Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging

We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.     

乳腺癌的X线表现和分型

目的分析139例乳腺癌影像表现和分型,旨在提高对本病诊断的准确性.方法回顾性观察139例经全数字化平板乳腺摄影(FFDM)检查、手术及病理证实的乳腺癌的X线表现和分型.结果 139例乳腺癌中肿块结节型88例,单纯钙化型39例,局部结构紊乱型11例,导管阻塞型1例.肿块结节型中检测到小于1 cm的微小癌和小癌16例.除导管阻塞型乳腺癌外其他各类型中均有钙化出现, 钙化总显示率为80.57%,单纯钙化型乳腺癌的钙化分布、数目、密度和形态有别于其他类型.临床扪及包块的乳腺癌见于肿块结节型和局部结构紊乱型,未扪及包块乳腺癌仅见单纯钙化型和导管阻塞型.结论乳腺癌不同类型有其特有X线表现,FFDM对乳腺癌的影像表现显示清晰,对小病灶探测率高,显示小于0.1 mm的微小钙化等有利于乳腺癌的诊断和分型.     

基于分形特征序列的乳腺X线图像分类方法

目的表征乳腺图像中肿块部分纹理特征,通过纹理分析实现乳腺图像中肿块部分与正常腺体部分的分类。方法应用分形特征值表征乳腺图像纹理特征,利用多级分形特征提取法将乳腺图像分解成一系列细节图像,提取出多个分形特征值;利用分类精度、ROC曲线及曲线下面积(AUC)进行特征选择构建分形特征序列,最后应用支持向量机(SVM)方法进行分类。结果对60幅图像的可疑病变区域进行分形特征序列提取分析,SVM交叉验证分类精度达84.50%。结论基于分形维数的乳腺图像分类方法不仅能对肿块与正常腺体进行图像分类,还可有效表征乳腺图像的纹理信息,有助于提高乳腺肿块诊断的准确率。     

Low back pain: state of art

Diagnosis of low back pain (LBP) is made by exclusion of secondary spinal diseases, identifiable in the first month of pain (acute LBP – ALBP) through the so-called “reds flags”, and only if pain persists over 4 weeks (sub-acute LBP – SALBP) using diagnostic exams. LBP classification is actually based on the localization (LBP and sciatica) and duration of pain: ALBP, SALBP, and chronic (CLBP) when it lasts over 6 months. ALBP prognosis is very good because it is auto-resolving in most of the cases; on the contrary, CLBP has a bad prognosis (very low rate of resolution even with treatment). The stage of most interest is SALBP, in which it is possible to identify risk factors (“yellow flags”) of chronicity and to avoid the development of a series of vicious cycles that, according to a bio-psycho-social model of illness, can lead the patient to CLBP. In CLBP it's mandatory to make the patient able to manage his problem, so to increase his quality of life and decrease disability and pain. Treatment approach to ALBP consist of reassuring the patient and providing accurate preventive information, recommendations to remain as active as possible, to avoid bed rest. In SALBP and CLBP, a multidisciplinary team rehabilitation approach is the most important one, combining educational, cognitive-behavioural and physical exercise treatments according to the individual needs. Pain killer therapies can be proposed, but bearing in mind their short-term effects.     

乳腺腺病与乳腺导管癌的MRI鉴别诊断及病理对照研究

目的探讨乳腺腺病与乳腺导管癌的动态增强磁共振成像(dynamic contrast enhanced magnetic resonance imaging,DCE-MRI)、扩散加权成像(diffusion weight imaging,DWI)鉴别诊断特征,及其与病理表现相关性。材料与方法回顾性收集分析经病理证实的105例乳腺腺病、78例乳腺导管癌患者的MRI资料。所有患者术前均行乳腺DWI、DCE-MRI扫描。分析两组患者的MRI表现特点及其与病理表现的相关性,采用χ~2检验比较两组的临床资料、病灶位置、大小、形态、时间-信号强度曲线(time-signal intensity curve,TIC)及强化方式等特征;采用单因素方差分析比较两组患者的表观扩散系数(apparent diffusion coefficient,ADC)值。结果 105例乳腺腺病呈肿块样强化(mass-like enhancement,MLE)50例,非肿块样强化(nonmass-like enhancement,NMLE)55例;78例乳腺导管癌中MLE52例,NMLE26例。腺病组MLE病变形态大多形态规则(37/50,74%)、边缘清晰(35/50,70%),两组MLE病变的强化方式、TIC类型的差异均有统计学意义(χ~2值分别为14.169和13.955,P均0.01);两组MLE病变的ADC值分别为(131.63±21.8)×10~(-3) mm~2/s、(104.21±18.54)×10~(-3) mm~2/s,两者的差异有明显统计学意义(F=52.167,P0.01);两组NMLE病变强化方式多样,其差异有统计学意义(χ~2值分别为4.478,P均0.05)。两组NMLE病变的ADC值分别为(136.23±14.8)×10~(-3) mm~2/s、(102.51±16.44)×10~(-3) mm~2/s,两者的差异有明显统计学意义(F=49.167,P0.01)。结论乳腺腺病的MRI表现具有一定的特征性,MLE病变多呈良性病变特点,NMLE病变形态与恶性病变相似,动态增强结合DWI有助于其与乳腺导管癌的鉴别诊断;乳腺腺病的间质纤维化可能是造成恶性征象出现的原因。     

Exercise therapy for low back pain: a small-scale exploratory survey of current physiotherapy practice in the Republic of Ireland acute hospital setting

A small-scale exploratory cross-sectional survey investigated the current use of a range of exercise therapy approaches for low back pain (LBP) by outpatient physiotherapists in the acute hospital setting in the Republic of Ireland, where the majority of publicly funded treatment is delivered. Of the 120 postal questionnaires distributed to 24 physiotherapy departments, 87 were returned (72.5% response rate). The results showed specific spinal stabilization exercises were the most popular exercise therapy for acute (39%; n = 35) and chronic (51%; n = 48) LBP, followed by the McKenzie approach (acute LBP (ALBP) 35.6%; n = 32: chronic LBP (CLBP) 17%; n = 16), and abdominal exercise (ALBP 11.1%; n = 10: CLBP 9.6%; n = 9). The most popular forms of exercise therapy used by outpatient physiotherapists in acute hospital settings in Ireland lack support from evidence-based clinical guidelines, and further large-scale high quality randomized controlled trials of these approaches are warranted. Further research should also establish the use of exercise therapy and attitudes to clinical guidelines of physiotherapists in other countries and healthcare settings.     

Sonographic appearance of ductal carcinoma in situ diagnosed with ultrasonographically guided large core needle biopsy: correlation with mammographic and pathologic findings.

The purpose of this study was to evaluate sonographic features of ductal carcinoma in situ diagnosed percutaneously at ultrasonographically guided large core needle biopsy. Of 619 biopsies, 203 breast carcinomas were diagnosed, of which nine were pure ductal carcinoma in situ. All ductal carcinoma in situ lesions appeared sonographically as hypoechoic masses without a pseudocapsule. Grade 1 lesions (n = 2; mean size, 9.5 mm), grade 2 lesions (n = 4; mean size, 18 mm) and grade 3 lesions (n = 3; mean size, 32 mm) had means of 0, 1, and 5 malignant sonographic features, respectively. Ductal carcinoma in situ appeared mammographically as a mass, with two of four grade 2 lesions and all grade 3 lesions demonstrating suspicious microcalcifications. One grade 3 ductal carcinoma in situ was spiculated. In conclusion, ductal carcinoma in situ lesions tended to show more malignant mammographic and sonographic features as histologic grade and size increased.     

乳腺导管内增生性病变中Survivin的表达及意义

目的 探讨乳腺良性、恶性病变中Survivin的表达及临床病理特征的关系。 方 法应用免疫组织化学SP法检测23例癌旁正常乳腺组织、28 例乳腺增生组织（其中20 例普通型增生,8 例非典型增生）、8 例导管内癌、98 例浸润性癌组织Survivin 的表达。 结果非典型增生上皮和导管内癌的Survivin水平高于正常乳腺腺上皮（P＜0.01）;浸润性导管癌组织中的Survivin表达率为49.0%高于正常乳腺腺上皮（P＜0.05）;与增生的乳腺组织和导管内癌组间差异无显著性。浸润性癌中的Survivin表达与分级、腋淋巴结转移、TNM分期有关,与病人的年龄、肿瘤大小、ER、PR无关。 结论Survivin在乳腺良恶性病变不同表达,提示其在乳腺癌发生、发展中起重要作用,可以为乳腺癌的诊断、治疗和预后提供依据。      

Rapid pseudo-H&E imaging using a fluorescence-inbuilt optical coherence microscopic imaging system

A technique using Linnik-based optical coherence microscopy (OCM), with built-in fluorescence microscopy (FM), is demonstrated here to describe cellular-level morphology for fresh porcine and biobank tissue specimens. The proposed method utilizes color-coding to generate digital pseudo-H&E (p-H&E) images. Using the same camera, colocalized FM images are merged with corresponding morphological OCM images using a 24-bit RGB composition process to generate position-matched p-H&E images. From receipt of dissected fresh tissue piece to generation of stitched images, the total processing time is <15 min for a 1-cm² specimen, which is on average two times faster than frozen-section H&E process for fatty or water-rich fresh tissue specimens. This technique was successfully used to scan human and animal fresh tissue pieces, demonstrating its applicability for both biobank and veterinary purposes. We provide an in-depth comparison between p-H&E and human frozen-section H&E images acquired from the same metastatic sentinel lymph node slice (∼10 µm thick), and show the differences, like elastic fibers of a tiny blood vessel and cytoplasm of tumor cells. This optical sectioning technique provides histopathologists with a convenient assessment method that outputs large-field H&E-like images of fresh tissue pieces without requiring any physical embedment.     

Ultrasound examination is useful for prediction of histologic type in invasive ductal carcinoma of the breast

The aim of this study was to estimate the histologic type of invasive ductal carcinoma of the breast according to the ultrasound (US) criteria and to identify the high-risk patients for lymph node metastases. An acceptable preoperative diagnosis of lymph node metastasis is essential when performing the reduction of lymphadenectomy. The positive relationship between histology and prognosis has been reported in breast cancer. However, few reports have examined the relationship between preoperative US findings and histology. Ultrasound examination was performed in 252 patients with invasive ductal carcinoma (91 papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for nodal metastasis were analyzed in clinicopathological findings. After nine criteria were defined based on US findings, all tumors were classified into US histologic type. According to the multivariate analysis, lymph node metastases was significantly associated with tumor size (p < 0.001), histology (p < 0.001) and age (p = 0.038). Histology was an important risk factor for nodal metastasis, especially in scirrhous carcinoma. When comparing the US classification and histology, the accuracy rate of US for papillotubular, solid-tubular and scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of depth-to-width, boundary echo and attenuation of the back echo was important. It is important to preoperatively estimate the histologic type by tumor property using US. Our US classifications may be useful to pick up high-risk patients for nodal metastasis in invasive breast cancer.     

Comparative study of the influence of imaging resolution on linear retardance parameters derived from the Mueller matrix

Polarization imaging techniques are emerging tools to provide quantitative information of anisotropic structures, such as the density and orientation distribution of fibers in tissue samples. Recently, it is found that when using Mueller matrix polarimetry to obtain the structural features of tissue samples, some information can be revealed by relatively low-resolution polarization parameter images. Thus, to analyze what kinds of anisotropic optical and structural information contained in high-resolution polarization images are preserved in low-resolution ones, here we carry out a comparative study of the influence of imaging resolution on the Mueller matrix derived linear retardance parameters. We measure the microscopic Mueller matrix of human healthy breast duct tissues and ductal carcinoma in situ (DCIS) tissues, which have distinct typical fibrous structures, using objectives with different numerical aperture. Then we quantitatively compare a group of image texture feature parameters of the linear retardance parameters images under high and low imaging resolutions. The results demonstrate that the fibers density information contained in the texture features of linear retardance δ parameter image are preserved well with the decline of imaging resolution. While for the azimuthal orientation parameter θ which closely related to the spatial location, we still need high imaging resolution to obtain quantitative structural information. The study provides an important criterion to decide which information of fibrous structures can be extracted accurately using transmission Mueller matrix microscope with low numerical aperture objectives.     

Watershed segmentation for breast tumor in 2-D sonography

Automatic contouring for breast tumors using medical ultrasound (US) imaging may assist physicians without relevant experience, in making correct diagnoses. This study integrates the advantages of neural network (NN) classification and morphological watershed segmentation to extract precise contours of breast tumors from US images. Textural analysis is employed to yield inputs to the NN to classify ultrasonic images. Autocovariance coefficients specify texture features to classify breasts imaged by US using a self-organizing map (SOM). After the texture features in sonography have been classified, an adaptive preprocessing procedure is selected by SOM output. Finally, watershed transformation automatically determines the contours of the tumor. In this study, the proposed method was trained and tested using images from 60 patients. The results of computer simulations reveal that the proposed method always identified similar contours and regions-of-interest (ROIs) to those obtained by manual contouring (by an experienced physician) of the breast tumor in ultrasonic images. As US imaging becomes more widespread, a functional automatic contouring method is essential and its clinical application is becoming urgent. Such a method provides robust and fast automatic contouring of US images. This study is not to emphasize that the automatic contouring technique is superior to the one undertaken manually. Both automatic and manual contours did not, after all, necessarily result in the same factual pathologic border. In computer-aided diagnosis (CAD) applications, automatic segmentation can save much of the time required to sketch a precise contour, with very high stability.     

MRI影像组学术前预测乳腺浸润性导管癌Ki-67表达

目的 观察基于MR弥散加权成像(DWI)及表观弥散系数(ADC)图影像组学术前预测乳腺浸润性导管癌Ki-67表达的价值.方法 回顾性分析212例经组织穿刺活检或手术病理证实的乳腺浸润性导管癌患者的乳腺DWI,以分层抽样方法按7∶3比例将其分为训练集(n=148)和验证集(n=64).分别基于DWI、ADC图及DWI+ ...     

乳腺粘液癌超声特征及免疫组化指标

  目的  分析乳腺粘液癌的超声图像特征及免疫组化指标,提高诊断粘液癌的准确性。  方法  回顾性分析56例乳腺癌肿块的超声特征（肿块最大径、纵横比、高回声晕、转移情况、弹性评分等）、剪切波速度（SWV_max、SWV_ratio、SWV_mean）及免疫组化检测结果（雌激素受体、孕激素受体、人表皮生长因子受体2、Ki-67）,将粘液癌患者作为实验组（n=24）,将浸润性导管癌患者作为对照组（n=32）,对比两组超声特征及免疫组化指标表达的差异性,并对超声特征及免疫组化指标进行相关性分析。  结果  与浸润性导管癌相比,粘液癌肿块多表现为边界清晰、有高回声晕、后方回声增强、弹性评分 < 4分且BI-RADS分类 < 4b类（χ2=4.419、5.171、6.162、4.743、14.000,P < 0.05）,SWV_max及雌激素受体、人表皮生长因子受体2的阳性率在两组中的差异具有统计学意义（t=- 2.069,χ2=4.371、4.051,P < 0.05）。  结论  乳腺粘液癌超声特征及免疫组化指标的表达与浸润性导管癌相比具有一定的差异,可为超声诊断乳腺癌类型及治疗方案的选择提供参考。      

Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging

Conventional histology with light microscopy is essential in the diagnosis of most liver diseases. Recently, a concept of real-time histology with optical biopsy has been advocated. In this study, live mice livers (normal, with fibrosis, steatosis, hepatocellular carcinoma and ischemia-reperfusion injury) were imaged by MPM-FLIM for stain-free real-time histology. The acquired MPM-FLIM images were compared with conventional histological images. MPM-FLIM imaged subsurface cellular and subcellular histopathological hallmarks of live liver in mice models at high resolution. Additional information such as distribution of stellate cell associated autofluorescence and fluorescence lifetime changes was also gathered by MPM-FLIM simultaneously, which cannot be obtained from conventional histology. MPM-FLIM could simultaneously image and quantify the cellular morphology and microenvironment of live livers without conventional biopsy or fluorescent dyes. We anticipate that in the near future MPM-FLIM will be evaluated from bench to bedside, leading to real-time histology and dynamic monitoring of human liver diseases.OCIS codes: (180.4315) Nonlinear microscopy, (170.3880) Medical and biological imaging, (170.6510) Spectroscopy, tissue diagnostics     

Relationship between ultrasound texture classification images and histology of atherosclerotic plaque

Structure and content of atherosclerotic plaque varies between patients and may be indicative of their risk for embolisation. This study aimed to construct parametric images of B-scan texture and assess their potential for predicting plaque morphology. Sequential transverse in vitro scans of 10 carotid plaques, excised during endarterectomy, were compared with macrohistology maps of plaque content. Multidiscriminant analysis combined the output of 157 statistical and textural algorithms into five separate texture classes, displayed as ultrasound (US) texture classification images (UTCI). Visual comparison between corresponding UTCI and histology maps found the five texture classes matched with the location of fibrin, elastin, calcium, haemorrhage or lipid. However, histology preparation removes calcium and lipid and, so, can affect the structural integrity of atherosclerotic plaques. Soft tissue regions smaller than the UTCI kernel, (0.87 mm × 0.85 mm × 3.9 mm), such as blood clots, are also difficult to detect by UTCI. These factors demonstrate limitations in the use of histology as a “gold standard” for US tissue characterisation.     

Computer-aided diagnosis for the classification of breast masses in automated whole breast ultrasound images

New automated whole breast ultrasound (ABUS) machines have recently been developed and the ultrasound (US) volume dataset of the whole breast can be acquired in a standard manner. The purpose of this study was to develop a novel computer-aided diagnosis system for classification of breast masses in ABUS images. One hundred forty-seven cases (76 benign and 71 malignant breast masses) were obtained by a commercially available ABUS system. Because the distance of neighboring slices in ABUS images is fixed and small, these continuous slices were used for reconstruction as three-dimensional (3-D) US images. The 3-D tumor contour was segmented using the level-set segmentation method. Then, the 3-D features, including the texture, shape and ellipsoid fitting were extracted based on the segmented 3-D tumor contour to classify benign and malignant tumors based on the logistic regression model. The Student’s t test, Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. From the Az values of ROC curves, the shape features (0.9138) are better than the texture features (0.8603) and the ellipsoid fitting features (0.8496) for classification. The difference was significant between shape and ellipsoid fitting features (p = 0.0382). However, combination of ellipsoid fitting features and shape features can achieve a best performance with accuracy of 85.0% (125/147), sensitivity of 84.5% (60/71), specificity of 85.5% (65/76) and the area under the ROC curve Az of 0.9466. The results showed that ABUS images could be used for computer-aided feature extraction and classification of breast tumors. (E-mail: rfchang@csie.ntu.edu.tw)     

乳腺癌中c-erbB-2与HIF-1基因表达相关性研究

目的探讨c-erbB-2与HIF 1基因过表达在乳腺癌进程中的内在相关性,寻找检测癌浸润转移的联合分子指标。方法乳腺癌组织芯片中200例样品经原位杂交检测c-erbB-2和HIF-1 mRNA表达,87例样本经荧光原位杂交检测c-erbB-2基因扩增。结果①185例乳腺癌样本中c-erbB-2和HIF 1基因有不同程度的共表达,浸润型的非特殊导管癌I级中c-erbB-2与HIF-1的表达2级以上的样本比率都超过70%。非特殊导管癌Ⅰ、Ⅱ级中c-erbB-2表达的样本比率高于HIF-1。c-erbB-2和HIF 1基因在非特殊导管癌Ⅰ、Ⅱ级中两者表达存在显著差异(P=0.003,P=0.036),小叶癌中两者表达无显著差异(P=0.607)。②浸润型的非特殊性导管癌Ⅰ级中c-erbB-2基因扩增与表达存在显著差异(P=0.046),非特殊性导管癌Ⅱ级与小叶癌中差异不显著(P=0.496m,P=0.878)。结论在乳腺癌浸润转移程度高时,c-erbB-2与HIF-1 mRNA的过表达一致,c-erbB-2扩增与其过表达一致,两者可成为乳腺癌浸润转移的联合分子指标。     

Frequency-dependent attenuation in breast tissue characterization

The aim of this study is to establish whether an index derived from the slope of the frequency-dependent ultrasonic attenuation can provide quantitative information on normal and pathological breast tissue. Ultrasonic measurements were performed by using pulsed transmitted ultrasound in the frequency range 2-8 MHz. Thirty-three specimens were selected for their probable pathologic classification, by macroscopic observation, before ultrasonic study, and subsequently histologically classified. Ultrasonic results suggest the possibility that the examined specimens fall into four groups: (1) fat, fibroadenoma, giant fibroadenoma, infiltrating ductal carcinoma, medullary carcinoma; (2) infiltrating lobular carcinoma, tubular carcinoma, scirrhous carcinoma; (3) fibrosis; (4) fibrofatty tissue, fibrocystic disease. Correlative morphological studies indicate that the employed index can classify breast tissues on the basis of their cellular and fibrous composition and the inhomogeneity of their structure.     

高频钼靶对早期乳腺癌的诊断分析

目的：探讨早期乳腺癌高频钼靶X线的征象。方法：采用高频钼靶常规乳腺摄影,对经手术及病理证实的25例早期乳腺癌的X线表现资料进行回顾性分析。结果：其中导管原位癌及导管原位伴早浸14例,浸润性导管癌8例,小叶原位癌及小叶癌早浸3例。其X线影像表现为：单纯簇状钙化者8例占32%（8/25）,单纯结节5例占20%（5/25）,星芒征5例占20%（5/25）,结节合并钙化4例占16%（4/25）,团片状密度增高影3例12%（3/25）。结论：高频钼靶可以清晰地显示早期乳腺癌的病变结构,是诊断早期乳腺癌首选而有效的方法。