双波长光耦合功能成像乳腺诊断系统

双波长光耦合功能成像乳腺诊断技术是一种基于两种特征脉冲波的生物医学光子功能成像的新技术。提出这种具有完全自主知识产权的“双波长光耦合功能成像乳腺诊断系统”,是基于人体乳腺癌变组织中含氧血红蛋白和去氧血红蛋白在两种波长分别为760和850 nm的近红外光上具有相反的吸收特性的原理,且诊断过程对人体零损伤,因此具有无辐射、经济、方便的优点。在设计中,依照脉冲光较连续光透过生物组织可以获取更多有效信息的新思路,结合对透射光电信号的功率谱和互相关功能图的分析方法,能从频谱中不稳定的突变信号定性检测出组织癌变后的血氧浓度变化。同时,借助相关性函数和系数的值,判定出两种波长(760/850 nm)透射信号的波形周期等参数的相似程度。经武汉大学人民医院对547例患者所做的临床诊断,分析结果如下:正常乳腺组织的功率谱曲线的单一性比较好,曲线较平稳;良性病变功率谱曲线波动大,且很不平稳;而恶性病变更加严重。正常乳腺组织在两种波长的近红外光照射下,相关系数在0.9左右;良性病变组织在两种波长照射下吸收特性差异大,相关系数普遍低于0.8,相关性较弱;恶性病变组织相关性低于0.5,趋近于零,相关性小。该结果能有力地支撑理论,表明该系统可以对乳腺疾病做初步诊断。     

一种基于近红外脉冲光的乳腺疾病诊断系统

目的 基于光的组织传播特性和去氧血红蛋白和含氧血红蛋白对近红外光的相反吸收特性,本文设计和实现了一种近红外脉冲光乳腺疾病诊断系统.方法 系统由光源、控制电路、采集卡、近红外CCD相机和计算机及应用程序组成,光源选用波长为760 nm和850 nm,外部电路同采集卡配合实现光源的时序发光.结果 该系统具备非侵入、无辐射、廉价的特性.结论 作为一种辅助诊断技术,本系统有很重要的临床研究价值和应用价值.     

近红外漫射光相关断层成像的乳腺光纤探头设计

为获得稳定的光学信号,提高近红外漫射光相关断层成像技术(diffuse correlation tomography,DCT)的诊断效率,本研究结合阵列式光开关,设计了一种适用于DCT的弧面式光学乳腺探头,可将DCT检测部位扩展到人体乳腺组织。为验证该乳腺探头的有效性及实用性,本研究设计了相应的乳腺仿体,并进行了仿体实验。结果表明,该乳腺探头可较好地契合DCT设备,并能捕捉微弱的血流变化,有望促进DCT技术在早期乳腺恶性肿瘤筛查中的临床应用。     

近红外脉冲光乳腺疾病诊断系统功率谱和互相关曲线分析

目的 提出一种乳腺疾病无损检测新技术及其分析方法.方法 基于近红外脉冲光的乳腺疾病诊断系统软件部分以VC为开发工具,主要实现图像同步采集、图像配准、分析处理和数据管理等功能,其中分析处理部分包含感兴趣点分析和区域分析两种方法,点分析主要包含功率谱曲线、相关性曲线和相关系数,区域分析则是计算区域内所有点相关系数形成由相关系数构成的伪彩图像.文中对一例典型的乳腺癌患者做了详细的诊断分析.结果 乳腺癌患者病变部位的相关系数一般小于0.6,其功率谱呈现很多次频峰,互相关曲线上出现很多毛刺.而正常人的相关系数基本都在0.8以上,其功率谱和互相关曲线较光滑.结论 该系统具备非侵入、无辐射、廉价的特性,通过对典型病例的光强分析展示了系统的临床使用价值.     

人体乳腺组织电阻抗特性的研究

以人体乳腺组织电阻抗特性为依据的乳腺电阻抗扫描成像技术的出现,为乳腺癌的早期检查与辅助诊断开辟了一个新的方向。人体乳腺组织的电阻抗特性反映了乳腺组织的病理生理状态,而对它的测量成为乳腺电阻抗扫描成像技术的前提和基础。主要讨论了人体乳腺组织电阻抗特性的测量方法、测量结果以及存在的问题,对乳腺电阻抗成像技术的应用前景进行了展望。     

模拟微血管的光声成像技术研究

目的：为了实现较深层组织内微血管的光声成像。方法：采用波长532nm、重复频率10Hz的脉冲激光作为激励源,宽带非聚焦针状探头以圆周扫描的方式采集时域光声信号,二维光学吸收分布图像由时域后向投影算法重建,以线扩展函数为依据测量系统的成像空间分辨率。结果：成像空间分辨率0．1mm,模拟微血管网络的光声图像与原始样品完全吻合。结论：对组织内癌症病灶的早期诊断具有较大的意义。     

近红外荧光散射断层成像的研究进展

近红外荧光光学断层成像(FODT)是以合适的荧光探针作为标记物或对比剂,用特定波长的红光激发荧光染料,使其发出波长长于激发光的近红外荧光,通过测量媒质边界处有限点的荧光强度,考虑光子在组织中传播的散射特性,来重建出组织内部的荧光光学特性的分布图像以及组织光学参数。这种成像方式具有无电离辐射、染料稳定、可长期监测和设备简单、成本低等优点,在肿瘤检测、基因表达、蛋白质分子检测和药物受体定位等方面有着很大的应用潜力。在给出近红外荧光散射断层成像典型系统的基础上,详述了近红外荧光在组织中的频域传播模型和重建算法;介绍了两家研究机构在此领域的研究进展;讨论了将该成像方法应用于临床的进一步的发展方向。     

近红外荧光散射断层成像的研究进展

近红外荧光光学断层成像(FODT)是以合适的荧光探针作为标记物或对比剂，用特定波长的红光激发荧光染料，使其发出波长长于激发光的近红外荧光，通过测量媒质边界处有限点的荧光强度，考虑光子在组织中传播的散射特性，来重建出组织内部的荧光光学特性的分布图像以及组织光学参数。这种成像方式具有无电离辐射、染料稳定、可长期监测和设备简单、成本低等优点，在肿瘤检测、基因表达、蛋白质分子检测和药物受体定位等方面有着很大的应用潜力。在给出近红外荧光散射断层成像典型系统的基础上，详述了近红外荧光在组织中的频域传播模型和重建算法；介绍了两家研究机构在此领域的研究进展；讨论了将该成像方法应用于临床的进一步的发展方向。     

一种电阻抗频谱法自动诊断乳腺组织疾病优化算法研究

乳腺组织疾病早期诊断具有十分重要的意义,基于电阻抗频谱法进行乳腺组织疾病早期诊断是近年来发展起来的乳腺临床检查技术,具有成本低、无损害、无创伤等优势.本研究采用电阻抗频谱法测量的64位妇女,106个乳腺样本的电阻抗特性数据,基于神经网络与支持向量机实现乳腺组织疾病的早期自动诊断.针对传统神经网络的过拟合问题,网络初始参数如何确定问题,以及支持向量机(SVM)分类器的惩罚因子C与核函数g如何有效确定问题,采用遗传算法全局寻优的方式,按适者生存的原则,进行参数的选择、交叉、变异,直到收敛到最适应环境的“染色体”上,即得到问题的最优解,从而实现网络权值与阈值以及SVM惩罚因子与核函数的参数寻优.改进后的算法诊断识别率分别由优化前的61.92％和51.92％,提高到优化后的76.15％和68.08％,为乳腺组织疾病的早期自动诊断提供了一种有效的参考方法.     

吲哚菁绿在影像医学中的应用

吲哚菁绿（ICG）是一种在近红外光谱范围内有较强吸收、毒性小、不参与体内生物转化、排泄迅速的荧光染料,是目前惟一被美国食品药品管理局（FDA）批准的,临床使用的近红外光学成像对比增强剂。由于近红外光学成像因近红外光在生物组织中具有更强的穿透能力,而且受其他因素影响较小,所以被广泛应用于功能成像和异常组织诊断的研究,在组织光学检测方面具有较大的发展前景。因此,ICG在生物医学成像、光动力治疗及病理组织检测等领域的应用持续升温。重点从临床应用角度综述了ICG在影像医学中的应用。     

强激光的生物学效应

强激光的生物学效应陈明哲张永珍（北京医科大学第三医院，北京１０００８３）ＡｂｓｔｒａｃｔＥｆｅｃｔｓｏｆｈｉｇｈ－ｌｅｖｅｌｌａｓｅｒｏｎｂｉｏｌｏｇｉｃａｌｔｉｓｓｕｅｉｎｃｌｕｄｅｔｈｅｒｍａｌｅｆｅｃｔ，ｐｒｅｓｓｕｒｅｅｆ－ｆｅｃｔ，ｅｌｅｃ...     

Reflectance measurements of layered media with diffuse photon-density waves: a potential tool for evaluating deep burns and subcutaneous lesions

The basic principles of a non-contact, near-infrared technique for the mapping of layered tissues are discussed theoretically and verified experimentally. The propagation properties of diffuse photon-density waves in tissues depend on the optical properties of the tissue. When a layered medium is irradiated by amplitude modulated light, the difference in optical properties between the layers is evident in the phase and amplitude of the diffuse reflection coefficient, which is a result of the interference of the partial waves propagating in the different layers. Thus, diffuse photon-density waves are applicable to the analysis of the structure of layered tissue. The probing depth is determined by the modulation frequency of the incident light. For modulation frequencies between several hundred megahertz and a few gigahertz, this allows us to analyse the properties of muscle tissue of up to 4-8 mm below the surface. Experimental results based on chicken breast muscle are given. As an example, the technique might be of use for evaluating the depth of necrosis and the blood volume fraction in deep burns.     

Development of a bidirectional transcutaneous optical data transmission system for artificial hearts allowing long-distance data communication with low electric power consumption

We have developed a wavelength division bidirectional transcutaneous optical data transmission system using amplitude shift keying (ASK) modulation. The bidirectional optical data transmission system consists of two kinds of light emitting diodes (LEDs) having different wavelengths and an ASK modulator and demodulator. Two narrow directional visible LEDs with a peak output wavelength of 590 nm were used to transmit data from inside the body to outside the body, and a narrow directional near-infrared LED with a peak output wavelength of 940 nm was used for transmission from outside the body to inside the body. The ASK modulator employs a carrier pulse signal (50 kHz) to support a maximum data transmission rate of 9600 bps. An in vitro experiment showed that the maximum tissue thickness of near-infrared optical data transmission without error was 45 mm; the figure was 20 mm for visible optical data transmission. There was no interference between the signals under full-duplex data transmission. Electric power consumption for the data transmission links was 122 mW for near-infrared light and 162 mW (81 mW × 2) for visible light. From the above results, a bidirectional transcutaneous optical data transmission system promises adequate performance for monitoring and control of an artificial heart.     

Characterization of normal breast tissue heterogeneity using time-resolved near-infrared spectroscopy

In recent years, extensive efforts have been made in developing near-infrared optical techniques to be used in detection and diagnosis of breast cancer. Variations in optical properties of normal breast tissue set limits to the performance of such techniques and must therefore be thoroughly examined. In this paper, we present intra- and intersubject as well as contralateral variations of optical and physiological properties in breast tissue as measured by using four-wavelength time-resolved spectroscopy (at 660, 786, 916 and 974 nm). In total, 36 volunteers were examined at five regions at each breast. Optical properties (absorption, mu(a), and reduced scattering, mu'(s)) are derived by employing diffusion theory. The use of four wavelengths enables determination of main tissue chromophores (haemoglobin, water and lipids) as well as haemoglobin oxygenation. Variations in all evaluated properties seen over the entire breast are approximately twice those for small-scale heterogeneity (millimetre scale). Intrasubject variations in optical properties are almost in all cases below 20% for mu'(s), and 40% for mu(a). Overall variations in water, lipid and haemoglobin concentrations are all in the order of 20%. Oxygenation is the least variable of the quantities evaluated, overall intrasubject variations being 6% on average. Extracted physiological properties confirm differences between pre- and post-menopausal breast tissue. Results do not indicate systematic differences between left and right breasts.     

Near-Infrared Optical Mammography for Breast Cancer Detection with Intrinsic Contrast

Optical methods to detect breast cancer on the basis of its increased opacity have been explored for some time. These methods have matured to a point in which they are capable of quantifying the optical properties of breast tissue and translating them into measures of concentrations of relevant tissue components. In particular, near-infrared spectroscopy has been employed to determine the concentrations of hemoglobin, water, and lipids, as well as oxygen saturation of hemoglobin and optical scattering properties in normal and cancerous breast tissue. Dynamic optical measurements can also identify abnormal hemodynamic patterns associated with breast cancer. We review, in this article, a number of results in the field, which show that cancerous tissue is associated with higher hemoglobin and water concentrations, and a lower lipid concentration with respect to normal breast tissue. Indications that breast cancers are characterized by lower hemoglobin saturation and stronger scattering decay as a function of wavelength are less robust, with variable results reported in the literature. Intrinsic sources of optical contrast associated with breast cancer can also be used to monitor individual response to neoadjuvant therapy.     

Transpupillary laser phototherapy of tumors and vascular anomalies of retina and choroid: theoretical approach and clinical implications.

BACKGROUND: Small retinal and choroidal tumors situated near the optic nerve or macula, such as retinoblastomas and malignant melanomas, as well as various other anomalies, in particular vascular malformations, may successfully be treated by photocoagulation. Model assumptions geared towards maximizing efficiency and minimizing undesirable side effects are forwarded, and the most important parameters subserving photothermal destruction, such as radiation field and thermal energy, analyzed. The influence exerted by physical traits of various tissues involved are also considered. METHODS: The model approximations presented are based on classical radiation and absorption laws, as well as on the scattering properties of the various tissues implicated, these being considered as a function of wavelength and their relevance to the photodestructive task at hand. Particular attention is paid to the rate processes and reaction kinetics of irradiated proteins. CONCLUSIONS: Radiation sources emitting in the near-infrared range of the electromagnetic spectrum, such as the diode (810 nm) and the cw Nd:YAG (1064 nm) lasers, are optimal for the treatment of tumors and large, voluminous entities (such as Hippel-Lindau angiomas), owing to the good tissue penetration properties of their light. Those emitting in the shorter wavelength range, such as the argon ion (488 and 514 nm) and first harmonic--mode Nd:YAG (532 nm) lasers, are not suitable for such tasks, but they are ideal for the destruction of fine sanguinous structures, within which their light is strongly absorbed but through which it penetrates poorly. For the treatment of large anomalous structures, a combined short/long wavelength--strategy should also be considered as a viable alternative. Such a "wavelength mixture" is emitted by the xenon high pressure lamp of the once renowned Meyer-Schwickerath light coagulator. The precision and safety of photothermal destruction methods depend, in the first approximation, upon the details of the pulse energy deposition (wavelength, pulse height and duration, pulse dynamics, mode composition, focussing), the choice of which is determined by the optical and thermal constants of the irradiated tissues. Higher pulse energies will, of course, be more effective in destroying neoplastic cells, but the risk of producing undesired collateral heat damage will also increase concomitantly. Until we can ascertain the physical properties of the pathological tissues treated with certainty, we will hardly be able to achieve more than an approximation of an ideal treatment strategy. But with increasing developments in in vivo-diagnostic techniques, we expect that this goal will be attainable in the not too distant future.     

组织不同深度血氧状况的光学监测系统

研制了一套基于相关检测技术的对组织不同深度的血氧进行同步监测的多路近红外光学系统。采用三个波长分别为735nm,805nm和850nm的近红外光测量组织的血氧参数,采用距光源不同间距的多路探测器同时监测不同组织深度的血氧变化,并采用相敏检波技术有效提高了系统的灵敏度。前臂阻断实验证实了该系统能有效测量不同深度组织血氧状况。     

In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy

Diffuse optical imaging (DOI) may be a beneficial diagnostic method for women with mammographically dense breast tissue. In order to evaluate the utility of DOI, we are developing broadband diffuse optical spectroscopy (DOS) to characterize the functional origins of optical signals in breast cancer patients. Broadband DOS combines multifrequency intensity-modulated and continuous-wave near-infrared light to quantify tissue absorption and scattering spectra from 650 to 1000 nm. Values of intrinsic physiological properties (oxy- and deoxy-hemoglobin, water, lipid, and scatter power) derived from absorption and scattering spectra provide detailed information on breast physiology. We present the results of clinical studies of 58 stage II/III malignant breast tumors using a noninvasive, handheld, broadband DOS probe. On average, eight positions were scanned over tumor and contralateral normal breast for each subject. Intrinsic physiological properties were statistically significantly different for malignant vs. normal tissues for all subjects, without patient age or tumor size/type stratification. Breast tissues containing malignant tumors displayed reduced lipid content ( approximately 20%) and increased water, deoxy-, and oxy-hemoglobin (>50% each) compared to normal breast tissues. Functional perturbations by the tumor were significantly larger than functional variations in normal tissues. A tissue optical index (TOI) derived from intrinsic physiological properties yielded an average two-fold contrast difference between malignant tumors and intrinsic tissue properties. Our results demonstrate that intrinsic optical signals can be influenced by functional perturbations characteristic of malignant transformation; cellular metabolism, extracellular matrix composition, and angiogenesis. Our findings further underscore the importance of broadband measurements and patient age stratification in breast cancer DOI.     

Dose response characteristics of new models of GAFCHROMIC films: dependence on densitometer light source and radiation energy

This paper presents a systematic study of the dose response characteristics of two new models and one commonly used model of GAFCHROMIC film: HS, XR-T, and MD55-2, respectively. We irradiated these film models with three different radiation sources: I-125, Ir-192, and 6 MV photon beam (6 MVX). We scanned the films with three different densitometers: a He-Ne laser with a wavelength of 633 nm, a spot densitometer with a wavelength of 671 nm, and a CCD camera densitometer with interchangeable LED boxes with wavelengths of 665 nm (red), 520 nm (green), and 465 nm (blue). We compared the film sensitivities in terms of net optical density (NOD) per unit dose in Gy. The sensitivity of each film model depends on radiation energy and the densitometer light source. Using He-Ne laser based densitometer as a reference standard, we found the sensitivities (NOD/Gy) for the red lights of wavelengths, 671 nm and 665 nm, are higher by factors of about 2.5 and 2, respectively. The sensitivities for green (520 nm) and blue (465 nm) lights are lower than that for He-Ne laser (633 nm) by factors of about 2 and 4, respectively. The energy dependence of the sensitivity varies with the film model, but is similar for all densitometer light sources. Comparing I-125 to Ir-192 and 6MVX, we note that (a) model XR-T is about eight times more sensitive, and (b) models HS and MD55-2 are about 40% less sensitive. Relative to MD55-2, XR-T is 12 times more sensitive for I-125 but comparable for Ir-192 and 6MVX, whereas HS is 2 to 3 times more sensitive in all cases. This set of results can serve as useful information for making decisions in selecting the film model and compatible densitometer to achieve the best accuracy of dosimetry in the appropriate dose range.     

量子点探针辅助的近红外荧光成像技术在肿瘤显影中的应用

肿瘤早期检测是精准并高效诊疗癌症的关键因素。荧光成像技术凭借其高灵敏度、高时空分辨率、无电离辐射和无创实时成像等优点,在生物医学领域,尤其在肿瘤检测方面展现出了广泛的应用前景。近红外光穿过生物组织时,受到的吸收和散射较少,因此在生物成像方面体现了高信噪比和强组织穿透能力。在众多荧光探针中,近红外发光的量子点探针因其量子产率高、抗光漂白性强、发射光可调和稳定性良好等特点在荧光成像方面显示出突出的优势。本文基于量子点探针的近红外荧光成像技术在肿瘤显影中的应用,介绍了量子点优异的光学性能,并重点讨论了硫化铅（PbS）和硫化银（Ag2S）近红外发光量子点探针在肿瘤成像方面的研究进展,并对近红外发光量子点探针的应用前景进行了展望。