Biomedical Optics (BIOMED) 2010 paper: BTuB7 OSA Technical Digest (CD)
Multi-Wavelength, Depth Resolved, Scattering
and Pathlength Corrected in-vivo NearInfrared Spectroscopy of Brain Tissue.
ILIAS TACHTSIDIS1, T.S. Leung1, A. Ghosh2, M.
Smith2, C.E. Cooper3, C.E. Elwell1
1 Biomedical
Optics Research Laboratory, Department of Medical Physics and Bioengineering, University
College London, Gower Street, London WC1E 6BT, Email: iliastac@medphys.ucl.ac.uk
2 Neurocritical
Care Unit, National Hospital for Neurology and Neurosurgery, University College London
Hospital, Queen Square, London, UK
3 Department
of Biological Sciences, University of Essex, Colchester Essex, UK
Introduction
isobestic
Specific Extinction Coefficient
(OD/M/cm)
5000
4500
4000
3500
λ1
λ2
Water Scaled
HbO2
HHb
ox-redCCO
3000
2500
2000
1500
1000
500
0
650 675 700 725 750 775 800 825 850 875 900 925 950
Wavelengths (nm)
1. With multi-spectral data, more chromophores can be
resolved while improving spectroscopic resolution.
Introduction
2. Multi-distance attenuation data reduces sensitivity to the
optical coupling and to the attenuation changes in the
superficial layers.
Introduction
Accurate absolute quantification of tissue chromophores requires
knowledge of light scattering.
I: Light Intensity
3. The tissue transport scattering (µs’), can be measured with
frequency (or time) domain instrumentation.
Instrumentation: Hybrid Optical Spectrometer [pHOS]
Multi-Distance Frequency Domain
Multi-Distance Broadband Spectrometer
Instrument 1
Four wavelength (690, 750, 790, 850nm) multi-distance
frequency domain (110MHz) spectrometer (MDFD).
The instrument allows for the quantitative assessment of
the absorption and scattering coefficients at two different
source-detector distances (3 and 3.5cm)at each
wavelength. [D.M. Hueber Phys. Med. Biol. 46, 41-62 (2001)]
Instrument 2
White light source (50W halogen bulb) with a short pass filter to minimise
temperature effects.
Four distances (2.0, 2.5, 3.0 and 3.5cm) utilising four detector fibres with different
diameters.
Optical bandwidth 504 -1068nm and mean wavelength resolution 4nm.
Detectors
Emitter
Detectors
Distal End
Instrumentation Operation
Background
Aim
Here we report on the use of our novel multi-distance frequency
and broadband domain system to measure brain oxygenation,
haemodynamics and metabolism during changes in cerebral
oxygenation secondary to carbon-dioxide induced changes in
cerebral blood flow (CBF) in a healthy adult.
Study Protocol and Systemic Measurements
+ CO2
Hypercapnia
Hyperventilation
Baseline
Hypocapnia
0
5
10
15
20
25
(minutes)
-Mean Velocity of Middle Cerebral Artery (Vmca)
-Mean Blood Pressure (MBP)
-Arterial Oxygen Saturation (SaO2)
-Breathing Gases including End-Tidal CO2 (EtCO2)
Results
EtCO2
10
9
Hypercapnia
Hypocapnia
70
(cm/sec)
8
7
(kPa)
Vmca
80
Hypercapnia
Hypocapnia
6
5
4
3
60
50
40
30
20
2
10
1
0
0
0
200
102
400
600
800
1000
1200
Time (seconds)
Hypocapnia
1400
0
200
400
600
800
1000
1200
1400
Time (seconds)
SaO2
MBP
180
Hypercapnia
Hypercapnia
Hypocapnia
160
140
(mmHg)
(%)
100
98
96
94
120
100
80
60
40
92
20
0
90
0
200
400
600
800
1000
Time (seconds)
1200
1400
0
200
400
600
800
1000
1200
Time (seconds)
1400
Optical Algorithm 1
MDFD
µa (MDFD)
µs’ (MDFD)
DPF( MDFD) =
3µs' ( MDFD)
Pathlength Detector 1
L1(790nm)=DPF(790nm) × 3.5cm
2 µa ( MDFD)
Specific Extinction Coefficient
(OD/M/cm)
(OD/M/cm
Fitting from 740 to 900nm
Pathlength Detector 2
L2(790nm)=DPF(790nm) × 3.0cm
Detector 1 (3.5cm):
∆[ HbO2 ] 
1
∆[ HHb] 
=


L1( 790 nm )
∆[oxCCO] ( Det1)
specific extinction coefficient multiplied
by the correction factors for the wavelength
dependence of the optical pathlength at
each wavelength
i: chromophores
j: wavelengths
∆A(λn) (Det1)
∆A(λn) (Det2)
∆A(λn) (Det3)
∆A(λn) (Det4)
Wavelengths (nm)
ε:
MDBBS
Detector 2 (3.0cm):
∆[ HbO2 ] 
1
∆[ HHb] 
=


L2( 790 nm )
∆[oxCCO] ( Det 2)
∆A( λ1) 


∆
A
(λ 2) 
−1
⋅ (ε i , j ) ⋅ 
...... 


∆A( λn ) 
( Det1)
∆A( λ1) 


A
∆
( λ 2) 
−1
⋅ (ε i , j ) ⋅ 
...... 


A
∆
 ( λn )  ( Det 2 )
µ’s
12.0
11.5
11.0
10.5
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
Hypocapnia
µa
0.15
Hypercapnia
Hypocapnia
0.13
0.12
0.11
0.10
690nm
790nm
0.09
750nm
850nm
690nm
790nm
750nm
850nm
0.08
0
200
400
600
800
1000
1200
1400
0
200
400
Pathlength (Det 1 3.5cm)
34
Hypocapnia
600
800
1000
1200
1400
Time (s)
Time (s)
30
Hypercapnia
32
28
30
26
(cm)
(cm)
Hypercapnia
0.14
(cm-1)
(cm-1)
MDFD Pathlength Measurement
28
26
Pathlength (Det 2 3.0cm)
Hypocapnia
Hypercapnia
24
22
24
690nm
790nm
750nm
850nm
22
20
690nm
750nm
790nm
850nm
18
0
200
400
600
800
Time (s)
1000
1200
1400
0
200
400
600
800
1000
Time (s)
1200
1400
pHOS Brain Tissue ∆[Concentrations]
From the changes in light attenuation (MDBBS) and using the
continuous measured Pathlength for 790nm (MDFD) the changes
in concentrations of [HbO2], [HHb] and [oxCCO] were calculated by
fitting from 740 to 900nm and correcting for the wavelength
dependency of DPF.
∆[Concentrations]
3.5cm (Det 1) ∆[Concentrations]
3.0cm (Det 2)
∆[
∆[
1.5
Hypocapnia
1.5
Hypercapnia
Hypercapnia
1.0
1.0
0.5
(µ
µM)
0.5
(µ
µM)
Hypocapnia
0.0
-0.5
0.0
-0.5
-1.0
-1.0
HbO2
oxCCO
HHb
-1.5
-1.5
HbO2
oxCCO
HHb
-2.0
0
200
400
600
800
1000
Time (s)
1200
1400
0
200
400
600
800
1000
Time (s)
1200
1400
Hybrid Spatially Resolved Algorithm
MDFD
MDBBS
Calculate Attenuation Slope:
∂Aλn/∂ρ
µa (MDFD)
Aλn (Det1)
µs’ (MDFD)
Aλn (Det2)
µ aSRS
( λn )
Power Law:
µs’ (λn) = bλ-a
a, b: free
parameters in
the fit
∂A( λn )

⋅  ln 10 ⋅
=

∂ρ
3 ⋅ µ 's( λn ) 
1
Scale µaSRS(λn) using µa (MDFD)
A
2 
−
ρ 
2
Aλn (Det3)
Aλn (Det4)
Absolute µaHybrid(λn)
Specific Extinction Coefficient
(OD/M/cm)
4500
4000
3500
HbO2
HHb
Water*10^6
Fitting from 680 to 860nm
3000
[ HbO2 ]
[ HHb] 


[ H 2 O] 
2500
2000
1500
1000
500
0
650 675 700 725 750 775 800 825 850 875 900 925 950 975 1000
Wavelengths (nm)
 µ aHybrid ( λ1) 
 Hybrid 
−1  µ a
(λ 2) 
= (ε i , j ) ⋅ 

......

 µ Hybrid 
( λn ) 
 a
i: chromophores
j: wavelengths
pHOS Brain Optical Measurement
µ’s
11.0
∂A/∂ρ
ρ
0.93
0.92
10.5
0.91
(OD/cm)
(cm-1)
10.0
9.5
9.0
8.5
0.90
0.89
0.88
0.87
0.86
8.0
0.85
7.5
0.84
7.0
680
0.83
680
700
720
740
780
800
820
840
860
740
760
780
800
820
µaSRS
µaHybrid
0.13
0.070
0.11
(cm-1)
0.12
0.065
0.09
0.055
0.08
0.050
680
0.07
680
740
760
780
800
Wavelengths (nm)
820
840
860
840
860
0.10
0.060
720
720
Wavelengths (nm)
0.075
700
700
Wavelengths (nm)
0.080
(cm-1)
760
700
720
740
760
780
800
820
Wavelengths (nm)
840
860
Results pHOS Brain Tissue Concentrations
[Concentrations]
60
Hypercapnia
Hypocapnia
72
50
70
(%)
40
(µ
µM)
[Tissue Saturation]
74
Hypercapnia
Hypocapnia
30
68
66
20
64
HbO2
HHb
HbT
10
0
62
60
0
200
400
600
800
1000
1200
1400
0
200
400
600
Hypocapnia
80
Hypercapnia
5
1200
1400
Hypercapnia
Hypocapnia
70
4
3
60
2
50
1
(%)
(µ
µM)
1000
[Water]
∆[Concentrations]
∆[
6
800
Time (s)
Time (s)
0
40
-1
30
-2
20
-3
HbO2
-4
HHb
-5
10
0
0
200
400
600
800
Time (s)
1000
1200
1400
0
200
400
600
800
Time (s)
1000
1200
1400
Results pHOS Brain Tissue Absorption Fitting
Baseline
0.13
[HbO2] : 31µM
[HHb] : 16µM
[Water]: 45%
0.12
0.11
(cm-1)
We estimate back µa from the
calculated absolute concentrations
and compare with the measured
µaHybrid to assess the fitting (residuals).
µaFitted
0.10
0.09
µaHybrid
0.08
0.07
680
700
720
740
760
780
800
820
840
860
Wavelengths (nm)
Hypocapnia
0.12
µM
[HbO2] : 29µ
[HHb] : 18µ
µM
[Water] : 37%
0.11
µaFitted
µM
[HbO2] : 34µ
[HHb] : 15µ
µM
[Water] : 45%
0.12
µaFitted
0.11
0.10
0.09
µaHybrid
0.08
Hypercapnia
0.13
(cm-1)
(cm-1)
0.13
0.10
0.09
0.08
0.07
µaHybrid
0.07
680
700
720
740
760
780
800
820
Wavelengths (nm)
840
860
680
700
720
740
760
780
800
820
Wavelengths (nm)
840
860
Discussion
• We demonstrated the use of our pHOS system to investigate
oxygenation, haemodynamics and metabolic signals in a
healthy adult head.
• The combination of multi-distance frequency domain and
broadband spectrometers allows:
1. to measure pathlength continuously and hence correctly scale
the changes in concentrations;
2. to obtain multi-wavelength, depth resolved measurements of
absorption.
• The second approach is especially important for NIRS
measurement of the adult brain where broad wavelength
coverage and increased sensitivity to deeper layers are
required.
Discussion
• These preliminary results show that during hypercapnia the
changes in haemoglobin concentrations calculated with the
conventional differential spectroscopy method are smaller than
those calculated using the hybrid SRS method, possibly
indicating different contributions from the intra- and extracerebral layers.
• This technology is currently being used for studies in human
adult volunteers and in critically ill brain-injured patients.
The pHOS system in use on a traumatic
brain injured patient at the National
Hospital for Neurology and Neurosurgery
in London, UK.
Acknowledgments
Many thanks to Prof. Matthias Kohl-Bareis and Dr Dennis
Hueber for technical advice and support.
The authors would like to thank the EPSRC (EP/D060982/1) for
the financial support of this work. This work was undertaken at
University College London Hospitals and partially funded by the
Department of Health's National Institute for Health Research.
Dr Ilias Tachtsidis is supported by The Wellcome Trust