Publications by authors named "Tobias Penzkofer"

76 Publications

Intra-scanner repeatability of quantitative imaging features in a 3D printed semi-anthropomorphic CT phantom.

Eur J Radiol 2021 Aug 9;141:109818. Epub 2021 Jun 9.

Department of Radiology, Charité - Universitätsmedizin Berlin, Germany; Berlin Institute of Health, Berlin, Germany.

Objectives: Radiomics has shown to provide novel diagnostic and predictive disease information based on quantitative image features in study settings. However, limited data yielded contradictory results and important questions regarding the validity of the methods remain to be answered. The purpose of this study was to evaluate how clinical imaging techniques affect the stability of radiomics features by using 3D printed anthropomorphic CT phantom to test for repeatability and reproducibility of quantitative parameters.

Methods: 48 PET/CT validated lymph nodes of prostate cancer patients (24 metastatic, 24 non-metastatic) were used as a template to create a customized 3D printed anthropomorphic phantom. We subsequently scanned the phantom five times with a routine abdominal CT protocol. Images were reconstructed using iterative reconstruction and two soft tissue kernels and one bone kernel. Radiomics features were extracted and assessed for repeatability and susceptibility towards image reconstruction settings using concordance correlation coefficients.

Results: Our analysis revealed 19 of 86 features (22 %) as highly repeatable (CCC ≥ 0.85) with low susceptibility towards image reconstruction protocols. Most features analyzed depicted critical non-repeatability with CCC's < 0.75 even under entirely consistent imaging acquisition settings. Edge enhancing kernels result in higher variances between the scans and differences in repeatability and reproducibility were detected between PSMA-positive and negative lymph nodes with overall more stable features seen in tumor positive lymph nodes.

Conclusions: Both, repeatability and reproducibility play a crucial role in the validation process of radiomics features in clinical routine. This phantom study shows that most radiomics features in contrast to previous studies, including phantom and clinical, do not depict sufficient intra-scanner repeatability to serve as reliable diagnostic tools.
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http://dx.doi.org/10.1016/j.ejrad.2021.109818DOI Listing
August 2021

Automatized Hepatic Tumor Volume Analysis of Neuroendocrine Liver Metastases by Gd-EOB MRI-A Deep-Learning Model to Support Multidisciplinary Cancer Conference Decision-Making.

Cancers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Department of Radiology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Background: Rapid quantification of liver metastasis for diagnosis and follow-up is an unmet medical need in patients with secondary liver malignancies. We present a 3D-quantification model of neuroendocrine liver metastases (NELM) using gadoxetic-acid (Gd-EOB)-enhanced MRI as a useful tool for multidisciplinary cancer conferences (MCC).

Methods: Manual 3D-segmentations of NELM and livers (149 patients in 278 Gd-EOB MRI scans) were used to train a neural network (-Net architecture). Clinical usefulness was evaluated in another 33 patients who were discussed in our MCC and received a Gd-EOB MRI both at baseline and follow-up examination ( = 66) over 12 months. Model measurements (NELM volume; hepatic tumor load (HTL)) with corresponding absolute (ΔNELM; ΔHTL) and relative changes (ΔNELM; ΔHTL) between baseline and follow-up were compared to MCC decisions (therapy success/failure).

Results: Internal validation of the model's accuracy showed a high overlap for NELM and livers (Matthew's correlation coefficient (φ): 0.76/0.95, respectively) with higher φ in larger NELM volume (φ = 0.80 vs. 0.71; = 0.003). External validation confirmed the high accuracy for NELM (φ = 0.86) and livers (φ = 0.96). MCC decisions were significantly differentiated by all response variables (ΔNELM; ΔHTL; ΔNELM; ΔHTL) ( < 0.001). ΔNELM and ΔHTL showed optimal discrimination between therapy success or failure (AUC: 1.000; < 0.001).

Conclusion: The model shows high accuracy in 3D-quantification of NELM and HTL in Gd-EOB-MRI. The model's measurements correlated well with MCC's evaluation of therapeutic response.
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http://dx.doi.org/10.3390/cancers13112726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199286PMC
May 2021

International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer.

Cancers (Basel) 2021 May 27;13(11). Epub 2021 May 27.

Clínica Girona, Institute Catalan of Health-IDI, University of Girona, 17004 Girona, Spain.

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data.

Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings.

Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models ( < 0.001 for all).

Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.
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http://dx.doi.org/10.3390/cancers13112627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198352PMC
May 2021

Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage Related to Different Oral Anticoagulants.

J Clin Med 2021 May 21;10(11). Epub 2021 May 21.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.

Background: There is a need to examine the effects of different types of oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) on perihematomal edema (PHE), which is gaining considerable appeal as a biomarker for secondary brain injury and clinical outcome.

Methods: In a large multicenter approach, computed tomography-derived imaging markers for PHE (absolute PHE, relative PHE (rPHE), edema expansion distance (EED)) were calculated for patients with OAC-ICH and NON-OAC-ICH. Exploratory analysis for non-vitamin-K-antagonist OAC (NOAC) and vitamin-K-antagonists (VKA) was performed. The predictive performance of logistic regression models, employing predictors of poor functional outcome (modified Rankin scale 4-6), was explored.

Results: Of 811 retrospectively enrolled patients, 212 (26.14%) had an OAC-ICH. Mean rPHE and mean EED were significantly lower in patients with OAC-ICH compared to NON-OAC-ICH, -value 0.001 and 0.007; whereas, mean absolute PHE did not differ, -value 0.091. Mean EED was also significantly lower in NOAC compared to NON-OAC-ICH, -value 0.05. Absolute PHE was an independent predictor of poor clinical outcome in NON-OAC-ICH (OR 1.02; 95%CI 1.002-1.028; -value 0.027), but not in OAC-ICH (-value 0.45).

Conclusion: Quantitative markers of early PHE (rPHE and EED) were lower in patients with OAC-ICH compared to those with NON-OAC-ICH, with significantly lower levels of EED in NOAC compared to NON-OAC-ICH. Increase of early PHE volume did not increase the likelihood of poor outcome in OAC-ICH, but was independently associated with poor outcome in NON-OAC-ICH. The results underline the importance of etiology-specific treatment strategies. Further prospective studies are needed.
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http://dx.doi.org/10.3390/jcm10112234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196746PMC
May 2021

FDG-PET/CT for pretherapeutic lymph node staging in non-small cell lung cancer: A tailored approach to the ESTS/ESMO guideline workflow.

Lung Cancer 2021 07 7;157:66-74. Epub 2021 May 7.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nuclear Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address:

Objectives: In patients with NSCLC, current ESTS and ESMO guidelines recommend invasive lymph node (LN) staging with EBUS-TBNA even if FDG-PET/CT is negative for mediastinal LNs if at least one of three risk factors is present (cN1, non-peripheral primary or primary >3 cm). Modified workflows to avoid unnecessary invasive procedures were evaluated.

Materials And Methods: Monocentric retrospective analysis of pretherapeutic FDG-PET/CT in 247 patients with NSCLC (62 % male; age, 68 [43-88] years) using an analog or digital PET/CT scanner. PET windowing was standardized. LNs were positive if 'LN uptake > mediastinal blood pool' or short axis >10 mm. Surgery or EBUS-TBNA served as reference for diagnostic accuracy per LN station. In all patients with negative mediastinal LNs by PET/CT, LN histology from surgery was available.

Results: Among 700 L N stations analyzed, 180 were malignant. Sensitivity and specificity of PET/CT per LN station were 93 % and 71 %. Following current guidelines, 76 patients with mediastinal negative PET/CT required confirmatory invasive staging. Only 5/76 patients had unexpected pN2 (all had adenocarcinoma). In a modified approach, confirmatory invasive staging was confined to patients with mediastinal negative PET/CT who showed all three risk factors. Using this modification, EBUS-TBNA could have been omitted in 62 (82 %) of the 76 patients who required EBUS-TBNA based on current recommendation. Among these 62 patients, only one patient had unsuspected pN2 (single-level) while the remaining 61 of 62 omitted EBUS-TBNA were deemed unnecessary because mediastinal LNs were confirmed to be negative. No multi-level pN2 would have been missed.

Conclusion: In the current analysis, 82 % of EBUS-TBNA procedures in patients with mediastinal negative PET/CT could have been omitted by modifying the current guideline workflow as proposed (i.e., restricting EBUS-TBNA in patients with cN0/1 to those with all three risk factors). This was consistent with different PET/CT scanners. Prospective confirmation is required.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.003DOI Listing
July 2021

ESUR/ESUI position paper: developing artificial intelligence for precision diagnosis of prostate cancer using magnetic resonance imaging.

Eur Radiol 2021 May 15. Epub 2021 May 15.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Artificial intelligence developments are essential to the successful deployment of community-wide, MRI-driven prostate cancer diagnosis. AI systems should ensure that the main benefits of biopsy avoidance are delivered while maintaining consistent high specificities, at a range of disease prevalences. Since all current artificial intelligence / computer-aided detection systems for prostate cancer detection are experimental, multiple developmental efforts are still needed to bring the vision to fruition. Initial work needs to focus on developing systems as diagnostic supporting aids so their results can be integrated into the radiologists' workflow including gland and target outlining tasks for fusion biopsies. Developing AI systems as clinical decision-making tools will require greater efforts. The latter encompass larger multicentric, multivendor datasets where the different needs of patients stratified by diagnostic settings, disease prevalence, patient preference, and clinical setting are considered. AI-based, robust, standard operating procedures will increase the confidence of patients and payers, thus enabling the wider adoption of the MRI-directed approach for prostate cancer diagnosis. KEY POINTS: • AI systems need to ensure that the benefits of biopsy avoidance are delivered with consistent high specificities, at a range of disease prevalence. • Initial work has focused on developing systems as diagnostic supporting aids for outlining tasks, so they can be integrated into the radiologists' workflow to support MRI-directed biopsies. • Decision support tools require a larger body of work including multicentric, multivendor studies where the clinical needs, disease prevalence, patient preferences, and clinical setting are additionally defined.
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http://dx.doi.org/10.1007/s00330-021-08021-6DOI Listing
May 2021

A reporting and analysis framework for structured evaluation of COVID-19 clinical and imaging data.

NPJ Digit Med 2021 Apr 12;4(1):69. Epub 2021 Apr 12.

Computational Radiology, Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

The COVID-19 pandemic has worldwide individual and socioeconomic consequences. Chest computed tomography has been found to support diagnostics and disease monitoring. A standardized approach to generate, collect, analyze, and share clinical and imaging information in the highest quality possible is urgently needed. We developed systematic, computer-assisted and context-guided electronic data capture on the FDA-approved mint Lesion software platform to enable cloud-based data collection and real-time analysis. The acquisition and annotation include radiological findings and radiomics performed directly on primary imaging data together with information from the patient history and clinical data. As proof of concept, anonymized data of 283 patients with either suspected or confirmed SARS-CoV-2 infection from eight European medical centers were aggregated in data analysis dashboards. Aggregated data were compared to key findings of landmark research literature. This concept has been chosen for use in the national COVID-19 response of the radiological departments of all university hospitals in Germany.
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http://dx.doi.org/10.1038/s41746-021-00439-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041811PMC
April 2021

A Novel Deep Learning Based Computer-Aided Diagnosis System Improves the Accuracy and Efficiency of Radiologists in Reading Biparametric Magnetic Resonance Images of the Prostate: Results of a Multireader, Multicase Study.

Invest Radiol 2021 Mar 18. Epub 2021 Mar 18.

From the Department of Radiology, University Hospital of Basel, Basel, Basel-Stadt, Switzerland Department of Radiology, NYU Langone Health, New York, NY Siemens Healthineers, Digital Technology and Innovation, Princeton, NJ Siemens Healthcare AG Advanced Clinical Imaging Technology, Lausanne, Vaud, Switzerland ScreenPoint Medical Department of Radiology, Radboud University Medical Center, Nijmegen, the Netherlands Diagnostikum Graz, Graz, Austria Patero Clinic, Moscow, Russia Eunpyeong St Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea Radiology Department, Changhai Hospital of Shanghai, Shanghai, China Charité, Universitätsmedizin Berlin Berlin Institute of Health, Berlin, Germany Siemens Healthineers Diagnostic Imaging, Erlangen, Germany.

Objective: The aim of this study was to evaluate the effect of a deep learning based computer-aided diagnosis (DL-CAD) system on radiologists' interpretation accuracy and efficiency in reading biparametric prostate magnetic resonance imaging scans.

Materials And Methods: We selected 100 consecutive prostate magnetic resonance imaging cases from a publicly available data set (PROSTATEx Challenge) with and without histopathologically confirmed prostate cancer. Seven board-certified radiologists were tasked to read each case twice in 2 reading blocks (with and without the assistance of a DL-CAD), with a separation between the 2 reading sessions of at least 2 weeks. Reading tasks were to localize and classify lesions according to Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and to assign a radiologist's level of suspicion score (scale from 1-5 in 0.5 increments; 1, benign; 5, malignant). Ground truth was established by consensus readings of 3 experienced radiologists. The detection performance (receiver operating characteristic curves), variability (Fleiss κ), and average reading time without DL-CAD assistance were evaluated.

Results: The average accuracy of radiologists in terms of area under the curve in detecting clinically significant cases (PI-RADS ≥4) was 0.84 (95% confidence interval [CI], 0.79-0.89), whereas the same using DL-CAD was 0.88 (95% CI, 0.83-0.94) with an improvement of 4.4% (95% CI, 1.1%-7.7%; P = 0.010). Interreader concordance (in terms of Fleiss κ) increased from 0.22 to 0.36 (P = 0.003). Accuracy of radiologists in detecting cases with PI-RADS ≥3 was improved by 2.9% (P = 0.10). The median reading time in the unaided/aided scenario was reduced by 21% from 103 to 81 seconds (P < 0.001).

Conclusions: Using a DL-CAD system increased the diagnostic accuracy in detecting highly suspicious prostate lesions and reduced both the interreader variability and the reading time.
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http://dx.doi.org/10.1097/RLI.0000000000000780DOI Listing
March 2021

Joint Imaging Platform for Federated Clinical Data Analytics.

JCO Clin Cancer Inform 2020 11;4:1027-1038

German Cancer Consortium, Heidelberg, Germany.

Purpose: Image analysis is one of the most promising applications of artificial intelligence (AI) in health care, potentially improving prediction, diagnosis, and treatment of diseases. Although scientific advances in this area critically depend on the accessibility of large-volume and high-quality data, sharing data between institutions faces various ethical and legal constraints as well as organizational and technical obstacles.

Methods: The Joint Imaging Platform (JIP) of the German Cancer Consortium (DKTK) addresses these issues by providing federated data analysis technology in a secure and compliant way. Using the JIP, medical image data remain in the originator institutions, but analysis and AI algorithms are shared and jointly used. Common standards and interfaces to local systems ensure permanent data sovereignty of participating institutions.

Results: The JIP is established in the radiology and nuclear medicine departments of 10 university hospitals in Germany (DKTK partner sites). In multiple complementary use cases, we show that the platform fulfills all relevant requirements to serve as a foundation for multicenter medical imaging trials and research on large cohorts, including the harmonization and integration of data, interactive analysis, automatic analysis, federated machine learning, and extensibility and maintenance processes, which are elementary for the sustainability of such a platform.

Conclusion: The results demonstrate the feasibility of using the JIP as a federated data analytics platform in heterogeneous clinical information technology and software landscapes, solving an important bottleneck for the application of AI to large-scale clinical imaging data.
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http://dx.doi.org/10.1200/CCI.20.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713526PMC
November 2020

Diagnostic performance of PI-RADS version 2.1 compared to version 2.0 for detection of peripheral and transition zone prostate cancer.

Sci Rep 2020 09 29;10(1):15982. Epub 2020 Sep 29.

Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.

The purpose of this study is to compare diagnostic performance of Prostate Imaging Reporting and Data System (PI-RADS) version (v) 2.1 and 2.0 for detection of Gleason Score (GS) ≥ 7 prostate cancer on MRI. Three experienced radiologists provided PI-RADS v2.0 scores and at least 12 months later v2.1 scores on lesions in 333 prostate MRI examinations acquired between 2012 and 2015. Diagnostic performance was assessed retrospectively by using MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy as the reference. From a total of 359 lesions, GS ≥ 7 tumor was present in 135 lesions (37.60%). Area under the ROC curve (AUC) revealed slightly lower values for peripheral zone (PZ) and transition zone (TZ) scoring in v2.1, but these differences did not reach statistical significance. A significant number of score 2 lesions in the TZ were downgraded to score 1 in v2.1 showing 0% GS ≥ 7 tumor (0/11). The newly introduced diffusion-weighted imaging (DWI) upgrading rule in v2.1 was applied in 6 lesions from a total of 143 TZ lesions (4.2%). In summary, PI-RADS v2.1 showed no statistically significant differences in overall diagnostic performance of TZ and PZ scoring compared to v2.0. Downgraded BPH nodules showed favorable cancer frequencies. The new DWI upgrading rule for TZ lesions was applied in only few cases.
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http://dx.doi.org/10.1038/s41598-020-72544-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525456PMC
September 2020

Enhancing the differentiation of pulmonary lymphoma and fungal pneumonia in hematological patients using texture analysis in 3-T MRI.

Eur Radiol 2021 Feb 21;31(2):695-705. Epub 2020 Aug 21.

Klinik für Radiologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.

Objectives: To evaluate texture analysis in nonenhanced 3-T MRI for differentiating pulmonary fungal infiltrates and lymphoma manifestations in hematological patients and to compare the diagnostic performance with that of signal intensity quotients ("nonenhanced imaging characterization quotients," NICQs).

Methods: MR scans were performed using a speed-optimized imaging protocol without an intravenous contrast medium including axial T2-weighted (T2w) single-shot fast spin-echo and T1-weighted (T1w) gradient-echo sequences. ROIs were drawn within the lesions to extract first-order statistics from original images using HeterogeneityCAD and PyRadiomics. NICQs were calculated using signal intensities of the lesions, muscle, and fat. The standard of reference was histology or clinical diagnosis in follow-up. Statistical testing included ROC analysis, clustered ROC analysis, and DeLong test. Intra- and interrater reliability was tested using intraclass correlation coefficients (ICC).

Results: Thirty-three fungal infiltrates in 16 patients and 38 pulmonary lymphoma manifestations in 19 patients were included. Considering the leading lesion in each patient, diagnostic performance was excellent for T1w entropy (AUC 80.2%; p < 0.005) and slightly inferior for T2w energy (79.9%; p < 0.005), T1w uniformity (79.6%; p < 0.005), and T1w energy (77.0%; p < 0.01); the best AUC for NICQs was 72.0% for T2NICQmean (p < 0.05). Intra- and interrater reliability was good to excellent (ICC > 0.81) for these parameters except for moderate intrarater reliability of T1w energy (ICC = 0.64).

Conclusions: T1w entropy, uniformity, and energy and T2w energy showed the best performances for differentiating pulmonary lymphoma and fungal pneumonia and outperformed NICQs. Results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.

Key Points: • Texture analysis in nonenhanced pulmonary MRI improves the differentiation of pulmonary lymphoma and fungal pneumonia compared with signal intensity quotients. • T1w entropy, uniformity, and energy along with T2w energy show the best performances for differentiating pulmonary lymphoma from fungal pneumonia. • The results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.
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http://dx.doi.org/10.1007/s00330-020-07137-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813714PMC
February 2021

Optimizing size thresholds for detection of clinically significant prostate cancer on MRI: Peripheral zone cancers are smaller and more predictable than transition zone tumors.

Eur J Radiol 2020 Aug 17;129:109071. Epub 2020 May 17.

Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, Germany. Electronic address:

Purpose: To evaluate if size-based cut-offs based on MR imaging can successfully assess clinically significant prostate cancer (csPCA). The goal was to improve the currently applied size-based differentiation criterion in PI-RADS.

Methods And Materials: MRIs of 293 patients who had undergone 3 T MR imaging with subsequent confirmation of prostate cancer on systematic and targeted MRI/TRUS-fusion biopsy were re-read by three radiologists. All identifiable tumors were measured on T2WI for lesions originating in the transition zone (TZ) and on DWI for lesions from the peripheral zone (PZ) and tabulated against their Gleason grade.

Results: 309 lesions were analyzed, 213 (68.9 %) in the PZ and 96 (31.1 %) in the TZ. ROC-Analysis showed a stronger correlation between lesion size and clinically significant (defined as Gleason Grade Group ≥ 2) prostate cancer (PCa) for the PZ (AUC = 0.73) compared to the TZ (AUC = 0.63). The calculated Youden index resulted in size cut-offs of 14 mm for PZ and 21 mm for TZ tumors.

Conclusion: Size cut-offs can be used to stratify prostate cancer with different optimal size thresholds in the peripheral zone and transition zone. There was a clearer separation of clinically significant tumors in peripheral zone cancers compared to transition zone cancers. Future iterations of PI-RADS could therefore take different size-based cut-offs for peripheral zone and transition zone cancers into account.
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http://dx.doi.org/10.1016/j.ejrad.2020.109071DOI Listing
August 2020

Validation of the PI-RADS language: predictive values of PI-RADS lexicon descriptors for detection of prostate cancer.

Eur Radiol 2020 Aug 26;30(8):4262-4271. Epub 2020 Mar 26.

Department of Radiology, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Objectives: To assess the discriminatory power of lexicon terms used in PI-RADS version 2 to describe MRI features of prostate lesions.

Methods: Four hundred fifty-four patients were included in this retrospective, institutional review board-approved study. Patients received multiparametric (mp) MRI and subsequent prostate biopsy including MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy. PI-RADS lexicon terms describing lesion characteristics on mpMRI were assigned to lesions by experienced readers. Positive and negative predictive values (PPV, NPV) of each lexicon term were assessed using biopsy results as a reference standard.

Results: From a total of 501 lesions, clinically significant prostate cancer (csPCa) was present in 175 lesions (34.9%). Terms related to findings of restricted diffusion showed PPVs of up to 52.0%/43.9% and NPV of up to 91.8%/89.7% (peripheral zone or PZ/transition zone or TZ). T2-weighted imaging (T2W)-related terms showed a wide range of predictive values. For PZ lesions, high PPVs were found for "markedly hypointense," "lenticular," "lobulated," and "spiculated" (PPVs between 67.2 and 56.7%). For TZ lesions, high PPVs were found for "water-drop-shaped" and "erased charcoal sign" (78.6% and 61.0%). The terms "encapsulated," "organized chaos," and "linear" showed to be good predictors for benignity with distinctively low PPVs between 5.4 and 6.9%. Most T2WI-related terms showed improved predictive values for TZ lesions when combined with DWI-related findings.

Conclusions: Lexicon terms with high discriminatory power were identified (e.g., "markedly hypointense," "water-drop-shaped," "organized chaos"). DWI-related terms can be useful for excluding TZ cancer. Combining T2WI- with DWI findings in TZ lesions markedly improved predictive values.

Key Points: • Lexicon terms describing morphological and functional features of prostate lesions on MRI show a wide range of predictive values for prostate cancer. • Some T2-related terms have favorable PPVs, e.g., "water-drop-shaped" and "organized chaos" while others show less distinctive predictive values. DWI-related terms have noticeable negative predictive values in TZ lesions making DWI feature a useful tool for exclusion of TZ cancer. • Combining DWI- and T2-related lexicon terms for assessment of TZ lesions markedly improves PPVs. Most T2-related lexicon terms showed a significant decrease in PPV when combined with negative findings for "DW hyperintensity."
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http://dx.doi.org/10.1007/s00330-020-06773-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338829PMC
August 2020

Hepatocellular adenomas: is there additional value in using Gd-EOB-enhanced MRI for subtype differentiation?

Eur Radiol 2020 Jun 21;30(6):3497-3506. Epub 2020 Feb 21.

Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Leipzig, Leipzig, Germany.

Purpose: To differentiate subtypes of hepatocellular adenoma (HCA) based on enhancement characteristics in gadoxetic acid (Gd-EOB) magnetic resonance imaging (MRI).

Materials And Methods: Forty-eight patients with 79 histopathologically proven HCAs who underwent Gd-EOB-enhanced MRI were enrolled (standard of reference: surgical resection). Two blinded radiologists performed quantitative measurements (lesion-to-liver enhancement) and evaluated qualitative imaging features. Inter-reader variability was tested. Advanced texture analysis was used to evaluate lesion heterogeneity three-dimensionally.

Results: Overall, there were 19 (24%) hepatocyte nuclear factor (HNF)-1a-mutated (HHCAs), 37 (47%) inflammatory (IHCAs), 5 (6.5%) b-catenin-activated (bHCA), and 18 (22.5%) unclassified (UHCAs) adenomas. In the hepatobiliary phase (HBP), 49.5% (39/79) of all adenomas were rated as hypointense and 50.5% (40/79) as significantly enhancing (defined as > 25% intralesional GD-EOB uptake). 82.5% (33/40) of significantly enhancing adenomas were IHCAs, while only 4% (1/40) were in the HHCA subgroup (p < 0.001). When Gd-EOB uptake behavior was considered in conjunction with established MRI features (binary regression model), the area under the curve (AUC) increased from 0.785 to 0.953 for differentiation of IHCA (atoll sign + hyperintensity), from 0.859 to 0.903 for bHCA (scar + hyperintensity), and from 0.899 to 0.957 for HHCA (steatosis + hypointensity). Three-dimensional region of interest (3D ROI) analysis showed significantly increased voxel heterogeneity for IHCAs (p = 0.038).

Conclusion: Gd-EOB MRI is of added value for subtype differentiation of HCAs and reliably identifies the typical heterogeneous HBP uptake of IHCAs. Diagnostic accuracy can be improved significantly by the combined analysis of established morphologic MR appearances and intralesional Gd-EOB uptake.

Key Points: •Gd-EOB-enhanced MRI is of added value for subtype differentiation of HCA. •IHCA and HHCA can be identified reliably based on their typical Gd-EOB uptake patterns, and accuracy increases significantly when additionally taking established MR appearances into account. •The small numbers of bHCAs and UHCAs remain the source of diagnostic uncertainty.
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http://dx.doi.org/10.1007/s00330-020-06726-8DOI Listing
June 2020

Safety Analysis of Iobitridol as a Nonionic Contrast Medium: A Postmarketing Multicenter Surveillance Study With 94,960 Patients Almost 20 Years After Introduction.

Invest Radiol 2020 03;55(3):144-152

From the Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin.

Objectives: Our study sought to reevaluate the safety and diagnostic efficacy of iobitridol as a nonionic contrast medium after almost 20 years of use.

Materials And Methods: This noninterventional postmarketing surveillance noncontrolled, multicenter (168 centers in Germany) study enrolled 94,960 patients receiving intravenous or intra-arterial iobitridol. The majority of the adjusted population (n = 92,550, 98.2%) underwent either computed tomography examination (n = 46,502, 49.3%) or intravenous urography (n = 46,048, 48.8%). A standardized questionnaire was used to ascertain patient's information, known risk factors, renal function status, premedication, type of examination, injection of contrast agent, imaging quality, diagnostic value, and safety.

Results: A total of 469 patients (0.49%) experienced an adverse event (AE), and 24 patients (0.025%) reported a serious AE (SAE). All patients recovered and no fatal event occurred. The prevalence of AE was significantly higher in patients with at least one risk factor, with premedication, with a history of AE, in female and patients younger than 60 years old (P < 0.05). Presence of at least one risk factor is the only predictive factor for the prevalence of SAE (P = 0.042). In patients with a history of AE, premedication did not significantly lower the AE rate (P = 0.737). No statistically significant difference in the prevalence of AE between the different combination of cortisone and/or antihistamines as pretreatment was found.

Conclusions: Iobitridol is a safe contrast medium with a high tolerability and efficacy. Presence of risk factors such as cardiovascular diseases, allergies, or asthma was the only significant predictive factor for an AE and an SAE. Premedication did not significantly lower the occurrence of an AE and an SAE.
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http://dx.doi.org/10.1097/RLI.0000000000000620DOI Listing
March 2020

[Artificial intelligence and radiomics in MRI-based prostate diagnostics].

Radiologe 2020 Jan;60(1):48-55

Institute of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Deutschland.

Clinical/methodical Issue: In view of the diagnostic complexity and the large number of examinations, modern radiology is challenged to identify clinically significant prostate cancer (PCa) with high sensitivity and specificity. Meanwhile overdiagnosis and overtreatment of clinically nonsignificant carcinomas need to be avoided.

Standard Radiological Methods: Increasingly, international guidelines recommend multiparametric magnetic resonance imaging (mpMRI) as first-line investigation in patients with suspected PCa.

Methodical Innovations: Image interpretation according to the PI-RADS criteria is limited by interobserver variability. Thus, rapid developments in the field of automated image analysis tools, including radiomics and artificial intelligence (AI; machine learning, deep learning), give hope for further improvement in patient care.

Performance: AI focuses on the automated detection and classification of PCa, but it also attempts to stratify tumor aggressiveness according to the Gleason score. Recent studies present good to very good results in radiomics or AI-supported mpMRI diagnosis. Nevertheless, these systems are not widely used in clinical practice.

Achievements And Practical Recommendations: In order to apply these innovative technologies, a growing awareness for the need of structured data acquisition, development of robust systems and an increased acceptance of AI as diagnostic support are needed. If AI overcomes these obstacles, it may play a key role in the quantitative and reproducible image-based diagnosis of ever-increasing prostate MRI examination volumes.
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http://dx.doi.org/10.1007/s00117-019-00613-0DOI Listing
January 2020

Value of contrast-enhanced ultrasound (CEUS) in Focal Liver Lesions (FLL) with inconclusive findings on cross-sectional imaging.

Clin Hemorheol Microcirc 2020 ;74(3):327-339

Department of Radiology, Charité - University Medicine Berlin, Germany.

Background: Contrast-enhanced ultrasound (CEUS) has been used as an additional imaging technique in order to evaluate focal liver lesions. CEUS is easy and fast to perform, overcomes the limitations of B-mode US.

Objective: To evaluate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in focal liver lesions (FLL) with unclear findings on computed tomography (CT) or magnetic resonance imaging (MRI).

Methods: In this single-center retrospective study, 146 patients with at least one FLL underwent additional CEUS of the liver to clarify inconclusive cross-sectional imaging findings. Ultrasonography was performed using B-mode imaging and CEUS after injection of sulphur hexafluoride microbubbles (second-generation contrast agent) within two months after ceMRI or ceCT and interpreted by an experienced radiologist (EFSUMB level 3). Histopathological reports, long-term follow-up or clinical course served as reference standard.

Results: Thirty-eight of the 146 patients had malignant and 108 benign FLL. Overall, CEUS had 92% sensitivity (95% -CI, 79-97) and 98% specificity (95% -CI, 93-99) with an AUC of 0.95 in correctly characterizing the lesion as malignant or benign. Sensitivity increased to 98% (95% -CI, 96-100) for benign lesions and decreased to 92% (95% -CI, 78-98) for malignant lesions. CEUS showed the highest diagnostical accuracy in lesion <1 cm with an AUC of 1.000, while the lowest accuracy was achieved in lesions >2 cm with an AUC of 0.924 due to a decreasing specificity of 86% (95% -CI, 87-100).

Conclusion: CEUS correctly distinguished malignant from benign FLL in cases with inconclusive cross-sectional imaging findings and achieved high levels of diagnostic accuracy. CEUS has added diagnostic value especially in small lesions ≤1 cm while specificity remains limited in larger lesions.
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http://dx.doi.org/10.3233/CH-190718DOI Listing
July 2020

Diagnostic Performance and Reliability of Non-Enhanced Imaging Characterization Quotients for the Differentiation of Infectious and Malignant Pulmonary Nodules in Hematological Patients Using 3T MRI.

Rofo 2020 Apr 24;192(4):327-334. Epub 2019 Oct 24.

Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.

Purpose:  To evaluate the diagnostic performance and reliability of non-enhanced imaging characterization quotients (NICQs) derived from magnetic resonance imaging (MRI) in the differential diagnosis of pulmonary nodules in hematological patients.

Materials And Methods:  A total of 83 lesions in 45 consecutive hematological patients were analyzed (10 bacterial pneumonias, 16 fungal pneumonias, 19 pulmonary lymphoma manifestations). The MRI protocol included T2-weighted single-shot fast spin echo (FSE) and T1-weighted gradient echo (GRE) sequences. T2-based T2-NICQ and T2-NICQ were calculated from signal intensities measured in the lesion, muscle, and fat ((SI - SI)/(SI - SI) * 100), and simple T1-based T1-Q from signal intensities of the lesion and muscle (SI/SI). Images were read by one radiologist with > 7 years and one with 1 year of experience. For statistical evaluation the Kruskal-Wallis or Mann-Whitney U-test, receiver operating characteristic (ROC) analysis with calculation of areas under the curve (AUC), and intraclass correlation coefficients (ICCs) were used.

Results:  Medians of T2-NICQs differed significantly when comparing infectious lesions and lymphoma manifestations in general (T2-NICQ 20.33 vs. 10.14; T2-NICQ 34.96 vs. 25.52) or fungal lesions and lymphoma manifestations in particular (T2-NICQ 19.00 vs. 10.14; T2-NICQ 34.49 vs. 25.25). The AUCs for T2-NICQs on the per-patient level ranged from 0.73 to 0.79. ICCs were at least > 0.85, except for intrarater testing of T2-NICQ (0.79).

Conclusion:  The overall diagnostic performance of T2-NICQs is adequate for differentiating infectious and fungal lesions from lymphoma manifestations. The results show good to excellent intra- and interrater agreement. We therefore consider NICQs helpful in the diagnostic workup of pulmonary nodules in hematological patients.

Key Points:   · Non-enhanced Imaging Characterization Quotients provide a fast and pragmatic approach for assessing pulmonary lesions in hematological patients.. · The diagnostic performance of Non-enhanced Imaging Characterization Quotients is adequate for differentiating infectious and fungal infiltrates from lymphoma manifestations.. · Non-enhanced Imaging Characterization Quotients show good to excellent intra- and interrater agreement..

Citation Format: · Nagel SN, Kim D, Wylutzki T et al. Diagnostic Performance and Reliability of Non-Enhanced Imaging Characterization Quotients for the Differentiation of Infectious and Malignant Pulmonary Nodules in Hematological Patients Using 3T MRI. Fortschr Röntgenstr 2020; 192: 327 - 334.
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http://dx.doi.org/10.1055/a-1005-7424DOI Listing
April 2020

Semi-automatic classification of prostate cancer on multi-parametric MR imaging using a multi-channel 3D convolutional neural network.

Eur Radiol 2020 Feb 29;30(2):1243-1253. Epub 2019 Aug 29.

Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Objective: To present a deep learning-based approach for semi-automatic prostate cancer classification based on multi-parametric magnetic resonance (MR) imaging using a 3D convolutional neural network (CNN).

Methods: Two hundred patients with a total of 318 lesions for which histological correlation was available were analyzed. A novel CNN was designed, trained, and validated using different combinations of distinct MRI sequences as input (e.g., T2-weighted, apparent diffusion coefficient (ADC), diffusion-weighted images, and K-trans) and the effect of different sequences on the network's performance was tested and discussed. The particular choice of modeling approach was justified by testing all relevant data combinations. The model was trained and validated using eightfold cross-validation.

Results: In terms of detection of significant prostate cancer defined by biopsy results as the reference standard, the 3D CNN achieved an area under the curve (AUC) of the receiver operating characteristics ranging from 0.89 (88.6% and 90.0% for sensitivity and specificity respectively) to 0.91 (81.2% and 90.5% for sensitivity and specificity respectively) with an average AUC of 0.897 for the ADC, DWI, and K-trans input combination. The other combinations scored less in terms of overall performance and average AUC, where the difference in performance was significant with a p value of 0.02 when using T2w and K-trans; and 0.00025 when using T2w, ADC, and DWI. Prostate cancer classification performance is thus comparable to that reported for experienced radiologists using the prostate imaging reporting and data system (PI-RADS). Lesion size and largest diameter had no effect on the network's performance.

Conclusion: The diagnostic performance of the 3D CNN in detecting clinically significant prostate cancer is characterized by a good AUC and sensitivity and high specificity.

Key Points: • Prostate cancer classification using a deep learning model is feasible and it allows direct processing of MR sequences without prior lesion segmentation. • Prostate cancer classification performance as measured by AUC is comparable to that of an experienced radiologist. • Perfusion MR images (K-trans), followed by DWI and ADC, have the highest effect on the overall performance; whereas T2w images show hardly any improvement.
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http://dx.doi.org/10.1007/s00330-019-06417-zDOI Listing
February 2020

Image-guided Irreversible Electroporation of Localized Prostate Cancer: Functional and Oncologic Outcomes.

Radiology 2019 07 4;292(1):250-257. Epub 2019 Jun 4.

From the Departments of Radiology (F.C., J.E., T.F., A.D.J.B., T.P., B.H.) and Urology (C.S., J.B., B.G.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Institute of Health, Berlin, Germany (F.C., T.P.); and Department of Urology, Berlin Institute for Urologic Research, Berlin, Germany (C.S.).

Background Irreversible electroporation (IRE) is a nonthermal ablative method based on the formation of nanoscale defects in cell membranes leading to cell death. Clinical experience with the technique for treatment of prostate cancer remains limited. Purpose To evaluate urogenital toxicity and oncologic outcome of MRI-transrectal US fusion-guided IRE of localized prostate cancer. Materials and Methods In this prospective study, men with biopsy-proven, treatment-naive, low- to intermediate-risk prostate cancer (prostate-specific antigen [PSA], ≤15 ng/mL; Gleason score, ≤3 + 4; clinical stage, ≤T2c; lesion size at multiparametric MRI, ≤20 mm) underwent focal MRI/transrectal US fusion-guided IRE between July 2014 and July 2017. Primary end point was the urogenital toxicity profile of focal IRE by using participant-reported questionnaires. Secondary end points were biochemical, histologic, and imaging measures of oncologic control. Analyses were performed by using nonparametric and χ test statistics. Results Thirty men were included (median age, 65.5 years); mean PSA level was 8.65 ng/mL and mean tumor size was 13.5 mm. One grade III adverse event (urethral stricture) was recorded. The proportion of men with erection sufficient for penetration was 83.3% (25 of 30) at baseline and 79.3% (23 of 29; > .99) at 12 months. Leak-free and pad-free continence rate was 90% (27 of 30) at baseline and 86.2% (25 of 29; > .99) at 12 months. Urogenital function remained stable at 12 months according to changes in the modified International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms, or ICIQ-MLUTS, and the International Index of Erectile Function, or IIEF-5, questionnaires ( = .58 and = .07, respectively). PSA level decreased from a baseline median value of 8.65 ng/mL (interquartile range, 5-11.4 ng/mL) to 2.35 ng/mL (interquartile range, 1-3.4 ng/mL) at 12 months ( < .001). At 6 months, 28 of 30 participants underwent posttreatment biopsy. The rate of in-field treatment failure was 17.9% (five of 28) as determined with multiparametric prostate MRI and targeted biopsies at 6 months. Conclusion After a median follow-up of 20 months, focal irreversible electroporation of localized prostate cancer was associated with low urogenital toxicity and promising oncologic outcomes. © RSNA, 2019
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http://dx.doi.org/10.1148/radiol.2019181987DOI Listing
July 2019

Evaluation of prostate MRI: can machine learning provide support where radiologists need it?

Eur Radiol 2019 Sep 9;29(9):4751-4753. Epub 2019 May 9.

Klinik für Radiologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.

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http://dx.doi.org/10.1007/s00330-019-06241-5DOI Listing
September 2019

Renal Denervation by Transaortic Periarterial Ethanol Injection: An Experimental Study in Porcines.

Cardiovasc Intervent Radiol 2018 Dec 7;41(12):1943-1951. Epub 2018 Aug 7.

Institute for Clinical Radiology, Hospitals of the Ludwig-Maximilians-University of Munich, Munich, Germany.

Aims: To evaluate the feasibility, safety and efficacy of renal sympathetic denervation via endoluminal transaortic periarterial ethanol injection.

Methods And Results: In 11 normotensive pigs transaortic puncture was performed with a 90-cm 21G needle with subsequent unilateral ethanol injection to the periarterial space. Needle placement was achieved using a 7F steerable sheath fluoroscopically positioned slightly above the renal artery origin. Blood pressure measurements and abdominal CT scans were performed immediately pre- and postintervention and 4 weeks later. After euthanasia norepinephrine concentration of both kidneys (RTNEC) was determined and renal arteries and surrounding tissues histologically examined to assess induced nerve fibre degeneration.

Results: All but one procedure were technically successful. One major complication with accidental ethanol injection into the renal artery and subsequent infarction occurred. One pig died from no intervention-related cardiac arrest. The 4-week follow-up was uneventful in the remaining 10 animals. RTNEC was significantly lower on the treated side in eight of ten pigs (mean decrease 36.6%) with correlating histopathological signs of nerve degeneration.

Conclusions: Renal sympathicolysis by transaortic periarterial ethanol injection was feasible and effective in a porcine model. This approach may be an alternative to catheter-based RFA or other methods of renal denervation.
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http://dx.doi.org/10.1007/s00270-018-2045-6DOI Listing
December 2018

Validation of Prostate Imaging Reporting and Data System Version 2 for the Detection of Prostate Cancer.

J Urol 2018 10 5;200(4):767-773. Epub 2018 May 5.

Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Purpose: The second version of the PI-RADS™ (Prostate Imaging Reporting and Data System) was introduced in 2015 to standardize the interpretation and reporting of prostate multiparametric magnetic resonance imaging. Recently low cancer detection rates were reported for PI-RADS version 2 category 4 lesions. Therefore the aim of the study was to evaluate the cancer detection rate of PI-RADS version 2 in a large prospective cohort.

Materials And Methods: The study included 704 consecutive men with primary or prior negative biopsies who underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy and 10-core systematic prostate biopsy between September 2015 and May 2017. All lesions were rated according to PI-RADS version 2 and lesions with PI-RADS version 2 category 3 or greater were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer.

Results: The overall cancer detection rate of PI-RADS version 2 categories 3, 4 and 5 was 39%, 72% and 91% for all prostate cancer, and 23%, 49% and 77% for all clinically significant prostate cancer, respectively. If only targeted biopsy had been performed, 59 clinically significant tumors (16%) would have been missed. The PI-RADS version 2 score was significantly associated with the presence of prostate cancer (p <0.001), the presence of clinically significant prostate cancer (p <0.001) and the ISUP grade (p <0.001).

Conclusions: PI-RADS version 2 is significantly associated with the presence of clinically significant prostate cancer. The cancer detection rate of PI-RADS version 2 category 4 lesions was considerably higher than previously reported. When performing targeted biopsy, the combination with systematic biopsy still provides the highest detection of clinically significant prostate cancer.
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http://dx.doi.org/10.1016/j.juro.2018.05.003DOI Listing
October 2018

Primary magnetic resonance imaging/ultrasonography fusion-guided biopsy of the prostate.

BJU Int 2018 08 17;122(2):211-218. Epub 2018 Apr 17.

Department of Urology, Charité - University Medicine Berlin, Berlin, Germany.

Objective: To examine the performance of a primary magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB), and in combination with an added systematic biopsy (SB).

Patients And Methods: Analysis of 318 consecutive biopsy-naïve men with suspicious multiparametric MRI (mpMRI; Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) undergoing transrectal TB and 10-core SB between January 2012 and December 2016. The indication for performing mpMRI was based on clinical parameters and decided by the treating urologist before admission. TB was performed with a sensor-based MRI/US fusion-guided platform. Clinically significant prostate cancer was defined as Gleason score ≥4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP] grade 3) or maximum cancer core length of ≥6 mm.

Results: A median (interquartile range) of 14 (13-14) biopsies per case were taken. The overall cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of prostate cancers and the SB alone detected 70%. The PI-RADS dependent CDR for the combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI-RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163 cases (51%). The number of missed or underestimated prostate cancers with a Gleason score ≥8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for SB alone in comparison with the results of the combination of TB and SB. The rate of insignificant prostate cancer was comparable for the combination of TB and SB and TB alone (50/318, 16% vs 50/318, 16%).

Conclusions: Pre-biopsy mpMRI is of incremental value in increasing the detection of clinically significant prostate cancer in biopsy-naïve patients with suspicion of prostate cancer. Combining TB with SB further improved the diagnostic accuracy without increasing the rate of insignificant prostate cancer.
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http://dx.doi.org/10.1111/bju.14212DOI Listing
August 2018

A direct comparison of contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer detection and prediction of aggressiveness.

Eur Radiol 2018 May 13;28(5):1949-1960. Epub 2017 Dec 13.

Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Institut für Radiologie, Berlin, Germany.

Introduction: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) analyse tissue vascularization. We evaluated if CEUS can provide comparable information as DCE-MRI for the detection of prostate cancer (PCa) and prediction of its aggressiveness.

Material And Methods: A post-hoc evaluation of 92 patients was performed. In each patient CEUS and DCE-MRI parameters of the most suspicious lesion identified on MRI were analysed. The predictive values for discrimination between benign lesions, low-/intermediate- and high-grade PCa were evaluated. Results of targeted biopsy served as reference standard (benign lesions, n=51; low- and intermediate-grade PCa [Gleason grade group 1 and 2], n=22; high-grade PCa [≥ Gleason grade group 3], n=19).

Results: In peripheral zone lesions of all tested CEUS parameters only time to peak (TTP) showed significant differences between benign lesions and PCa (AUC 0.65). Of all tested DCE-MRI parameters, rate constant (K) was the best discriminator of high-grade PCa in the whole prostate (AUC 0.83) and in peripheral zone lesions (AUC 0.89).

Conclusion: DCE-MRI showed a superior performance for detection of PCa and prediction of its aggressiveness. CEUS and DCE-MRI performed better in peripheral zone lesions than in transition zone lesions.

Key Points: • DCE-MRI gathers information about vascularization and capillary permeability characteristics of tissues. • DCE-MRI can detect PCa and predict its aggressiveness. • CEUS also gathers information about vascularization of tissues. • For detection of PCa and prediction of aggressiveness DCE-MRI performed superiorly. • Both imaging techniques performed better in peripheral zone lesions.
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http://dx.doi.org/10.1007/s00330-017-5192-2DOI Listing
May 2018

Electromagnetically Navigated In Situ Fenestration of Aortic Stent Grafts: Pilot Animal Study of a Novel Fenestrated EVAR Approach.

Cardiovasc Intervent Radiol 2018 Jan 18;41(1):170-176. Epub 2017 Aug 18.

Department of Diagnostic and Interventional Radiology, RWTH Aachen University Hospital, Aachen, Germany.

Purpose: Assess electromagnetically guided in situ fenestration of juxtarenal aortic stent grafts in an in vivo model.

Methods: Using a newly developed electromagnetic guidance system together with a modified, electromagnetically guidable catheter with steerable tip, an electromagnetically trackable guidewire and a custom in situ fenestrateable stent graft, a series of seven animal experiments was performed. In a swine model, stent grafts were placed juxtarenally, covering the renal arteries. Subsequently, the perfusion of the renal arteries was restored using electromagnetically guided in situ fenestration of the graft at the renal ostia followed by covered stent placement. Intervention times and technical success were assessed.

Results: The individual components were successfully combined for the animal experiments. Thirteen of fourteen fenestration experiments in seven animals were successful in restoring perfusion through in situ fenestration. Fenestration (catheter introduction-guidewire placement in renal artery across graft) could be achieved in on average 10.5 ± 9.2 min, and subsequent covered stent placement (guidewire placement-covered stent placement) took on average 32.7 ± 17.5 min. No significant differences between left and right side reperfusion times could be detected. Reperfusion in <30 min was achieved in 3/14 attempts.

Conclusion: Electromagnetically navigated in situ aortic fenestration for juxtarenal aortic stent grafts was feasible in a healthy animal model. Identified remaining challenges were: shortening the procedure to avoid long warm ischemia times, using an aortic aneurysm animal model, and improving the stability of the stent graft material.
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http://dx.doi.org/10.1007/s00270-017-1769-zDOI Listing
January 2018

Pulmonary MRI at 3T: Non-enhanced pulmonary magnetic resonance Imaging Characterization Quotients for differentiation of infectious and malignant lesions.

Eur J Radiol 2017 Apr 19;89:33-39. Epub 2017 Jan 19.

Klinik und Hochschulambulanz für Radiologie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Electronic address:

Objective: To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions.

Materials And Methods: Thirty-eight pulmonary lesions in 29 patients were evaluated. Seventeen patients were immunocompromised (11 infections and 6 lymphomas) and 12 served as controls (4 bacterial pneumonias, 8 solid tumors). Ten of the 15 infections were acute. Signal intensities (SI) were measured in the lesion, chest wall muscle, and subcutaneous fat. Scaled SIs as Non-enhanced Imaging Characterization Quotients ((SI-SI)/(SI-SI)*100) were calculated from the T2-weighted images using the mean SI (T2-NICQ) or the 90th percentile of SI (T2-NICQ) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Q: SI/SI).

Results: Infectious pulmonary lesions showed a higher T2-NICQ (40.1 [14.6-56.0] vs. 20.9 [2.4-30.1], p<0.05) and T2-NICQ (74.3 [43.8-91.6] vs. 38.5 [15.8-48.1], p<0.01) than malignant lesions. T1-Q was higher in malignant lesions (0.85 [0.68-0.94] vs. 0.93 [0.87-1.09], p<0.05). Considering infections only, T2-NICQ was lower when anti-infectious treatment was administered >24h prior to MRI (81.8 [71.8-97.6] vs. 41.4 [26.6-51.1], p<0.01). Using Youden's index (YI), the optimal cutoff to differentiate infectious from malignant lesions was 43.1 for T2-NICQ (YI=0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ (YI=0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ and T1-Q increased diagnostic performance (YI=0.72, 0.77 sensitivity, 0.95 specificity).

Conclusion: Considering each quotient alone, T2-NICQ showed the best diagnostic performance and could allow differentiation of acute infectious from malignant pulmonary lesions with high specificity. Combining T2-NICQ with T1-Q increased overall performance, especially regarding sensitivity.
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http://dx.doi.org/10.1016/j.ejrad.2017.01.012DOI Listing
April 2017

Reconstructions Using RIF in Motion Mapping Technique Have Substantially Less Arrhythmogenic Artifacts in Dual-source Coronary CTA.

Acad Radiol 2017 02 20;24(2):167-174. Epub 2016 Dec 20.

Department of Diagnostic and Interventional Radiology, University Hospital, Philipps University Marburg, Marburg, Germany.

Rationale And Objectives: Particularly for patients with heart arrhythmias, conventional BestSystole (BS) and BestDiastole (BD) reconstruction techniques in computed tomography (CT) frequently show artifacts that hinder the readability of the coronary tree. To address this problem, this paper presents an alternative reconstruction method that combines the technique "reconstructions with identical filling" (RIF) with motion mapping: This new technique is called "RIF in motion mapping" (RIMM). This study compares the diagnostic quality of images generated with RIMM to that of the other reconstruction techniques.

Materials And Methods: Having shown major artifacts in standard reconstructions, the CT datasets of 23 patients with suspected coronary artery disease or prior to transcatheter aortic valve replacement were selected manually. Each dataset was evaluated with four reconstruction techniques: BS, BD, RIF, and RIMM. Two radiologists, blinded to the applied reconstruction type, then evaluated the entire coronary tree of each sample using the 15-segment American Heart Association model and the six-grade Likert scale.

Results: Of the 345 analyzed coronary segments, the RIMM technique showed a significant number of images with reliable diagnostic quality (n = 228, 66%) as compared to RIF (P = 0.002) and BS/BD reconstructions (P < 0.001). Per coronary segment, vessel, and patient, the RIMM technique scored significantly better than the conventional BS/BD reconstructions (P = 0.003) and better than the RIF reconstructions with regard to the right coronary artery (P = 0.041).

Conclusions: This new technique works: Using RIMM on the worst CT images substantially erased many of these artifacts, thereby enabling the radiologists to clearly visualize these segments. As RIMM considerably eliminates artifacts, this new CT reconstruction technique can help make a fast reliable evaluation of a patient's coronary tree. Thus, this enhanced visualization of cardiac images by RIMM avoids the need for further invasive diagnostic procedures.
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http://dx.doi.org/10.1016/j.acra.2016.09.014DOI Listing
February 2017

L1Base 2: more retrotransposition-active LINE-1s, more mammalian genomes.

Nucleic Acids Res 2017 01 18;45(D1):D68-D73. Epub 2016 Oct 18.

Institut für Medizinische Genetik und Humangenetik, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

LINE-1 (L1) insertions comprise as much as 17% of the human genome sequence, and similar proportions have been recorded for other mammalian species. Given the established role of L1 retrotransposons in shaping mammalian genomes, it becomes an important task to track and annotate the sources of this activity: full length elements, able to encode the cis and trans acting components of the retrotransposition machinery. The L1Base database (http://l1base.charite.de) contains annotated full-length sequences of LINE-1 transposons including putatively active L1s. For the new version of L1Base, a LINE-1 annotation tool, L1Xplorer, has been used to mine potentially active L1 retrotransposons from the reference genome sequences of 17 mammals. The current release of the human genome, GRCh38, contains 146 putatively active L1 elements or full length intact L1 elements (FLIs). The newest versions of the mouse, GRCm38 and the rat, Rnor_6.0, genomes contain 2811 and 492 FLIs, respectively. Most likely reflecting the current level of completeness of the genome project, the latest reference sequence of the common chimpanzee genome, PT 2.19, only contains 19 FLIs. Of note, the current assemblies of the dog, CF 3.1 and the sheep, OA 3.1, genomes contain 264 and 598 FLIs, respectively. Further developments in the new version of L1Base include an updated website with implementation of modern web server technologies. including a more responsive design for an improved user experience, as well as the addition of data sharing capabilities for L1Xplorer annotation.
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http://dx.doi.org/10.1093/nar/gkw925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210629PMC
January 2017

Diffusion-weighted endorectal MR imaging at 3T for prostate cancer: correlation with tumor cell density and percentage Gleason pattern on whole mount pathology.

Abdom Radiol (NY) 2017 03;42(3):918-925

Department of Radiology, Brigham and Women's Hospital, Boston, MA, 02115, USA.

Objective: To determine if tumor cell density and percentage of Gleason pattern within an outlined volumetric tumor region of interest (TROI) on whole-mount pathology (WMP) correlate with apparent diffusion coefficient (ADC) values on corresponding TROIs outlined on pre-operative MRI.

Methods: Men with biopsy-proven prostate adenocarcinoma undergoing multiparametric MRI (mpMRI) prior to prostatectomy were consented to this prospective study. WMP and mpMRI images were viewed using 3D Slicer and each TROI from WMP was contoured on the high b-value ADC maps (b0, 1400). For each TROI outlined on WMP, TCD (tumor cell density) and the percentage of Gleason pattern 3, 4, and 5 were recorded. The ADC, ADC, ADC, and ADC were also calculated in each case from the ADC maps using 3D Slicer.

Results: Nineteen patients with 21 tumors were included in this study. ADC values for TROIs were 944.8 ± 327.4 vs. 1329.9 ± 201.6 mm/s for adjacent non-neoplastic prostate tissue (p < 0.001). ADC, ADC, and ADC values for higher grade tumors were lower than those of lower grade tumors (mean 809.71 and 1176.34 mm/s, p = 0.014; 10th percentile 613.83 and 1018.14 mm/s, p = 0.009; ratio 0.60 and 0.94, p = 0.005). TCD and ADC (ρ = -0.61, p = 0.005) and TCD and ADC (ρ = -0.56, p = 0.01) were negatively correlated. No correlation was observed between percentage of Gleason pattern and ADC values.

Conclusion: DWI MRI can characterize focal prostate cancer using ADC, ADC, and ADC, which correlate with pathological tumor cell density.
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http://dx.doi.org/10.1007/s00261-016-0942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357151PMC
March 2017
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