||Development of Near Infrared Spectroscopy System for Assessing Hemodynamic Changes of Rat’s Brain
||Institute of Biomedical Engineering
near infrared spectroscopy
frequency-division intensity modulation
fast Fourier transform demodulation
Although varied approaches have been developed for assessing the cerebral activity, the neurological scoring and behavior assessment cannot provide quantitative assessment with high temporal resolution. The aim of this study is to design a non-invasive electrophysiological and optical system to quantify the brain activity in animal model. An integrated system combining scalp EEG and continuous-wave near infrared spectroscopy (CW-NIRS) was developed for measuring somatosensory evoked potentials (SSEPs) and cerebral hemodynamic responses. SSEP sensing electrodes and NIRS optical fibers were placed on scalp simultaneously for concurrent electrical and optical signal acquisitions. The circuit of EEG recording includes two channels preamplifier which comprised instrumentation amplifiers to improve the signal to noise ratio. The CW-NIRS was employed using frequency-division intensity modulation and Fast Fourier Transform (FFT) demodulation techniques for multichannel measurement. To validate the performance of the system, the phantom test and in-vivo measurements had been performed. The SSEP and event-related optical signals (EROS) was successfully recorded by our designed system with noninvasive approach. The real-time assessment of cerebral activities should be useful for future diagnosis and assessment for the treatment effect of cerebrovascular diseases.
List of Tables V
List of Figures V
Chapter 1 Introduction 1
1.1 Neurovascular coupling and event-related optical signals 1
1.2 Somatosensory evoked potential 2
1.3 Brain imaging techniques 3
1.4 Principles of near infrared spectroscopy 4
1.4.1 Modified Beer-Lambert law 5
1.4.2 The strategies of optical separation and major type of NIRS systems 8
1.5 Motivation and the aims of the study 10
Chapter 2 Materials and Methods 11
2.1 Instrument of measuring for neurovascular coupling 11
2.1.1 Measurement of SSEP 11
2.1.2 Measurement of hemodynamic response 14
2.1.3 The architecture of probe for non-invasive measurement 19
2.2 Experimental design 20
2.2.1 Animal preparation 20
2.2.2 Measurement of SSEP 21
2.2.3 Experiment of arterial occlusion on human forearm 22
2.2.4 Experiment of common carotid artery ligation on rat 23
2.2.5 Experiment of event-related optical signal (EROS) 23
Chapter 3 Results 25
3.1 System validation 25
3.1.1 Validation of electrical stimulator 25
3.1.2 Measurement of SSEP 26
3.1.3 Validation of CW-NIRS system 27
3.2 Hemodynamic response of vascular occlusion in vivo 34
3.2.1 The hemodynamic response of human arm occlusion 34
3.2.2 Hemodynamic response of common carotid artery ligation on rat 36
3.2.3 Measurement of event-related optical signal 38
Chapter 4 Discussion and Conclusion 40
List of Tables
Table 2.1 Specifications of light source. (PD-LD) 15
Table 3.1 The experimental parameters for SSEP measurement. 27
Table 3.2 The experimental parameters for human forearm occlusion. 35
Table 3.3 The experimental parameters for CCAL experiment. 37
List of Figures
Figure 1.1 The connectivity between vessels and neurons. The vessels provide blood and nutrient to the surround neuron during the neural activation (D'Esposito et al., 2003). 1
Figure 1.2 SEP response due to unilateral forepaw stimulation. The vertical line is time mark of stimuli (S), T is SEP signal with P1, P2 and N1 major components (Franceschini et al., 2008). 3
Figure 1.3 (a) Banana-shaped photon path of hemodynamic measurement(Bunce et al., 2006). (b) Absorption coefficient of principle chromophores includes water (solid), Hb (dotted line), HbO2 (dashdoted line), and lipids (dashed line) in the NIR region (Nissila et al., 2005). 5
Figure 1.4 Influence of light absorption on optical measurement with different structures of (a) transmission mode (straight trajectory) and (b) reflection mode (diffuse trajectory) (Rolfe, 2000). 5
Figure 1.5 Extinction spectra of oxy-hemoglobin, deoxy-hemoglobin (Matcher et al., 1994) and the wavelength equipped in our system. The isobestic point which means the specific extinction coefficients of HbO and Hb are equal at 800 nm. 7
Figure 1.6 (a) Continuous wave, (b) frequency-domain, and (c) time-domain measurement sensitivities to absorption and scatter by tissue (Nishimura et al., 2007). 9
Figure 2.1 The schematic diagram of assessment system (Franceschini et al., 2008). 11
Figure 2.2 Circuit diagram of the modified Howland circuit for electrical stimulation. 12
Figure 2.3 (a) Structure of commercial spring electrode with retractable tip can fit well to the scalp and provide better stability for signal recording. (b) The layout of recording pin and bio-potential preamplifier can be mounted closely to animal head. 13
Figure 2.4 The recording system for SSEP. The system contains of constant current stimulator and bio-potential recording system with non-invasive approach. The unilateral forepaw stimulation was performed to induce SSEP. 14
Figure 2.5 Functional block diagram of CW NIRS. 16
Figure 2.6 The P-type and N-type auto power control (APC) circuit. 16
Figure 2.7 The commercial avalanche photodiode module (APD) and its spectral response. 17
Figure 2.8 (a) The schematic diagram of the cranial probe which was located on 0-1 mm anterior to the bregma and 4-5 mm lateral of the midline to measure the greatest response of the median SEP area. (b) The arrangement of optical fiber and multi-electrode. This probe can achieve different arrangement of source-detector distance for optical measurement. 19
Figure 2.9 Illustration of the arrangement of cranial probes. 20
Figure 2.10 (a) The ball-tip needle was inserted into the both lateral of middle finger to induce SSEP. (b) Preamplifier and optical fiber mounted on a rat head for SSEP and EROS measurement. 21
Figure 2.11 Measurement of arterial occlusion on forearm for validation purpose. The optical probe was holding on the forearm of subject, over the extensor digitorum muscle. 22
Figure 2.12 (a) The surgical operation and (b) optical measurement during common carotid artery ligation. 23
Figure 2.13 The waveform of electrical stimulation in one cycle. The electrical stimulation contained 10 s of rest, 10 s of stimulation period and 20 s of rest in one cycle. 24
Figure 3.1 (a) Two-channel constant current stimulator, with BNC connector, power connector and output stimulator. (b) The linear relationship between impedance and voltage level under constant current of 1.5 mA. 25
Figure 3.2 Typical SSEP response measured by non-invasive approach. The major components appear within 60 msec after the stimulation. The major components of SSEP (P1, N1, and P2) were determined by signal process. 26
Figure 3.3 (a) The sinusoidal wave generating circuit which consists of 4-channel wave generators, IC AD9833. (b) The CW-NIRS system equipped with dual channel source-detector pairs. 28
Figure 3.4 The sinusoidal wave signal at frequencies of 2.9, 3.7, 4.7 and 5.1 kHz. 29
Figure 3.5 (a) The experimental setup for validation of performance of APD and effectiveness of modulation. (b) Fourier transform for AM signal modulated by 3.9 kHz and 4.3 kHz. 30
Figure 3.6 The stability test of one-hour laser power on N-type APC and P-type APC. The x-axis is time (s). The y-axis is power (W). The stability of the output light source was determined by the calculation of peak to peak divided by the mean value of the source power. 31
Figure 3.7 The trends of specific wavelength during hemodynamic response. X-axis is time and y-axis is the amplitude of optical signal. The dashed line represents the segment of different stage. 32
Figure 3.8 Demodulation of modulated signal. (a) The optical signal measured from human extensor digitorum muscle is demodulated in to (b) signal of 830nm and (c) optical signal at 690nm. 33
Figure 3.9 The temporal change of oxy- and deoxy- hemoglobin measured by CW-NIRS and a commercial NIRS system (ISS). 34
Figure 3.10 The correlation coefficients of the signals measured by those two systems were calculated to obtain the similarity of the two signals. 36
Figure 3.11 Temporal profile of Δ[HbO2] and Δ[Hb] measured from (a) 10mm and (b) 5mm distance between source and detector. 37
Figure 3.12 EROS time courses at 2 Hz stimulation for averaging 18 iterations, showing the relative magnitudes of Δ[Hb] and Δ[HbO2]. The dashed line represents the period of stimulation. The solid line is Δ[HbO2] and dashed line curve is Δ[Hb]. The x-axis is time and y-axis is relative concentration of hemoglobin. (a) and (b) are the hemodynamic responses in rat brain during left forepaw stimulation. (c) and (d) are the hemodynamic responses of right forepaw stimulation. 39
Bunce S, Izzetoglu M, Izzetoglu K, Onaral B, Pourrezaei K (2006) Functional near-infrared spectroscopy. Engineering in Medicine and Biology Magazine, IEEE 25:54-62.
Crenshaw A, Komandur S, Johnson P (2010) Finger flexor contractile properties and hemodynamics following a sustained submaximal contraction: A study using electrical stimulation and near-infrared spectroscopy. International Journal of Industrial Ergonomics 40:153-160.
D'Esposito M, Deouell L, Gazzaley A (2003) Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nature Reviews Neuroscience 4:863-872.
Everdell N, Gibson A, Tullis I, Vaithianathan T, Hebden J, Delpy D (2005) A frequency multiplexed near-infrared topography system for imaging functional activation in the brain. Review of Scientific Instruments 76:093705.
Franceschini M, Fantini S, Thompson J, Culver J, Boas D (2003) Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near infrared optical imaging. Psychophysiology 40:548-560.
Franceschini M, Nissila I, Wu W, Bonmassar G, Boas D (2006) Neurovascular Coupling in the Rat Somatosensory Cortex: A Non-Invasive Diffuse Optical Imaging and Electroencephalography Study. Optical Society of America.
Franceschini M, Nissila I, Wu W, Diamond S, Bonmassar G, Boas D (2008) Coupling between somatosensory evoked potentials and hemodynamic response in the rat. NeuroImage 41:189-203.
Gibson A, Dehghani H (2009) Diffuse optical imaging. Philosophical Transactions A 367:3055.
Gibson A, Hebden J, Arridge S (2005) Recent advances in diffuse optical imaging. Physics in Medicine and Biology 50:R1.
Gratton G, Fabiani M (2001) Shedding light on brain function: The event-related optical signal. Trends in Cognitive Sciences 5:357-363.
Hallacoglu B, Sassaroli A, Fantini S, Troen AM (2011) Cerebral perfusion and oxygenation are impaired by folate deficiency in rat: absolute measurements with noninvasive near-infrared spectroscopy. Journal of Cerebral Blood Flow & Metabolism.
Hillman E (2007) Optical brain imaging in vivo: techniques and applications from animal to man. Journal of biomedical optics 12:051402.
Kocsis L, Herman P, Eke A (2006) The modified Beer-Lambert law revisited. Physics in Medicine and Biology 51:N91.
Kondo Y, Sakatani K, Igarashi T, Hoshino T, Murata Y, Tejima E, Kano T, Katayama Y (2010) Comparison of Somatosensory Evoked Potentials and Cerebral Blood Oxygenation Changes in the Sensorimotor Cortex During Activation in the Rat. Oxygen Transport to Tissue XXXI 245-249.
Leybaert L (2005) Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling. Journal of Cerebral Blood Flow & Metabolism 25:2-16.
London UC (2005) Specific Extinction Spectra of Tissue Chromophores. vol. 2011 London. Retrieved July 1, 2011, from
Matcher S, Cope M, Delpy D (1994) Use of the water absorption spectrum to quantify tissue chromophore concentration changes in near-infrared spectroscopy. Physics in Medicine and Biology 39:177.
Matthews F, Soraghan C, Ward TE, Markham C, Pearlmutter BA (2008) Software platform for rapid prototyping of NIRS brain computer interfacing techniques. pp 4840-4843: IEEE.
Mochizuki H, Ugawa Y, Terao Y, Sakai KL (2006) Cortical hemoglobin-concentration changes under the coil induced by single-pulse TMS in humans: a simultaneous recording with near-infrared spectroscopy. Experimental brain research 169:302-310.
Muthalib M, Jubeau M, Millet GY, Maffiuletti NA, Nosaka K (2009) Comparison between electrically evoked and voluntary isometric contractions for biceps brachii muscle oxidative metabolism using near-infrared spectroscopy. European journal of applied physiology 107:235-241.
Nighswander-Rempel SP, Kupriyanov VV, Shaw RA (2005) Assessment of optical path length in tissue using neodymium and water absorptions for application to near-infrared spectroscopy. Journal of biomedical optics 10:024023.
Nishimura E, Stautzenberger J, Robinson W, Downs T, Downs J (2007) A new approach to functional near-infrared technology. IEEE Engineering in Medicine and Biology Magazine 26:25.
Nissila I, Noponen T, Heino J, Kajava T, Katila T (2005) Diffuse optical imaging. Advances in electromagnetic fields in living systems 77-129.
PD-LD I PL63/65/67 Series Visible Laser Diode Modules. p 2.
Rolfe P (2000) In vivo near-infrared spectroscopy. Biomedical Engineering 2.
Sakatani K, Iizuka H, Young W (1990) Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion. Stroke 21:124.
Siegel AM, Culver JP, Mandeville JB, Boas DA (2003) Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation. Physics in Medicine and Biology 48:1391.
Silva A, Lee S, Yang G, Iadecola C, Kim S (1999) Simultaneous blood oxygenation level-dependent and cerebral blood flow functional magnetic resonance imaging during forepaw stimulation in the rat. Journal of Cerebral Blood Flow & Metabolism 19:871-879.
Son I, Yazici B (2006) Near Infrared Imaging and Spectroscopy for Brain Activity Monitoring. Advances in sensing with security applications 341-372.
Strangman G, Boas D, Sutton J (2002) Non-invasive neuroimaging using near-infrared light. Biological Psychiatry 52:679-693.
Strangman G, Franceschini MA, Boas DA (2003) Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters. NeuroImage 18:865-879.
Wu D, Anastassios B, Xiong W, Madhok J, Jia X, Thakor N (2010) Study of the Origin of Short-and Long-latency SSEP during Recovery from Brain Ischemia in a Rat Model. Neuroscience Letters.
Yamashita Y, Maki A, Koizumi H (2001) Wavelength dependence of the precision of noninvasive optical measurement of oxy-, deoxy-, and total-hemoglobin concentration. Medical Physics 28:1108.