本文選題：眼部 + 信號��； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：從認(rèn)知層面發(fā)掘目標(biāo)信息,利用現(xiàn)有硬件系統(tǒng)進(jìn)行信號采集,通過軟件系統(tǒng)及特定數(shù)學(xué)算法對所拾取信號進(jìn)行處理分析,并在干擾噪聲中準(zhǔn)確提取目標(biāo)信號的過程,稱之為信號檢測分析。1954年該理論由Tanner WP首次提出。 眼球作為中樞神經(jīng)系統(tǒng)的延伸部分,其在穩(wěn)定的眼內(nèi)壓支撐下不斷將所接收的光學(xué)信號轉(zhuǎn)變?yōu)殡娦盘?為生物體提供豐富地視覺刺激。如何以現(xiàn)有理論認(rèn)知為支撐,利用硬件及軟件系統(tǒng)準(zhǔn)確采集,處理及分析有用的眼部信號,是眼部信號檢測分析理論實(shí)際應(yīng)用中的核心及難點(diǎn)。 本研究主要分為四大部分：1.在現(xiàn)有臨床檢測方法對晝夜眼壓波動信號拾取過程具有局限性的理論支撐下,第一部分主要通過醫(yī)工交叉,利用機(jī)械測量原理,建立采集、提取及分析眼內(nèi)壓波動信號的新方法；2.在基于眼部血流量異常直接參與視神經(jīng)疾病進(jìn)展過程的理論支撐下,第二,三,四部分主要利用現(xiàn)有無創(chuàng)檢測技術(shù)及相應(yīng)儀器(相干光斷層掃描),在選取最佳測量方法后,提取正常人,屈光不正及青光眼患者眼部視網(wǎng)膜及脈絡(luò)膜信號進(jìn)行分析,處理。觀察脈絡(luò)膜組織與視網(wǎng)膜退行性變的關(guān)系及有氧運(yùn)動前后正常人與原發(fā)性開角型青光眼患者脈絡(luò)膜信號的反應(yīng)差異性。 一、基于磁斥力連續(xù)性眼壓測量原理與方法研究 目的：利用“永磁鐵磁斥力測量”原理提取眼內(nèi)壓信號,有望達(dá)到24h眼內(nèi)壓監(jiān)測的最終目的。 原理：永磁鐵間距漸進(jìn)性縮小,磁斥力逐漸增加,當(dāng)磁斥力(使力磁環(huán)與受力磁環(huán)間的排斥力)增大與眼內(nèi)壓平衡時,繼續(xù)縮短磁間距,角膜將在外力作用下發(fā)生形變。此時在示波器所獲取的電壓-位移曲線中可觀察到小幅波動。波動處電壓輸出信號(U)與眼內(nèi)壓(P)相關(guān)。通過建立U、P對應(yīng)關(guān)系的數(shù)學(xué)模型,從壓力曲線信號中提取U信號,間接可得眼壓P信號大小。 方法：以35mmHg作為眼壓信號檢測上限,利用“有限元仿真方法”評估導(dǎo)致角膜發(fā)生形變所需永磁鐵磁斥力大小及其位移范圍。建立模擬眼球灌注模型,構(gòu)建機(jī)械測量裝置,提取不同壓力下傳感器電壓輸出信號。 結(jié)果：1.N40H稀土永磁鐵材料能夠達(dá)到本研究需求,產(chǎn)生足夠磁斥力壓迫角膜發(fā)生形變。2.不同壓力下電壓-位移曲線波動點(diǎn)處傳感器輸出電壓信號不同。伴隨模擬眼球內(nèi)壓力逐漸升高(10mmHg,30mmHg,50mmHg),壓力傳感器輸出電壓信號相應(yīng)升高,二者相關(guān)性良好。 結(jié)論：利用此種方法通過拾取電容壓力感受器電壓輸出信號間接反映眼內(nèi)壓波動,整體測量過程無創(chuàng),快速,有望達(dá)到無創(chuàng)24h眼壓監(jiān)測的最終目的。 二、經(jīng)眼瞼眼內(nèi)壓檢測系統(tǒng)的研究 目的：利用“生物組織彈性力學(xué)差異原理”提取眼內(nèi)壓信號,有望達(dá)到使用者自測眼壓的最終目的。 原理：“經(jīng)眼瞼眼內(nèi)壓檢測系統(tǒng)”基于生物組織的彈性力學(xué)差異。利用眼球不同組織間存在的“力-形變”差異獲取眼壓信號。 方法：本研究采用機(jī)械力學(xué)“壓縮測量方法”對眼瞼及眼球壁(角膜組織)進(jìn)行彈性壓縮,通過電容壓力傳感器獲取壓力反射信號。聯(lián)合位移傳感器(可變電阻器)由示波器采集并繪制出電壓-位移曲線,曲線“拐點(diǎn)”處代表不同組織交界面,拐點(diǎn)后曲線斜率與眼內(nèi)壓相關(guān)。計算拐點(diǎn)后曲線斜率,觀察曲線斜率與眼內(nèi)壓相關(guān)性,完成該系統(tǒng)的初步研究工作。 結(jié)果：1.本研究測量眼內(nèi)壓范圍13-33mmHg,可以達(dá)到大多數(shù)原發(fā)性開角型青光眼患者眼壓信號幅度。2.在不同灌注壓力下,重復(fù)測量4次,實(shí)驗(yàn)結(jié)果示電壓-位移曲線重復(fù)性良好。3.伴隨眼內(nèi)壓逐漸升高,拐點(diǎn)后電壓-位移曲線斜率相應(yīng)增大,線性擬合后可以通過電壓-位移曲線斜率K間接獲得眼內(nèi)壓幅值。 結(jié)論：經(jīng)眼瞼眼內(nèi)壓測量系統(tǒng)原理可行,結(jié)果重復(fù)性佳,能夠?qū)崟r反映眼內(nèi)壓變化,可以達(dá)到使用者自測眼壓的最終目的。 第二部分：不同方法提取脈絡(luò)膜厚度信息的差異性研究 目的：招募正常受試者為研究對象,運(yùn)用相干光斷層掃描技術(shù)提取人眼脈絡(luò)膜組織信號,分別選用海德堡測量軟件及ImageJ測量軟件對脈絡(luò)膜厚度進(jìn)行測量分析,進(jìn)行不同測量方法可重復(fù)性及一致性的相關(guān)統(tǒng)計學(xué)分析,選取出最優(yōu)測量方法為后續(xù)研究奠定基礎(chǔ)。 方法：36名正常受試者納入此項(xiàng)研究。利用相干光斷層掃描技術(shù)采集中心凹及旁中心凹直徑6mm范圍內(nèi)脈絡(luò)膜組織圖像。分別由Heidelberg eye explore software(版本5.3.3.0,海德堡,德國)及Image J software (version1.42,美國)進(jìn)行脈絡(luò)膜厚度測量。運(yùn)用Bland-Altmann統(tǒng)計學(xué)方法對不同測量方法測量結(jié)果一致性及可重復(fù)性進(jìn)行分析比較。 結(jié)果：1. Image J軟件測量重復(fù)系數(shù)(39.9186)高于海德堡測量軟件(27.3525)；2.兩種方法測量結(jié)果一致性分析顯示,95%可信區(qū)間為-18.437～63.949um；3.95%可信區(qū)間精確性分析顯示：其上限范圍16.102～111.796um；下限范圍-66.29～21.41umm。 結(jié)論：Image J測量軟件重復(fù)性及一致性較Heidelberg測量軟件高,應(yīng)該成為研究者日后脈絡(luò)膜厚度測量的可選用軟件之一。 第三部分：近視患者脈絡(luò)膜厚度及感光細(xì)胞層厚度變化的研究 目的：通過招募正常人及近視患者作為研究人群,利用相干光斷層掃描技術(shù)提取人眼脈絡(luò)膜及視網(wǎng)膜組織信號,有望尋找脈絡(luò)膜與視網(wǎng)膜組織退行性變間的相互關(guān)系。 方法：64例受試者依據(jù)屈光狀態(tài)分為三組：組Ⅰ：正視組(+1.0D～-1.OD)；組Ⅱ：輕中度近視組(-1.0D～-6.0D)；組Ⅲ：高度近視組(-6.0D)。運(yùn)用頻域相干光斷層掃描技術(shù)(spectral domain optic coherence tomography, SD-OCT)提取脈絡(luò)膜及視網(wǎng)膜組織圖像信號。利用Image J軟件提取視網(wǎng)膜厚度(Retinal thickness, RT),視網(wǎng)膜神經(jīng)纖維層厚度(retinal nerve fiber layer thickness, RNFLT),視網(wǎng)膜神經(jīng)節(jié)細(xì)胞層厚度(ganglion layer thickness, GLT),視網(wǎng)膜感光細(xì)胞層厚度(photoreceptor layer thickness, PRLT)及脈絡(luò)膜厚度(choroidal thickness, ChT)信息。 結(jié)果：與正視者相比,高度近視患者感光細(xì)胞層厚度,視網(wǎng)膜厚度及脈絡(luò)膜厚度均顯著降低(P0.05)；單因素及多因素線性回歸分析方法均提示感光細(xì)胞層厚度變化與脈絡(luò)膜厚度變化緊密相關(guān)。 結(jié)論：高度近視患者不僅脈絡(luò)膜厚度較正常人降低,感光細(xì)胞層厚度同樣降低。二者構(gòu)成神經(jīng)血管單元。脈絡(luò)膜厚度變化會導(dǎo)致感光細(xì)胞層厚度變化,反之亦然。 目的：本研究將原發(fā)性開角型青光眼(primary open angle glaucoma, POAG)患者作為主要研究人群,利用相干光斷層掃描技術(shù)(optic coherence tomography,OCT)提取受試者脈絡(luò)膜組織圖像信號,利用非接觸式眼壓計提取眼內(nèi)壓信號,探究有氧運(yùn)動前及有氧運(yùn)動后正常受試者與POAG患者眼部脈絡(luò)膜厚度及眼內(nèi)壓力變化情況。 方法：34例受試者分為兩組：正常對照組(17人/17只眼)及原發(fā)性開角型青光眼組(17人/17只眼)。受試者在安靜坐位休息十分鐘期間完成國際身體活動問卷填寫工作(International physical activity questionnaire, IPAQ),靜坐十分鐘后完成運(yùn)動前眼內(nèi)壓(intraocular pressure, IOP),收縮期血壓(systolic blood pressure,SBP),舒張期血壓(diastolic blood pressure, DBP),心率(heart rate, HR),視野及脈絡(luò)膜圖像信號采集工作；進(jìn)行20mmin慢跑有氧運(yùn)動(每4分鐘定時監(jiān)測血氧飽和度及心率變化)；運(yùn)動后依次進(jìn)行眼壓,血壓,脈絡(luò)膜圖像信號采集工作。利用Image J軟件(version1.42, National Institutes of Health, Bethesda, Maryland,USA)提取脈絡(luò)膜厚度信息(choroidal thickness, ChT)。通過公式計算國際身體活動問卷評分(IPAQ score),最大心率百分比(HR%max),平均動脈壓(meanaterial pressure, MAP)及眼灌注壓數(shù)值(ocular perfusion pressure, OPP)。運(yùn)用獨(dú)立樣本T檢驗(yàn),獨(dú)立樣本配對T檢驗(yàn),箱圖統(tǒng)計學(xué)分析方法及受試者工作特征曲線分析(receiver oprating characteristic curve, ROC曲線)對運(yùn)動前后眼壓,平均動脈壓,眼灌注壓及脈絡(luò)膜厚度進(jìn)行相關(guān)統(tǒng)計學(xué)分析。 結(jié)果：1.有氧運(yùn)動后對照組及POAG組患者脈絡(luò)膜厚度均顯著降低,差異具有統(tǒng)計學(xué)意義(P0.05)；2.有氧運(yùn)動后對照組及POAG組患者眼壓均顯著降低(P0.05)；平均動脈壓及眼灌注壓均顯著升高(P0.05);3. POAG組運(yùn)動后眼壓,平均動脈壓及脈絡(luò)膜厚度波動幅度均與對照組存在統(tǒng)計學(xué)差異(P0.05)； 4.受試者工作曲線提示運(yùn)動前后脈絡(luò)膜厚度變化曲線下面積(areas under curve,AUC)為71.9%,眼壓變化AUC為21.8%。脈絡(luò)膜厚度變化在區(qū)分正常人及POAG患者的過程中具有中等程度分辨作用。 結(jié)論：1.運(yùn)動后交感神經(jīng)系統(tǒng)興奮性升高可能是導(dǎo)致脈絡(luò)膜厚度降低,眼壓降低及眼灌注壓升高的主要原因。2. POAG患者自主神經(jīng)病變可能是導(dǎo)致其運(yùn)動后眼壓,平均動脈壓及脈絡(luò)膜厚度波動幅度均與對照組存在顯著差異的原因。3.本研究采用中等強(qiáng)度運(yùn)動,研究結(jié)果顯示,正常人主要通過提高平均動脈壓增加眼部血流灌注,而運(yùn)動后POAG患者主要通過降低眼內(nèi)壓增加眼部血流灌注。故課題組提出以下假設(shè)：在日常生活中(低,中強(qiáng)度運(yùn)動),眼內(nèi)壓持續(xù)性波動幅度較正常人增加可能是部分POAG患者視功能損害不斷進(jìn)展的危險因素之一。如何為不同青光眼患者確定合適的運(yùn)動量可能是下一步需要研究的新方向。
[Abstract]:From the cognitive level, the target information is excavated, the signal is collected by the existing hardware system, the pickup signal is processed and analyzed through the software system and the specific mathematical algorithm, and the target signal is accurately extracted in the interference noise. It is called the Tanner WP first proposed for the signal detection and analysis in.1954.
The eyeball, as an extension of the central nervous system, constantly transforms the received optical signals into electrical signals under stable intraocular pressure and provides abundant visual stimuli for the organisms. How to accurately collect, handle and analyze useful eye signals by using the existing theoretical cognition and using hardware and software systems, and to analyze and analyze useful eye signals, is an eye letter. The core and difficulty in the practical application of the theory of number detection and analysis.
This study is divided into four main parts: (1.) under the theoretical support of the existing clinical detection methods for the pickup process of the diurnal intraocular pressure fluctuation signal, the first part mainly through the medical cross, using the principle of mechanical measurement, to establish a new method of collecting, extracting and analyzing the wave signal of the intraocular pressure; 2. based on the abnormal direct eye blood flow. Under the theoretical support of the progress of optic nerve disease, the second, third and four parts mainly use the existing non-invasive detection techniques and corresponding instruments (coherent optical tomography) to extract the normal people, ametropia and glaucoma patients' eye net membrane and choroid signal after selecting the best measurement techniques and corresponding instruments (coherent optical tomography). The relationship between weave and retinal degeneration, and the difference in response to choroidal signals between normal subjects and patients with primary open angle glaucoma before and after aerobic exercise.
First, the principle and method of continuous intraocular pressure measurement based on magnetic repulsion force.
Objective: to extract intraocular pressure signals from the principle of "permanent magnet magnetic repulsion force measurement" is expected to achieve the ultimate goal of 24h intraocular pressure monitoring.
Principle: the distance between the permanent magnet is gradually reduced and the magnetic repulsion gradually increases. When the magnetic repulsion (the repulsive force between the force magnetic ring and the force magnetic ring) increases and the intraocular pressure is balanced, the magnetic distance will continue to be shortened, and the cornea will be deformed under the external force. At this time, the small amplitude fluctuation can be observed in the electric pressure displacement curve obtained by the oscilloscope. The pressure output signal (U) is related to the intraocular pressure (P). By establishing the mathematical model of the corresponding relationship between U and P, the U signal is extracted from the signal of the pressure curve, and the size of the intraocular pressure P signal can be obtained indirectly.
Methods: using 35mmHg as the upper limit of IOP signal detection, the size and displacement range of permanent magnet magnetic repulsive force needed to cause corneal deformation was evaluated by "finite element simulation method". A simulated eyeball perfusion model was established, and a mechanical measuring device was built to extract the voltage output signal of sensor under different pressure.
Results: 1.N40H rare earth permanent magnet materials can meet the needs of this study, producing sufficient magnetic repulsion force to oppress the cornea and the voltage displacement curve of.2. under different pressures. The output voltage signal of the sensor is different at the fluctuation point of the voltage displacement curve under different pressure. With the gradual increase of the simulated intraocular pressure (10mmHg, 30mmHg, 50mmHg), the output voltage signal of the pressure sensor is raised correspondingly. The two has a good correlation.
Conclusion: this method can indirectly reflect the fluctuation of intraocular pressure by picking up the voltage output signal of capacitive baroreceptor. The overall measurement process is noninvasive and fast. It is expected to achieve the ultimate goal of non-invasive 24h intraocular pressure monitoring.
Two, study on the detection system of eyelid intraocular pressure
Objective: to extract the intraocular pressure signal from the "principle of elasticity difference in biological tissue", which is expected to achieve the ultimate goal of user self-monitoring.
Principle: "the eyelid intraocular pressure detection system" is based on the differences in the elastic mechanics of biological tissues. The IOP signal is obtained by using the "force deformation" difference between the different eyeball tissues.
Methods: the study adopts the mechanical mechanical "compression measurement" to compress the eyelid and the eyeball wall (corneal tissue) and obtain the pressure reflection signal through a capacitive pressure sensor. The joint displacement sensor (variable resistor) collects and draws the voltage displacement curve by the oscilloscope, and the curve "turning point" represents the different tissue junction. The slope of the curve after the inflection point is related to the intraocular pressure. The slope of the curve after the inflection point is calculated, and the correlation between the slope of the curve and the intraocular pressure is observed, and the preliminary research work of the system is completed.
Results: 1. the range of intraocular pressure (13-33mmHg) was measured in this study. The amplitude.2. of intraocular pressure in most patients with primary open angle glaucoma could be measured repeatedly under different perfusion pressures and 4 times. The results showed that the repeatability of the voltage displacement curve was good.3. with the intraocular pressure, and the slope of the voltage displacement curve increased after the inflection point. After fitting, the amplitude of intraocular pressure can be indirectly obtained by the slope of voltage displacement curve K.
Conclusion: the principle of the eyelid intraocular pressure measurement system is feasible, the result is good repeatability, it can reflect the changes of intraocular pressure in real time, and can achieve the ultimate aim of user's self measurement of intraocular pressure.
The second part: the difference of extracting choroidal thickness by different methods.
Objective: to recruit normal subjects as the research object, use the coherent optical tomography to extract the choroidal tissue signal of human eyes, and select the Heidelberg measurement software and ImageJ software to measure the choroid thickness, and analyze the repeatability and consistency of the different measurement methods, and choose the optimal measurement. The method laid the foundation for the follow-up study.
Methods: 36 normal subjects were included in this study. The choroidal tissue images were collected by coherent optical tomography in the 6mm range of the central fovea and parabparal concave. The choroidal thickness was measured by Heidelberg eye explore software (version 5.3.3.0, Heidelberg, Germany) and Image J software (version1.42, USA), using Bl. And-Altmann statistical method was used to analyze and compare the consistency and repeatability of the results of different measurement methods.
Results: 1. Image J software measurement repetition coefficient (39.9186) is higher than Heidelberg measurement software (27.3525); 2. two methods of measurement results consistency analysis shows that 95% confidence interval is -18.437 to 63.949um; 3.95% confidence interval accuracy analysis shows that the upper limit range is 16.102 to 111.796um; the lower limit range -66.29 to 21.41umm.
Conclusion: the repeatability and consistency of the Image J measurement software is higher than that of the Heidelberg software. It should be one of the available software for the researchers to measure the choroidal thickness in the future.
The third part: the changes of choroid thickness and photoreceptor cell thickness in myopic patients.
Objective: to extract the choroidal and retinal tissue signals by using coherent optical tomography to find the relationship between the choroidal and retinal tissue degeneration by recruiting normal people and myopic patients as the research population.
Methods: 64 subjects were divided into three groups according to the diopter state: group I: Group (+1.0D to -1.OD); group II: mild to moderate myopia group (-1.0D ~ -6.0D); group III: high myopia group (-6.0D). Use frequency domain coherent optical tomography (spectral domain optic coherence tomography, SD-OCT) to extract the image of choroid and retina tissue Image J software is used to extract the retinal thickness (Retinal thickness, RT), retinal nerve fiber layer thickness (retinal nerve fiber layer thickness, RNFLT), retinal ganglion cell layer thickness (ganglion), retinal photosensitive cell layer thickness, and choroid thickness Oroidal thickness, ChT) information.
Results: the thickness of photoreceptor layer, the thickness of retina and the thickness of choroid were significantly decreased (P0.05) in the patients with high myopia. The single factor and multi factor linear regression analysis suggested that the changes of the thickness of the photoreceptor layer were closely related to the changes of the choroid thickness.
Conclusion: not only the thickness of the choroid in the patients with high myopia is lower, but the thickness of the photoreceptor layer is also reduced. The two groups constitute the neurovascular unit. The change of the choroidal thickness will lead to the change of the thickness of the photoreceptor layer, and vice versa.
Objective: in this study, the patients with primary open angle glaucoma (primary open angle glaucoma (POAG)) were used as the main research population, using the coherent optical tomography (optic coherence tomography, OCT) to extract the image signal of the choroid tissue of the subjects, and to extract the intraocular pressure signal by non-contact tonometer, and to explore the preoperative and the aerobic exercise. Changes of ocular choroidal thickness and intraocular pressure in normal subjects and POAG patients after aerobic exercise.
Methods: 34 subjects were divided into two groups: the normal control group (17 /17 eyes) and the primary open angle glaucoma group (17 /17 eyes). The subjects completed the international physical activity questionnaire (International physical activity questionnaire, IPAQ) during the rest period of rest ten minutes, and completed the pre exercise eye after ten minutes of sitting. Pressure (intraocular pressure, IOP), systolic blood pressure (systolic blood pressure, SBP), diastolic blood pressure (diastolic blood pressure, DBP), heart rate (heart), visual field and choroidal image signal acquisition, and aerobic exercise (monitoring blood oxygen saturation and heart rate changes every 4 minutes); after exercise Image J software (version1.42, National Institutes of Health, Bethesda, Maryland, USA) extraction of choroidal thickness information (choroidal thickness). The formula is used to calculate the international body activity questionnaire, the maximum heart rate percentage, and the mean arterial pressure. Naterial pressure, MAP) and eye perfusion pressure value (ocular perfusion pressure, OPP). Independent sample T test, independent sample paired T test, box graph statistical analysis method and subject work characteristic curve analysis (receiver oprating characteristic), intraocular pressure, mean arterial pressure, eye perfusion pressure and pulse before and after exercise The thickness of the collaterals was analyzed statistically.
Results: 1. after aerobic exercise, the choroidal thickness of the control group and the POAG group decreased significantly, and the difference was statistically significant (P0.05); 2. after aerobic exercise, the intraocular pressure of the control group and the POAG group were significantly decreased (P0.05); the mean arterial pressure and the ocular perfusion pressure were significantly increased (P0.05); the intraocular pressure after exercise, the mean arterial pressure and the choroid membrane in the 3. POAG group were observed. There was a significant difference in thickness fluctuation between the control group and the control group (P0.05).
The work curve of 4. subjects suggested that the area under the curve of choroidal thickness (areas under curve, AUC) before and after the movement was 71.9%, and the change of intraocular pressure AUC to 21.8%. choroid thickness was of moderate resolution in the process of distinguishing between normal and POAG patients.
Conclusion: 1. the increased excitability of the sympathetic nervous system after exercise may be the main cause of the decrease of choroidal thickness, the decrease of intraocular pressure and the increase of intraocular perfusion pressure in.2. POAG patients, which may be the cause of the intraocular pressure, the mean arterial pressure and the amplitude of the choroidal thickness are significantly different from those in the control group.3. The study uses moderate intensity exercise. The results show that normal people increase the blood flow of the eye mainly by increasing the mean arterial pressure, and the POAG patients mainly increase ocular blood flow by lowering intraocular pressure after exercise. Therefore, the group proposes the following hypothesis: in daily life (low, moderate intensity exercise), the constant fluctuation range of intraocular pressure is more than that of the normal people. The increase in normal people may be one of the risk factors for progressive visual impairment in some POAG patients. How to determine the appropriate amount of exercise for different glaucoma patients may be a new direction in the next step.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R770.4

【共引文獻(xiàn)】

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