乳腺癌X线表现分析

目的分析乳腺癌典型及不典型X线征象,提高对乳腺癌不典型X线表现的认识。方法对61例经手术病理证实的乳腺癌资料进行回顾性分析。结果61例乳腺癌主要X线征象:肿块39例;微小钙化30例;不伴肿块及微小钙化的乳腺局部结构紊乱4例、星芒征3例、非对称性密度增高3例。结论肿块及微小钙化是乳腺癌最主要、最直接的X线征象,但部分乳腺癌X线上缺乏上述2种表现,单纯以结构紊乱、非对称性密度增高或星芒征为主要表现。提高对此类乳腺癌不典型X线表现的认识,有利于防止误、漏诊。     

Breast cancer imaging with PET and SPECT agents: an in vivo comparison

Several radiopharmaceuticals and imaging techniques are proposed for breast cancer imaging. Since limited data are available of the uptake of SPECT and PET radiopharmaceuticals in malignant breast tumors and their metastases the aim of this study was to compare the uptake values and to correlate these data with imaging findings. Methods: We have studied the uptake of F-18 FDG, Tc-99m MIBI and Tc-99m (V)DMSA in 31 tumors using immunosuppressed rats implanted with HH-16 clone 4 mammary tumor cells. Tumor gamma camera and PET imaging was performed to gain biokinetic data and uptake values by ROI-analysis. Results: Tumor uptake was highest for F-18 FDG > Tc-99m (V)DMSA > Tc-99m MIBI. The uptake ratios (tumor to muscle) correlated well with the ratios calculated by ROI-analysis determined by imaging. Conclusions: In this in-vivo model, F-18 FDG revealed the best uptake and imaging properties and may be the radiopharmaceutical of choice for routine breast cancer imaging.     

微小钙化在早期乳腺癌X线诊断中的应用价值

目的探讨乳腺钙化在全数字化乳腺X线摄影中的表现特征及其对早期乳腺癌的诊断价值。方法回顾性分析160例乳腺X线钼靶片中表现为微小钙化的病例,观察钙化的数目、形态、大小、分布、密度等,并与手术病理结果做对照。结果乳腺良、恶性疾病均可出现钙化。本组病例乳腺恶性病变112例,其中导管原位癌24例,浸润性导管癌88例,良性病变48例。钙化呈簇状分布、沿导管方向走行或呈蠕虫型、混合型形态的钙化多见于乳腺癌,弥漫性分布及粗颗粒型或融合型形态的钙化多见于乳腺良性病变。结论分析乳腺X线片中微小钙化形态学表现、密度、数目、走向分布及钙化与肿块的关系,能显著提高乳腺良恶性病变的诊断正确率,对早期乳腺癌的诊断具有极其重要价值。     

乳腺癌组织中骨桥蛋白和骨连接蛋白的表达及其与微钙化形成的关系

目的探讨骨桥蛋白（osteopontin，OPN）和骨连接蛋白（osteonectin，ON）在乳腺癌组织中的表达及其与微钙化形成的关系。方法根据钼靶X线片中微钙化的有无及数目的多少（20枚），将93例乳腺癌分为无钙化组、少量钙化组、大量钙化组，用免疫组织化学方法检测各组OPN、ON的表达水平及其与微钙化的关系。同时，选取3例含微钙化的乳腺癌组织行组织病理连续切片和透射电镜观察。结果组织切片显示：钙化不仅出现于坏死灶内，生长活跃的癌细胞巢内及周围组织同样可见颗粒状钙化；透射电镜观察显示：生长活跃的乳腺癌细胞胞质内可见深电子密度的钙盐颗粒；乳腺癌组织中OPN、ON高表达（79．6％、77．4％）且与钼靶片中微钙化的出现相关，随着钙化数目的增多，两者表达程度逐渐增强，钙化组与无钙化组比较差异有统计学意义（χ^2值分别为11．454、5．540，P值均〈0．05）；多钙化组与无钙化组比较，差异也具有统计学意义（χ^2值分别为13．738、7．659，P值均〈0．05）。免疫组织化学染色显示钙化周围OPN、ON高表达。结论乳腺癌组织中OPN、ON高表达，且表达水平与微钙化密切相关。OPN、ON可能参与了乳腺癌微钙化的形成过程。     

Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.

PURPOSE: To develop an optical imaging method to determine the expression level of tumoral matrix metalloproteinase-2 (MMP-2) in vivo. MATERIALS AND METHODS: An optical contrast agent was developed that was highly activatable by means of MMP-2-induced conversion. Signal characteristics of the probe were quantified ex vivo with a recombinant enzyme. Animal tumor models were established with MMP-2-positive (human fibrosarcoma cell line, n = 4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n = 4) tumor cell lines. Both tumors were implanted into nude mice and were optically imaged after intravenous administration of the MMP-2-sensitive probe. RESULTS: The MMP-2-sensitive probe was activated by MMP-2 in vitro, producing up to an 850% increase in near-infrared fluorescent signal intensity. This activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors were easily identified as high-signal-intensity regions as early as 1 hour after intravenous injection of the MMP-2 probe, while contralateral MMP-2-negative tumors showed little to no signal intensity. A nonspecific control probe showed little to no activation in MMP-2-positive tumors. CONCLUSION: It is feasible to image MMP-2 enzyme activity in vivo by using near-infrared optical imaging technology and "smart" matrix metalloproteinase-sensitive probes.     

Near-infrared optical imaging of protease activity for tumor detection

PURPOSE: To build and test an optical imaging system that is sensitive to near-infrared fluorescent molecular probes activated by specific enzymes in tumor tissues in mice. MATERIALS AND METHODS: The imaging system consisted of a source that delivered 610-650-nm excitation light within a lighttight chamber, a 700-nm longpass filter for selecting near-infrared fluorescence emission photons from tissues, and a charge-coupled device (CCD) for recording images. The molecular probe was a biocompatible autoquenched near-infrared fluorescent compound that was activated by tumor-associated proteases for cathepsins B and H. Imaging experiments were performed 0-72 hours after intravenous injection of the probe in nude mice that bore human breast carcinoma (BT-20). RESULTS: The imaging system had a maximal spatial resolution of 60 microns, with a field of view of 14 cm2. The detection threshold of the nonquenched near-infrared fluorescent dye was subpicomolar in the imaging phantom experiments. In tissue, 250 pmol of fluorochrome was easily detected during the 10-second image acquisition. After intravenous injection of the probe into the tumor-bearing animals, tumors as small as 1 mm became detectable because of tumor-associated enzymatic activation of the quenched compound. CONCLUSION: Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment.     

乳腺X线片中成簇样微小钙化对乳腺癌的诊断价值

目的 探讨乳腺癌成簇样微小钙化在乳腺X线片中的特征性表现。材料与方法 经手术病理证实并在乳腺X线片中可见微小钙化乳腺癌108例,良性病变50例。经2位有经验放射科医生采用7项指标分析微小钙化,判断病变良、恶性,运用χ^2检验和Logistic回归方法评价各项指标对乳腺癌的诊断价值。结果 微小钙化判断乳腺癌最有价值的指标为：（1）每平方厘米微小钙化数目（N／S）大于20个,总数目大于30个。（2）钙化点间密度不均、大小不一。（3）钙化形态为细沙型、混合型、蠕虫样或粗颗粒型。结论 乳腺X线片中微小钙化形态学表现、密度、大小及数目对乳腺癌的诊断具有重要价值。     

Molecular markers,pathology, and ultrasound features of invasive breast cancer

IntroductionUltrasound is commonly used in breast cancer screening and diagnosis. The use of ultrasound features to predict the subtypes of invasive breast cancer is of great clinical significance, since it facilitates a fast and early diagnosis and treatment. The correlation between breast lesion ultrasound features and the breast cancer subtypes requires further investigation.Methods388 patients with invasive breast cancer were retrospectively analyzed by two sonographers. The tumor size, shape, margin, echogenicity, echotexture, posterior echo attenuation microcalcification, and blood vessel density were recorded. The correlation between the tumor ER, PR, HER2, and Ki67 status, the molecular subtypes, and the ultrasound features was analyzed using the chi-square test, Fisher's exact test, and multiple logistic regression.ResultsER and PR positivity were correlated with a low histologic grade, lymph node metastasis, and smaller-sized tumors. A hyperechoic or a mixed echogenicity was rare in the tumors of all groups but was enriched in the ER and PR tumors (9.57% and 7.64%, respectively, p < 0.01). A high percentage of posterior echo attenuation was found in the Ki67 low (53.94%) and ER+ (51.28%) tumors. Furthermore, heterogeneous and microcalcifications were enriched in HER2-positive tumors. In terms of the molecular subtypes, the luminal A subtype group had the lowest lymph node positivity and the smallest primary tumor size. The luminal B subtype had the lowest percentage of hyperechoic or mixed tumors. The HER2 subtype was positively correlated with microcalcification. Finally, TNBC showed the highest percentage of hyperechoic or mixed tumors and the lowest percentage of posterior echo attenuation and microcalcification.ConclusionTumor pathologic and ultrasound features were correlated with invasive breast tumor molecular marker positivity and its molecular subtypes.     

Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes

PURPOSE: To determine if different expression levels of tumor cathepsin-B activity in well differentiated and undifferentiated breast cancers could be revealed in vivo with optical imaging. MATERIALS AND METHODS: A well differentiated human breast cancer (BT20, n = 8) and a highly invasive metastatic human breast cancer (DU4475, n = 8) were implanted orthotopically in athymic nude mice. Tumor-bearing animals were examined in vivo with near-infrared fluorescence (NIRF) imaging 24 hours after intravenous injection of an enzyme-sensing imaging probe. Immunohistochemistry, Western blotting (on cells and whole tumor samples), and correlative fluorescence microscopy were performed. RESULTS: Both types of breast cancers activated the NIRF probe so that tumors became readily detectable. However, in tumors of equal size, there was a 1.5-fold higher fluorescence signal in the highly invasive breast cancer (861 arbitrary units +/- 88) compared with the well differentiated lesion (566 arbitrary units +/- 36, P <.01). Western blotting confirmed a higher cathepsin-B protein content in the highly invasive breast cancer (DU4475) of about 1.4-fold (whole tumor samples) to 1.7-fold (cells). Immunohistochemistry and fluorescence microscopy findings confirmed the imaging findings. CONCLUSION: Cathepsin-B enzyme activity can be determined in vivo with NIRF optical imaging, while differences in tumoral expression may correlate with tumor aggressiveness.     

Tomographic fluorescence imaging of tumor vascular volume in mice

PURPOSE: To prospectively determine the feasibility of imaging vascular volume fraction (VVF) and its therapeutic inhibition in mouse models of cancer with three-dimensional fluorescence molecular tomography (FMT). MATERIALS AND METHODS: All studies were approved by the institutional animal review committee and were in accordance with National Institutes of Health guidelines. CT26 colon tumor-bearing mice were imaged with FMT after intravenous administration of long-circulating near-infrared fluorescent blood-pool agents optimized for two nonoverlapping excitation wavelengths (680 and 750 nm). A total of 58 mice were used for imaging VVF to evaluate the following: (a) differences in ectopically and orthotopically implanted tumors (n = 10), (b) cohorts of mice (n = 24) treated with anti-vascular endothelial growth factor (VEGF) antibody, (c) serial imaging in same animal to determine natural course of angiogenesis (n = 4), and (d) dose response to anti-VEGF therapy (n = 20). To compare groups receiving antiangiogenic chemotherapy, analysis of variance was used. RESULTS: Fluorochrome concentrations derived from FMT measurements were reconstructed with an accuracy of +/-10% at 680 nm and +/-7% at 750 nm and in a depth-independent manner, unlike at reflectance imaging. FMT measurements of vascular fluorescent probes were linear, with concentration over several orders of magnitude (r > 0.98). VVFs of colonic tumors, which varied considerably among animals (3.5% +/- 1.5 [standard deviation]), could be depicted with in vivo imaging in three dimensions with less than 5 minutes of imaging and less than 3 minutes of analysis. The natural course of angiogenesis and its inhibition could be reliably imaged and depicted serially in different experimental setups. CONCLUSION: FMT is a tomographic optical imaging technique that, in conjunction with appropriate fluorescent probes, allows quantitative visualization of biologic processes.     

全数字化乳腺摄影对临床未触及肿块乳癌的诊断价值

目的　探讨全数字化乳腺摄影对临床未触及乳癌的诊断价值。方法　收集 2 0 0 3 -0 4～ 0 7门诊及体检 412例中遇到的 3 4例乳癌 ,其中临床触及肿块的 2 2例 ,未触及肿块的 12例。全部病例采用全数字化乳腺摄影机检查 ,并经病理证实 ,检查体位常规采用CC位 (头尾位 )、MLO位 (内外斜位 ) ,必要时加照侧位及局部点片。对临床未触及包块的乳癌 ,均行术前定位。结果　 2 2例临床触及肿块的乳癌中 ,髓样癌 4例 ,硬癌 2例 ,浸润性导管癌 16例。 12例临床未触及包块的乳癌中 ,X线呈现微小钙化 6例 ,其中癌前病变 1例、导管原位癌 2例、导管浸润性癌 3例 ;呈现微小结节 2例 ,其中 1例导管原位癌、1例导管浸润癌 ;呈现微小结节半结节内微小钙化 2例 ,1例导管原位癌、1例导管浸润癌 ;呈现结构紊乱区 1例 ,为小叶原位癌 ,结构紊乱区伴微小钙化 1例 ,为浸润导管癌。结论　全数字化乳腺摄影能清晰显示乳腺癌的直接及间接征象 ,尤其对临床未触及包块的乳癌具有更重要的诊断价值     

Detection of incidental breast tumors by noncontrast spiral computed tomography of the chest

PURPOSE: The aim of this study was to investigate the frequency of breast tumors and breast cancers with noncontrast spiral chest computed tomography (CT). MATERIAL AND METHODS: A clinical study was conducted to evaluate findings in the mammary region of 1008 consecutive patients with no mammary symptoms or signs who underwent noncontrast spiral CT of the chest from April 2003 to March 2006. RESULTS: Six cases of breast abnormality were detected among the 1008 women. Three were primary breast cancers, one was metastatic breast cancer, and two were benign tumors. All four breast cancer patients were over 70 years old. The characteristics of the tumor margins on CT scans corresponded to the mammography and ultrasonography findings. The mammographic background density ranged from inhomogeneous high-density breast to fatty breast. The detection rate of primary breast cancer by noncontrast spiral CT was 0.30%. CONCLUSION: Noncontrast spiral chest CT occasionally detects nonsymptomatic breast cancers, especially in elderly patients.     

乳腺癌钼靶X线片误诊分析(附15例报告)

目的　进一步提高乳腺癌影像诊断水平。方法　收集 15例经手术病理证实乳腺癌钼靶X线误诊病例 ,回顾性分析其X线表现及临床资料。结果　 15例中 ,4例呈小纤维腺瘤样表现 ,3例发现粒数极少的微细钙化 ,3例表现为局部腺体结构不良 ,2例表现为导管增生腺体内多发小片影 ,2例为小灶致密影 ,1例无任何异常。其中 4例临床未触及肿物。结论　通过对上述几种X线影像征象的认识 ,强调触诊与影像的紧密结合 ,在提高乳腺癌钼靶X线诊断率、减少误诊中具有重要价值     

Reproducibility--an important factor determining the quality of computer-aided detection (CAD) systems

PURPOSE: To test the reproducibility of markings on mammography films set by a commercial computer aided detection (CAD) system. PATIENTS AND METHODS: One hundred unilateral mammography examinations (each in CC and MLO) of 100 patients with mammographically detected suspicious foci, which were histopathologically proven to be malignant, were scanned three times with the CAD system, retrospectively. Every fifth patient of the institutional tumor case sampler was enrolled in the study. Only cases with one visible lesion were included in the study. Reproducibility and sensitivity (in both the strict and the broader sense) were determined. Strict sensitivity means the correct set of markers in both images, whereas broader sensitivity means the correct set in at least one of the images. Sixteen of 100 malignancies were indicated by focal suspicious microcalcification clusters, 53 tumors by masses and 31 cases by both signs of breast cancer. The CAD evaluation was divided into only two different markers: one for microcalcifications and one for masses. Thus, 47 (16+31) tumor-induced microcalcifications and 84 (53+31) malignancy-related masses were checked using the CAD system. RESULTS: Eighteen of 100 unilateral mammography examinations revealed identical patterns in all three scans (18% reproducibility). Eleven of 47 suspicious focal microcalcification clusters and 43/84 masses were correctly marked on both mammographic views in all three CAD scans (strict and broader sensitivity, 23.4 and 51.1%, respectively). Six of 47 microcalcification clusters and 8/84 masses were totally missed in all images by the system (false negative rate, 12.8 and 9.6%, respectively). CONCLUSION: Reproducibility is essential for CAD systems. Currently, reproducibility of the used CAD system appears to be insufficient for clinical routine. Improvement of the system characteristics would make such systems valuable as a 'second reader' in clinical examination.     

Effect of tamoxifen in an experimental model of breast tumor studied by dynamic contrast-enhanced magnetic resonance imaging and different contrast agents

OBJECTIVES: The aim of this study was to compare the efficacy of gadoteridol, B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37-albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor implanted in rats. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10 mammary adenocarcinoma cells (13762 MAT B III). Treatment with tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and, 24 hours later, using (Gd-DTPA)37-albumin. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging data showed that tamoxifen treatment decreased vascular permeability to B22956/1, whereas no difference was detectable in permeability to gadoteridol or to (Gd-DTPA)37-albumin. No effect on fractional plasma volume was detected with either of contrast agents. CONCLUSIONS: B22956/1 is superior to both small Gd chelates and macromolecular contrast agents in the assessment of the effect of tamoxifen treatment on tumor vasculature.     

Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging

RATIONALE AND OBJECTIVES: To evaluate the efficacy of a novel tumor receptor-specific small-peptide-near-infrared dye conjugate for tumor detection by optical imaging. METHODS: A novel, near-infrared dye-peptide conjugate was synthesized and evaluated for tumor-targeting efficacy in a well-characterized rat tumor model (CA20948) known to express receptors for the chosen peptide. A simple continuous-wave optical imaging system, consisting of a near-infrared laser diode, a cooled CCD camera, and an interference filter, was used in this study. RESULTS: Tumor retention of two non-tumor-specific dyes, indocyanine green and its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate) was retained in the CA20948 tumor, with an excellent tumor-tonormal-tissue ratio in the six rats examined. CONCLUSIONS: Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.     

Absolute oxygen tension (pO(2)) in murine fatty and muscle tissue as determined by EPR.

The absolute partial pressure of oxygen (pO(2)) in the mammary gland pad and femoral muscle of female mice was measured using EPR oximetry at 700 MHz. A small quantity of lithium phthalocyanine (LiPc) crystals was implanted in both mammary and femoral muscle tissue of female C3H mice. Subsequent EPR measurements were carried out 1-30 days after implantation with or without control of core body temperature. The pO(2) values in the tissue became stable 2 weeks after implantation of LiPc crystals. The pO(2) level was found to be higher in the femoral muscle than in the mammary tissue. However, the pO(2) values showed a strong dependence on the core body temperature of the mice. The pO(2) values were responsive to carbogen (95% O(2), 5% CO(2)) breathing even 44-58 days after the implantation of LiPc. The LiPc linewidth was also sensitive to changes in the blood supply even 60 days after implantation of the crystals. This study further validates the use of LiPc crystals and EPR oximetry for long-term non-invasive assessment of pO(2) levels in tissues, underscores the importance of maintaining normal body core temperature during the measurements, and demonstrates that mammary tissue functions at a lower pO(2) level than muscle in female C3H mice.     

A wide variety of dynamic contrast-enhanced MR appearances of breast cancer: pathologic correlation study

PURPOSE: The aim of this study was to elucidate the characteristic magnetic resonance (MR) appearance of breast cancers, as well as, its variations and to investigate the pathology providing different patterns of dynamic-MR appearances. MATERIALS AND METHODS: Fifty-two women with cancer underwent mastectomy (52 tumors resected) and had MR imaging at our institution between April 2001 and March 2004. MR images of T1WI, T2WI, dynamic-MRI and contrast-enhanced T1WI were obtained and evaluated. Dynamic-MR images were correlated with pathological findings. RESULTS: Common MR appearance of breast cancer was a focal mass either with irregular or spiculated margins with similar signal intensity on T1WI as and similar to higher signal intensity on T2WI compared to the normal mammary gland. On static contrast-enhanced T1WI, apparent enhancement was typically observed. On dynamic MRI, tumor-rim-enhancement on an early phase image and washout enhancement pattern on dynamic images, both characteristic for breast cancer, were observed, however, the prevalence of them was relatively low, which could be explained by the variation of histopathology among breast cancer nodules. CONCLUSION: In diagnosing breast masses on MRI, as well as the common and characteristic findings of breast cancer, the variations of MR findings and their underlying histopathology should also be considered.     

乳腺癌钼靶X线微钙化与癌细胞ER、PR表达关系的研究

目的分析钼靶片中乳腺癌微钙化与ER、PR表达及临床病理关系,评价微钙化征象预测ER、PR表达的可行性。方法乳腺癌病例115例,钼靶X线片由3位有经验的影像诊断医师阅片,明确钙化并根据钙化及相关表现分组。免疫组化采用SP法,根据癌细胞核内染色判断ER、PR表达情况。各钙化组分别与ER、PR表达情况进行比较分析。结果乳腺癌钼靶片中微钙化的有无、微钙化数目、钙化类型与肿瘤细胞ER、PR表达无明显相关性(P>0.05)。乳腺癌微钙化多见于导管癌,占53.33%,是钼靶片中无肿块表现乳腺癌的主要X线征象。微钙化表现与乳腺癌临床TNM分期无关(P>0.05)。乳腺癌钼靶片微钙化表现常伴腋下淋巴结转移(24/47例),而钙化数目较少(<20枚)的乳腺癌更易伴有腋下淋巴结转移(16/24例)。结论微钙化在钼靶片乳腺癌诊断中,特别是在早期癌以及无肿块表现的乳腺癌诊断中具有重要意义。但是,微钙化表现与ER、PR表达无明显相关性,尚不能作为乳腺癌ER、PR表达的预测指标。     

Animal-based model to investigate the minimum tumor size detectable with an electrical impedance scanning technique

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the minimum tumor size detectable with electrical impedance scanning (EIS) in laboratory animals. MATERIALS AND METHODS: VX2 tumor cells (1 mm3) were implanted bilaterally into the upper leg musculature of five white New Zealand rabbits. EIS and ultrasound (US) were performed before, during, and immediately after implantation and on every 2nd day thereafter until tumors could be visualized with both modalities. This was followed by an extended follow-up regimen until a tumor size of 1 cm3 was reached. Rabbits were anesthetized subcutaneously. RESULTS: Tumors could not be implanted in one rabbit. Neither EIS nor US were performed in one rabbit due to severe skin alterations at the implantation site. No focal increase in conductance was visible before or immediately after tumor injection. The smallest tumor identified with EIS was determined with US to be approximately 8 mm3. The mean tumor size at initial detection was 52 mm3 (determined with EIS). In two cases, the tumor was first seen with US (EIS detection was delayed with a delay of 1 and 2 days, respectively). In all remaining cases, tumors were detected simultaneously with both EIS and US. All tumors were visible with EIS. CONCLUSION: The animal-based model is feasible. VX2 tumors are detectable with EIS. Tumors characterized by a focal spot at EIS could be detected starting at a tumor size of 7.5 mm3.