Felix Diekmann

Dual-energy contrast-enhanced digital mammography: initial clinical results of a multireader, multicase study

IntroductionThe purpose of this study was to compare the diagnostic accuracy of dual-energy contrast-enhanced digital mammography (CEDM) as an adjunct to mammography (MX) ± ultrasonography (US) with the diagnostic accuracy of MX ± US alone.MethodsOne hundred ten consenting women with 148 breast lesions (84 malignant, 64 benign) underwent two-view dual-energy CEDM in addition to MX and US using a specially modified digital mammography system (Senographe DS, GE Healthcare). Reference standard was histology for 138 lesions and follow-up for 12 lesions. Six radiologists from 4 institutions interpreted the images using high-resolution softcopy workstations. Confidence of presence (5-point scale), probability of cancer (7-point scale), and BI-RADS scores were evaluated for each finding. Sensitivity, specificity and ROC curve areas were estimated for each reader and overall. Visibility of findings on MX ± CEDM and MX ± US was evaluated with a Likert scale.ResultsThe average per-lesion sensitivity across all readers was significantly higher for MX ± US ± CEDM than for MX ± US (0.78 vs. 0.71 using BIRADS, p = 0.006). All readers improved their clinical performance and the average area under the ROC curve was significantly superior for MX ± US ± CEDM than for MX ± US ((0.87 vs 0.83, p = 0.045). Finding visibility was similar or better on MX ± CEDM than MX ± US in 80% of cases.ConclusionsDual-energy contrast-enhanced digital mammography as an adjunct to MX ± US improves diagnostic accuracy compared to MX ± US alone. Addition of iodinated contrast agent to MX facilitates the visualization of breast lesions.

Tomosynthesis and contrast-enhanced digital mammography: recent advances in digital mammography

Digital mammography is more and more replacing conventional mammography. Initial concerns about an inferior image quality of digital mammography have been largely overcome and recent studies even show digital mammography to be superior in women with dense breasts, while at the same time reducing radiation exposure. Nevertheless, an important limitation of digital mammography remains: namely, the fact that summation may obscure lesions in dense breast tissue. However, digital mammography offers the option of so-called advanced applications, and two of these, contrast-enhanced mammography and tomosynthesis, are promising candidates for improving the detection of breast lesions otherwise obscured by the summation of dense tissue. Two techniques of contrast-enhanced mammography are available: temporal subtraction of images acquired before and after contrast administration and the so-called dual-energy technique, which means that pairs of low/high-energy images acquired after contrast administration are subtracted. Tomosynthesis on the other hand provides three-dimensional information on the breast. The images are acquired with different angulations of the X-ray tube while the object or detector is static. Various reconstruction algorithms can then be applied to the set of typically nine to 28 source images to reconstruct 1-mm slices with a reduced risk of obscuring pathology. Combinations of both advanced applications have only been investigated in individual experimental studies; more advanced software algorithms and CAD systems are still in their infancy and have only undergone preliminary clinical evaluation.

Digital mammography using iodine-based contrast media: initial clinical experience with dynamic contrast medium enhancement.

Purpose:We sought to evaluate the potential of dynamic contrast enhancement after the intravenous administration of an iodine-based contrast medium in full-field digital mammography. Material and Methods:A protocol for image acquisition was established for contrast-enhanced mammography and the mammography unit (Senographe 2000D, GE Healthcare, Buc, France) changed as required. The effect of the protocol parameters on imaging was investigated. Subsequently, 21 patients with 25 suspicious lesions of the breast (10 benign, 1 borderline, and 14 malignant) underwent mammography with administration of an iodine-based contrast medium (Ultravist 370, Schering AG, Berlin, Germany), after approval of ethical committee as well as permission of German federal office for Radiation protection, and informed consent from each patient was obtained. Three sequential digital mammographic images of the respective breast were acquired after administration of the contrast medium at a dose of 1 mL/kg body weight and a flow of 4 mL/s. The postcontrast images were acquired 60, 120, and 180 seconds after administration. Subsequently, the precontrast image was logarithmically subtracted from the postcontrast images. Enhancement of the lesions was measured in absolute terms as well as relative to the enhancement of the glandular tissue. The subtracted images were evaluated for lesion depiction and dynamic contrast enhancement. Lesion-enhancement kinetics were compared with the histologic findings. Results:All malignant lesions were identified on the contrast-enhanced images of digital mammography. Three of the tumors (2 malignant, 1 benign) were detected only by contrast-enhanced mammography and not by standard mammography. Dynamic enhancement curves of benign and malignant tumors in contrast-enhanced mammography look similar to the curves known from gadolinium-enhanced magnetic resonance imaging. Nevertheless differentiation between malignant and benign tumors based on the enhancement patterns cannot be directly taken over from magnetic resonance imaging, as suggested by our initial results. The results are somewhat better when tumor enhancement relative to surrounding glandular tissue is used instead of absolute enhancement. Conclusion:The results of this preliminary study suggest that contrast-enhanced digital mammography is a potentially useful tool for the detection and the differentiation of benign and malignant breast lesions.

Breast cancer: early- and late-fluorescence near-infrared imaging with indocyanine green--a preliminary study.

PURPOSE To assess early- and late-fluorescence near-infrared imaging, corresponding to the vascular (early-fluorescence) and extravascular (late-fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer detection and benign versus malignant breast lesion differentiation. MATERIALS AND METHODS The study was approved by the ethical review board; all participants provided written informed consent. Twenty women with 21 breast lesions were examined with near-infrared imaging before, during, and after intravenous injection of ICG. Absorption and fluorescence projection mammograms were recorded simultaneously on a prototype near-infrared imaging unit. Two blinded readers independently assessed the images and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence mammograms. Imaging results were compared with histopathologic findings. Lesion contrast and diameter on the fluorescence mammograms were measured, and Cohen κ, Mann-Whitney U, and Spearman ρ tests were conducted. RESULTS The absorption-corrected fluorescence ratio mammograms showed high contrast (contrast value range, 0.25-0.64) between tumors and surrounding breast tissue. Malignant lesions were correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign lesions were correctly defined in six (reader 1) and five (reader 2) of eight cases with late-fluorescence imaging. Lesion visibility scores for malignant and benign lesions were significantly different on the fluorescence ratio mammograms (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and specificity reached 92% ± 8 (standard error of mean) and 75% ± 16, respectively, for fluorescence ratio imaging compared with 100% ± 0 and 25% ± 16, respectively, for conventional mammography alone. CONCLUSION Preliminary data suggest that early- and late-fluorescence ratio imaging after ICG administration can be used to distinguish malignant from benign breast lesions.

Evaluation of contrast-enhanced digital mammography.

PURPOSE The goal of this prospective study was to evaluate the possible diagnostic benefits of contrast-enhanced digital mammography (CEDM) over conventional mammography. MATERIALS AND METHODS Our analysis included data from 70 patients with a total of 80 lesions (30 malignant and 50 benign). A series of contrast-enhanced images was acquired from each patient using a modified imaging system (GE Senographe 2000D with copper filter) suitable for displaying iodine contrast medium. After the mask image had been taken, the contrast medium was administered using a dosage of 1ml/kg body weight at a rate of 4ml/s. Three contrast-enhanced images in the cranio-caudal projection plane were then captured at intervals of 60s. The mask image was logarithmically subtracted from the contrast-enhanced images. We performed a ROC analysis of diagnostic quality with three readers. RESULTS On average, 5.66 more malignant lesions were detected with the addition of digital dynamic contrast mammography versus conventional mammography alone. The sensitivity was increased from an average of 0.43 in conventional mammography to an average of 0.62 with contrast mammography. Even in dense breast parenchyma, the sensitivity increased from an average of 0.35-0.59. In the multi-reader-ROC analyses of all readers, the differences in the AUC with p=0.02 (BI-RADS) proved statistically significant in all cases. The Wilcoxon test showed that Readers I and II primarily used the CEDM to upgrade enhancing lesions to a higher BI-RADS category or a higher probability of malignancy. These two readers benefited most from the CEDM in the ROC analysis. CONCLUSION Overall, we conclude that the addition of dynamic digital subtraction mammography to conventional mammography can significantly improve diagnostic quality. The increased sensitivity is particularly pronounced in the case of dense breast tissue.

Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for Breast MR Imaging (DETECT Trial)

PURPOSE To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis.

New contrast media designed for x-ray energy subtraction imaging in digital mammography.

Rationale and Objectives:In contrast-enhanced dual-energy subtraction imaging 2 images acquired postcontrast media administration at different energies are subtracted to highlight structures hidden in the absence of contrast media. X-ray spectra of the newly developed digital full-field mammography units (GE Senographe 2000 D) are dominated by the emission lines of the Mo or Rh anodes. The K–edge of Zirconium (Zr) is flanked by these 2 emission lines. Thus, the attenuation of Zr should experience a pronounced change of attenuation in parallel with a change of anodes. Under clinically relevant conditions, the contrasting behavior of Zr should be compared with that of other elements having K-edge energies outside the window spanned by the 2 anode emission lines. Methods:Solutions containing the contrasting elements Br, Y, Zr, I, and Gd were investigated for dual-energy subtraction in digital mammography with the 2 anode/filter settings (Mo/Mo and Rh/Rh). These solutions were investigated in phantom studies in the energy range conventionally used in mammography. Additionally, the contrasting behavior of Zr and I was compared in an in vivo study in rats. Results:The sweeping over the K–edge by alternating between the Mo and Rh anodes increases the detection of Zr in energy subtraction imaging at constant high voltage. This procedure does not lead to sufficient contrast enhancement for iodine-based contrast media which become detectable by increasing the high voltage to 40–49 kV. Conclusion:The instrumental and physical data outlined predestine Zr as contrasting element with a high potential for energy subtraction imaging in digital mammography in the energy range conventionally applied.

Detection and classification of contrast-enhancing masses by a fully automatic computer-assisted diagnosis system for breast MRI

To evaluate a fully automatic computer‐assisted diagnosis (CAD) method for breast magnetic resonance imaging (MRI), which considered dynamic as well as morphologic parameters and linked those to descriptions laid down in the Breast Imaging Reporting and Data System (BI‐RADS) MRI atlas.

Development of Low-Dose Photon-counting Contrast-enhanced Tomosynthesis with Spectral Imaging

PURPOSE To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. MATERIALS AND METHODS All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. RESULTS Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. CONCLUSION The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity.

Near-infrared laser computed tomography of the breast first clinical experience.

RATIONALE AND OBJECTIVES The purpose of the present study was to evaluate a near-infrared (NIR) laser breast imaging system (Computed Tomography Laser Mammography [CTLM]) as an adjunct to mammography by means of receiver-operating characteristic (ROC) analysis. The NIR technique used in this study is based on the absorption of NIR light by hemoglobin. Malignant tumors can be detected by imaging their neovascularization. MATERIALS AND METHODS Eighty-two patients were examined by both CTLM and mammography. Seventy-nine of the 82 patients underwent biopsies, and three patients had 2-year follow up. Three-dimensional scans were acquired with an NIR laser computed tomographic scanner (the CTLM system) at a slice thickness of 4 mm. Mammograms were analyzed alone and together with CTLM images. RESULTS Histology revealed 37 benign and 42 malignant lesions. For the combination of mammography and CTLM, the area under the ROC curve was significantly larger than for mammography alone. In addition, it was shown that the difference in area under the ROC curve between the combination of both methods and mammography alone was considerably larger for dense breasts than for radiolucent breasts, although these differences were not statistically significant. CONCLUSION CTLM, used as an adjunct, may serve as a feasible tool to improve the diagnostic capabilities of mammography.