Experimental determination of linear attenuation coefficient of normal,benign and malignant breast tissues

The linear attenuation coefficients for normal (adipose and glandular) and neoplastic (benign and malignant) breast tissues were measured using monoenergetic X-ray beams at the energy range of 8–30 keV, combining narrow beam geometry and high energy resolution obtained using a diffracted X-ray beam. The measured values are compared with predicted ones calculated according to the mixture rule and with previous experimental data showing a good agreement within the experimental uncertainties. Our results show that there is some degree of overlap among glandular, benign and malignant values. Nevertheless, significant differences (p < 0.05) exist in the linear attenuation coefficient between glandular and malignant at energies below 28 keV. Finally, a fitting procedure was applied to values for each group (mean and extremes values) in order to summarize all data.     

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.     

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.     

Neutron kerma coefficient: Reference tissue for tumours

Neutron kerma coefficients were calculated in different media: 4 malignant tumours, 5 normal tissues and 3 tissue substitute in the range 11 eV–29 MeV. The objective was to identify which is the material that better reproduces the behavior of these tumours and tissues. These tissues have clinical interest in interstitial brachytherapy applications with fast neutron source (Cf-252).The small differences of elemental composition among these tissues produce variation in the neutron kerma coefficients. The results show that the neutron kerma coefficients for malignant tumours are smaller than soft tissue from 6% to 9%. Also, the muscle is the tissue that best represents the dosimetric behavior for the tumours and tissues analyzed in this paper for neutron energies >1 keV, where this coefficients show minor variation.     

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。     

The determination of zinc,copper and iron oxidation state in invasive ductal carcinoma of breast tissue and normal surrounding tissue using XANES

X‐ray absorption near‐edge structure (XANES) spectroscopy was used to examine the oxidation state of Zn, Fe and Cu in 22 normal and 23 tumour regions spread over 30 formalin‐fixed, paraffin‐embedded tissue samples of human primary invasive breast cancer. A micro‐mapping analysis of the metal distribution in the tissue was performed prior to the XANES analysis to identify and localise the metals in the tumour and normal tissue regions. The aim of this study was to identify the oxidation state of Zn, Fe and Cu in normal and tumour tissues of the breast, in order to correlate the oxidation state of these elements with the carcinogenesis process. The position of the Zn K‐edge in normal and tumour tissues suggests that Zn exists in a bounded form. The shape of the Cu K‐edge XANES spectra and the first derivative spectra of normal and tumour tissues shows that a significant portion of the total copper is present as Cu (I). Nevertheless, the position of the edges in the normal and tumour tissue spectra does not exclude the presence of Cu (II). The shape and position of both normal and tumour regions of the tissue suggest that they contain mixtures of Fe (II) and Fe (III) ions with a significant fraction being Fe (III). However, normal tissue regions were found to have a higher fraction of Fe (II) compared to the tumour tissues. In order to estimate the best target for therapy, more information is required about the relative abundance of Zn, Fe and Cu binding proteins, their oxidation state and their localisation at the subcellular level. Copyright © 2010 John Wiley & Sons, Ltd.     

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。     

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.     

A generalized method of converting CT image to PET linear attenuation coefficient distribution in PET/CT imaging

The accuracy of attenuation correction in positron emission tomography scanners depends mainly on deriving the reliable 511-keV linear attenuation coefficient distribution in the scanned objects. In the PET/CT system, the linear attenu- ation distribution is usually obtained from the intensities of the CT image. However, the intensities of the CT image relate to the attenuation of photons in an energy range of 40 keV-140 keV. Before implementing PET attenuation correction, the intensities of CT images must be transformed into the PET 511-keV linear attenuation coefficients. However, the CT scan parameters can affect the effective energy of CT X-ray photons and thus affect the intensities of the CT image. Therefore, for PET/CT attenuation correction, it is crucial to determine the conversion curve with a given set of CT scan parameters and convert the CT image into a PET linear attenuation coefficient distribution. A generalized method is proposed for con- verting a CT image into a PET linear attenuation coefficient distribution. Instead of some parameter-dependent phantom calibration experiments, the conversion curve is calculated directly by employing the consistency conditions to yield the most consistent attenuation map with the measured PET data. The method is evaluated with phantom experiments and small animal experiments. In phantom studies, the estimated conversion curve fits the true attenuation coefficients accurately, and accurate PET attenuation maps are obtained by the estimated conversion curves and provide nearly the same correction results as the true attenuation map. In small animal studies, a more complicated attenuation distribution of the mouse is obtained successfully to remove the attenuation artifact and improve the PET image contrast efficiently.     

硅烷与硅的质量衰减截面实验测量

用高能质子激发单元素靶或化合物靶产生的特征X射线源,系统地测量了1.486—15.165千电子伏能区里硅烷和8.041—29.109千电子伏能区里硅元素的质量衰减系数.不仅在实验上验证了布喇格相加规则在气体化合物中的适用性,而且得到了1.4一6千电子伏能区里硅元素的质量衰减截面,从而填补了硅元素在该能区的数据空白.从实验测得的总截面中减去康普顿散射和漫散射截面,便得到硅元素的光电截面值,并与理论值进行了比较. 关键词：     

Optical biopsy of breast cancer tissue

In this paper, we report results of Fluorescence Emission Spectra (FES) and Stokes Shift Spectra (SSS) of 19 cancer tissue of invasive ductal carcinoma of different grades in comparison with normal breast tissues (obtained away from tumor regions). We were able to get distinct differences in the spectral features of normal and malignant tissues in terms of the ratios of concentrations of biomolecules like tryptophan, collagen and NADH. The sensitivity and specificity were in the range of 75%. What was all the more important was the parallelism in the spectral features of normal and malignant breast tissue pieces of above set of subjects. The objective of our research is to evolve one such protocol and the first step is the spectral characterization of in vitro optical analyses of excised tumor tissues.     

Raman spectroscopic analysis of breast cancer tissues: identifying differences between normal,invasive ductal carcinoma and ductal carcinoma in situ of the breast tissue

A relatively non‐destructive method employing Raman spectroscopy for the analysis of histopathological specimens is described. Raman spectroscopy has allowed qualitative analysis of the same specimen used for histopathological evaluation. Breast cancer tissues have been analysed to demonstrate the feasibility of the chemical changes taking place in the biological tissue, which can be identified precisely, and the results are reproducible. Raman analysis of tissue sections provides distinct spectra that can be used to distinguish between the nuclear grades of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Sixty cases of breast carcinoma including DCIS and IDC and seven cases of normal breast tissues were studied employing the Raman spectroscopic technique. This study reports for the first time spectral differences between DCIS grades. It is concluded that Raman spectroscopy can objectively distinguish between DCIS and IDC grades and is non‐destructive and reproducible. It should become possible in future to use Raman spectroscopy as an informative and quantitative method suitable for classification of grades and diagnosis of breast carcinoma. Copyright © 2007 John Wiley & Sons, Ltd.     

Measurement of the X‐ray mass attenuation coefficients of silver in the 5–20 keV range

The X‐ray mass attenuation coefficients of silver were measured in the energy range 5–20 keV with an accuracy of 0.01–0.2% on a relative scale down to 5.3 keV, and of 0.09–1.22% on an absolute scale to 5.0 keV. This analysis confirms that with careful choice of foil thickness and careful correction for systematics, especially including harmonic contents at lower energies, the X‐ray attenuation of high‐Z elements can be measured with high accuracy even at low X‐ray energies (<6 keV). This is the first high‐accuracy measurement of X‐ray mass attenuation coefficients of silver in the low energy range, indicating the possibility of obtaining high‐accuracy X‐ray absorption fine structure down to the L₁ edge (3.8 keV) of silver. Comparison of results reported here with an earlier data set optimized for higher energies confirms accuracy to within one standard error of each data set collected and analysed using the principles of the X‐ray extended‐range technique (XERT). Comparison with theory shows a slow divergence towards lower energies in this region away from absorption edges. The methodology developed can be used for the XAFS analysis of compounds and solutions to investigate structural features, bonding and coordination chemistry.     

A combined experimental and theoretical approach to determine X‐ray atomic fundamental quantities of tin

The knowledge of atomic fundamental parameters, such as the mass attenuation coefficients or fluorescence yields with low uncertainties, is of decisive importance in elemental quantification involving X‐ray fluorescence analysis techniques. For example, several databases giving the mass attenuation coefficients are accessible and frequently used within a large community of users. These compilations are most often in good agreement for photon energies in the hard X‐ray ranges. However, they significantly differ for low photon energies and around the absorption edges of the elements. In the case of the fluorescence yields, some authors made a review of measured values found in the literature. However, reliable measurements are not so many illustrating the inherent difficulties. Mass attenuation coefficients of tin were determined experimentally in the photon energy range from 100 eV to 35 keV by using monochromatized synchrotron radiation at SOLEIL (France). The fluorescence yields of the 3 L‐subshells of tin were also determined using a reflection geometry setup and the X‐ray fluorescence setup of Physikalisch‐Technische Bundesanstalt. The Coster–Kronig factors for the tin L‐shells were also experimentally determined. The application of high‐accuracy experimental techniques resulted in low uncertainty mass attenuation coefficients and L‐subshell fluorescence yields that are directly compared with existing databases and with updated relativistic configuration mixing Dirac–Fock calculations including Quantum electrodynamics (QED) corrections.     

Raman spectroscopic analysis differentiates between breast cancer cell lines

Breast cancer incident rates are increasing in women worldwide with the highest incidence rates reported in developing countries. Major breast cancer screening approaches like mammography, ultrasound, clinical breast examination (CBE) and magnetic resonance imaging (MRI) are currently used but have their own limitations. Optical spectroscopy has attained great attention from biomedical researchers in recent years due to its non‐invasive and non‐destructive detection approach. Chemometrics is one of the powerful tools used in spectroscopic research to enhance its sensitivity. Raman spectroscopy, a vibrational spectroscopic approach, has been used to explore the chemical fingerprints of different biological tissues including normal and malignant types. This approach was used to characterize and differentiate two breast cancer and one normal breast cell lines (MDA‐MB‐436, MCF‐7 and MCF‐10A) using dispersive Raman spectroscopy. Raman spectra of the cell lines have revealed that basic differences in the concentration of biochemical compounds such as lipids, nucleic acids and protein Raman peaks were found to differ in intensity, and principal component analysis (PCA) was able to identify variations that lead to accurate and reliable separation of the three cell lines. Linear discriminant analysis (LDA) model of three cell lines was predicted with 100% sensitivity and 91% specificity. We have shown that a combination of Raman spectroscopy and chemometrics are capable of differentiation between breast cancer cell lines. These variations may be useful in identifying new spectral markers to differentiate different subtypes of breast cancer although this needs confirmation in a larger panel of cell lines as well as clinical material. Copyright © 2015 John Wiley & Sons, Ltd.     

The use of X‐ray interaction data to differentiate malignant from normal breast tissue at surgical margins and biopsy analysis

X‐ray interaction data, including measuring bio‐metal levels and scattering characteristics, are being shown to be a possible discriminating variable in the classification of human tissues. However, a major concern when using X‐ray interaction data in breast cancer material is that the samples are rarely 100% tumour because of the invasive nature of the disease. The work reported here includes a methodology to help overcome this limitation as the experimental protocol includes mapping the data to histological analysis of the measured samples. This work has shown how important it is to relate the measured X‐ray parameters to the histology of the samples, particularly the clinical information that describes the percentage of tumour within each sample. Levels of K, Ca, Zn, Fe, Cu, Br and Rb were evaluated using X‐ray fluorescence and compared between tumour breast tissue and normal surrounding breast tissue. The coherent scattering properties of each sample were also examined using an angular dispersive X‐ray diffraction technique. Multivariate modelling using soft independent modelling of class analogy was used to classify samples kept out of the modelling procedure. A significant increase (p < 0.01) in the levels of Rb, Zn and K was found in the tumour samples. The levels of these elements show a correlation with the percentage of tumour reported to be present in a given sample. The results of classifying unknown tissue samples are presented using two‐class and three‐class models that help to reveal the importance of sample histology in studies involving breast cancers. Copyright © 2013 John Wiley & Sons, Ltd.     

Ultrasound beam shift induced by short-beaked common dolphin's(Delphinus delphis) tissues as an attenuating gradient material

To understand sound propagation and beam formation, the physical properties of soft tissues from the biosonar system of odontocetes should be explored. Based on the acoustic impedance distributions of biosonar systems, these processes have been examined via numerical simulations. In this study, the images of a short-beaked common dolphin(Delphinus delphis) were obtained via computed tomography. Then, the dolphin was dissected to extract tissue samples for additional examination. In addition to the speed of sound and density measurements, the acoustic attenuation coefficients of the biosonar system in the forehead were tested. The results revealed that the inner layer of the forehead was characterized using low sound speed, low density, and high attenuation. Acoustic fields and beam patterns were then evaluated by setting acoustic attenuation coefficients at different levels. Sounds propagating along the low-attenuation path had a lesser reduction in amplitude. Beam directivities in near and far fields suggested that changes in attenuation distribution would cause beam patterns to shift. These results indicated the complexity of a dolphin's sonar emission system and helped improve our understanding of sound energy attenuation via studies on the forehead of odontocetes.     

材料非线性衰减系数的二次谐波测量方法研究

采用有限幅值法测量材料在基波和非线性引起的二次谐波作用下的衰减系数:利用准线性下的KZK方程推导基波和二次谐波的声压分布,并提取波束修正系数;采用短纯音信号进行非线性实验,对检测得到的基波和二次谐波声压进行衍射修正处理,有效抑制衍射对衰减系数测量的不利影响,继而通过线性拟合的方法计算得到更精确的基波和二次谐波的衰减系数。以水为例进行实验,研究了实验测量所得衰减系数的频率依赖关系,结果表明在非线性条件下水的衰减系数与频率间存在较强的线性关系,而线性条件下衰减系数随频率呈现二次方增长的特性则不适用于非线性条件。该研究提出了准确测量非线性声波衰减系数的方法,为更有效地应用非线性超声检测提供理论依据。      

Raman spectroscopic diagnosis of breast cancers: evaluation of models

Breast cancer is the leading cancer affecting women. Conventional screening and diagnostic methods are shown to suffer from well‐described limitations. The aim of this study was to evaluate Raman spectroscopic models, which were developed earlier, by blinded tissue samples. We have recorded Raman spectra of 69 blinded tissue samples. In each sample, six or more spectra were recorded at different locations. Pretreated spectra were matched against normal, malignant and benign standard sets to obtain a match/mismatch status, which in turn was correlated with histopathology. Among 69 samples analyzed, 61 could be unambiguously diagnosed as 29 normal, 17 malignant and 15 benign, as their spectra matched with only one standard set and mismatched against the others. In the cases of the remaining tissue samples, matching them against pathological sets was the determining criteria. These samples were diagnosed as pathological since at least one of the spectra of these tissues had matched with pathological sets. Thus, we demonstrate a good correlation between histopathology and Raman spectroscopic diagnosis. Therefore, findings of the study further support the efficacy of Raman spectroscopic models that were developed by us. Prospectively, by developing models for as many pathological conditions as possible followed by rigorous validation, objective/unambiguous Raman spectroscopic diagnosis of breast pathologies can be realized. Copyright © 2008 John Wiley & Sons, Ltd.     

Use of the EUR LiB 15/5 data set for radiation shielding calculations in iron

Abstract

The shielding effect of an iron sphere assembly has been tested for a Pu-α-Be neutron source placed in the center of the shield assembly. Emergent neutron and gamma spectra were measured with a stilbene scintillation counter. Discrimination between neutrons and gammas was achieved by the pulse shape discrimination technique based on the zero crossing method. Calculations have been made using the one-dimensional transport code ANISN-Westinghouse version (ANISN-W) and the EUR LiB 15/5 cross section data set. The agreement between measurements and calculations indicates that the cross section set and the calculation model are suitable for studying the iron shielding experiments over the neutron energy range 1.35–10 MeV and the gamma energy range 0.3–6 MeV. Total macroscopic cross sections for fast neutrons, linear attenuation coefficients for gamma rays and half-value thicknesses for neutrons and gammas for the whole energy range and at different energies have been obtained.