Dimitrios L. Arvanitis

Characterization of breast lesions with CE-MR multimodal morphological and kinetic analysis: Comparison with conventional mammography and high-resolution ultrasound

OBJECTIVE Evaluation of the diagnostic value of magnetic resonance mammography and comparison with conventional mammography and ultrasonography in cases of women with suspicious breast lesions. SUBJECTS AND METHODS Sixty-nine women (age range 39-68 years) with 78 focal breast lesions were examined with mammography, ultrasonography and dynamic magnetic resonance mammography. The lesions were classified according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon of the American College of Radiology for each diagnostic method. Histological reports were available after biopsy or surgical excision of the lesions. RESULTS Pathological examination confirmed that 53 lesions were malignant and 25 benign. Conventional mammography estimated a total of 59/78 lesions as malignant with 44 true positive lesions, ultrasonography estimated a total of 50/78 lesions as malignant with 44 true positive lesions and magnetic resonance mammography estimated a total of 66/78 lesions as malignant with 52 true positive lesions. Sensitivity and specificity of magnetic resonance mammography in the diagnosis of malignancy was 98.1% and 44%, of conventional mammography 83% and 40% and of ultrasonography 83% and 76%. Negative predictive value for magnetic resonance mammography was 91.7%, for ultrasonography 67.9% and for mammography 52.6% for malignancies. CONCLUSION Magnetic resonance mammography has the highest negative predictive value compared with mammography and ultrasound in cases of suspicious breast lesions. The combination of morphologic and enhancement criteria can improve the diagnostic capability of magnetic resonance mammography (MRM) in breast lesion characterization.

Expression of Heregulin in Human Coronary Atherosclerotic Lesions

Background: Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease. Methods: Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA.hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors. Results: We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in breast cancer epithelial cells. CYR61 was expressed in both normal and atheromatic specimens, but its expression was significantly enhanced in macrophages of the intima. Activation of primary human macrophages results in increased expression of both HRG and CYR61. In addition, studies in endothelial cells where no endogenous HRG is present showed that HRG induces expression of CYR61 and secretion of VEGF. Conclusions: HRG may, therefore, play an important role in the development of coronary artery disease and the expansion of the atherosclerotic plaque and may locally regulate the expression of the angiogenetic factor CYR61.

The contribution of diffusion tensor imaging and magnetic resonance spectroscopy for the differentiation of breast lesions at 3T.

Background Conventional breast magnetic resonance imaging (MRI), including dynamic contrast-enhanced MR mammography (DCE-MRM), may lead to ambiguous diagnosis and unnecessary biopsies. Purpose To investigate the contribution of proton MR spectroscopy (1H-MRS) combined with diffusion tensor imaging (DTI) metrics in the discrimination between benign and malignant breast lesions. Material and Methods Fifty-one women with known breast abnormalities from conventional imaging were examined on a 3T MR scanner. DTI was performed during breast MRI, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in the breast lesions and the contralateral normal breast. FA and ADC were compared between malignant lesions, benign lesions, and normal tissue. 1H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. Results In our study 1H-MRS showed a sensitivity of 93.5%, specificity 80%, and accuracy 88.2%. FA was significantly higher in breast carcinomas compared to benign lesions. However, no significant difference was observed in ADC between benign and malignant lesions. The combination of Cho presence and FA achieved higher levels of accuracy and specificity in discriminating malignant from benign lesions over Cho presence or FA alone. Conclusion In conclusion, applying DTI and 1H-MRS together, adds incremental diagnostic value in the characterization of breast lesions and may sufficiently improve the low specificity of conventional breast MRI.

Incidental Non-Cardiac Findings of a Coronary Angiography with a 128-Slice Multi-Detector CT Scanner: Should We Only Concentrate on the Heart?

Objective To evaluate the spectrum, prevalence, and significance of incidental non-cardiac findings (INCF) in patients referred for a non-invasive coronary angiography using a 128-slice multi-detector CT (MDCT). Materials and Methods The study subjects included 1,044 patients; 774 males (mean age, 59.9 years) and 270 females (mean age, 63 years), referred for a coronary CT angiography on a 128-slice MDCT scanner. The scans were acquired from the level of the carina to just below the diaphragm. To evaluate INCFs, images were reconstructed with a large field of view (> 300 mm) covering the entire thorax. Images were reviewed in the axial, coronal, and sagittal planes, using the mediastinal, lung, and bone windows. The INCFs were classified as severe, indeterminate, and mild, based on their clinical importance, and as thoracic or abdominal based on their locations. Results Incidental non-cardiac findings were detected in 56% of patients (588 of 1,044), including 435 males (mean age, 65.6 years) and 153 females (mean age, 67.9 years). A total of 729 INCFs were observed: 459 (63%) mild (58% thoracic, 43% abdominal), 96 (13%) indeterminate (95% thoracic, 5% abdominal), and 174 (24%) severe (87% thoracic, 13% abdominal). The prevalence of severe INCFs was 15%. Two severe INCFs were histologically verified as lung cancers. Conclusion The 128-slice MDCT coronary angiography, in addition to cardiac imaging, can provide important information on the pathology of the chest and upper abdomen. The presence of severe INCFs is not rare, especially in the thorax. Therefore, all organs in the scan should be thoroughly evaluated in daily clinical practice.

Ultrastructural immunostaining of infiltrating ductal breast carcinomas with the monoclonal antibody H: A comparative study with cytokeratin 8

The monoclonal antibody H (mAbH) detects an epitope consisting of an O-linked N -acetyl glucosamine (O-GlcNAc) and neighboring amino acids. This epitope has been found by using extracts from the MCF-7 human breast carcinoma cell line in immunoblotting experiments, on cytokeratin 8 (CK8) and 5 other polypeptides. In the present study, a double immunogold method was applied for the colocalization of CK8 and mAbH epitope on epoxy thin sections in 18 cases of infiltrating ductal breast carcinomas (IDBC) and in 6 cases of fibroadenomas, to study the accurate subcellular distribution of CK8 in breast cancer cells, as compared to the 5 polypeptides, recognized by mAbH. Furthermore, a detailed quantitative evaluation of the double immunolocalization over the cellular compartments of cancer cells was undertaken with the aid of a computerized image analysis system and the results were assessed statistically. The distribution pattern of CK8 and the mAbH epitope in the neoplastic mammary epithelial cells was similar in IDBC as compared to fibroadenomas, while the gold labeling intensity of these epitopes differed over the cellular compartments between malignant and benign biopsies. The results reveal the significance of the role of CK8 and O-GlcNAc glycosylation in the biology of the neoplastic mammary cells in vivo, determining their malignant potential.

Cytokine effects on cell survival and death of A549 lung carcinoma cells

PURPOSE IL-13, TNF-α and IL-1β have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-α and IL-1β alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. RESULTS Using MTT and flow cytometry, IL-13, TNF-α and IL-1β pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-κB [NF-κB], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Using Western blot, IL-13, TNF-α and IL-1β treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-IκBα proteins, decreased IκBα protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-α treated cells showed time-dependent increase of FLIPL expression. CONCLUSION IL-13, TNF-α and IL-1β attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-κB, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-α cell survival effects may also be due to increased expression of FLIPL protein.

Application value of 3T 1H-magnetic resonance spectroscopy in diagnosing breast tumors

Background Assessment of breast lesions with magnetic resonance imaging (MRI) provides a means for lesion detection and diagnosis. Proton (hydrogen-1) magnetic resonance spectroscopy (1H-MRS) has been proposed as a useful diagnostic technique in providing metabolic information of suspicious breast lesions. Purpose To determine the clinical significance of in-vivo single voxel 1H-MRS at 3T in the assessment of benign and malignant breast lesions in combination with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Material and Methods Twenty-four women with known breast abnormalities from conventional imaging (mammography, ultrasonography) underwent DCE-MRI at a 3T MR scanner and 26 breast lesions were detected. Breast lesions were assessed according BI-RADS classification. Single voxel 1H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. All lesions were confirmed histologically from the surgically excised specimens. Sensitivity, specificity, and accuracy of the 1H-MRS, of the BI-RADS classification and of their combination (DCE-MRI + 1H-MRS) were calculated. Results Fifteen out of 26 lesions proved to be malignant and 11 proved to be benign. In our study 1H-MRS showed sensitivity 80%, specificity 81.8%, and accuracy 80.7%. DCE-MRI showed sensitivity 100%, specificity 63.6%, and accuracy 84.6%. The combination of DCE-MRI and 1H-MRS provided higher accuracy (96.4%), as well as higher specificity 81.8% compared to BI-RADS classification. Conclusion The combined use of 1H-MRS and DCE-MRI found to have improved diagnostic performance in the assessment of equivocal breast lesions. 1H-MRS can be used as a useful adjunct during lesion characterization in clinical routine in cases classified as BI-RADS 3 and 4.

Reactive astrocytes upregulate one or more gene products that are recognized by monoclonal antibody H

Abstract. We generated a panel of monoclonal antibodies (mAbs) selected to recognize components from a Triton X-100 extract of ovine oligodendrocytes. One of these Abs, mAb H, recognizes an O-linked N-acetyl glucosamine residue in a specific conformation and/or environment. mAb H stained, weakly, two bands with Mr×10–3 of 209 and 62 in lysates of cultured rat astrocytes, suggesting antigens of low abundance. We have employed immunohistochemistry to investigate the cell and tissue distribution of the mAb H antigen(s). In normal rat and human brains, the sparse reaction products detected were confined, mostly, to fibrous astrocytes. In sharp contrast, when pathological specimens from a variety of brain lesions, including anisomorphic and isomorphic gliosis, were examined, a strong reaction with mAb H was in evidence in all reactive astrocytes, independent of the origin or nature of the lesions. This we interpret as meaning that the gene product(s) recognized by this mAb is (are) upregulated or induced following injury to the brain. Hence, epitope H represents a new addition to the list of molecules that are affected by brain injury. Structural and functional identification of the antigen(s) should shed light on its (their) relevance to the pathophysiology of the disease process.

Fast sequences MR imaging at the investigation of painful skeletal sites in patients with hip osteonecrosis

BackgroundMultiple osteonecrotic foci can be clinically silent when located in metaphyses and becomes painful when it affects juxta-articular areas. The purpose of this study was to assess the value of fast MR imaging to depict the underlying pathology in cases with skeletal pain other than the already diagnosed hip osteonecrosis.Methods/designBetween 2008 and 2013, 49 patients with already diagnosed hip osteonecrosis reported symptoms of deep skeletal pain in an anatomical site different from the affected hip joint. All patients after thorough history & clinical examination underwent evaluation with x-rays and a single fat suppressed sequence with MR Imaging applying either T2-w TSE or STIR-TSE at the painful site. False positive and false negative findings were recorded for the conventional x-rays and compared to MRI.DiscussionForty four (89.8%) patients were positive for osteonecrotic lesions in this study and 76 symptomatic osteonecrosis lesions were revealed at 14 distinct anatomic sites. The agreement between the x-ray findings and the MR imaging regarding osteonecrosis was 46.9%. Plain x-rays showed 43.4% sensitivity, 100% specificity, 100% positive predictive value and 10.4% negative predictive value.Fast MR imaging with fat suppressed sequences is necessary and adequate as a single method for the investigation of painful skeletal sites in patients with already diagnosed hip osteonecrosis. It allows early diagnosis of the potentially debilitating multiple juxta-articular lesions and consequently their prompt management.

Comparison of PD BLADE with fat saturation (FS), PD FS and T2 3D DESS with water excitation (WE) in detecting articular knee cartilage defects.

The purpose of this study, is to compare the sequences: 1) proton density (PD) BLADE (BLADE is a PROPELLER-equivalent implementation of the Siemens Medical System) with fat saturation (FS) coronal (COR), 2) PD FS COR, 3) multi-planar reconstruction (MPR) with 3mm slice thickness and 4) multi-planar reconstruction (MPR) with 1.5mm slice thickness, both from the T2 3D-double-echo steady state (DESS) with water excitation (WE) sagittal (SAG), regarding their abilities to identify changes in the femorotibial condyle cartilage in knee MRI examinations. Thirty three consecutive patients with osteoarthritis (18 females, 15 males; mean age 56years, range 37-71years), who had been routinely scanned for knee examination using the previously mentioned image acquisition techniques, participated in the study. A quantitative analysis was performed based on the relative contrast (ReCON) measurements, which were taken both on normal tissues as well as on pathologies. Additionally, a qualitative analysis was performed by two radiologists. Motion and pulsatile flow artifacts were evaluated. The PD BLADE FS COR sequence produced images of higher contrast between Menisci and Cartilage, Fluid and Cartilage, Pathologies and Cartilage as well as of the Conspicuousness Superficial Cartilage and it was found to be superior to the other sequences (p<0.001). The sequences T2 3D DESS 1.5mm and T2 3D DESS 3mm were significantly superior to the PD BLADE FS COR and the PD FS COR sequences in the visualization of Bone and Cartilage and the Conspicuousness Deep Surface Cartilage. This pattern of results is also confirmed by the quantitative analysis. PD FS BLADE sequences are ideal for the depiction of the cartilage pathologies compared to the conventional PD FS and T2 3D DESS sequences.