Confocal microscopy [detecting and diagnosing cancers]

Optical technologies, such as reflectance and fluorescence microscopy, may help detect and diagnose cancers that originate in the epithelium. The epithelium is the layer of tissue that is exposed to the environment and lines the body's cavities. Cancers that originate in the epithelium include cervical, oral, colon, lung, stomach, bladder and skin cancers. The curable precursors to cervical cancer are cervical epithelial lesions that have larger and more densely spaced nuclei. A fiber-optic confocal microscope (FOCM) has been developed at the Optical Spectroscopy Lab, University of Texas at Austin, to help detect and diagnose these lesions in vivo. With the aid of acetic acid as a contrast agent, the FOCM shows nuclear size and density information throughout the epithelium, presenting the same information as histology but without removing, staining and slicing cervical epithelial tissue. (There are also spatial resolution requirements for showing cell nuclei.) The Optical Spectroscopy Lab continues to develop confocal microscopic instrumentation, new contrast agents, and image processing techniques to improve early detection of precancerous cervical lesions.     

Microwaves for breast cancer detection?

Microwave imaging for medical applications has been of interest for many years. Microwave images are maps of the electrical property distributions in the body. The electrical properties of various tissues may be related to their physiological state. For example, the properties of tissues change with temperature. One application of microwave imaging that has been proposed is monitoring hyperthermia, which is the application of heat to tissue. In this case, the changing electrical properties indicate the successful deposition of heat in the tissue of interest. Other changes in electrical properties may be caused by disease. There is some evidence of changes in the properties of cancerous tissues when compared to normal tissues. Cancer detection with microwave imaging is based on this contrast in electrical properties. Microwave imaging for breast cancer detection has also interested many researchers.     

A high-resolution MACROscope with differential phase contrast, transmitted light, confocal fluorescence, and hyperspectral capabilities for large-area tissue imaging

Recent advances in imaging technology have contributed greatly to biological science. Confocal fluorescence microscopes can acquire two-dimensional and three-dimensional images of biological samples such as live or fixed cells and tissues. Specimens that are large (e.g., a 10 mm/spl times/10 mm tissue section) and overfill the field of view (FOV) of typical microscope objectives require the use of image tiling to cover the entire specimen. This can be time consuming and cause artifacts in the composite image. The MACROscope system (Biomedical Photometrics Inc., Waterloo, ON, Canada) is a confocal device with a 22 mm/spl times/70 mm FOV designed for imaging large tissue sections in a single frame. The prototype demonstrated here can obtain images in reflected, transmitted, fluorescence, phase contrast, and hyperspectral modes. The new spectral imaging mode is characterized with a series of test targets, and sampled spectra are compared to a commercial spectrometer. Fluorescence images of human SiHa tumor xenografts stained with CD31-Cy3, showing blood vessel location, and EF5-Cy5, showing areas of tissue hypoxia, were collected. Differential phase contrast images of the same section, as well as human epithelial cells, were recorded to assess the phase contrast mode. Additionally, fluorescence images of Cytokeratin-Cy3 stained squamous cell carcinoma tissue sections were captured. Finally, red, green, blue transmitted light images of human tongue were obtained. This new device avoids the need for image tiling and provides simultaneous imaging of multiple fluorescently labeled tissue-specific markers in large biological samples. This enables time- and cost-efficient imaging of (immuno)histopathological samples. This device may also serve in the imaging of high-throughput DNA and tissue arrays.     

A hyperspectral imaging system for in vivo optical diagnostics

This paper details the basic principles and instrumental systems as well as applications of hyperspectral imaging system in the biomedical field. The development of an HSI system that combines recent advances in several photonic technologies, including an AOTF, a 2-D CCD detector, and imaging fiber optics. The integration of these technologies leads to a versatile and powerful imaging system that can rapidly record spectral images of samples. This imaging system could find useful applications in medical diagnostics applications where rapid in vivo detection of complex samples is required. The HSI technique has the potential for in site optical diagnosis on tissue and it can be use for guidance of surgical intervention and treatment. The optical diagnostic approaches may either be an imaging modality or a spectroscopic modality. The spectroscopic diagnostics may also provide real-time assessment of tissue response to therapy.     

光声、光热效应对早期乳腺癌的检测和治疗

提出了一种利用组织的光声、光热效应对早期乳腺癌检测和治疗的方法。采用蒙特卡罗仿真,模拟了近红外光到达人体乳腺组织时的能量沉积分布,仿真了由此产生的压力信号;再在肿瘤组织中加入了纳米金粒子,使近红外光在人体乳腺中产生的能量沉积聚集到肿瘤附近,从而在特定部位产生较高的温度。结果表明,光声信号的探测能有效的定位组织中肿瘤的位置,确定肿瘤大小、形状等特性,且在加入半径50 nm的纳米金粒子后,对靶组织的加热效率得到了提升,可提高特定组织光照后的温度,且对周边组织影响较小,基本可达到对早期乳腺癌的检测和治疗效果。     

Fluorescence lifetime imaging: an application to the detection ofskin tumors

A portable system based on fluorescence lifetime imaging has been developed and tested for the detection of skin tumors in humans. The Heme precursor δ-aminolevulinic acid, which promotes the preferential accumulation of the endogenous Protoporphyrin IX (PpIX) in proliferative tissues, is used as an exogenous marker to target the tumor, δ-aminolevulinic acid is topically administered to the patient 1 h before the measurement. Then, using a gated intensified camera, two or more images of the sample are acquired after different delays with respect to the excitation pulses. The images are processed in real time in order to calculate the spatial map of the fluorescence decay time of the sample. The localization of the tumor is based on the longer decay time detected in neoplastic tissues as a result of the stronger emission of PpIX, which has a long decay time, and the reduction in the short living natural tissue fluorescence     

Advances in oral cancer detection using optical coherence tomography

Optical coherence tomography (OCT) is a new modality capable of cross sectional imaging of biological tissue. Due to its many technical advantages such as high image resolution, fast acquisition time, and noninvasive capabilities, OCT is potentially useful in various medical applications. Because OCT systems can function with a fiber optic probe, they are applicable to almost any anatomic structures accessible either directly, or by endoscopy. OCT has the potential to provide a fast and noninvasive means for early clinical detection, diagnosis, screening, and monitoring of precancer and cancer. With an imaging depth range of 2-3 mm, OCT diagnostics are particularly suitable for the oral mucosa. Currently, it is difficult to detect premalignant and malignant oral lesions due to their often multifocal nature and need for repeated biopsies. The goal of this study was to evaluate the feasibility of OCT for the diagnosis of multiple stages of oral cancer progression. In this paper, we present not only conventional 2-D OCT images, but also 3-D volume images of normal and precancerous lesions. Our results demonstrate that OCT is a potential tool for cancer detection with comprehensive diagnostic images.     

Spectral polarization imaging of human rectum-membrane-prostate tissues

Human rectum-membrane-prostate tissue samples were studied using a near-infrared spectral polarization imaging technique to detect small objects and structural changes inside prostate tissues through the rectum. Four modeling samples were made with a small piece of absorber or prostate tissue dyed with a contrast agent (indocyanine green) embedded inside a large piece of prostate tissue in rectum-membrane-prostate structures. The depth of the foreign objects underneath the surface of the rectum-membrane-prostate structures was varied from a millimeter to a centimeter to obtain the critical imaging distance. Different spectral polarization imaging methods with and without contrast agents were performed and compared. The results show that small objects hidden inside the host prostate tissues in the rectum-membrane-prostate structures at depths of 2.5, 4.0, and 7.5 mm can be imaged and identified using the scattering light imaging, tissue emission wing imaging, and contrast agent fluorescence imaging methods, respectively. Our results indicate the potential of imaging and detecting structural changes and cancers inside prostate tissue though rectum-membrane-prostate tissues using this noninvasive spectral polarization imaging technique.     

Beyond 30 MHz [applications of high-frequency ultrasound imaging]

Most medical ultrasound imaging systems operate in the frequency range from 3 to 10 MHz and can resolve objects approximately 1 mm in size. In the mid 1980s, new transducer materials led to the development of the first transducers suitable for high-frequency (30-100 MHz) clinical imaging. These high-frequency transducers can provide images of subsurface structures with microscopic resolution. In this article, the authors introduce the basic principles of high-frequency ultrasound imaging and discuss six applications of this new technology: eye imaging, skin imaging, catheter-based intravascular imaging, intra-articular imaging, high-frequency flow imaging, and in-vivo imaging of mouse embryonic development. These examples illustrate a few of the potential applications of high-frequency ultrasound in medicine and biology     

污秽绝缘子的紫外成像检测

绝缘子积污是电力系统常见的一种现象,严重时可能引起绝缘子串闪络,导致大面积、长时间的停电事故,现已经成为对电网安全最具威胁的因素之一。目前的检测手段存在固有的缺陷和局限性,如红外检测存在检测盲区,不能检测早期故障。笔者研究了如何用紫外成像法检测绝缘子的绝缘状况,采用固体涂层法模拟线路上的绝缘子串积污,通过导电杆对积污绝缘子串加压,用CoroCAM504紫外成像仪观察其紫外成像图。实验结果表明,紫外光子数的最大值与对应时间段的泄漏电流的最大值有着较好的对应关系。在环境湿度较大,如毛毛雨、雾等天气条件下,用紫外成像仪可检测积污程度在a级以上的绝缘子,这为紫外成像仪在工程中的应用提供了一定的依据。现场应用实例也验证了紫外成像检测的有效性。     

Computer assisted diagnosis for digital mammography

This article describes the application of wavelet transform for image enhancement in medical imaging. The initial clinical application is the enhancement of microcalcification clusters (MCCs) in digitized mammograms to improve both their visualization and their detection using computer assisted diagnostic (CAD) methods. The potential universal application for improved visual interpretation of medical images using a computer monitor is also demonstrated. The early detection of MCCs is important in screening programs since their presence is often associated with a high incidence of breast cancer. The enhancement of MCCs is an excellent model for real world evaluation of the wavelet transform. The detection of MCCs presents a significant challenge to the performance characteristics of X-ray imaging sensors and image display monitors since microcalcifications vary in size, shape, signal intensity, and contrast and may be located in areas of very dense parenchymal tissue, making their detection difficult. The classification of MCCs, in turn, as benign or malignant, requires their morphology and detail to be preserved     

Determination of epithelial tissue scattering coefficient using confocal microscopy

Most models of light propagation through tissue assume the scattering properties of the various tissue layers are the same. The authors present evidence that the scattering coefficient of normal cervical epithelium is significantly lower than values previously reported for bulk epithelial tissue. They estimated the scattering coefficient of normal and precancerous cervical epithelium using measurements of the reflectance as a function of depth from confocal images. Reflectance measurements were taken from ex vivo cervical biopsies and fit to an exponential function based upon Beer's law attenuation. The mean scattering coefficients derived were 22 cm/sup -1/ for normal tissue and 69 cm/sup -1/ for precancerous tissue. These values are significantly lower than previously reported for bulk epithelial tissues and suggest that scattering of bulk tissue is dominated by the stroma. They also suggest that computational models to describe light propagation in epithelial tissue must incorporate different scattering coefficients for the epithelium and stroma. Further, the lower scattering of the epithelium suggests greater probing depths for fiber optic probes used by optical diagnostic devices which measure reflectance and fluorescence in epithelial tissue. The difference in scattering between normal and precancerous tissue is attributed to increased nuclear size, optical density, and chromatin texture. The scattering coefficients measured here are consistent with predictions of numerical solutions to Maxwell's equations for epithelial cell scattering.     

Optimizing the visualization of WB-PET images

For oncological studies, the whole-body PET (WB-PET) image plays an important role in detecting and staging various cancers, but there are some potential pitfalls in traditional display methods that need to be improved. The purpose of this study is to develop several data-processing techniques to overcome these problems and provide better image quality for visual interpretation of scans. We have developed a 3-D integrated display system that fully utilizes the scan data derived from routine PET imaging protocols. This system is applicable to all PET scan data and particularly helpful for the visual interpretation of the upper torso. In our experiments, the system provided anatomical hints without the help of any other imaging modalities and was an efficient tool for the diagnosis of PET studies. Our study suggests that routine WB-PET image interpretation should consist of both emission and transmission images to optimize the perception of data and improve the accuracy of lesion localization.     

基于K均值聚类的组织损伤等级判定研究

利用高强度聚焦超声(HIFU)对新鲜离体猪肉组织进行辐照,可对猪肉组织造成3个等级程度的损伤。从B超图像处理方向出发,提出一种基于K均值聚类并结合双参数的组织损伤等级判定方法。通过B超仪器实时获取HIFU辐照前后的134例猪肉组织图像,并做预处理获得焦斑区域的减影图像。再提取减影图像的灰度均值和小波系数均值,利用K均值聚类的方法对猪肉样本组织的损伤等级进行分类处理。实验结果表明,灰度均值参数能较好地区分第2、3等级程度的损伤,小波系数均值能较好地区分第1、2等级程度的损伤,而基于K均值聚类并结合双参数的分类方法结合了前两者的优点,在组织损伤等级的总辨识率上分别提高了5.23%和3.43%,更能准确地判定组织的损伤等级,便于临床医生客观地监控HIFU治疗过程,对提高HIFU疗效有实际意义。     

Review and Recent Development of Angle-Resolved Low-Coherence Interferometry for Detection of Precancerous Cells in Human Esophageal Epithelium

The combination of low-coherence interferometry with angle-resolved light scattering measurements has been shown to be a powerful method for determining the structure of cell nuclei within intact tissue samples. The nuclear morphology data have been used as a biomarker of neoplastic change in a wide range of settings. Here, we review the development of angle-resolved low-coherence interferometry (a/LCI) for assessing the health status of human esophageal epithelial tissues based on depth-resolved measurements of the morphology of cell nuclei. The design and implementation of clinical instrumentation are reviewed, and results from ex vivo human tissue measurements are presented to validate the capabilities of the technique. In addition to the review of earlier papers, new results are presented, which demonstrate the first application of a portable a/LCI system with a flexible endoscopic probe to assessing depth-resolved nuclear morphology in a clinical setting. High sensitivity for the detection of precancerous tissues is demonstrated.     

Picosecond electronic time-gated imaging of bones in tissues

Two-dimensional in vivo optical images of metacarpal bones of a human palm and in vitro images of turkey and chicken bones embedded in tissues were obtained in the near-infrared region using femtosecond pulse transillumination and picosecond electronic time-sliced detection technique. A small hole drilled in chicken bone and embedded in chicken breast tissue was imaged using early arriving light. Time-gated fluorescence images of an interior marrow region of a bone injected with a fluorescent dye were recorded. The techniques have potential for monitoring bone fracture, bone diseases such as, osteoporosis and arthritis, and diseases that originate in or affect bone marrow     

Sensitivity of laser opto-acoustic imaging in detection of smalldeeply embedded tumors

Current imaging modalities fail to detect small tumors in the breast. Opto-acoustic tomography is a novel technique for early cancer detection with promising diagnostic capability. The experimental limit of sensitivity and maximal depth of the laser opto-acoustic detection for small model tumors located within bulk phantom tissue were studied. Two phantoms with optical properties similar to that of breast tissue in the near infrared spectral range were used in these studies: turbid gelatin slabs with the thickness of 100 mm and chicken breast muscle slabs with the thickness of up to 80 mm. Gelatin spheres with enhanced absorption coefficient relative to the background absorption and liver tissue were used to simulate small tumors. The experiments demonstrated the capability of laser optoacoustic imaging to detect and localize phantom tumors with the diameter of 2 mm at a depth of up to 60 mm within the gelatin phantoms and 3×2×0.6-mm piece of liver tissue within 80-mm chicken breast tissue. Theoretical studies on sensitivity of opto-acoustic detection at various diameters, depths of location, and absorption coefficients of small tumors were performed using the experimental data. Our results suggest that the opto-acoustic imaging may occupy a significant niche in early detection of cancer in the breast and other organs     

Texture analysis of CT images

The present study has shown some promise in the use of texture for the extraction of diagnostic information from CT images. A number of features are obtained from abdominal CT scans of the liver using the spatial domain statistical texture analysis methods: SGLDM, GLRLM, and GLDM. This study investigated whether (a) the texture could be used to discriminate among the various tissue types that are inaccessible to human perception and, (b) if so, then what are the most useful feature parameters for such an application? The efficacies of the different methods were evaluated from the consistency of the computed values within a class and from their differences with other classes. The study has demonstrated the use of texture for tissue characterization of CT images. In particular, we have been successful in identifying the onset of disease in liver tissue, which can not be recognized even by trained human observers. Three useful features, namely entropy (H), local homogeneity (L) and grey level distribution (GLD), have been found effective for pattern recognition. The performance of these features has been compared on the basis of statistical significance. The results show that, except for L, (Direction 0°) all feature parameters perform equally well and detect early malignancy with a confidence level of above 99%-a finding that will not only help in automation, but more importantly, in early detection of malignancy in the liver     

Depth-resolved holography through turbid media usingphotorefraction

A technique based on photorefractive holography for imaging objects obscured by a scattering medium is presented. Using ultrashort pulse illumination, depth-resolved whole-field images of three dimensional objects embedded in scattering media have been obtained. Bulk photorefractive crystals and photorefractive multiple quantum-well (MQW) devices have been investigated as the hologram recording element. Images have been obtained through media of up to 16 scattering mean free paths with a system based on bulk rhodium-doped barium titanate (Rh:BaTiO₃). Using MQW devices, a real-time image acquisition (<0.4 ms) has been demonstrated when imaging through eight scattering mean free paths. The relative merits of photorefractive holography are discussed, including its potential to provide a higher dynamic range of detection than traditional photographic film based or electronic holography. This could be important for in vivo imaging through biological tissue     

An Alternative Approach to Analyze Fluorescence Lifetime Images as a Base for a Tumor Early Diagnosis System

Fluorescence lifetime imaging is a very promising imaging method for early detection of malignant tumors. It offers many advantages over conventional fluorescence methods, especially because the acquired signal does not rely on the fluorophore concentration in the tissue. As in all imaging method, the goal is to determine the exact location of a malignant tumor. However, since we are dealing with optical imaging, the inverse problem, i.e., extracting the tumor location coordinates is not an easy task to fulfill. In this paper, we describe an alternative method of interpreting the fluorescence lifetime image. The method extracts four features from each decay curve. We show that from these features one can extract the location of the tumor. The theoretical model is compared to the experimental results obtained from tissue-like phantoms.