Optical spectroscopy vs. the surgical suite [cancer detection]

A novel non-invasive technique for detecting cancer and precancer offers a viable adjunct to biopsies. Here, we summarize the principles of optical spectroscopy and present some of the highlights obtained with the successful application of fluorescence and Raman spectroscopy for cancer and precancer detection     

An Image Model and Segmentation Algorithm for Reflectance Confocal Images of In Vivo Cervical Tissue

The automatic segmentation of nuclei in confocal reflectance images of cervical tissue is an important goal toward developing less expensive cervical precancer detection methods. Since in vivo confocal reflectance microscopy is an emerging technology for cancer detection, no prior work has been reported on the automatic segmentation of in vivo confocal reflectance images. However, prior work has shown that nuclear size and nuclear-to-cytoplasmic ratio can determine the presence or extent of cervical precancer. Thus, segmenting nuclei in confocal images will aid in cervical precancer detection. Successful segmentation of images of any type can be significantly enhanced by the introduction of accurate image models. To enable a deeper understanding of confocal reflectance microscopy images of cervical tissue, and to supply a basis for parameter selection in a classification algorithm, we have developed a model that accounts for the properties of the imaging system and of the tissues. Using our model in conjunction with a powerful image enhancement tool (anisotropic median-diffusion), appropriate statistical image modeling of spatial interactions (Gaussian Markov random fields), and a Bayesian framework for classification-segmentation, we have developed an effective algorithm for automatically segmenting nuclei in confocal images of cervical tissue. We have applied our algorithm to an extensive set of cervical images and have found that it detects 90% of hand-segmented nuclei with an average of 6 false positives per frame.     

宫腔镜对阴道超声发现子宫内膜异常的诊治价值

目的：研究阴道超声发现子宫内膜异常患者的宫腔镜诊治价值。方法：对827例经阴道超声检查发现子宫内膜异常的患者行官腔镜检查,并行诊断性刮宫或宫腔内病变电切,组织物送病检。结果：以病检结果为诊断标准,宫腔镜检查对子宫内膜息肉、子宫粘膜下肌瘤、正常子宫内膜、宫颈管息肉及子宫内膜癌的诊断符合率均明显高于阴道超声检查（P〈0．01）;宫腔镜检查对子宫内膜病变诊断的敏感性和特异性分别是95．23％和86,82％,而阴道超声检查对子宫内膜病变诊断的敏感性和特异性分别是83．99％和41．23％。结论：对阴道超声检查发现子宫内膜异常的患者应常规行宫腔镜检查并取组织活检,才能提高诊断符合率,减少误诊和漏诊。     

Ensembles of radial basis function networks for spectroscopicdetection of cervical precancer

The mortality related to cervical cancer can be substantially reduced through early detection and treatment. However, current detection techniques, such as Pap smear and colposcopy, fail to achieve a concurrently high sensitivity and specificity. In vivo fluorescence spectroscopy is a technique which quickly, noninvasively and quantitatively probes the biochemical and morphological changes that occur in precancerous tissue. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired from 361 cervical sites from 95 patients at 337-, 380-, and 460-nm excitation wavelengths. The multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs required to discriminate healthy tissue samples from precancerous tissue samples. The use of connectionist methods such as multilayered perceptrons, radial basis function (RBF) networks, and ensembles of such networks was investigated. RBF ensemble algorithms based on fluorescence spectra potentially provide automated and near real-time implementation of precancer detection in the hands of nonexperts. The results are more reliable, direct, and accurate than those achieved by either human experts or multivariate statistical algorithms     

585nm脉冲染料激光治疗皮肤血管性疾病所致的副作用

目的:观察585nm脉冲染料激光治疗血管性疾病所致的副作用。方法:分析500例经585nm脉冲染料激光治疗后的副反应。结果:500例接受治疗的患者中发生副反应者89例。其中色素沉着35例、色素减退12例、萎缩性瘢痕40例、增生性瘢痕2例。出现副反应与疾病种类、治疗能量无关,与治疗次数有关。结论:585nm脉冲染料激光治疗血管性疾病无连续激光治疗后所致的增生性瘢痕、持续性色素沉着等副作用,用于治疗血管性疾病是比较安全的。     

A novel optical imaging method for the early detection, quantitative grading, and mapping of cancerous and precancerous lesions of cervix

This paper describes a novel optical imaging method for the in vivo early detection, quantitative staging, and mapping of cervical cancer and precancer. A multispectral imaging system was developed, which is capable of performing time-resolved imaging spectroscopy. The system was used in order to assess quantitatively the alterations in the light scattering properties of the cervix, induced selectively and reversibly in cervical neoplasias, after the application of acetic acid solution. Spectral imaging and analysis of cervix show that the maximum contrast between acetic acid responsive and nonresponsive areas is obtained at 525 +/- 15 nm, which is further enhanced by cutting off the regular component of tissue reflection, with the aid of two linear cross polarizers. Successive snapshot imaging at this spectral band enables the quantitative assessment of the temporal alterations in the intensity of the backscattered light, in any spatial location of the examined area. Initial clinical trials show that optical contrast enhancement results in a notable improvement of the sensitivity in detecting incipient lesions. It was also shown that the measured temporal characteristics of the phenomenon contain specific information, which enables the differentiation between neoplastic and nonneoplastic lesions, as well as between neoplasias of different grade. The demonstrated improved sensitivity and specificity highlight the potential of the method in both clinical research and noninvasive diagnosis.     

Histochemical appearance of gamma-glutamyltranspeptidase in the rat liver after transplacental exposure to diethylnitrosamine and postnatal administration of phenobarbital

Phenobarbital administration during 7 weeks after partial hepatectomy is shown to be a sufficient promoting factor for induction of hyperplastic nodules in the rat liver initiated by the single DENA injection to pregnant rats. Histochemical distribution of gamma-glutamyltranspeptidase was a marker for identification of hyperplastic nodules.     

微波辐射对雌性小鼠的影响

本文介绍了以频率2450MHz的连续波，单位面积功率密度为30－34mW/cm2的微波辐射，对雌性小鼠组织中CAMP水平变化及胚胎发育和子宫内膜上皮细胞的影响，实验结果表明微波辐射后的小鼠脑组织中 AMP水平明显增高，并出现胎儿死亡和流产，通过扫描电镜的观察发现受照小鼠子宫内膜上皮细胞膜表面的微绒毛已全部消失和解体。     

Immunosuppressive activity of the blood serum of patients with cancer of the corpus uteri

In 40 patients with endometrial carcinoma of I-IV stage reaction of suppression of migration and adhesion of leukocytes (RSML and RSAL) in response to antigen prepared from the same tumour and in the presence of autoserum of blood of these patients, was studied. The index of antibody-forming cells (IAFC) and percentage of rosette-producing cells (RPC) in mice spleen after their infusion before immunization by sheep erythrocytes blood serum of the mentioned patients were also investigated. It was ascertained, that in all cases with using of autoserum of patients with endometrial carcinoma, especially on late stages, significant diminution of positive RSML and RSAL and decrease of IAFC and RPC take place. It was concluded that blood serum of patients with endometrial carcinoma gives evidence of immunosuppressive activity at late stages of the process.     

The modifying influence of adenosylcobalamin on the transplacental carcinogenic effect of N-nitroso-N-ethylurea in organ cultures of the kidneys of DBA/2 mice

Transplacental effect of cobalamin coenzyme, adenosylcobalamin (Adocbl), on the carcinogenic action of N-nitroso-N-ethylurea (ENU) was studied in culture of the mouse embryonic kidney tissue by histoautoradiography. Coenzyme methylmalonyl-CoA-mutase, Adocbl, injected into DBA/2 mice in the prenatal period did not stimulate the proliferative activity of epithelial cells of the embryonic kidney. The treatment with Adocbl did not intensify hyperplastic changes common for the early stages of carcinogenesis. The frequency of hyperplastic changes mainly of focal proliferation in kidney explants with the combined administration was considerably lower than with the isolated action of the carcinogen and amounted to 8.7% and 21.5%, respectively (P less than 0.001).     

高强度超声切除离体人子宫内膜癌的实验研究

目的：探讨高强度超声（High intensity ultrasound,HIU）切除离体人子宫内膜癌的有效性及可行性。方法：收集人子宫内膜癌标本15例,用频率7.5MHz,声强50W/cm2的超声进行辐照,每次辐照时间5秒至20秒,辐照后进行TTC染色及光镜下观察损伤范围及程度。结果：随着超声辐照时间的延长,损伤深度在逐渐增大,最大损伤深度可达到12mm,出现在单次辐照20秒;HIU辐照后的子宫内膜癌及其下部分肌层TTC染色不着色,辐照区内癌细胞发生凝固性坏死。结论：声强50W/cm2的HIU能有效损伤离体子宫内膜癌,超声对子宫内膜癌的损伤深度与辐照时间有关。     

大白鼠乳腺药物致癌的傅里叶红外光谱研究

运用傅里叶变换红外光谱技术对二甲基苯蒽(DMBA)药物致乳腺癌的大白鼠的正常、增生和癌变组织进行了检测.其分析结果表明:大白鼠乳腺正常与癌变组织的红外光谱存在着明显差异.某些特征谱带(如:1745cm-1,1378cm-1,1465cm-1,970cm-1)发生频移,谱带强度发生改变.探讨这些差异为医生进一步研究人乳腺癌变的机理提供了一些依据.     

绝经后阴道流血的宫腔镜诊断与激光治疗

探讨宫腔镜对绝经后阴道流血的病因诊断和激光治疗的安全性和有效性。方法:对139例绝经后阴道流血患者作宫腔镜检查,根据镜下诊断结果分别行诊断性刮宫和宫腔镜直视下Nd:YAG激光治疗。结果:以病理标准为金标准,则宫腔镜诊断子宫内膜癌及子宫肉瘤的敏感性为100％,特异性为100％。诊断子宫内膜息肉的敏感性为97.1％,特异性为100％。诊断粘膜下肌瘤的敏感性为100％,特异性为100％。诊断萎缩性子宫内膜炎的敏感性为100％,特异性为100％。宫腔镜诊断与病理学诊断具有高度的一致性。所有手术均顺利进行,平均手术时间3.0±10.2分钟(3～30分钟),患者对宫腔镜检查的耐受性较好,术中术后未发生严重并发症,术后B超随访1～3月宫腔内赘生物均消失。结论:宫腔镜检查对绝经后阴道流血的病因具有较高的诊断价值,宫腔镜下激光治疗宫腔内良性病变如子宫内膜息肉和子宫粘膜下肌瘤安全可行。     

The Role of Engineering Principles in the Medical Utilization of Electromagnetic Energies from kHz to Visible Light - Examples

The use of RF/microwaves in medicine has increased dramatically over the last ten years. RF and microwave therapies for the treatment of cancer in humans are well documented, and are presently used in many cancer centers. RF treatment for supra ventricular arrhythmias, and more recently for the treatment of ventricular tachycardia, are currently employed by major hospitals. RF/microwave are also used in human subjects for the treatment of benign prostatic hyperplasia (BPH). In the last few years, several otolaryngological centers have been utilizing RF to treat upper airway obstruction and to alleviate sleep apnea. Many centers also utilize RF for the treatment of gastro-esophageal disease (GERD), for pain management, and for endometrial ablation. Balloon microwave catheters for ablating solid tumors, then forming cavities in those tumors for the local delivery of therapeutic agents, are currently being investigated. New modalities are being studied, such as RF/microwave for the enhancement of drug absorption and microwave septic wound treatment, microwave imaging for the detection of breast cancer, epidemiological studies on the effects of rats’ exposure to microwave, as well as tissue regeneration using electromagnetic fields. In addition, technology is presently being developed that allows for permanent implantation of microwave wireless sensors in humans. A permanently implantable intra-cranial pressure monitor is one such application of the latter technology. Many more areas of research are currently being investigated, a partial list of which is summarized here.     

Microfluidic arrays for bioimprint of cancer cells

We report the development and characterization of a microfluidics-based bioimprint process using high-density microchannel arrays for cell-culture and polymer delivery. The tubeless PDMS arrays consist of multiple independent microchannels and allow for parallelized bioimprint via automated dispensing and passive pumping. Using the microchannels, a 400 nm thin test pattern was replicated into a methacrylate biopolymer to demonstrate process applicability. Bioimprints of cobalt chloride stimulated Ishikawa endometrial cancer cells exhibiting exocytosis-like pore structures were compared with controls using AFM to exemplify a process application. The devices can be used for high-throughput cell assays, cell developmental studies and the formation of phenotype-specific biomimetic scaffolds.     

基于个性化网络标志物的药物推荐方法研究

基于个性化标志物的药物推荐研究,有助于实现个性化用药及推动精准医疗的发展。该文利用基因表达谱数据及蛋白质网络信息,基于基因2维高斯分布方法筛选出个性化网络标志物。进而综合考虑靶基因的重要性和药物的副作用,提出了一种计算药物对个性化标志物影响权重的方法。将该方法应用于肺腺癌、肾透明细胞癌和子宫内膜癌数据集,通过启发式搜索方法,得到每个疾病样本重要药物推荐列表。结果表明,推荐的药物列表在同种癌症不同样本中既存在一致性,也表现出很大的差异性,如药物种类及药物排序差异,这说明个性化药物在疾病治疗中的重要性及必要性。通过从药物数据库中搜索药物组合对疾病治疗的影响作用表明,该文方法筛选得到的许多药物组合对具体疾病治疗具有积极影响,这进一步证明该文基于个性化网络标志物的药物推荐方法的准确性。该文的研究将有效促进精准化医疗的发展。     

Uterus-Derived Decellularized Extracellular Matrix-Mediated Endometrial Regeneration and Fertility Enhancement

Tissue-specific decellularized extracellular matrix recapitulates the complexity of natural ECMs, creating an organ-specific microenvironment based on its intrinsic characteristics. Here, hydrogels containing uterus-derived decellularized extracellular matrix (UdECMs) from the endometrium-specific layer or the entire uterus are developed. UdECMs serve as effective organ-specific biomaterials, displaying that intrauterine UdECM administration induces endometrial regeneration and fertility enhancement. Moreover, UdECM administration alters the profile of natural killer cell subpopulations to exhibit more mature and less cytotoxic features, providing a favorable uterine environment for successful implantation and decidualization. Interestingly, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 as key regulatory factors that contribute to UdECM-mediated endometrial regeneration are discovered. Furthermore, ex vivo culture of human uterine tissues reveals that UdECMs of different origins exhibit distinct therapeutic effects based on the endometrial conditions of patients, suggesting their uses as a therapeutic intervention providing personalized regenerative medicine for infertile patients with a poor uterine environment.     

Injectable 3D-Printed Porous Scaffolds for Adipose Stem Cell Delivery and Endometrial Regeneration

Stem-cell-based therapeutic strategies are promising in the clinical treatment of intrauterine adhesions (IUAs), while endometrial regeneration still hardly restores the structure and function of the endometrium because of the inadequate microenvironment for the grafted stem cells and subsequent limited therapeutic efficiency. Herein, an injectable porous hydrogel scaffold (PH scaffold) with customizable shapes is presented by using a microfluidic-based 3D printing technique for adipose-derived stem cells (ADSCs) delivery to enhance endometrial regeneration. These scaffolds display a controllable interconnected porous structure, which not only facilitates the encapsulation of ADSCs within the scaffold but also supports the recovery to their original shapes after injection. Furthermore, the cell viability of the laden ADSCs is well-maintained post-injection, exhibiting promotive effects on cell migration, proliferation, and tube formation. Based on these features, an ADSCs-laden PH scaffold with a hollow endometrium-mimicking morphology is designed and in situ injected into the damaged endometrium in rats of IUAs. These results show that the ADSCs-laden PH scaffolds can enhance functional endometrial regeneration by suppressing the inflammatory response, promoting cell proliferation, and improving vascularization. Thus, it is believed that such unique 3D-printed porous scaffolds are promising candidates for cell delivery, which also provides a minimally-invasive and effective strategy for endometrial regeneration.     

Performance estimation of diagnostic tests for cervical precancer based on fluorescence spectroscopy: effects of tissue type, sample size, population, and signal-to-noise ratio

Fluorescence spectroscopy may provide a cost-effective tool to improve precancer detection. We describe a method to estimate the diagnostic performance of classifiers based on optical spectra, and to explore the sensitivity of these estimations to factors affecting spectrometer cost. Fluorescence spectra were obtained at three excitation wavelengths in 92 patients with an abnormal Papanicolaou smear and 51 patients with no history of an abnormal smear. Bayesian classification rules were developed and evaluated at multiple misclassification costs. We explored the sensitivity of classifier performance to variations in tissue type, sample size, tested population, signal to noise ratio (SNR), and number of excitation and emission wavelengths. Sensitivity and specificity could be evaluated within +/- 7%. Minimal decrease in diagnostic performance is observed as SNR is reduced to 15, the number of excitation-emission wavelength combinations is reduced to 15 or the number of excitation wavelengths is reduced to one. Diagnostic performance is compromised when ultraviolet excitation is not included. Significant spectrometer cost reduction is possible without compromising diagnostic ability. Decision-analytic methods can be used to rate designs based on incremental cost-effectiveness.     

利用球-旋转椭球模型研究上皮组织散射特性

组织模型在组织成像机理及光学疾病诊断技术的研究和改进中发挥着重要作用。然而上皮组织细胞中不仅包含球形散射体,往往还包含椭球形散射体。目前对包含椭球散射体的上皮组织模型的研究还鲜有报道。建立了上皮组织的球-旋转椭球散射模型,利用Monte Carlo算法仿真分析了模型参数的变化对前向散射光强分布及穆勒矩阵极分解参量的影响。结果表明,旋转椭球散射系数、体积和长短轴比的增大均会导致组织模型的去偏作用增强,其中散射系数对去偏的影响最显著;各向异性分布的旋转椭球具有相位延迟作用,且相位延迟随椭球散射系数及长短轴比的增大而增大,随椭球体积的增大而减小。该研究对早期癌变诊断技术的研究具有一定指导意义。