Susanne Diekmann

4-D Imaging in Cerebrovascular Disorders by Using 320-Slice CT: Feasibility and Preliminary Clinical Experience

RATIONALE AND OBJECTIVES The authors report study protocols and initial clinical experience in assessing patients with acute and chronic cerebrovascular disorders using the recently introduced technique of volume computed tomography (VCT). MATERIALS AND METHODS Thirteen patients with presumptive cerebrovascular insufficiency underwent VCT using a 320-slice scanner (detector width, 160 mm), including time-resolved whole-brain perfusion and cerebral angiography (four-dimensional computed tomographic angiography [CTA] and computed tomographic perfusion [CTP]). Unenhanced cranial CT (cCT) and helical cervicocranial CT (three-dimensional CTA) were added according to clinical requirements. Study protocols are presented, and image quality, data management, and radiation exposure issues are discussed. RESULTS In 12 of 13 patients, the procedure was performed successfully on admission; in the other patient, the study was aborted for clinical reasons and repeated. Total scan time amounted to about 5 minutes, and data reconstruction times were up to 10 minutes. About 9000 primary images were generated, partially in the enhanced Digital Imaging and Communications in Medicine format, thus requiring new data postprocessing and management strategies. Image artifacts restricted the use of single-rotation cCT and incremental VCT (three-dimensional CTA). Overall exposure figures (computed tomographic dose index and dose-length product) were increased by 65% on average when three-dimensional CTA was added to volume cCT and four-dimensional CTA and CTP (5.0 mSv and 2178 mGy . cm, respectively). CONCLUSION Preliminary clinical experience indicates that whole-brain four-dimensional CTA and CTP is a robust technique that provides relevant clinical information with respect to whole-brain perfusion as well as cerebral hemodynamics. The exposure benefit of deriving time-resolved perfusion and vessel images from one source data set is compromised when adding three-dimensional CTA to the protocol. Other acquisition techniques specific to VCT, such as single-rotation cCT and incremental three-dimensional CTA, suffer from restrictions in terms of image quality at present.

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.

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.

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.

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.

Contrast-to-noise ratios of different elements in digital mammography: evaluation of their potential as new contrast agents.

Purpose:To determine the contrast-to-noise ratios (CNRs) of different elements at different energies using various anode/filter combinations currently employed in digital mammography. The elements investigated included not only elements already used in conventional contrast agents such as gadolinium and iodine but also other elements to investigate their potential as mammographic contrast agents. Materials and Methods:The CNRs of 20 mmol/L bismuth (Bi), gadolinium (Gd), ytterbium (Yb), dysprosium (Dy), and iodine (I) were determined at different slice thicknesses (0.25, 0.5, and 1 cm) of the element solution with an additional 4-cm Plexiglas in relation to water (to simulate dense glandular tissue), oil, and air. The following anode/filter combinations were used: Mo/Mo in the range of 22–34 kVp, Mo/Rh in the range of 36–40 kVp, Rh/Rh in the range of 42–46 kVp, and Mo/Cu in the range of 47–49 kVp. In the range of 22–46 kVp, the mAs were chosen to achieve a fairly uniform dose range (of 4.38–4.71 mGy). Doses were measured using the PTW DIADOS diagnostic dosimeter. The element solutions were examined with a GE Senographe 2000D. Results:Bismuth showed the best CNR for all energies investigated and in relation to both water and oil. In the energy range below 46 kVp, bismuth (CNR at 30 kVp/50 mAs and 1/0.5/0.25 cm slice thickness: 9.9/6.1/3.4) was followed by Yb (5.9/3.5/2.0), Dy (5.3/3.2/1.9), Gd (4.2/2.5/1.6), and iodine (2.4/1.8/1.5). Bismuth had the best CNR relative to both water (values given above) and oil (Bi: 20.7/11.2/5; Yb: 16.9/8.6/3.6; Dy: 16.6/8.4/3.5; Gd: 15.21/7.5/3.2; I: 13.8/6.3/3.2). The CNR of Bi was also superior to that of the other elements investigated at high energy in combination with copper filters (eg, CNR at 49 kVp Mo/Cu at slice thicknesses of 1/0.5/0.25 cm, relative to water: 9.6/6.0/4.0) but now followed by iodine (7.9/5.3/3.5), Yb (5.8/4.0/2.9), Dy (5.4/3.7/2.8), and Gd (4.7/3.2/2.7). Iodine was the only element of those investigated whose contrast-to-noise ratio was improved with the use of a copper filter at high energies based on its K-edge (increase in CNR from 2.9 to 7.9 from 40 to 49 kVp at 1-cm slice thickness). Nevertheless, the improved CNR of iodine was below that of Bi at low energies and for Mo/Mo or Mo/Rh filters. The contrast of water/fat tended to decrease slightly at higher energies (CNR of water/air at 42 kVp: 33.9, at 48 kVp: 25.6; CNR of oil/air at 42 kVp: 23.8, at 48 kVp: 21.9). Conclusion:Copper filters and higher energies are useful for visualizing iodine-based contrast agents in contrast-enhanced mammography because they markedly improve the CNR relative to water. This technique further benefits from the fact that the CNR of water and fat relative to air markedly decreases at higher energies and with the use of copper filters. Bismuth was found to have a much better CNR than iodine for all energies investigated including the low energy ranges typically used in mammography. These results suggest that bismuth is a potential candidate for a specific mammographic contrast agent.

In patients with DCIS: is it sufficient to histologically examine only those tissue specimens that contain microcalcifications?

The purpose was to investigate in patients with histologically proven DCIS to what extent there is agreement between radiographically proven microcalcifications of specimens obtained by vacuum-assisted biopsy and the histologic diagnosis of microcalcifications and DCIS, and second, to assess the accuracy of biopsy in relation to the number of specimens obtained in patients with high-grade and low-grade DCIS. Four hundred twenty specimens from 35 patients who were diagnosed with DCIS were examined radiographically and histologically for the presence of microcalcifications. The results were analyzed using the McNemar-test. In addition, the average numbers of biopsy specimens necessary for diagnosing low-grade DCIS and high-grade DCIS were compared using the t-test. Specimen radiography had a PPV of 0.50 and a NPV of 0.85 for the demonstration of DCIS. Differences in localization between radiographically proven microcalcifications and DCIS were statistically significant (p < 0.01). The difference between the mean numbers of specimens required per patient for correctly diagnosing high-grade or low-grade DCIS was statistically significant (p < 0.01). Specimen radiography is very limited in identifying those specimens that are crucial for diagnosing DCIS. The rate of underestimation is expected to be higher for low-grade than for high-grade DCIS. The findings suggest that all samples obtained by vacuum-assisted breast biopsy should be histologically examined.

Evaluation of a wavelet-based computer-assisted detection system for identifying microcalcifications in digital full-field mammography

Purpose: To evaluate a new wavelet‐based computer‐assisted detection (CAD) system for detecting and enhancing microcalcifications. Material and Methods: A total of 280 mammograms acquired by full‐field digital mammography (Senographe 2000D; G.E. Medical Systems Milwaukee, Wisc., USA) were analyzed with and without a new wavelet‐based CAD system for detecting and enhancing microcalcifications. The mammograms comprised roughly equal numbers of cases from each of the BIRADS (Breast Imaging, Reporting and Data System, according to the American College of Roentgenology) categories 1–5. Histologic confirmation was available for all of the 180 cases assigned BIRADS categories 3–5. Four readers interpreted all 280 images for suspicious microcalcifications using a scale of 1–5. The readers alternately assessed 5 images with and 5 without CAD. In a second reading immediately following the first, the readers had to reassess the 280 mammograms. The images that had already been interpreted without CAD were now presented with CAD and vice versa. The images were interpreted as soft copies on a diagnostic mammography workstation (Image Diagnost GmbH, Neufahrn/Munich, Germany). All images interpreted with CAD were presented with enhancement of microcalcifications by wavelet algorithms and prompting of microcalcifications. ROC (receiver operating characteristic) analyses were performed, and image interpretation time with and without CAD was measured. Results: The overall time for interpretation required by all 4 readers together was 483 min with CAD compared to 580 min without CAD. ROC analysis revealed no significant advantage of CAD for the individual readers. Readers 3 (0.811/0.817) and 4 (0.799/0.843) had a slightly improved AUC (area under the curve) with CAD. Readers 1 and 2 had a slightly lower AUC with CAD (0.832 versus 0.861 and 0.818 versus 0.849). Conclusion: The CAD system significantly (P<0.05, t test) speeded up image interpretation with respect to the identification of microcalcifications, while the diagnostic quality remained almost identical under the study conditions.

Infratentorial progressive multifocal leukencephalopathy in a patient with pulmonary sarcoidosis

Sirs, A 56-year-old woman was referred to our hospital in July 2007 because of cerebellar ataxia, tetraparesis, dysphagia and dysarthrophonia which had progressed over the last 9 months. In 1988 the patient was diagnosed with pulmonary sarcoidosis and since treated with varying doses of glucocorticoids. A magnetic resonance imaging (MRI) scan of the brain from February 2007 showed a left pontine T2 weighted hyperintense lesion (Fig. 1a). The patient was diagnosed with probable neurosarcoidosis and treated with a pulse of i.v. methylprednisolone (500 mg/day for 5 consecutive days) followed by oral prednisolone (40– 100 mg/day over the next weeks). However, despite treatment neurological symptoms further progressed and the patient was transferred to our neurological ward. Laboratory testing revealed lymphocytopenia in differential blood count (relative: 3%, absolute: 0.31/nl) with normal leukocyte levels. Serological tests for possible autoimmune and infective etiologies were negative. Cerebral spinal fluid (CSF) examination was normal besides detection of oligoclonal bands only in CSF. Molecular testing revealed a polyclonal Tand B-cell population. To exclude Whipple0s disease a biopsy of duodenal mucosa was performed and found normal. Thorax-CT was consistent with pulmonary sarcoidosis. MRI scans showed T2-weighted and fluid-attenuated inversion recovery hyperintensities in pons and cerebellum (Fig. 1b, c) without Gadolinium enhancement. Smaller (7 mm), similar signal intensities were found supratentorially in the frontal subcortical white matter on both sides (Fig. 1d). Intravenous methylprednisolone at 500 mg/day was administered for 5 consecutive days followed by administration of methotrexate at 10 mg orally once. Soon thereafter, the patient developed bacterial pneumonia, was transferred to the neurointensive care unit, antibiotically treated and mechanically ventilated. Stereotactic brain biopsy of the cerebellum showed areas of demyelination additionally marked by the presence of several foamy macrophages. JC virus (JCV) was detected in biopsy sample by immunohistochemistry (Fig. 2). In addition, JCV DNA was detected by polymerase chain reaction (PCR) in cerebellar tissue, CSF, serum and later in urine, establishing the diagnosis of progressive multifocal leukoencephalopathy (PML). Therapy with oral prednisolone was immediately stopped. Treatment with cidofovir 5 mg/kg plus probenicid was initiated and repeated 1 week later. However, the patient developed bacterial sepsis with multi-organ failure. She died of cardiovascular failure 11 months after first neurological symptoms occurred. This case shows a brainstem/cerebellar manifestation of PML in a patient with sarcoidosis. PML is a demyelinating CNS disease caused by re-activation of a latent JCV L. Neeb (&) L. Harms M. Endres Department of Neurology, Charite Universitaetsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: lars.neeb@charite.de

Correlation between enhancement characteristics of MR mammography and capillary density of breast lesions

OBJECTIVE To correlate capillary density of breast lesions using the markers D2-40, CD31, and CD34 with early and late enhancement of magnetic resonance mammography (MRM). MATERIALS AND METHODS The local ethics committee approved this study, and informed consent was avail-able from all patients. The study included 64 women with 66 histologically proven breast lesions (41 malignant, 25 benign). MR-enhancement 1 min after contrast medium administration was determined in the tumor (It1/It0 ratio) and in comparison to the surrounding tissue (It1/It1-fat ratio). Capillary density was quantified based on immunohistological staining with D2-40, CD31, and CD34 in breast tumors and surrounding breast tissue. Mean capillary densities were correlated with contrast enhancement in the tumor and surrounding breast tissue. The Kruskal-Wallis test was used to test whether lesions with different MR enhancement patterns differed in terms of capillary density. RESULTS For CD34, there was statistically significant correlation between capillary density and tumor enhancement (r = 0.329, p = 0.012), however not for the malignant or benign groups separately. Mean vessel number identified by staining with D2-40 and CD31 did not correlate significantly with tumor enhancement (D2-40: r = -0.188, p = 0.130; CD31: r = 0.095, p = 0.448). There were no statistically significant differences in capillary density between breast lesions with delayed enhancement or a plateau and lesions showing washout (Kruskal-Wallis test. D2-40: p = 0.173; CD31: p = 0.647; CD34: p = 0.515). CONCLUSION Of the three markers tested, CD34 showed best correlation between early contrast enhancement on MRM and capillary density. Further studies are necessary to clearly demonstrate an association between capillary density and contrast enhancement in breast tumors and surrounding tissue.