Imaging of human breast tissue using polarization sensitive optical coherence tomography

We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.     

中红外光纤技术用于肿瘤在体原位诊断的研究

本文采用傅里叶变换红外光谱法与中红外光纤及ATR探头联用,首次实现了肿瘤组织的在体原位检测,即在有血液循环的活体组织中获得了具有很好信噪比的中红外光谱。实验结果表明在体原位的正常和肿瘤组织的光谱特征同我们先前液氮冰冻样品以及新鲜离体检测的结果是相似的,即符合液氮和新鲜离体样品研究中所得到的鉴别癌症与正常组织光谱变化规律,例如图1所列出的肠癌的原位在体光谱,与离体癌变组织光谱相似,这一创新结果表明中红外光纤-红外光谱仪联用可能发展成一种外科手术中无损、快速、准确的在体检测的方法。     

中红外光纤技术用于腮腺肿瘤诊断的研究

采用傅里叶变换红外光谱法与中红外光导纤维联用技术对１１例肿瘤，７例正常腮腺和１例舍格伦综合症的红外光谱进行了对比研究。结果发现正常腮腺和舍格伦综合症的红外光谱很相似，而与肿瘤的光谱存在着明显差别，同时也观察到良性与恶性肿瘤的光谱在若干波段处也有所不同．     

Diffuse optical measurement of blood flow in breast tumors

Blood flow contrast between tumor and normal tissues in patients with malignant and benign breast cancer was measured by diffuse optical correlation methods. The measurements were carried out with a hand-held optical probe that was manually scanned over the tumor-bearing breast. Increased blood flow was observed in tumor regions relative to healthy tissue, and control subjects did not exhibit significant blood flow heterogeneity. The measurements introduce a new optical contrast for diffuse optical mammography.     

人乳腺癌组织的显微拉曼光谱研究

研究了人类正常与癌变乳腺组织的显微拉曼光谱特性。与正常乳腺组织相比,癌变组织的核酸骨架磷酸离子vs(PO^-2)特征谱线由1082移到1097cm^-1、强度加强,位于817cm^-1的RNA主链vs(O-P-O)的谱线强度增加;蛋白质酰胺Ⅰ和酰胺Ⅲ两个特征谱带从1657,1273cm^-1分别位移到1662和1264cm^-1,其中1264cm^-1谱线的宽度和强度均增加,某些氨基酸残基的C—O谱线向高波数位移,色氨酸特征峰1368cm^-1在癌变组织中几乎观察不到;脂类特征谱线减少。上述谱线变化表明,癌变组织中核酸的相对含量增加、主链结构发生变化;蛋白质结构同时呈现α-螺旋、无规卷曲、卢．折叠以及β-回折4种构象特征,其分子间的氢键近乎断裂,蛋白质变得松散和无序,色氨酸残基的吲哚环呈现“暴露式”;脂类含量减少。研究表明,显微拉曼光谱可以为乳腺癌变的生化机理研究以及活体诊断提供有力的实验依据。     

衰减全反射红外光谱用于人乳腺癌组织的研究

通过对32例人乳腺良、恶性肿瘤的衰减全反射红外光谱的对比研究发现,它们之间存在明显而规律的光谱差异,反映了乳腺良、恶性病变组织中,蛋白质、核酸和脂类等生物大分子的构型与构象以及相对含量上的差别.研究表明:傅里叶变换红外光谱可以从分子水平上揭示良、恶性肿瘤的分子结构信息,极有潜力成为一种临床原位诊断肿瘤的新方法.     

Comparison of molecular images as defined by Raman spectra between normal mucosa and squamous cell carcinoma in the oral cavity

Raman spectroscopy has been effectively applied to clinically differentiate normal and cancerous mucosal tissues. Micro‐Raman spectroscopy provides a tool to better understand the molecular basis for the Raman clinical signal. The objective of the current study was to utilize micro‐Raman spectroscopy to define the molecular/spectral differences between normal and abnormal squamous cell carcinoma (SCC) in oral mucosa (in vitro). Understanding this may help in identifying unique spectra or may be useful for in vivo application of this technology. Micro‐Raman (confocal) spectroscopy was used to obtain molecular images of normal and SCC cells of human oral mucosa. Four fresh flashed‐frozen tumor and four matched normal tongue specimens were studied. The spectra covered a wavenumber range from 300 to 4000 cm⁻¹ with a spectral resolution of 8 cm⁻¹ and a spatial resolution of 1.0 µm. The cells were located within thin sections of tongue mucosa biopsies. The excitation wavelength of 515 nm was used. We were able to obtain Raman images with rich information about the spectroscopic and structural features within the cytoplasm, cell membrane, and cell nuclei. Significant spectral differences were observed between the Raman images of normal and malignant squamous cells. The heterogeneity of tumor cells within the abnormal tissue was also demonstrated. Spectral differences demonstrated between both tissue types have provided important information regarding the origins of specific signals within the cells of each tissue type. In our search for specific spectral biomarkers, we believe that a cell surface protein, greatly upregulated in SCC cells, was discovered at 1583 cm⁻¹. Copyright © 2010 John Wiley & Sons, Ltd.     

Measurement of linear attenuation coefficients of normal and malignant breast tissues using synchrotron radiation

The linear attenuation coefficients of normal and malignant breast tissues have been measured in the energy range of 8–18 keV using Indus‐2 synchrotron source. The intensity of the incident as well as transmitted X‐ray photons in normal and malignant breast tissues is measured with AXUV 100GX silicon photodiode detector. Using these intensities, the linear attenuation coefficients of normal and malignant breast tissues have been measured. The measured linear attenuation coefficient values of cancer tissue are found to be higher than that of normal tissue throughout measured energy region. Copyright © 2016 John Wiley & Sons, Ltd.     

直肠组织的高分辨魔角旋转核磁共振波谱研究

文章对6例直肠癌变及正常组织进行高分辨魔角旋转核磁共振波谱研究,结果显示直肠癌变和正常组织的核磁共振氢谱存在明显差异。这可以通过特征峰面积与0.88处峰积分面积的比值上的差异看出：（1）在化学位移0.75～1.55之间,癌组织各种氨基酸[缬氨酸,异亮氨酸,亮氨酸]与脂肪酸甲基的比值（I₂/I₁）,癌组织乳酸盐与脂肪酸甲基的比值(I₄/I₁)都明显增大。（2）在化学位移1.55～2.90之间,癌变组织中亮氨酸、赖氨酸、异亮氨酸与脂肪酸甲基的比值（I₇/I₁）, 谷氨酸、谷氨酰胺、缬氨酸、琥珀酸与脂肪酸甲基的比值((I₉+I₁₁)/I₁)、天冬氨酸与脂肪酸甲基的比值((I₁₂+I₁₄)/I₁)都较正常组织明显增大。（3）在化学位移2.90～3.49之间,癌变组织氨基酸与脂肪酸甲基的比值（I₁₅/I₁）、胆碱类与脂肪酸甲基的比值((I₁₆+I₁₇)/I₁)、牛磺酸与脂肪酸甲基的比值((I₁₈+I₁₉)/I₁)都较正常组织明显增大。（4）在化学位移3.49～4.50之间,其他代谢物与脂肪酸甲基的比值（I₂₀/I₁）,以及甘油基与脂肪酸甲基的比值（I₂₂/I₁）在癌变组织中都有增大的趋势。（5）化学位移4.5～10之间,癌变组织的核苷酸发生了变化,癌变组织的不饱和脂肪酸与脂肪酸甲基的比值（I₂₄/I₁）明显减小。（6）在化学位移-8～0.75之间,癌变组织的谱峰有减少的趋势。通过上述分析可知,通过癌变与正常组织代谢物NMR谱峰的差异,可以区分癌变和正常组织。说明核磁共振波谱技术可能发展成为一种诊断直肠癌的新方法。     

Contrast-enhanced microwave imaging of breast tumors: a computational study using 3-D realistic numerical phantoms

The detection of early-stage tumors in the breast by microwave imaging is challenged by both the moderate endogenous dielectric contrast between healthy and malignant glandular tissues and the spatial resolution available from illumination at microwave frequencies. The high endogenous dielectric contrast between adipose and fibroglandular tissue structures increases the difficulty of tumor detection due to the high dynamic range of the contrast function to be imaged and the low level of signal scattered from a tumor relative to the clutter scattered by normal tissue structures. Microwave inverse scattering techniques, used to estimate the complete spatial profile of the dielectric properties within the breast, have the potential to reconstruct both normal and cancerous tissue structures. However, the ill-posedness of the associated inverse problem often limits the frequency of microwave illumination to the UHF band within which early-stage cancers have sub-wavelength dimensions. In this computational study, we examine the reconstruction of small, compact tumors in three-dimensional numerical breast phantoms by a multiple-frequency inverse scattering solution. Computer models are also employed to investigate the use of exogenous contrast agents for enhancing tumor detection. Simulated array measurements are acquired before and after the introduction of the assumed contrast effects for two specific agents currently under consideration for breast imaging: microbubbles and carbon nanotubes. Differential images of the applied contrast demonstrate the potential of the approach for detecting the preferential uptake of contrast agents by malignant tissues.     

傅里叶变换中红外光谱法检测脑膜瘤的研究

采用傅里叶变换衰减全反射中红外光谱法检测了24例液氮冻存的脑膜瘤离体样品(其中良性肿瘤12例,有恶性倾向的肿瘤12例),对得到的红外光谱进行整理分析,发现不同类型脑膜瘤组织(如纤维型脑膜瘤和内皮型脑膜瘤)的红外光谱存在着差异,并且同一种类型的脑膜瘤组织,其恶性倾向的程度不同,他们的红外光谱也表现出较为明显的区别,因此,我们可以从各个特征吸收峰的峰位、峰形及峰强等信息的变化来区分脑膜瘤,并可以初步鉴别脑膜瘤的性质;研究结果发现,通过某些特征吸收峰(如1 160cm-1)峰位的变化来鉴别脑膜瘤的性质与病理诊断结果的符合率大于85%,说明傅里叶变换衰减全反射中红外光谱法有可能发展成为一种对样品无损伤、快速的脑肿瘤诊断新方法。     

采用氧合血红蛋白吸收带的漫反射光谱比率R（540）/R（575）检测浅表性膀胱癌

采用氧合血红蛋白在540和575 nm吸收带的漫反射光谱比率(R540/R575)对人浅表性膀胱癌进行了鉴别诊断,实验采用带积分球附件的分光光度计获取组织的漫反射光谱。结果表明:正常膀胱的粘膜/粘膜下层组织的漫反射光谱比率(R540/R575)在组织离体后2 h的平均值为111%,3 h的平均值为107%,4 h的平均值为104%,5 h的平均值为102%,而浅表性的膀胱癌的粘膜/粘膜下层组织的漫反射光谱比率(R540/R575)在组织离体后2 h的平均值为98.4%,3 h的平均值为95.5%,4 h的平均值为93.1%,5 h的平均值为91.6%,正常膀胱与浅表性膀胱癌的粘膜/粘膜下层组织在组织离体后2,3,4和5 h的漫反射光谱比率(R540/R575)均有显著性的差异(p<0.05),分别为12.6%,11.5%,10.9%和10.4%。这结论为快速、低成本、非入侵的浅表性膀胱癌的光活检提供了一种新的方法。     

Breast disease evaluation with fat-suppressed magnetic resonance imaging.

Thirty patients with a variety of pathologically confirmed malignant and benign pathologic lesions of the breast were evaluated with a spectrally selective fat suppression imaging technique to obtain fat-suppressed images of the breast. The technique, a selective partial inversion-recovery (SPIR) method, demonstrated the architectural relationship of malignant and benign tumors with respect to the normal water-containing elements of the breast. These relationships included signs of advanced malignant disease such as tissue retraction, invasive growth, and multicentricity, which appeared on the fat-suppressed images. Fat-suppressed imaging provided useful information for assessing the breasts of both pre- and postmenopausal women, especially in the latter group, where fatty involution of the breast is common. Microcysts, which are normally not visualized by conventional methods, were demonstrated and associated with patients having confirmed fibrocystic disease of the breast. As expected, the SPIR technique did not improve the ability to distinguish between tissues having similar T1 and T2 relaxation time values, such as malignant tumors and normal breast parenchymal tissues. The technique was able to demonstrate that the intense lipid signal, known to be responsible for obscuring the borders of water-fat interfaces and small tumors, could be eliminated in a variety of pathological settings.     

人体肿瘤组织的光谱识别

本文对人体胃肿瘤组织和正常组织的激光诱导荧光光谱进行了研究。结果表明：对于肿瘤组织，其光谱的强度和形状都不同于正常组织，对肿瘤组织区分的符合率为８９％，对正常组织区分的符合率为９１％。另外，还对病人的胃肿瘤组织进行了光谱实时测定。     

IR spectroscopic methods for diagnosis of oncological pathologies in human tissues (Review)

Modern problems in the diagnosis of oncological pathologies using spectroscopic methods of analysis are considered. Fourier-transform IR spectroscopy methods are illustrated by investigation of tissues of breast, thyroid gland, stomach, kidney, lung, and skin excised during surgical intervention. IR spectra of surgical material are compared with data of histological analysis. Spectra of proteins and lipids in malignant neoplasms differ from those in benign tumors and in tissues beyond the pathological focus. Differences in protein spectra are attributed to changes in the supramolecular structure due to cleavage of intramolecular C=OH–N hydrogen bonds. Differences in IR spectra of lipids in neoplasms, when compared with those in normal tissues, are caused by changes in the structure of side chains of fatty-acid radicals appearing in malignant tumors. Spectral signatures of malignant pathology are revealed.     

A double constrained robust capon beamforming based imaging method for early breast cancer detection

Ultra-wideband （UWB） microwave images are proposed for detecting small malignant breast tumors based on the large contrast of electric parameters between a malignant tumor and normal breast tissue. In this study, an antenna array composed of 9 antennas is applied to the detection. The double constrained robust capon beamforming （DCRCB） algorithm is used for reconstructing the breast image due to its better stability and high signal-to-interference-plus-noise ratio （SINR）. The successful detection of a tumor of 2 mm in diameter shown in the reconstruction demonstrates the robustness of the DCRCB beamforming algorithm. This study verifies the feasibility of detecting small breast tumors by using the DCRCB imaging algorithm.     

人体不同组织的拉曼光谱研究

测试了人体甲状腺、卵巢、输卵管、肺、子宫平滑肌、子宫颈等组织的拉曼光谱。结果显示,用氩离子激光514.5 nm激发,人体组织拉曼光谱的荧光背景强,在500～3 500 cm-1范围,肺和宫颈组织未显示特征带,甲状腺和子宫组织则显示了较多的带。在600～1800 cm-1范围,子宫、输卵管组织只显示了类胡萝卜素的拉曼带。正常甲状腺组织的光谱和甲状腺滤泡癌组织的光谱之间显示出明显差异,后者没有呈现1 585和1 634 cm-1特征带;正常肺组织与肺癌组织的拉曼光谱也有较大区别,肺癌组织的光谱强度比正常组织的低得多。拉曼光谱技术在临床医学诊断方面将会发挥重要的作用。     

胃粘膜组织共焦显微拉曼光谱分类研究

采用基于小波变换的光谱去噪和背景扣除预处理技术,对32例(其中:13例正常,19例癌变)胃粘膜组织拉曼光谱进行分析,克服了手动背景扣除的一些缺点,并观察到一些新的光谱特征。基于此,给出能对所有正常组织和癌变组织进行有效分类的特征量和判据。通过研究这些特征量与胃粘膜组织癌变发展阶段之间的定量关系,可望实现胃癌的早期诊断。     

乳腺组织的拉曼光谱线性模型研究

本研究甄选10个代表乳腺组织拉曼活性成分的基谱,在国内首次构建一种乳腺组织拉曼谱的线性回归模型。用2 000多个正常和非正常乳腺组织拉曼谱对该模型进行统计检验,模型显著性F检验的置信度全部为1,多元决定系数的平均值为0.95,表明线性模型假设成立、拟合效果良好。10个基谱代表脂肪、细胞质、细胞间质、DNA、血液、β-胡萝卜素、胆固醇等的拉曼谱,基谱的归一化拟合系数间接反映出这些成分的相对含量。用该模型拟合正常和肿瘤乳腺组织的拉曼宏观谱,病变前后细胞质和DNA的拟合系数增大、脂肪拟合系数减小,这反映出它们相对含量的增减,与已知的病理学结果一致。该研究有助于理解乳腺肿瘤组织的生化变化,并可能为分析该变化提供了有效手段。     

Determination of Ca,Fe, Cu and Zn and their correlations in breast cancer and normal adjacent tissues

An experimental procedure using monoenergetic Synchrotron Radiation x‐ray Fluorescence (SR‐XRF) method was studied, justified and applied to determine trace elements concentrations of normal and neoplastic human breast tissues in the same individual. Scattered radiation from each sample was used as an internal standard in x‐ray emission spectroscopy in order to construct calibration curves used to determine Ca, Fe, Cu and Zn concentrations in 52 breast tissue specimens (26 neoplastic and 26 adjacent normal tissues). This work showed that this experimental alternative is approximately matrix independent and also allows a reduction in instrumental variables. Our results showed, as expected, that Ca, Fe, Cu and Zn concentrations levels were significantly higher in neoplastic than in healthy breast tissues (all p < 0.001). It was also observed that Fe and Cu levels are correlated in malignant breast tissues as well as Ca and Zn levels, indicating that these elements' concentrations are related, in agreement with the hypothesis that there is a connection between Fe and Cu with both increased cellular activity and blood supply in the formation of neoplasies in breast tissue, and between Ca and Zn as regulators of neoplasies growth, since these metals are present in active matrix metalloproteinases (MMPs). Copyright © 2008 John Wiley & Sons, Ltd.