBLA

Main problem: B (DPF) and G depend on wavelength, geometry, subject, ...

Partial solution:

Monitor changes, not absolute values


Principles of Time-Resolved fNIRS

’s , a

time

Intensity


Time-resolved fNIRS

log10I

a

time

log10I

Effect of absorption

Time positiondo not change!

Slope changes

’s

time

Effect of scattering

Slope do not change!

Time positionchanges


Motor task on human subject:- Time-gate analysis

’s1 , a1

’s2 , a2

’s0 , a0S0

S1

S2a2

Martelli et al. Perturbation model for light propagation through diffusive layered media Phys. Med. Biol. 50 2159-2166 (2005)

scalp/skull

csf

brain

Head is not homogeneous!

I

timeSteinbrink et al. Phys Med Biol 46:879-896 (2001)Del Bianco et al. Phys Med Biol 47:4131-4144 (2002)

Semi-empirical approach: time-gate analysis


-0.10

-0.08

-0.06

-0.04

-0.02

0.00

0.02

0.04

0.06

0.08

0.10

0 500 1000 1500 2000 2500

time-gate delay (ps)

max

co

ntr

ast

690 nm

820 nm

Motor task on human subject:- Time-gate & microscopic Lambert-Beer law

[ Nomura et al., Phys Med Biol 42:1009-1022 (1997) ]

iiiaaa 0

vttR

tRia

i

i

;,

;,ln

0

2

2

22

1

2

11

2

2

HbOHHba

HbOHHba

HbOHHb

HbOHHb

690 nm

-0.10

-0.08

-0.06

-0.04

-0.02

0.00

0.02

0.04

0.06

0.08

0.10

0 20 40 60 80 100

time (s)

log

(I/I

o)

Early gate (0-750 ps)Late (2000-2750 ps)

baseline task recovery

820 nm

-0.10

-0.08

-0.06

-0.04

-0.02

0.00

0.02

0.04

0.06

0.08

0.10

0 20 40 60 80 100

time (s)

log

(I/I

o)

Early gate (0-750 ps)Late (2000-2750 ps)



PoliMi multi-channel time-resolved fNIRS system- new set-up: S16-D64

clock

CHIP

delay

2x2 fused splitter

50%

50%

2x4 fusedsplitter

R1R2

R3R4

S16

S9

S8

S1

sync

820 nm

690 nm

Laserdriver

variable ND

variable ND

1x9 fiber switch

1x9 fiber switch

4 anodesPMT-1

4 anodesPMT-2

4 anodesPMT-3

4 anodesPMT-4

4 chrouter-1

4 chrouter-2

4 chrouter-3

4 chrouter-4

8 champ-1

8 champ-2

F1

F16

clock

TCSPC-1

TCSPC-2

TCSPC-3

TCSPC-4

PicoQuant

PDL800

Piezojena

F-SM19

Hamamatsu

R5900-20-M4

Becker & Hickl, SPC-134, HRT-41, HAFC-26

OZOptics

VISNIR5050

Microchip TechnologydsPIC30F6014


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

System characterization:- detection section

See poster ME21 Contini et al. for details

4 anode PMT + high sensitivity: SS20 0.6%, SS25 6.0% @820 nm

+ large area (9x9 mm2 each quadrant)

— temporal resolution (TTS 300 ps)

4 fiber bundles in each quadrant total number of fiber bundles 64

… now limited to 16!!

18 mm

3 mm


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



System characterization:- Linearity for absorption


• Inter-channel dispersion (CV) < 9%• Integral non-linearity < 3%

• Negligible coupling between a and s’

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0 0.1 0.2 0.3 0.4 0.5

True absorption (cm-1)

Mea

s. a

bso

rpti

on (

cm-1

)

A B C D

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0 5 10 15 20 25

True scattering (cm-1) M

eas.

ab

sorp

tion

(cm

-1) 8

7

6

5

4

3

2

1

• Results for 690 nm, no major differences at 820 nm


System characterization:- Noise

0.01%

0.10%

1.00%

10.00%

100.00%

1.E+03 1.E+04 1.E+05 1.E+06 1.E+07

counts (ph)

CV

(%

)

2004 - abs

2006 - abs

2006 - late gate

@ 200K counts

CV2004 - abs: 2%

CV2006 - abs: 0.4%

CV2006 - late gate: 0.1%

• Pifferi et al., “ ...The Medphot Protocol”, Applied Optics 44:2104-2114 (2005)


Motor task on human subject:- protocol

Motor area for right hand identified by Transcranial Magnetic Stimulation (TMS)

Protocol: 20 s baseline, 20 s task (finger tapping with right hand at 2Hz), 40 s recovery9 repetitions, acquisition time 1s

D2S2

2 cm

solid phantomvolounteer

D1S1

2 cm


Motor task on human subject:- HHb and O2Hb

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

0 10 20 30 40 50 60 70 80

time (s)

con

tras

t (

M)

HHb

O2Hb baseline task recovery

chan 1

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

0 10 20 30 40 50 60 70 80

time (s)

con

tras

t (

M)

HHb

O2Hb


solid phantom

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 80 160 240 320 400 480 560 640 720

time (s)

con

tras

t (

M)

HHb

O2Hb

9 repetitions


Motor task on human subject:- HHb and O2Hb (single trials)

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60 80

time (s)

con

tras

t (

M)

HHb

O2Hb

15s task: 1 repetition

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60 80

time (s)

con

tras

t (

M)

HHb

O2Hb

10s task : 1 repetition

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60 80

time (s)

con

tras

t (

M)

HHb

O2Hb

5s task : 1 repetition


Motor task on human subject:- mapping HHb and O2Hb

S1 S2 S3 S4

D1 D4 D7 D6 D9

D3 D2 D5 D8 D11

2 cm

Protocol: 20 s baseline, 20 s task (finger tapping with right hand at 2Hz), 40 s recovery4 repetitions, acquisition time 250 ms


Time-resolved fNIRS of primate brain:- first results

S1 D1 1 mm fiber1 cm

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

0 30 60 90 120 150

time (s)co

ntr

ast

(M

)

HHbO2Hb

task rest

Optodes in direct contact with the dura

Task: grasp food


Future Perspectives

Zappa et al., “Complete single-photon counting and timing module in a microchip” Optics Letters 30:1327-1329 (2005)

Detection & Acquisition: IC SPAD

Leon-Saval et al., “Multimode fiber devices with single-mode performance”, Optics Letters 30:2545-2527 (2005)

Optics: photonic crystal devicesSource: whitelight fiber laser

www.fianium.com


Time-Resolved fNIRS at Null Source-Detector Separation

Torricelli et al. Phys Rev Lett 95, 078101 (2005)

Improved contrast and resolution


“Future” Perspectives?

Steven Spielberg, "Minority Report”(2002)

"Pre-Crime" Image Thoughts of PreCogs(2054)

Philip K. Dick, ”The Minority Report”(1956)

Thanks to Turgut Durduran, Upenn

Time-resolved functional near-infrared spectroscopy A.Torricelli, D.Contini, A.Pifferi, L.Spinelli...

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