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研究生：	楊豐懋 Yang, Feng-Mao
論文名稱：	發展近紅外光譜系統應用於評估大鼠腦部血氧反應 Development of Near Infrared Spectroscopy System for Assessing Hemodynamic Changes of Rat’s Brain
指導教授：	陳家進 Chen, Jia-Jin
學位類別：	碩士 Master
系所名稱：	工學院 - 醫學工程研究所 Institute of Biomedical Engineering
論文出版年：	2011
畢業學年度：	99
語文別：	英文
論文頁數：	46
中文關鍵詞：	神經血管連結、近紅外光譜系統、分頻強度調變、快速傅利葉轉換解調
外文關鍵詞：	neurovascular coupling, near infrared spectroscopy, frequency-division intensity modulation, fast Fourier transform demodulation
相關次數：	點閱：120 下載：2
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關於腦部活性的評估目前已經發展出許多技術與方法，神經行為學評估表是最常被使用的，這種方法雖然在使用上相當容易，但無法量測高時間解析度下神經活性量化的數值。因此，本研究目的在於設計一套非侵入式的神經電生理與光學量測系統用來評估動物體的腦部活性。此系統包含兩大部分，用以量測大鼠體感覺誘發電位的腦波量測系統以及量測腦部血氧動力學反應的近紅外光譜系統，其中，用來測量電生理的電極與偵測腦血氧動力學的光纖可同時的配置於定位架上，以量測大鼠的腦波訊號與腦血氧反應。腦波量測系統包含雙通道的前置放大器，可用來放大微小訊號進而提高訊雜比；近紅外光譜系統採用分頻強度調變與快速傅利葉轉換解調達成多通道之血氧反應量測。在研究結果的部分，為了驗證系統的量測效能，本研究所研發之系統已完成大鼠腦部之血氧反應量測，此外，此系統以非侵入的方式量測大鼠體感覺誘發電位與事件相關之血氧反應並可用於腦部活性的即時量測，未來可應用到腦血管疾病之相關研究。

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.

摘要	I
Abstract	II
誌謝	III
Contents	IV
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
References	43
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

                                    

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校內：2013-08-23公開
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