Ultracompact, EEG-compatible NIRS System · Electrode and optodeplacement on EEG cap. P5 P6 C3a C3p...

1
Ultracompact, EEG-compatible NIRS System NIRx Medizintechnik Christoph H. Schmitz 1,2 and Stefan P. Koch 2 1 NIRx MedizintechnikGmbH, Berlin 2 Charite UniversitätsmedizinBerlin, Dept. Neurology, Berlin, Germany OBJECTIVE The development of a miniaturized, portable NIRS system, to be integrated with EEG for BCI applications. Here, we present our most recent step toward this goal, a table-top multi-channel NIRS imager utilizing direct LED illumination and digital signal processing. INTRODUCTION Principles of Near-Infrared Spectroscopy (NIRS): Uses low-energy optical radiation (~700-900 nm) Scatter-dominated light propagation in tissue Transmission up to few cm Sensitive to absorption changes caused by hemodynamics: measures relative changes in oxygenated and de-oxygenated Hemoglobin (ΔHbO, ΔHbR) Requires contact based measurements through ‘optodes’ (usually fiber optic bundles, sometimes integrated electronic sensors) One optode pair (transmitter (source) + receiver (detector)) constitutes one data channel. Scalp Bone Cortex CSF Source / Detector 1 Detector 2 Detector 3 Hb HbO 2 400 500 600 700 800 900 1000 Wavelength [nm] 10 3 10 4 10 5 10 6 10 2 Molar extinction coeff. [cm -1 M -1 ] Illumination • Time-multiplexed source position encoding • Simultaneous, frequency-encoded dual-wavelength illumination (760, 850 nm): P i,j = P dc + P mod sin(2πf m,i /f s j + φ i ) • Direct tissue contact light emitting diodes (LED) • 90° Optode head design integrates into EEG electrode • LEDs vs. Lasers: • ~10 mW total optical power per λ @ ~50 mA • Spectral width ~30 nm • Emission angle (FWHM) ±20° Simultaneous NIRS-EEG validation Paradigm: Alternating self-paced, visually cued finger tapping Left (20 s) rest (20 s) right (20 s) rest (20 s)… [9 times] NIRS measurement: 2 Sources, 4 Detectors (per hemisphere: 1 S x 2 D), f sample = 22.5 Hz Customized EEG cap (EASYCAP GmbH) for electrode/optode placement (Fig. 5) Signal analysis in MATLAB™ based NILAB (Charite Berlin): Band pass filter, modified Beer-Lambert law, block-averaging EEG measurement: 13-channel recording with BrainAmp (Brain Products GmbH): f sample = 1.0 kHz, FCz as reference, BW = DC to 250 Hz Band pass filter [0.5 Hz, 100Hz], epoched for each condition (-3 s to +25 s relative to stimulus onset) Wavelet-based time-frequency (TF) analysis (Morlet, 12 cycles, 5-25 Hz) on single trial basis Averaging of single trial TF results; baseline (-1 to 0 s) subtraction Detection and Signal Processing • Fiber-optic bundles (= 2.4 mm) with bent tip • Photo diode in unbiased photovoltaic mode (large dynamic range) • Gain-switched amplification maximizes dynamic range • Direct analog-to-digital conversion of modulated signal • Demodulation in PC software (LabVIEW™) following an algorithm described in [Lasker et al.]: 1. Component-wise multiplication of signal vector V and synthesized orthogonal reference signals I i,j = cos(2πf m,i /f s j) and Q i,j = sin(2πf m.i /f s j): X’ i,j = V j I i,j ; Y’ i,j = V j Q i,j 2. Time-average the resulting vectors to obtain the in-phase and quadrature amplitudes X i = 1/N j N X i,j ; Y i = 1/N j N Y i,j 3. Compute the magnitude to obtain the detector reading R d : R d,i = sqrt(X i 2 + Y i 2 ) 4. Averaging exactly over an interval that is an integer multiple of the modulation period N = k / f m,i (where k = 1,2,…) and using commensurable modulation frequencies results in perfect wavelength discrimination. Noise considerations: • Detection limit is determined by electronic noise at highest gain • Dominant noise source is thermal (Johnson) noise of the feedback resistor. Detection bandwidth BW is determined by low-pass RC filter (f 3dB = 480 Hz) and anti-aliasing filter (4 th order Chebyshev f cutoff = 2.0 kHz): BW = 2.0 kHz – 2/π 0.48 kHz = 1.25 kHz V n = sqrt(4kB T R BW). For T=300K, R=10 8 Ω: V n = 46 μV rms • Highest gain = 1000 V n,gain = 46 mV rms • Averaging over 100 samples reduces noise by factor 10 V n,demod = 4.6 mV rms (Measured: V n = 5 mV rms ) • Noise equivalent power (NEP): V sig = V noise = 5 mV rms V p = √2 V rms = 7 mV p I p = V p / 10 11 Ω = 7×10 -14 A NEP = 2W/A × I p = 0.14 pW p RESULTS Instrument Performance Sensitivity: better 0,5 pW NEP Stability: better 0.01% Drift: < 1%/hr after warm up Dynamic range (theo): [ 1 V / 10 4 V/A] / [5 mV / 10 11 V/A] = 2×10 9 = 93 dB pwr ∆c(mmol/l) tapping side left right HbO HbR -10 0 10 20 30 40 -5 0 5 x 10 -3 ch: 2 -10 0 10 20 30 40 -4 -2 0 2 x 10 -3 ch: 6 -10 0 10 20 30 40 -5 0 5 x 10 -3 ch: 1 -10 0 10 20 30 40 -4 -2 0 2 x 10 -3 ch: 5 0 10 20 c3post 0 10 20 1 1 2 2 c4post 0 10 20 0 10 20 1 1 2 2 tapping side left right -1 0 1 ∆ power [a.u.] frequency [Hz] time [s] left (C3) right (C4) Probe side 0 10 20 25 20 15 10 5 0 10 20 time [s] 0 100 200 300 400 500 600 700 -5 0 5 x 10 -3 1 0 100 200 300 400 500 600 700 -5 0 5 x 10 -3 2 0 100 200 300 400 500 600 700 -5 0 5 x 10 -3 3 0 100 200 300 400 500 600 700 -5 0 5 x 10 -3 4 time (s) tapping side left right ∆c HbR (mmol/l) left right probe position 0 5 10 15 20 25 30 35 40 -4 -2 0 2 4 6 8 10 x 10 -4 LED Laser Diode Experimental Results EEG No spectral interferences from LED optode • Sustained μ-desynch (α- & β-range) during contralateral tap NIRS Promises: Non-invasive, harmless Good time resolution (~10 Hz) Can be made small, inexpensive Little subject restriction, long term monitoring Integrates well with other methods (EEG, MRI,…) NIRS Challenges: Penetration depth ~cm Spatial resolution ~mm-cm Sensitive to artifacts from motion, surface- near ‘global’ hemodynamics Probe setup INSTRUMENTATION Size: 33 cm (L) × 27 cm (W) × 17 cm (H) Mass < 10 kg Channels: 1-8 sources, 1-16 detectors Scan rate: > 8 Hz (8 sources) Illumination: 760/850 nm LED Digital signal demodulation Figure 1. Left: Schematic depiction of NIRS imaging of brain hemodynamics. Right: Spectra of HbO and HbR; vertical lines indicate imaging wavelengths. Abbreviations: HbO: oxy-hemoglobin; HbR: deoxy-hemoglobin; LED: light emitting diode; P: power; fm: modulation frequency; i: wavelength index; j: sample index; λ: wavelength; V: measured discrete signal vector; I i ,Q i : discrete in-phase and out-of phase reference vectors; X i ,Y i : in-phase and out-of phase amplitudes; R d,i : detector reading; fs: sampling frequency; BW: bandwidth; k B : Boltzmann‘s constant; R: resistance; V: voltage; I: current; PTIA PTIA 10 kV/A, 100 MV/A PGA 1, 10, 100, 1000 HP FIFO LP SH REG SH REG FIFO f m1 f m2 gains timing USB DAQ card signals Backplane Detector channel (1...16) LED driver (1...8) 16:1 MUX ADC DO DAC 1,2 CTR USB CTRL PD LED λ1 λ2 To PC Figure 4. Top row: Hand gripping task result illustrating comparable crosstalk and separability for LED (760/850 nm, left) vs. Laser (760/830 nm, right) illumination. Bottom row: Low-profile LED optodes, from left to right: Connected to ring electrode; optode only with retaining ring; mounted to electrode in EEG cap. Figure 2. Picture of the instrument. Shown is version with 2 sources, 4 detectors, and 4 trigger connectors for experiment synchronization. NIRS Prototypical activation for motor task is observed: HbO↑ & HbR ↓; sustained response to tapping HbO: Susceptible to physiological noise, therefore less indicative for tapping side HbR: Stronger decrease contralateral to tapping side Robust, condition related single-trial response DISCUSSION No interferences in EEG signals Excellent signal-to noise ratio in HbO and HbR Fast and flexible probe placement for concurrent EEG/NIRS measurement Robustness of single trial response promising for real-time applications (BCI, neuro-feedback) Portability/compactness allows field studies Figure 3. Functional diagram of NIRS imager (omitted: power supply, trigger channels). PD: photo diode; PTIA: programmable transimpedance amplifier; PGA: programmable gain amplifier; HP: RC high-pass filter (f 3db = 482 Hz); LP: 4th order Chebyshev low-pass filter (f pass = 2.0 kHz); FIFO: first-in-first-out buffer; SHREG: serial- to-parallel shift register; f mod : modulation frequencies; MUX: multiplexer; ADC: analog-to-digital converter; DAC: digital-to-analog converter; DO: digital out lines; CTR: counter; CTRL: controller. Figure 5. Electrode and optode placement on EEG cap. P5 P6 C3a C3p S1 Ref C4a C4p S2 C3a C4p Electrode EEG reference NIRS Detector NIRS Source Figure 6. EEG time-frequency results. Figure 7. NIRS results. Top: Block-averaged vs. single-trial response. Bottom: Continuous time courses for nine consecutive trials. REFERENCES C.H. Schmitz, et al., "Instrumentation for fast functional optical tomography," Rev. Sci. Instrum., Vol. 73, pp. 429-439 (2002). J.M. Lasker, et al., "Digital-signal-processor-based dynamic imaging system for optical tomography," Rev. Sci. Instrum, Vol. 78, 083706 (2007).

Transcript of Ultracompact, EEG-compatible NIRS System · Electrode and optodeplacement on EEG cap. P5 P6 C3a C3p...

Page 1: Ultracompact, EEG-compatible NIRS System · Electrode and optodeplacement on EEG cap. P5 P6 C3a C3p S1 Ref C4a C3a S2 C4p C4p Electrode EEG reference NIRS Detector NIRS Source Figure

Ultracompact, EEG-compatible NIRS System

NIRx Medizintechnik

Christoph H. Schmitz1,2 and Stefan P. Koch2

1NIRx Medizintechnik GmbH, Berlin2Charite Universitätsmedizin Berlin, Dept. Neurology, Berlin, Germany

OBJECTIVE

The development of a miniaturized, portable NIRS system, to be

integrated with EEG for BCI applications. Here, we present our most

recent step toward this goal, a table-top multi-channel NIRS imager

utilizing direct LED illumination and digital signal processing.

INTRODUCTIONPrinciples of Near-Infrared Spectroscopy (NIRS):

• Uses low-energy optical radiation (~700-900 nm)

• Scatter-dominated light propagation in tissue

• Transmission up to few cm

• Sensitive to absorption changes caused by hemodynamics:

measures relative changes in oxygenated and de-oxygenated

Hemoglobin (ΔHbO, ΔHbR)

• Requires contact based measurements through ‘optodes’ (usually

fiber optic bundles, sometimes integrated electronic sensors)

• One optode pair (transmitter (source) + receiver (detector))

constitutes one data channel.

Scalp

Bone

Cortex

CSF

Source / Detector 1

Detector 2

Detector 3

Hb

HbO2

400 500 600 700 800 900 1000

Wavelength [nm]

103

104

105

106

102Mol

ar e

xtin

ctio

n co

eff.

[cm -

1 M-1

]

Illumination

• Time-multiplexed source position encoding

• Simultaneous, frequency-encoded dual-wavelength illumination

(760, 850 nm):

Pi,j = Pdc + Pmod sin(2π fm,i/fs j + φi)

• Direct tissue contact light emitting diodes (LED)

• 90° Optode head design integrates into EEG electrode

• LEDs vs. Lasers:

• ~10 mW total optical power per λ @ ~50 mA

• Spectral width ~30 nm

• Emission angle (FWHM) ±20°

Simultaneous NIRS-EEG validation

Paradigm:

• Alternating self-paced, visually cued finger tapping

• Left (20 s) rest (20 s) right (20 s) rest (20 s)… [9 times]

NIRS measurement:

• 2 Sources, 4 Detectors (per hemisphere: 1 S x 2 D), fsample = 22.5 Hz

• Customized EEG cap (EASYCAP GmbH) for electrode/optode

placement (Fig. 5)

• Signal analysis in MATLAB™ based NILAB (Charite Berlin): Band pass

filter, modified Beer-Lambert law, block-averaging

EEG measurement:

• 13-channel recording with BrainAmp (Brain Products GmbH): fsample

= 1.0 kHz, FCz as reference, BW = DC to 250 Hz

• Band pass filter [0.5 Hz, 100Hz], epoched for each condition (-3 s to

+25 s relative to stimulus onset)

• Wavelet-based time-frequency (TF) analysis (Morlet, 12 cycles, 5-25

Hz) on single trial basis

• Averaging of single trial TF results; baseline (-1 to 0 s) subtraction

Detection and Signal Processing

• Fiber-optic bundles (∅ = 2.4 mm) with bent tip

• Photo diode in unbiased photovoltaic mode (large dynamic range)

• Gain-switched amplification maximizes dynamic range

• Direct analog-to-digital conversion of modulated signal

• Demodulation in PC software (LabVIEW™) following an algorithm

described in [Lasker et al.]:

1. Component-wise multiplication of signal vector V and

synthesized orthogonal reference signals

Ii,j = cos(2π fm,i/fs j) and Qi,j = sin(2π fm.i/fs j):

X’i,j = Vj Ii,j ; Y’i,j = Vj Qi,j

2. Time-average the resulting vectors to obtain the in-phase and

quadrature amplitudes

Xi = 1/N ∑jN Xi,j ; Yi = 1/N ∑j

N Yi,j

3. Compute the magnitude to obtain the detector reading Rd:

Rd,i = sqrt(Xi2 + Yi

2 )

4. Averaging exactly over an interval that is an integer multiple

of the modulation period

N = k / fm,i (where k = 1,2,…)

and using commensurable modulation frequencies results in

perfect wavelength discrimination.

Noise considerations:

• Detection limit is determined by electronic noise at highest gain

• Dominant noise source is thermal (Johnson) noise of the feedback

resistor. Detection bandwidth BW is determined by low-pass RC

filter (f3dB = 480 Hz) and anti-aliasing filter (4th order Chebyshev fcutoff

= 2.0 kHz):

BW = 2.0 kHz – 2/π 0.48 kHz = 1.25 kHz

• Vn = sqrt(4kB T R BW). For T=300K, R=108 Ω:

Vn = 46 μVrms

• Highest gain = 1000 Vn,gain = 46 mVrms

• Averaging over 100 samples reduces noise by factor 10 Vn,demod =

4.6 mVrms (Measured: Vn = 5 mVrms)

• Noise equivalent power (NEP): Vsig = Vnoise = 5 mVrms

Vp = √2 Vrms = 7 mVp Ip = Vp / 1011 Ω = 7×10-14 A NEP = 2W/A

× Ip = 0.14 pWp

RESULTS

Instrument Performance

• Sensitivity: better 0,5 pW NEP

• Stability: better 0.01%

• Drift: < 1%/hr after warm up

• Dynamic range (theo):

[ 1 V / 104 V/A] / [5 mV / 1011 V/A] = 2×109 = 93 dBpwr

∆c

(mm

ol/

l)

tapping side

left

right

HbO HbR-10 0 10 20 30 40-5

0

5

x 10-3 ch: 2

-10 0 10 20 30 40-4

-2

0

2x 10-3 ch: 6

-10 0 10 20 30 40-5

0

5

x 10-3 ch: 1

-10 0 10 20 30 40-4

-2

0

2x 10-3 ch: 5

0 10 20

c3post

0 10 20

10

15

20

25c4post

0 10 20

0 10 20

10

15

20

25

tap

pin

gsi

de

left

right

-1

0

1

∆p

ow

er

[a.u

.]

fre

qu

en

cy[H

z]

time [s]

left (C3) right (C4)Probe side

0 10 20

25

20

15

10

50 10 20

time [s]

0 100 200 300 400 500 600 700-5

0

5x 10

-3 1

0 100 200 300 400 500 600 700-5

0

5x 10

-3 2

0 100 200 300 400 500 600 700-5

0

5x 10

-3 3

0 100 200 300 400 500 600 700-5

0

5x 10

-3 4

time (s)

tapping side

left right

∆c

Hb

R(m

mo

l/l)

left

right

probe position

0 5 10 15 20 25 30 35 40-4

-2

0

2

4

6

8

10x 10

-4

LEDLaser Diode

Experimental Results

EEG

• No spectral interferences from LED optode

• Sustained μ-desynch (α- & β-range) during contralateral tap

NIRS Promises:

• Non-invasive, harmless

• Good time resolution (~10 Hz)

• Can be made small, inexpensive

• Little subject restriction, long term monitoring

• Integrates well with other methods (EEG, MRI,…)

NIRS Challenges:

• Penetration depth ~cm

• Spatial resolution ~mm-cm

• Sensitive to artifacts from motion, surface- near ‘global’

hemodynamics

• Probe setup

INSTRUMENTATION

• Size: 33 cm (L) × 27 cm (W) × 17 cm (H)

• Mass < 10 kg

• Channels: 1-8 sources, 1-16 detectors

• Scan rate: > 8 Hz (8 sources)

• Illumination: 760/850 nm LED

• Digital signal demodulation

Figure 1. Left: Schematic depiction of NIRS imaging of brain hemodynamics. Right:

Spectra of HbO and HbR; vertical lines indicate imaging wavelengths.

Abbreviations: HbO: oxy-hemoglobin; HbR: deoxy-hemoglobin; LED: light emitting diode; P: power; fm: modulation frequency;

i: wavelength index; j: sample index; λ: wavelength; V: measured discrete signal vector; Ii,Qi: discrete in-phase and out-of phase reference vectors; Xi,Yi: in-phase

and out-of phase amplitudes; Rd,i: detector reading; fs: sampling frequency; BW: bandwidth; kB: Boltzmann‘s constant; R: resistance; V: voltage; I: current;

PTIA

PTIA

10 kV/A,

100 MV/A

PGA

1, 10,

100, 1000

HP

FIFO

LP

SH REG

SH REG

FIFO

fm1

fm2

gains

timing

USB DAQ card

signals

Backplane

Detector

channel

(1...16)

LED driver (1...8)

16:1

MUXADC

DO

DAC

1,2

CTR USB

CT

RL

PD

LED

λ1

λ2

To PC

Figure 4. Top row: Hand gripping task result illustrating comparable crosstalk and

separability for LED (760/850 nm, left) vs. Laser (760/830 nm, right) illumination.

Bottom row: Low-profile LED optodes, from left to right: Connected to ring

electrode; optode only with retaining ring; mounted to electrode in EEG cap.

Figure 2. Picture of the instrument. Shown is version with 2 sources, 4 detectors, and

4 trigger connectors for experiment synchronization.

NIRS

• Prototypical activation for motor task is observed: HbO↑ & HbR ↓;

sustained response to tapping

• HbO: Susceptible to physiological noise, therefore less indicative for

tapping side

• HbR: Stronger decrease contralateral to tapping side

• Robust, condition related single-trial response

DISCUSSION

• No interferences in EEG signals

• Excellent signal-to noise ratio in HbO and HbR

• Fast and flexible probe placement for concurrent EEG/NIRS

measurement

• Robustness of single trial response promising for real-time

applications (BCI, neuro-feedback)

• Portability/compactness allows field studies

Figure 3. Functional diagram of NIRS imager (omitted: power supply, trigger

channels). PD: photo diode; PTIA: programmable transimpedance amplifier; PGA:

programmable gain amplifier; HP: RC high-pass filter (f3db = 482 Hz); LP: 4th order

Chebyshev low-pass filter (fpass = 2.0 kHz); FIFO: first-in-first-out buffer; SHREG: serial-

to-parallel shift register; fmod: modulation frequencies; MUX: multiplexer; ADC:

analog-to-digital converter; DAC: digital-to-analog converter; DO: digital out lines;

CTR: counter; CTRL: controller.

Figure 5. Electrode and optode placement on EEG cap.

P5 P6

C3a

C3p

S1

Ref

C4a

C4pS2C3a

C4p

Electrode EEG reference NIRS Detector NIRS Source

Figure 6. EEG time-frequency results.

Figure 7. NIRS results. Top: Block-averaged vs. single-trial response. Bottom:

Continuous time courses for nine consecutive trials.

REFERENCES

C.H. Schmitz, et al., "Instrumentation for fast functional optical tomography," Rev. Sci. Instrum., Vol. 73, pp. 429-439 (2002).

J.M. Lasker, et al., "Digital-signal-processor-based dynamic imaging system for optical tomography," Rev. Sci. Instrum, Vol. 78, 083706 (2007).