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  • 1
    Language: English
    In: PloS one, 2014, Vol.9(3), pp.e90461
    Description: In pancreatic cancer, there is a clear unmet need to identify new serum markers for either early diagnosis, therapeutic stratification or patient monitoring. Proteomic analysis of tumor cell secretomes is a promising approach to indicate proteins released from tumor cells in vitro. Ectodomain shedding of transmembrane proteins has previously been shown to contribute significant fractions the tumor cell secretomes and to generate valuable serum biomarkers. Here we introduce a soluble form of the giant cadherin Fat1 as a novel biomarker candidate. Fat1 expression and proteolytic processing was analyzed by mass spectrometry and Western blotting using pancreatic cancer cell lines as compared to human pancreatic ductal epithelial cells. RNA expression in cancer tissues was assessed by in silico analysis of publically available microarray data. Involvement of ADAM10 (A Disintegrin and metalloproteinase domain-containing protein 10) in Fat1 ectodomain shedding was analyzed by chemical inhibition and knockdown experiments. A sandwich ELISA was developed to determine levels of soluble Fat1 in serum samples. In the present report we describe the release of high levels of the ectodomain of Fat1 cadherin into the secretomes of human pancreatic cancer cells in vitro, a process that is mediated by ADAM10. We confirm the full-length and processed heterodimeric form of Fat1 expressed on the plasma membrane and also show the p60 C-terminal transmembrane remnant fragment corresponding to the shed ectodomain. Fat1 and its sheddase ADAM10 are overexpressed in pancreatic adenocarcinomas and ectodomain shedding is also recapitulated in vivo leading to increased Fat1 serum levels in some pancreatic cancer patients. We suggest that soluble Fat1 may find an application as a marker for patient monitoring complementing carbohydrate antigen 19-9 (CA19-9). In addition, detailed analysis of the diverse processed protein isoforms of the candidate tumor suppressor Fat1 can also contribute to our understanding of cell biology and tumor behavior.
    Keywords: Gene Expression Regulation, Neoplastic ; Adam Proteins -- Metabolism ; Amyloid Precursor Protein Secretases -- Metabolism ; Cadherins -- Metabolism ; Membrane Proteins -- Metabolism ; Pancreatic Neoplasms -- Metabolism
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: International journal of cancer, 15 March 2011, Vol.128(6), pp.1384-92
    Description: Various strategies have been tested to identify serum biomarkers in patients with cancer. Recently, the entire of proteins released by cultured tumor cells into the media, the so-called secretome, has been suggested as a promising source for biomarker discovery. Ectodomains of membrane proteins cleaved from the cell surface represent a surprisingly abundant and apparently stable subset of this subproteome. Aiming for the detection of serum biomarkers for patients with colorectal cancer (CRC), we have previously detected significant amounts of the soluble form of E-cadherin in the secretomes of CRC cells. Here, we report a comprehensive analysis of sE-cadherin levels in sera from patients with CRC, colorectal adenoma, inflammatory bowel disease and familial adenomatous polyposis (FAP). Whereas mean sE-cadherin levels in patients with inflammatory bowel disease (mean: 4.7 μg/ml, SD: 1.5 μg/ml), with adenomas (mean: 4.6 μg/ml, SD: 3.0 μg/ml) and early stage cancers (mean: 4.9 μg/ml, SD: 4.7 μg/ml) do not significantly differ from healthy controls (mean: 4.8 μg/ml, SD: 1.9 μg/ml), patients with Stage III and Stage IV carcinomas display a significant increase (mean: 6.1 μg/ml, SD: 2.6 μg/ml). In individual patients with late-stage CRC, sE-cadherin serum levels directly reflect their disease status over time. These findings suggest a potential application of sE-cadherin as an alternative diagnostic biomarker for monitoring disease particularly in patients with carcinoembryonic antigen negative tumors. In patients with FAP, on the other hand, we also detected a significant increase of serum sE-cadherin levels (mean: 5.8 μg/ml, SD: 2.8 μg/ml), but this was regardless of their tumor load and colectomy status.
    Keywords: Adenoma -- Blood ; Adenomatous Polyposis Coli -- Blood ; Biomarkers, Tumor -- Blood ; Cadherins -- Blood ; Colorectal Neoplasms -- Blood ; Inflammatory Bowel Diseases -- Blood
    ISSN: 00207136
    E-ISSN: 1097-0215
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  • 3
    In: Current Opinion in Urology, 2018, Vol.28(1), pp.35-41
    Description: PURPOSE OF REVIEW: Recent advances in anticancer immunotherapy have revolutionized the treatment of metastatic renal cell (RCC) and urothelial carcinoma. In this review, we discuss the mechanisms of action of these new therapeutic approaches, explicate the common adverse events, and highlight different imaging-based response criteria. RECENT FINDINGS: The recent introduction of immune-checkpoint inhibitors led to substantial advances in therapy of metastatic RCC and urothelial carcinoma. Because of the distinct effector mechanisms of these new substances, atypical response patterns such as transient enlargements of tumor lesions, appearance of new lesions after therapy, no measurable decrease in tumor size, or delayed responses are observed in medical imaging studies. This indicates that the established imaging-based response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines has shortcomings to comprehensively evaluate treatment effects. SUMMARY: While monitoring response to immunotherapy still relies on RECIST criteria, immune-related response criteria have been established to better address the imaging changes occurring under immunotherapy. Further studies with long-term follow-up are needed to properly identify and predict response after treatment beyond progression. Because of the expanding clinical use of immune checkpoint inhibitors, radiologists, urologist, and oncologists should be familiar with common imaging findings under this respective therapy.
    Keywords: Carcinoma, Renal Cell -- Diagnostic Imaging ; Carcinoma, Transitional Cell -- Diagnostic Imaging ; Immunotherapy -- Methods ; Urinary Tract -- Diagnostic Imaging ; Urologic Neoplasms -- Diagnostic Imaging;
    ISSN: 0963-0643
    E-ISSN: 14736586
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  • 4
    In: Journal of Experimental Botany, 2011, Vol. 62(6), pp.2169-2178
    Description: Stable isotope signatures of Zn have shown great promise in elucidating changes in uptake and translocation mechanisms of this metal in plants during environmental changes. Here this potential was tested by investigating the effect of high Zn concentrations on the isotopic fractionation patterns of Phragmites australis (Cav.) Trin. ex Steud. Plants were grown for 40 d in a nutritive solution containing 3.2 μM (sufficient) or 2 mM (toxic) Zn. The Zn isotopic composition of roots, rhizomes, shoots, and leaves was analysed. Stems and leaves were sampled at different heights to evaluate the effect of long-distance transport on Zn fractionation. During Zn sufficiency, roots, rhizomes, and shoots were isotopically heavy (δ 66 Zn JMC Lyon =0.2‰) while the youngest leaves were isotopically light (–0.5‰). During Zn excess, roots were still isotopically heavier (δ 66 Zn=0.5‰) and the rest of the plant was isotopically light (up to –0.5‰). The enrichment of heavy isotopes at the roots was attributed to Zn uptake mediated by transporter proteins under Zn-sufficient conditions and to chelation and compartmentation in Zn excess. The isotopically lighter Zn in shoots and leaves is consistent with long-distance root to shoot transport. The tolerance response of P. australis increased the range of Zn fractionation within the plant and with respect to the environment.
    Keywords: Isotope Fractionation ; Mc - Icp - Ms ; Metallomics ; Metals ; Nutrition ; 〈Kwd〉〈Italic〉Phragmites Australis〈/Italic〉〈/Kwd〉 ; Reed
    ISSN: 0022-0957
    E-ISSN: 1460-2431
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  • 5
    Language: English
    In: International Journal of Computer Assisted Radiology and Surgery, 2018, Vol.13(6), pp.787-796
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11548-018-1751-5 Byline: Jakob Weiss (1), Nicola Rieke (1), Mohammad Ali Nasseri (2), Mathias Maier (2), Abouzar Eslami (3), Nassir Navab (1,4) Keywords: Optical coherence tomography; iOCT; Instrument tracking; Ophthalmic tool tracking; Geometric modeling Abstract: Purpose Intraoperative optical coherence tomography (iOCT) is an increasingly available imaging technique for ophthalmic microsurgery that provides high-resolution cross-sectional information of the surgical scene. We propose to build on its desirable qualities and present a method for tracking the orientation and location of a surgical needle. Thereby, we enable the direct analysis of instrument--tissue interaction directly in OCT space without complex multimodal calibration that would be required with traditional instrument tracking methods. Method The intersection of the needle with the iOCT scan is detected by a peculiar multistep ellipse fitting that takes advantage of the directionality of the modality. The geometric modeling allows us to use the ellipse parameters and provide them into a latency-aware estimator to infer the 5DOF pose during needle movement. Results Experiments on phantom data and ex vivo porcine eyes indicate that the algorithm retains angular precision especially during lateral needle movement and provides a more robust and consistent estimation than baseline methods. Conclusion Using solely cross-sectional iOCT information, we are able to successfully and robustly estimate a 5DOF pose of the instrument in less than 5.4 ms on a CPU. Author Affiliation: (1) 0000000123222966, grid.6936.a, Computer Aided Medical Procedures, Technische Universitat Munchen, Boltzmannstr. 3, 85748, Garching, Germany (2) 0000 0004 0477 2438, grid.15474.33, Augenklinik und Poliklinik, Klinikum rechts der Isar der Technische Universit Munchen, 81675, Munich, Germany (3) 0000 0004 0379 7801, grid.424549.a, Carl Zeiss Meditec AG, 81379, Munich, Germany (4) 0000 0001 2171 9311, grid.21107.35, Johns Hopkins University, Baltimore, MD, USA Article History: Registration Date: 22/03/2018 Received Date: 29/01/2018 Accepted Date: 22/03/2018 Online Date: 30/03/2018
    Keywords: Optical coherence tomography ; iOCT ; Instrument tracking ; Ophthalmic tool tracking ; Geometric modeling
    ISSN: 1861-6410
    E-ISSN: 1861-6429
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  • 6
    Language: English
    In: La Radiologia medica, April 2017, Vol.122(4), pp.280-287
    Description: To evaluate noise-optimized monoenergetic postprocessing of dual-energy CT (DE-CT) on image quality in patients with incidental pulmonary embolism in single-pass portal-venous phase CT (CT). 20 Consecutive patients with incidental pulmonary embolism in contrast-enhanced oncological follow-up DE-CT examination were included in this study. Images were acquired with a 3rd generation DE-CT system in DE mode (100/Sn150 kV) and activated tube current modulation 90 s after contrast agent administration. Subsequently, virtual monoenergetic images (MEI+) were reconstructed at five different keV levels (40, 55, 70, 85, 100) and compared to the standard linearly blended (M_0.8) CT images. Image quality was assessed qualitatively (vascular contrast and detectability of embolism, image noise, iodine influx artifact; two independent readers; 5-point Likert scale; 5 = excellent) and quantitatively by calculating signal-to-noise (SNR) and contrast-to-noise ratios (CNR). Highest vessel contrast and highest detectability of embolism were observed in MEI+ at 40 keV (4.7 ± 0.4) and 55 keV (4.2 ± 0.6) with significant differences as compared to CT (3.6 ± 0.5) and high keV reconstructions (70, 85, 100; p ≤ 0.01). Image noise significantly increased at 40 keV MEI+ compared to all other MEI+ reconstructions and CT (p 〈 0.001). SNR and CNR calculations were highest at 40 keV MEI+ followed by 55 keV and CT with significant differences to high keV MEI+ (85-100). Computed MEI+ at low keV levels allow for improved vessel contrast and visualisation of incidental pulmonary embolism in patients with portal-venous phase CT scans by substantially increasing CNR and SNR.
    Keywords: Improved Iodine Contrast ; Incidental Pulmonary Embolism ; Noise-Optimized Monoenergetic Postprocessing ; Oncological CT Staging ; Neoplasms -- Diagnostic Imaging ; Pulmonary Embolism -- Diagnostic Imaging ; Radiographic Image Interpretation, Computer-Assisted -- Methods ; Tomography, X-Ray Computed -- Methods
    ISSN: 00338362
    E-ISSN: 1826-6983
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  • 7
    In: Journal of Magnetic Resonance Imaging, February 2018, Vol.47(2), pp.459-467
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/jmri.25784/abstract Byline: Jakob Weiss, Mike Notohamiprodjo, Petros Martirosian, Jana Taron, Marcel D. Nickel, Manuel Kolb, Fabian Bamberg, Konstantin Nikolaou, Ahmed E. Othman Purpose To evaluate the feasibility of a self-gated free-breathing volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (CS) for contrast-enhanced multiphase liver MRI. Materials and Methods We identified 23 patients who underwent multiphase gadobutrol-enhanced liver magnetic resonance imaging (MRI) using 1) a prototype free-breathing VIBE sequence with respiratory self-gating and CS (VIBE.sub.CS), and 2) a standard breath-hold VIBE (VIBE.sub.STD) on the same 1.5T scanner at two timepoints. VIBE.sub.CS was continuously acquired for 128 seconds and a time-series of 16 timepoints was jointly reconstructed from the dataset. The unenhanced, arterial, portal-venous, and venous timepoints with the best image quality were selected and compared to the corresponding VIBE.sub.STD series serving as reference. Image quality was assessed qualitatively (image quality, sharpness, lesion conspicuity, vessel contrast, noise, motion/other artifacts; two readers independently; 5-point Likert scale; 5 = excellent) and quantitatively (vessel contrast [VC], coefficient-of-variation [CV]) Statistics were performed using Wilcoxon-sign-rank (ordinal) and paired t-test (continuous variables). Results Image quality and lesion conspicuity revealed no significant differences between the sequences (P AaAaAeAc[yen] 0.3). VIBE.sub.STD showed a tendency higher motion artifacts (P AaAaAeAc[yen] 0.07). Image sharpness significant increased in VIBE.sub.CS as compared to VIBE.sub.STD (P [less than or equal to] 0.03). Arterial phase vessel contrast appeared significantly lower in VIBE.sub.CS than in VIBE.sub.STD (P = 0.04). VIBE.sub.CS showed reconstruction artifacts not present in VIBE.sub.STD (P = 0.001). Image noise was significantly lower in VIBE.sub.CS than in VIBE.sub.STD (P [less than or equal to] 0.004). Arterial phase VC was significantly lower in VIBE.sub.CS than in VIBE.sub.STD (P = 0.01). CV revealed no differences between sequences (P = 0.7). Conclusion VIBE.sub.CS is feasible for continuous free-breathing contrast-enhanced multiphase liver MRI, providing similar image quality and lesion conspicuity as VIBE.sub.STD. Level of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:459-467.
    Keywords: Free‐Breathing Contrast‐Enhanced Multiphase Liver Mri ; Respiration Self‐Gating ; Compressed Sensing ; Liver Mri
    ISSN: 1053-1807
    E-ISSN: 1522-2586
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  • 8
    In: Journal of Magnetic Resonance Imaging, November 2017, Vol.46(5), pp.1507-1515
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/jmri.25665/abstract Byline: Jakob Weiss, Petros Martirosian, Jana Taron, Ahmed E. Othman, Thomas Kuestner, Michael Erb, Jens Bedke, Fabian Bamberg, Konstantin Nikolaou, Mike Notohamiprodjo Keywords: prostate cancer; diffusion-weighted imaging; simultaneous multislice acquisition; accelerated prostate MRI Purpose To assess the feasibility of simultaneous multislice (SMS) single-shot echo-planar-imaging (EPI) for accelerated diffusion-weighted imaging (DWI) of the prostate. Materials and Methods For phantom measurements a dedicated DWI phantom with different sucrose concentrations was used. In addition, 10 volunteers and 16 patients with suspected prostate cancer were examined for in vivo measurements. All examinations were performed with a 3T magnetic resonance imaging (MRI) system. A prototype simultaneous multislice EPI sequence (DW-EPI.sub.SMS; acquisition time 3:14min) was acquired and compared to a single-shot EPI sequence (DW-EPI.sub.SS; acquisition time 6:12min) serving as a standard of reference. Different image quality parameters of EPI.sub.SMS were assessed qualitatively (overall image quality, anatomic differentiability, lesion conspicuity, image noise, distortion; two independent readers; 5-point Likert-scale [5=excellent]) and quantitatively (ADC-values by calculating interclass correlation [ICC] and Bland-Altman limits of agreement [LoA] as measures for reproducibility) and compared to DW-EPI.sub.SS. Results DW-EPI.sub.SMS allowed for a substantially reduced acquisition time as compared to DW-EPI.sub.SS (E50%). Bland-Altman plots revealed robust measurement repeatability for DW-EPI.sub.SMS in the phantom study. Overall image quality did not significantly differ between DW-EPI.sub.SMS and DW-EPI.sub.SS (b1500 images P=0.5; ADC maps P=0.7). Only in b1500 DW images was subjective image noise rated significantly higher in DW-EPI.sub.SS than in DW-EPI.sub.SMS (P=0.006). Quantitative analysis of ADC-values revealed not significant differences between DW-EPI.sub.SMS and DW-EPI.sub.SS (P=0.7) and high measures for reproducibility ICC a[yen]0.96. Conclusion Simultaneous multislice DWI is feasible for accelerated prostate MRI allowing for a substantially reduced examination time with similar image quality and ADC-values as compared to a standard of reference DWI sequence. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1507-1515.
    Keywords: Prostate Cancer ; Diffusion‐Weighted Imaging ; Simultaneous Multislice Acquisition ; Accelerated Prostate Mri
    ISSN: 1053-1807
    E-ISSN: 1522-2586
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  • 9
    Language: English
    In: European Radiology, 2017, Vol.27(3), pp.985-994
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00330-016-4433-0 Byline: Jakob Weiss (1), Jana Taron (1), Ahmed E. Othman (1), Robert Grimm (2), Matthias Kuendel (1), Petros Martirosian (1), Christer Ruff (1), Christina Schraml (1), Konstantin Nikolaou (1), Mike Notohamiprodjo (1) Keywords: Magnetic resonance imaging; Radial VIBE; Gd-EOB-DTPA; Artefacts; Liver Abstract: Objective To evaluate feasibility of a 3D-isotropic self-gated radial volumetric interpolated breath-hold examination (VIBE) for late-phase MRI of the liver. Material and methods 70 patients were included and underwent liver MRI at 1.5 T. Depending on the diagnosis, either Gd-EOB-DTPA (35 patients) or gadobutrol (35 patients) were administered. During late (gadobutrol) or hepatocyte-specific phase (Gd-EOB-DTPA), a radial prototype sequence was acquired and reconstructed using (1) self-gating with 40 % acceptance (rVIBE.sub.40) (2) with 100 % acceptance of the data (rVIBE.sub.100) and compared to Cartesian VIBE (cVIBE). Images were assessed qualitatively (image quality, lesion conspicuity, artefacts 5-point Likert-scale: 5=excellent two independent readers) and quantitatively (coefficient-of-variation (CV) contrast-ratio) in axial and coronal reformations. Results In eight cases only rVIBE provided diagnostic image quality. Image quality of rVIBE.sub.40 was rated significantly superior (p〈0.05) in Gd-EOB-DTPA-enhanced and coronal reformatted examinations as compared to cVIBE. Lesion conspicuity was significantly improved (p〈0.05) in coronal reformatted Gd-EOB-DTPA-enhanced rVIBE.sub.40 in comparison to cVIBE. CV was higher in rVIBE.sub.40 as compared to rVIBE.sub.100/cVIBE (p〈0.01). Gadobutrol-enhanced rVIBE.sub.40 and cVIBE showed higher contrast-ratios than rVIBE.sub.100 (p〈0.001), whereas no differences were found in Gd-EOB-DTPA-enhanced examinations. Conclusion Self-gated 3D-isotropic rVIBE provides significantly superior image quality compared to cVIBE, especially in multiplanar reformatted and Gd-EOB-DTPA-enhanced examinations. Key Points acents Radial VIBE acquisition reduces motion artefacts. acents Gd-EOB-DTPA-enhanced scans provide improved image quality. acents Non-diagnostic liver MRI examinations may be reduced by radial k-spaces sampling. Author Affiliation: (1) Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Stra[sz]e 3, 72076, Tuebingen, Germany (2) Siemens Healthcare MR, Erlangen, Germany Article History: Registration Date: 20/05/2016 Received Date: 12/01/2016 Accepted Date: 20/05/2016 Online Date: 08/06/2016
    Keywords: Magnetic resonance imaging ; Radial VIBE ; Gd-EOB-DTPA ; Artefacts ; Liver
    ISSN: 0938-7994
    E-ISSN: 1432-1084
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  • 10
    Language: English
    In: La radiologia medica, 2017, Vol.122(11), pp.822-828
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11547-017-0793-z Byline: Jakob Weiss (1,2), Andreas Pomschar (2), Carsten Rist (2), Klement Neumaier (3), Minglun Li (3), Wilhelm Flatz (2), Kolja Thierfelder (2), Mike Notohamiprodjo (1,2) Keywords: Abdomen; Gastrointestinal imaging; Ultralow-dose fluoroscopy; Technical evaluation Abstract: Purpose To establish an optimized ultralow-dose digital pulsed fluoroscopy (FP) protocol for upper gastrointestinal tract examinations and to investigate the radiation dose and image quality. Materials and methods An Alderson-Rando-Phantom with 60 thermoluminescent dosimeters was used for dose measurements to systematically evaluate the dose--area product (DAP) and organ doses of the optimized FP protocol with the following acquisition parameters: 86.7 kV 77 mA 0.9 mm.sup.3, automatic image noise and contrast adaption. Subjective image quality, depiction of contrast agent and image noise (5-point Likert scale 5 = excellent) were assessed in 41 patients, who underwent contrast-enhanced FP with the aforementioned optimized protocol by two radiologists in consensus. A conventional digital radiograph (DR) acquisition protocol served as the reference standard for radiation dose and image quality analyses. Results Phantom measurements revealed a general dose reduction of approximately 96% per image for the FP protocol as compared to the DR standard. DAP could be reduced by 97%. Significant dose reductions were also found for organ doses, both in the direct and scattered radiation beam with negligible orbital (FP 5.6 x 10.sup.-3 vs. DR 0.11 p = 0.02) and gonadal dose exposure (female FP 2.4 x 10.sup.-3 vs. DR 0.05 male FP 8 x 10.sup.-4 vs. DR 0.03 p a[currency] 0.0004). FP provided diagnostic image quality in all patients, although reading scores were significantly lower for all evaluated parameters as compared to the DR standard (p 〈 0.05). Conclusion Ultralow-dose FP is feasible for clinical routine allowing a significant reduction of direct and scattered dose exposure while providing sufficient diagnostic image quality for reliable diagnosis. Author Affiliation: (1) Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, University of Tuebingen, Hoppe-Seyler-Stra[sz]e 3, 72076, Tuebingen, Germany (2) Department of Diagnostic and Interventional Radiology, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany (3) Department of Radiooncology and Radiotherapy, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany Article History: Registration Date: 13/07/2017 Received Date: 12/04/2017 Accepted Date: 12/07/2017 Online Date: 22/07/2017
    Keywords: Abdomen ; Gastrointestinal imaging ; Ultralow-dose fluoroscopy ; Technical evaluation
    ISSN: 0033-8362
    E-ISSN: 1826-6983
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