Evelyn Wenkel

Detection of Coronary Artery Stenoses by Contrast-Enhanced, Retrospectively Electrocardiographically-Gated, Multislice Spiral Computed Tomography

Background—Multislice spiral computed tomography (MSCT) with retrospectively ECG-gated image reconstruction permits coronary artery visualization. We investigated the method’s ability to identify high-grade coronary artery stenoses and occlusions. Methods and Results—A total of 64 consecutive patients were studied by MSCT (4×1 mm cross-sections, 500-ms rotation, table feed 1.5 mm/rotation, intravenous contrast agent, retrospectively ECG-gated image reconstruction). All coronary arteries and side branches with a luminal diameter ≥2.0 mm were assessed concerning evaluability and the presence of high-grade stenoses (>70% diameter stenosis) or occlusions. Results were compared with quantitative coronary angiography. Of 256 coronary arteries (left main, left anterior descending, left circumflex and right coronary artery, including their respective side branches), 174 could be evaluated (68%). In 19 patients (30%), all arteries were evaluable. Artifacts caused by coronary motion were the most frequent reason for unevaluable arteries. Overall, 32 of 58 high-grade stenoses and occlusions were detected by MSCT (58%). In evaluable arteries, 32 of 35 lesions were detected, and the absence of stenosis was correctly identified in 117 of 139 arteries (sensitivity, 91%; specificity, 84%). If analysis was extended to all stenoses with >50% diameter reduction, sensitivity was 85% (40 of 47) and specificity was 76% (96 of 127). Conclusions—MSCT with retrospective ECG gating permits the detection of coronary artery stenoses with high accuracy if image quality is sufficient, but its clinical use may presently be limited due to degraded image quality in a substantial number of cases, mainly due to rapid coronary motion.

Investigation of Aortocoronary Artery Bypass Grafts by Multislice Spiral Computed Tomography With Electrocardiographic-Gated Image Reconstruction

MK, Popma JJ, Leon MB. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia: a serial intravascular ultrasound study. Circulation 1997;95:1366–1369. 17. Kastrati A, Shoming A, Elezi S, Shuhlen H, Dirschinger J, Hadamitzky M, Wehinger A, Hausleiter J, Walter H, Neumann FJ. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30:1428–1436. 18. Akiyama T, Moussa I, Reimers B, Ferraro M, Kobayashi Y, Blengino S, Di Francesco L, Finci L, Di Mario C, Colombo A. Angiographic and clinical outcome following coronary stenting of small vessels. A comparison with coronary stenting of large vessels. J Am Coll Cardiol 1998;32:1610–1618. 19. Lau KW, Ding ZP, Sim LL, Sigwart U. Clinical and angiographic outcome after angiographically-guided stent placement in small coronary vessels. Am Heart J 2000;139:830–839.

Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection.

Introduction MicroRNAs (miRNAs, miRs) are a class of small, non-coding RNA molecules with relevance as regulators of gene expression thereby affecting crucial processes in cancer development. MiRNAs offer great potential as biomarkers for cancer detection due to their remarkable stability in blood and their characteristic expression in many different diseases. We investigated whether microarray-based miRNA profiling on whole blood could discriminate between early stage breast cancer patients and healthy controls. Methods We performed microarray-based miRNA profiling on whole blood of 48 early stage breast cancer patients at diagnosis along with 57 healthy individuals as controls. This was followed by a real-time semi-quantitative Polymerase Chain Reaction (RT-qPCR) validation in a separate cohort of 24 early stage breast cancer patients from a breast cancer screening unit and 24 age matched controls using two differentially expressed miRNAs (miR-202, miR-718). Results Using the significance level of p<0.05, we found that 59 miRNAs were differentially expressed in whole blood of early stage breast cancer patients compared to healthy controls. 13 significantly up-regulated miRNAs and 46 significantly down-regulated miRNAs in our microarray panel of 1100 miRNAs and miRNA star sequences could be detected. A set of 240 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 78.8%, and a sensitivity of 92.5%, as well as an accuracy of 85.6%. Two miRNAs were validated by RT-qPCR in an independent cohort. The relative fold changes of the RT-qPCR validation were in line with the microarray data for both miRNAs, and statistically significant differences in miRNA-expression were found for miR-202. Conclusions MiRNA profiling in whole blood has potential as a novel method for early stage breast cancer detection, but there are still challenges that need to be addressed to establish these new biomarkers in clinical use.

On a dark-field signal generated by micrometer-sized calcifications in phase-contrast mammography

We show that a distribution of micrometer-sized calcifications in the human breast which are not visible in clinical x-ray mammography at diagnostic dose levels can produce a significant dark-field signal in a grating-based x-ray phase-contrast imaging setup with a tungsten anode x-ray tube operated at 40 kVp. A breast specimen with invasive ductal carcinoma was investigated immediately after surgery by Talbot-Lau x-ray interferometry with a design energy of 25 keV. The sample contained two tumors which were visible in ultrasound and contrast-agent enhanced MRI but invisible in clinical x-ray mammography, in specimen radiography and in the attenuation images obtained with the Talbot-Lau interferometer. One of the tumors produced significant dark-field contrast with an exposure of 0.85 mGy air-kerma. Staining of histological slices revealed sparsely distributed grains of calcium phosphate with sizes varying between 1 and 40 μm in the region of this tumor. By combining the histological investigations with an x-ray wave-field simulation we demonstrate that a corresponding distribution of grains of calcium phosphate in the form of hydroxylapatite has the ability to produce a dark-field signal which would-to a substantial degree-explain the measured dark-field image. Thus we have found the appearance of new information (compared to attenuation and differential phase images) in the dark-field image. The second tumor in the same sample did not contain a significant fraction of these very fine calcification grains and was invisible in the dark-field image. We conclude that some tumors which are invisible in x-ray absorption mammography might be detected in the x-ray dark-field image at tolerable dose levels.

Toward simultaneous PET/MR breast imaging: Systematic evaluation and integration of a radiofrequency breast coil

PURPOSE With the recent introduction of integrated whole-body hybrid positron emission tomography/magnetic resonance (PET/MR) scanners, simultaneous PET/MR breast imaging appears to be a potentially attractive new clinical application. In this study, the technical groundwork toward performing simultaneous PET/MR breast imaging was developed and systematically evaluated in phantom experiments and breast cancer patient hybrid imaging. METHODS Measurements were performed on a state-of-the-art whole-body simultaneous PET/MR system (Biograph mMR, Siemens AG, Erlangen, Germany). The PET signal attenuating effects of a MR-only four-channel radiofrequency (RF) breast coil that is present in the PET field-of-view (FoV) during a simultaneous PET/MR data acquisition has been investigated and quantified. For this purpose, a dedicated PET/MR visible breast phantom featuring four modular inserts with various structures (no insert, MR insert, PET insert, and PET/MR insert) was developed. In addition to a systematic evaluation of MR-only image quality, the following phantom scans were performed using (18)F radio tracer: (1) PET emission scan with only the homogeneous breast phantom; (2) PET emission scan additionally with the RF breast coil in the PET FoV. Attenuation correction (AC) of PET data was performed with CT-based three-dimensional (3D) hardware attenuation maps (μ-maps) of the RF coil and breast phantom. Finally, a simultaneous PET/MR breast imaging was performed in two breast cancer patients. RESULTS The modular breast phantom allowed for systematic evaluation of various MR, PET, and PET/MR image quality parameters. The RF breast coil provided MR images of good image quality, unaffected by PET imaging. The global attenuation of the RF breast coil on the PET emission data was approximately 11%. This hardware attributed PET signal attenuation was successfully corrected by using an appropriate CT-based 3D μ-map of the RF breast coil. Imaging of two breast cancer patients confirmed the successful integration of the RF breast coil into the concept of simultaneous PET/MR breast imaging. CONCLUSIONS The successful integration of a four-channel RF breast coil with a defined table position together with the CT-based μ-maps provides a technical basis for future clinical PET/MR breast imaging applications.

Grating-based darkfield imaging of human breast tissue

Mastectomy specimens were investigated using a Talbot-Lau X-ray imaging set-up. Significant structures in the darkfield were observed, which revealed considerably higher contrast than those observed in digital mammography. Comparison with the histomorphometric image proofs that the darkfield signal correlates with a tumor region containing small calcification grains of 3 to 30μm size.

Direct MR Galactography: Feasibility Study

PURPOSE To compare T1- and T2-weighted direct magnetic resonance (MR) galactography, indirect MR galactography, and conventional galactography in women with pathologic nipple discharge. MATERIALS AND METHODS The study was approved by the institutional review board. Written informed consent was obtained from all patients. Twenty-three women (age range, 30-85 years) with pathologic nipple discharge and pathologic conventional galactographic findings underwent physical examination, ultrasonography, and MR imaging before surgery. A T2-weighted sequence of the affected breast was performed before (indirect MR galactography), and T1- and T2-weighted sequences were performed after (direct MR galactography), gadopentetate dimeglumine was injected into the discharging duct. MR galactographic findings were analyzed and compared with conventional galactographic findings. Sequences used were T2-weighted three-dimensional constructive interference in steady state (CISS), T1-weighted volumetric interpolated breath-hold examination (VIBE), and T1-weighted fast low-angle shot (FLASH). RESULTS The 23 patients had a total of 57 findings at conventional galactography. Indirect MR galactography with CISS showed pathologic findings in eight (42%) of 19 patients and showed 15 (33%) of 46 of all findings. Direct MR galactography with CISS showed pathologic findings in 23 (100%) of 23 patients and 47 (82%) of 57 of all findings, that with VIBE showed pathologic findings in 19 (83%) of 23 patients and 38 (67%) of 57 of all findings, and that with FLASH showed pathologic findings in 16 (100%) of 16 patients and 31 (80%) of 39 of all findings. There was a significant (P < .01) difference between indirect MR galactography and all direct MR galactography sequences in the detection of ductal disease. Eight (35%) of 23 women showed additional findings at direct MR galactography in comparison with standard MR imaging sequences. CONCLUSION MR galactography has the potential to be used in the diagnostic work-up of pathologic nipple discharge. Direct MR galactography shows more disease than does indirect MR galactography. The highest detection rate for ductal disease compared with that at conventional galactography was found with the direct MR galactography CISS and FLASH sequences.

Diffusion-Weighted MR Imaging of Benign and Malignant Breast Lesions Before and After Contrast Enhancement

PURPOSE Many publications describe the use of diffusion-weighted imaging (DWI) in breast MRI. This article addresses the question of when to apply the DWI sequence in the course of the scan protocol. The effect of T1-shortening contrast media (CM) on the ADC values of breast lesions is investigated. MATERIALS AND METHODS Data were acquired on a 1.5 T scanner. 60 patients with 79 lesions (20 benign, 59 malignant) were included. The DWI sequence (4 mm slice thickness, b-values: 50, 400, 800) was applied before and after CM administration. Before calculating the ADC map, the b50, b400 and b800 series were analyzed concerning lesion displacement. ADC values before and after CM application were compared. RESULTS The mean lesion size was 1.5 ± 0.8 cm. On the basis of the b50 and b400 measurements, the mean ADC value of benign lesions was 1.89 ± 0.30 × 10-3 mm2/s before and 1.85 ± 0.28 ×10-3 mm2/s after CM administration. The consecutive values for two pure mucinous carcinomas were 1.88 × 10-3 mm2/s and 1.81 × 103 mm2/s and for the remaining malignant lesions 1.00 ± 0.18 × 10-3 mm2/s and 0.88 ± 0.21 × 10-3 mm2. On the basis of the b50, b400 and b800 measurements, the mean ADC value of benign lesions was 1.99 ± 0.37 × 10-3 mm2/s before and 1.97 ± 0.30 × 10-3 mm2/s after CM application, whereas the mean ADC value of the malignant lesions was 0.90 ± 0.14 × 10-3 mm2/s before and 0.80 ± 0.14 × 10-3 mm2/s after CM application. While there was no significant change for benign lesions, the ADC value decrease in post-contrast malignant lesions was highly significant. CONCLUSION DWI after CM is possible and even leads to slightly better lesion discrimination between benign and malignant. However, further studies need to be performed to verify this. Citation Format: • Janka R, Hammon M, Geppert C et al. Diffusion-Weighted MR Imaging of Benign and Malignant Breast Lesions Before and After Contrast Enhancement. Fortschr Röntgenstr 2014; 186: 130 - 135.

Does direct MR galactography have the potential to become an alternative diagnostic tool in patients with pathological nipple discharge

PURPOSE To compare direct magnetic resonance galactography (dMRG) and conventional galactography (CGal). MATERIALS AND METHODS Thirty women underwent CGal and dMRG. Duct localization and the depth of the assumed underlying pathology in CGal and dMRG were analyzed. RESULTS Comparing CGal and dMRG, there was no significant difference regarding sector localization, but for depth of pathology (P=.023). CONCLUSION Duct localization with dMRG was possible with the same reliability as with CGal. Thus, dMRG may have the potential to become an alternative method to CGal.

Fulvestrant: A Further Treatment Option for Patients with Metastatic Uterine Cancer?

Background: Metastatic uterine cancer is notoriously difficult to treat, presenting a poor prognosis and a median survival time of less than 1 year. We present the successful use of the antiestrogen fulvestrant in an endocrine therapy-naïve patient with advanced uterine cancer. Case Report: A 64-year-old female presented with advanced uterine cancer 7.0 × 6.0 × 5.5 cm in size, with infiltration of the bladder. Previous chemotherapy and radiotherapy had been unsuccessful in preventing disease progression, and the patient developed hepatic metastases. As the tumor expressed a high level of estrogen receptor, treatment with fulvestrant 250 mg/month was initiated. Results: 25 months after commencing fulvestrant treatment, the tumor had decreased in size to 4.8 × 3.5 × 3.2 cm, and the hepatic metastases were no longer detectable. Throughout treatment, the patient maintained a Karnofsky performance index of 90%. Conclusion: We suggest that fulvestrant may be an active and well-tolerated treatment option for patients with estrogen receptor- positive advanced uterine cancer.