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Introduction: Clinical assessment of upper limb sensorimotor function post-stroke is often constrained by low sensitivity and limited information on movement quality. To address this gap, recent studies proposed a standardized instrumented drinking task, as a representative daily activity combining different components of functional arm use. Although kinematic movement quality measures for this task are well-established, and optical motion capture (OMC) has proven effective in their measurement, its clinical application remains limited. Inertial Measurement Units (IMUs) emerge as a promising low-cost and user-friendly alternative, yet their validity and clinical relevance compared to the gold standard OMC need investigation., Method: In this study, we conducted a measurement system comparison between IMUs and OMC, analyzing 15 established movement quality measures in 15 mild and moderate stroke patients performing the drinking task, using five IMUs placed on each wrist, upper arm, and trunk., Results: Our findings revealed strong agreement between the systems, with 12 out of 15 measures demonstrating clinical applicability, evidenced by Limits of Agreement (LoA) below the Minimum Clinically Important Differences (MCID) for each measure., Discussion: These results are promising, suggesting the clinical applicability of IMUs in quantifying movement quality for mildly and moderately impaired stroke patients performing the drinking task., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Unger, de Sousa Ribeiro, Mokni, Weikert, Pohl, Schwarz, Held, Sauerzopf, Kühnis, Gavagnin, Luft, Gassert, Lambercy, Awai Easthope and Schönhammer.)

Rationale and Objectives: Finding comparison to relevant prior studies is a requisite component of the radiology workflow. The purpose of this study was to evaluate the impact of a deep learning tool simplifying this time-consuming task by automatically identifying and displaying the finding in relevant prior studies., Materials and Methods: The algorithm pipeline used in this retrospective study, TimeLens (TL), is based on natural language processing and descriptor-based image-matching algorithms. The dataset used for testing comprised 3872 series of 246 radiology examinations from 75 patients (189 CTs, 95 MRIs). To ensure a comprehensive testing, five finding types frequently encountered in radiology practice were included: aortic aneurysm, intracranial aneurysm, kidney lesion, meningioma, and pulmonary nodule. After a standardized training session, nine radiologists from three university hospitals performed two reading sessions on a cloud-based evaluation platform resembling a standard RIS/PACS. The task was to measure the diameter of the finding-of-interest on two or more exams (a most recent and at least one prior exam): first without use of TL, and a second session at an interval of at least 21 days with the use of TL. All user actions were logged for each round, including time needed to measure the finding at all timepoints, number of mouse clicks, and mouse distance traveled. The effect of TL was evaluated in total, per finding type, per reader, per experience (resident vs. board-certified radiologist), and per modality. Mouse movement patterns were analyzed with heatmaps. To assess the effect of habituation to the cases, a third round of readings was performed without TL., Results: Across scenarios, TL reduced the average time needed to assess a finding at all timepoints by 40.1% (107 vs. 65 seconds; p < 0.001). Largest accelerations were demonstrated for assessment of pulmonary nodules (-47.0%; p < 0.001). Less mouse clicks (-17.2%) were needed for finding evaluation with TL, and mouse distance traveled was reduced by 38.0%. Time needed to assess the findings increased from round 2 to round 3 (+27.6%; p < 0.001). Readers were able to measure a given finding in 94.4% of cases on the series initially proposed by TL as most relevant series for comparison. The heatmaps showed consistently simplified mouse movement patterns with TL., Conclusion: A deep learning tool significantly reduced both the amount of user interactions with the radiology image viewer and the time needed to assess findings of interest on cross-sectional imaging with relevant prior exams., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Halid Ziya Yerebakan reports a relationship with Siemens Medical Solutions USA Inc that includes: employment. Yoshihisa Shinagawa reports a relationship with Siemens Medical Solutions USA Inc that includes: employment. Gerardo Hermosillo reports a relationship with Siemens Medical Solutions USA Inc that includes: employment. Simon Allen-Raffl reports a relationship with Siemens Medical Solutions USA Inc that includes: employment., (Copyright © 2023. Published by Elsevier Inc.)

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the 'Hamburg Declaration'. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the 'Global Alliance for the Promotion of Physical Activity' to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The 'Hamburg Declaration' calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings., Competing Interests: Competing interests: EV is Editor in Chief of BMJ Open Sports & Exercise Medicine., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: High breast density is a well-known risk factor for breast cancer. This study aimed to develop and adapt two (MLO, CC) deep convolutional neural networks (DCNN) for automatic breast density classification on synthetic 2D tomosynthesis reconstructions., Methods: In total, 4605 synthetic 2D images (1665 patients, age: 57 ± 37 years) were labeled according to the ACR (American College of Radiology) density (A-D). Two DCNNs with 11 convolutional layers and 3 fully connected layers each, were trained with 70% of the data, whereas 20% was used for validation. The remaining 10% were used as a separate test dataset with 460 images (380 patients). All mammograms in the test dataset were read blinded by two radiologists (reader 1 with two and reader 2 with 11 years of dedicated mammographic experience in breast imaging), and the consensus was formed as the reference standard. The inter- and intra-reader reliabilities were assessed by calculating Cohen's kappa coefficients, and diagnostic accuracy measures of automated classification were evaluated., Results: The two models for MLO and CC projections had a mean sensitivity of 80.4% (95%-CI 72.2-86.9), a specificity of 89.3% (95%-CI 85.4-92.3), and an accuracy of 89.6% (95%-CI 88.1-90.9) in the differentiation between ACR A/B and ACR C/D. DCNN versus human and inter-reader agreement were both "substantial" (Cohen's kappa: 0.61 versus 0.63)., Conclusion: The DCNN allows accurate, standardized, and observer-independent classification of breast density based on the ACR BI-RADS system., Key Points: • A DCNN performs on par with human experts in breast density assessment for synthetic 2D tomosynthesis reconstructions. • The proposed technique may be useful for accurate, standardized, and observer-independent breast density evaluation of tomosynthesis., (© 2023. The Author(s).)

Objectives: To develop and test a Retina U-Net algorithm for the detection of primary lung tumors and associated metastases of all stages on FDG-PET/CT., Methods: A data set consisting of 364 FDG-PET/CTs of patients with histologically confirmed lung cancer was used for algorithm development and internal testing. The data set comprised tumors of all stages. All lung tumors (T), lymphatic metastases (N), and distant metastases (M) were manually segmented as 3D volumes using whole-body PET/CT series. The data set was split into a training (n = 216), validation (n = 74), and internal test data set (n = 74). Detection performance for all lesion types at multiple classifier thresholds was evaluated and false-positive-findings-per-case (FP/c) calculated. Next, detected lesions were assigned to categories T, N, or M using an automated anatomical region segmentation. Furthermore, reasons for FPs were visually assessed and analyzed. Finally, performance was tested on 20 PET/CTs from another institution., Results: Sensitivity for T lesions was 86.2% (95% CI: 77.2-92.7) at a FP/c of 2.0 on the internal test set. The anatomical correlate to most FPs was the physiological activity of bone marrow (16.8%). TNM categorization based on the anatomical region approach was correct in 94.3% of lesions. Performance on the external test set confirmed the good performance of the algorithm (overall detection rate = 88.8% (95% CI: 82.5-93.5%) and FP/c = 2.7)., Conclusions: Retina U-Nets are a valuable tool for tumor detection tasks on PET/CT and can form the backbone of reading assistance tools in this field. FPs have anatomical correlates that can lead the way to further algorithm improvements. The code is publicly available., Key Points: • Detection of malignant lesions in PET/CT with Retina U-Net is feasible. • All false-positive findings had anatomical correlates, physiological bone marrow activity being the most prevalent. • Retina U-Nets can build the backbone for tools assisting imaging professionals in lung tumor staging., (© 2023. The Author(s).)

The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I. KEY POINTS: • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features. • A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician., (© 2022. The Author(s).)

The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively "Part I" and "Part II." The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR. KEY POINTS: • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • Imaging-derived biomarkers and their potential use in risk stratification are evolving; their correct interpretation and use in clinical practice must be well-understood. • A correct imaging strategy and scan protocol will produce the best possible results for disease evaluation., (© 2022. The Author(s).)

Background: A concise visualization framework of related reports would increase readability and improve patient management. To this end, temporal referrals to prior comparative exams are an essential connection to previous exams in written reports. Due to unstructured narrative texts' variable structure and content, their extraction is hampered by poor computer readability. Natural language processing (NLP) permits the extraction of structured information from unstructured texts automatically and can serve as an essential input for such a novel visualization framework., Objective: This study proposes and evaluates an NLP-based algorithm capable of extracting the temporal referrals in written radiology reports, applies it to all the radiology reports generated for 10 years, introduces a graphical representation of imaging reports, and investigates its benefits for clinical and research purposes., Methods: In this single-center, university hospital, retrospective study, we developed a convolutional neural network capable of extracting the date of referrals from imaging reports. The model's performance was assessed by calculating precision, recall, and F1-score using an independent test set of 149 reports. Next, the algorithm was applied to our department's radiology reports generated from 2011 to 2021. Finally, the reports and their metadata were represented in a modulable graph., Results: For extracting the date of referrals, the named-entity recognition (NER) model had a high precision of 0.93, a recall of 0.95, and an F1-score of 0.94. A total of 1,684,635 reports were included in the analysis. Temporal reference was mentioned in 53.3% (656,852/1,684,635), explicitly stated as not available in 21.0% (258,386/1,684,635), and omitted in 25.7% (317,059/1,684,635) of the reports. Imaging records can be visualized in a directed and modulable graph, in which the referring links represent the connecting arrows., Conclusions: Automatically extracting the date of referrals from unstructured radiology reports using deep learning NLP algorithms is feasible. Graphs refined the selection of distinct pathology pathways, facilitated the revelation of missing comparisons, and enabled the query of specific referring exam sequences. Further work is needed to evaluate its benefits in clinics, research, and resource planning., (©Laurent Binsfeld Gonçalves, Ivan Nesic, Marko Obradovic, Bram Stieltjes, Thomas Weikert, Jens Bremerich. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 21.12.2022.)

Purpose: Airway wall thickening is a consequence of chronic inflammatory processes and usually only qualitatively described in CT radiology reports. The purpose of this study is to automatically quantify airway wall thickness in multiple airway generations and assess the diagnostic potential of this parameter in a large cohort of patients with Chronic Obstructive Pulmonary Disease (COPD)., Materials and Methods: This retrospective, single-center study included a series of unenhanced chest CTs. Inclusion criteria were the mentioning of an explicit COPD GOLD stage in the written radiology report and time period (01/2019-12/2021). A control group included chest CTs with completely unremarkable lungs according to the report. The DICOM images of all cases (axial orientation; slice-thickness: 1 mm; soft-tissue kernel) were processed by an AI algorithm pipeline consisting of (A) a 3D-U-Net for det detection and tracing of the bronchial tree centerlines (B) extraction of image patches perpendicular to the centerlines of the bronchi, and (C) a 2D U-Net for segmentation of airway walls on those patches. The performance of centerline detection and wall segmentation was assessed. The imaging parameter average wall thickness was calculated for bronchus generations 3-8 (AWT 3-8 ) across the lungs. Mean AWT 3- 8 was compared between five groups (control, COPD Gold I-IV) using non-parametric statistics. Furthermore, the established emphysema score %LAV-950 was calculated and used to classify scans (normal vs. COPD) alone and in combination with AWT 3-8. RESULTS: A total of 575 chest CTs were processed. Algorithm performance was very good (airway centerline detection sensitivity: 86.9%; airway wall segmentation Dice score: 0.86). AWT 3-8 was statistically significantly greater in COPD patients compared to controls (2.03 vs. 1.87 mm, p < 0.001) and increased with COPD stage. The classifier that combined %LAV-950 and AWT 3-8 was superior to the classifier using only %LAV-950 (AUC = 0.92 vs. 0.79)., Conclusion: Airway wall thickness increases in patients suffering from COPD and is automatically quantifiable. AWT 3-8 could become a CT imaging parameter in COPD complementing the established emphysema biomarker %LAV-950., Clinical Relevance Statement: Quantitative measurements considering the complete visible bronchial tree instead of qualitative description could enhance radiology reports, allow for precise monitoring of disease progression and diagnosis of early stages of disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Three co-authors are employees of Siemens Healthineers: Jonathan I. Sperl, Dominik Neumann, and Abishek Balachandran. They had no influence on the methodology of this study and on the published results. All other authors have no conflict of interest. This study did not receive funding., (Copyright © 2022. Published by Elsevier B.V.)

Objective: This study trained and evaluated algorithms to detect, segment, and classify simple and complex pleural effusions on computed tomography (CT) scans., Materials and Methods: For detection and segmentation, we randomly selected 160 chest CT scans out of all consecutive patients (January 2016-January 2021, n = 2659) with reported pleural effusion. Effusions were manually segmented and a negative cohort of chest CTs from 160 patients without effusions was added. A deep convolutional neural network (nnU-Net) was trained and cross-validated (n = 224; 70%) for segmentation and tested on a separate subset (n = 96; 30%) with the same distribution of reported pleural complexity features as in the training cohort (eg, hyperdense fluid, gas, pleural thickening and loculation). On a separate consecutive cohort with a high prevalence of pleural complexity features (n = 335), a random forest model was implemented for classification of segmented effusions with Hounsfield unit thresholds, density distribution, and radiomics-based features as input. As performance measures, sensitivity, specificity, and area under the curves (AUCs) for detection/classifier evaluation (per-case level) and Dice coefficient and volume analysis for the segmentation task were used., Results: Sensitivity and specificity for detection of effusion were excellent at 0.99 and 0.98, respectively (n = 96; AUC, 0.996, test data). Segmentation was robust (median Dice, 0.89; median absolute volume difference, 13 mL), irrespective of size, complexity, or contrast phase. The sensitivity, specificity, and AUC for classification in simple versus complex effusions were 0.67, 0.75, and 0.77, respectively., Conclusion: Using a dataset with different degrees of complexity, a robust model was developed for the detection, segmentation, and classification of effusion subtypes. The algorithms are openly available at https://github.com/usb-radiology/pleuraleffusion.git., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To introduce a widely applicable workflow for pulmonary lobe segmentation of MR images using a recurrent neural network (RNN) trained with chest CT datasets. The feasibility is demonstrated for 2D coronal ultrafast balanced SSFP (ufSSFP) MRI., Methods: Lung lobes of 250 publicly accessible CT datasets of adults were segmented with an open-source CT-specific algorithm. To match 2D ufSSFP MRI data of pediatric patients, both CT data and segmentations were translated into pseudo-MR images that were masked to suppress anatomy outside the lung. Network-1 was trained with pseudo-MR images and lobe segmentations and then applied to 1000 masked ufSSFP images to predict lobe segmentations. These outputs were directly used as targets to train Network-2 and Network-3 with non-masked ufSSFP data as inputs, as well as an additional whole-lung mask as input for Network-2. Network predictions were compared to reference manual lobe segmentations of ufSSFP data in 20 pediatric cystic fibrosis patients. Manual lobe segmentations were performed by splitting available whole-lung segmentations into lobes., Results: Network-1 was able to segment the lobes of ufSSFP images, and Network-2 and Network-3 further increased segmentation accuracy and robustness. The average all-lobe Dice similarity coefficients were 95.0 ± 2.8 (mean ± pooled SD [%]) and 96.4 ± 2.5, 93.0 ± 2.0; and the average median Hausdorff distances were 6.1 ± 0.9 (mean ± SD [mm]), 5.3 ± 1.1, 7.1 ± 1.3 for Network-1, Network-2, and Network-3, respectively., Conclusion: Recurrent neural network lung lobe segmentation of 2D ufSSFP imaging is feasible, in good agreement with manual segmentations. The proposed workflow might provide access to automated lobe segmentations for various lung MRI examinations and quantitative analyses., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: It is known from histology studies that lung vessels are affected in viral pneumonia. However, their diagnostic potential as a chest CT imaging parameter has only rarely been exploited. The purpose of this study is to develop a robust method for automated lung vessel segmentation and morphology analysis and apply it to a large chest CT dataset., Methods: In total, 509 non-enhanced chest CTs (NECTs) and 563 CT pulmonary angiograms (CTPAs) were included. Sub-groups were patients with healthy lungs (group&#95;NORM, n = 634) and those RT-PCR-positive for Influenza A/B (group&#95;INF, n = 159) and SARS-CoV-2 (group&#95;COV, n = 279). A lung vessel segmentation algorithm (LVSA) based on traditional image processing was developed, validated with a point-of-interest approach, and applied to a large clinical dataset. Total blood vessel volume in lung (TBV) and the blood vessel volume percentage (BV%) of three blood vessel size types were calculated and compared between groups: small (BV5%, cross-sectional area < 5 mm 2 ), medium (BV5-10%, 5-10 mm 2 ) and large (BV10%, >10 mm 2 )., Results: Sensitivity of the LVSA was 84.6% (95 %CI: 73.9-95.3) for NECTs and 92.8% (95 %CI: 90.8-94.7) for CTPAs. In viral pneumonia, besides an increased TBV, the main finding was a significantly decreased BV5% in group&#95;COV (n = 14%) and group&#95;INF (n = 15%) compared to group&#95;NORM (n = 18%) [p < 0.001]. At the same time, BV10% was increased (group&#95;COV n = 15% and group&#95;INF n = 14% vs. group&#95;NORM n = 11%; p < 0.001)., Conclusion: In COVID-19 and Influenza, the blood vessel volume is redistributed from small to large vessels in the lung. Automated LSVA allows researchers and clinicians to derive imaging parameters for large amounts of CTs. This can enhance the understanding of vascular changes, particularly in infectious lung diseases., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pericardial effusions (PEFs) are often missed on Computed Tomography (CT), which particularly affects the outcome of patients presenting with hemodynamic compromise. An automatic PEF detection, segmentation, and classification tool would expedite and improve CT based PEF diagnosis; 258 CTs with (206 with simple PEF, 52 with hemopericardium) and without PEF (each 134 with contrast, 124 non-enhanced) were identified using the radiology report (01/2016−01/2021). PEF were manually 3D-segmented. A deep convolutional neural network (nnU-Net) was trained on 316 cases and separately tested on the remaining 200 and 22 external post-mortem CTs. Inter-reader variability was tested on 40 CTs. PEF classification utilized the median Hounsfield unit from each prediction. The sensitivity and specificity for PEF detection was 97% (95% CI 91.48−99.38%) and 100.00% (95% CI 96.38−100.00%) and 89.74% and 83.61% for diagnosing hemopericardium (AUC 0.944, 95% CI 0.904−0.984). Model performance (Dice coefficient: 0.75 ± 0.01) was non-inferior to inter-reader (0.69 ± 0.02) and was unaffected by contrast administration nor alternative chest pathology (p > 0.05). External dataset testing yielded similar results. Our model reliably detects, segments, and classifies PEF on CT in a complex dataset, potentially serving as an alert tool whilst enhancing report quality. The model and corresponding datasets are publicly available.

Authors implemented an artificial intelligence (AI)-based detection tool for intracranial hemorrhage (ICH) on noncontrast CT images into an emergent workflow, evaluated its diagnostic performance, and assessed clinical workflow metrics compared with pre-AI implementation. The finalized radiology report constituted the ground truth for the analysis, and CT examinations ( n = 4450) before and after implementation were retrieved using various keywords for ICH. Diagnostic performance was assessed, and mean values with their respective 95% CIs were reported to compare workflow metrics (report turnaround time, communication time of a finding, consultation time of another specialty, and turnaround time in the emergency department). Although practicable diagnostic performance was observed for overall ICH detection with 93.0% diagnostic accuracy, 87.2% sensitivity, and 97.8% negative predictive value, the tool yielded lower detection rates for specific subtypes of ICH (eg, 69.2% [74 of 107] for subdural hemorrhage and 77.4% [24 of 31] for acute subarachnoid hemorrhage). Common false-positive findings included postoperative and postischemic defects (23.6%, 37 of 157), artifacts (19.7%, 31 of 157), and tumors (15.3%, 24 of 157). Although workflow metrics such as communicating a critical finding (70 minutes [95% CI: 54, 85] vs 63 minutes [95% CI: 55, 71]) were on average reduced after implementation, future efforts are necessary to streamline the workflow all along the workflow chain. It is crucial to define a clear framework and recognize limitations as AI tools are only as reliable as the environment in which they are deployed. Keywords: CT, CNS, Stroke, Diagnosis, Classification, Application Domain © RSNA, 2022., Competing Interests: Disclosures of Conflicts of Interest: M.S. No relevant relationships. T.W. No relevant relationships. A.S. No relevant relationships. A.B. No relevant relationships. M.N.P. No relevant relationships. K.A.B. No relevant relationships., (2022 by the Radiological Society of North America, Inc.)

Background: Manually performed diameter measurements on ECG-gated CT-angiography (CTA) represent the gold standard for diagnosis of thoracic aortic dilatation. However, they are time-consuming and show high inter-reader variability. Therefore, we aimed to evaluate the accuracy of measurements of a deep learning-(DL)-algorithm in comparison to those of radiologists and evaluated measurement times (MT)., Methods: We retrospectively analyzed 405 ECG-gated CTA exams of 371 consecutive patients with suspected aortic dilatation between May 2010 and June 2019. The DL-algorithm prototype detected aortic landmarks (deep reinforcement learning) and segmented the lumen of the thoracic aorta (multi-layer convolutional neural network). It performed measurements according to AHA-guidelines and created visual outputs. Manual measurements were performed by radiologists using centerline technique. Human performance variability (HPV), MT and DL-performance were analyzed in a research setting using a linear mixed model based on 21 randomly selected, repeatedly measured cases. DL-algorithm results were then evaluated in a clinical setting using matched differences. If the differences were within 5 mm for all locations, the cases was regarded as coherent; if there was a discrepancy >5 mm at least at one location (incl. missing values), the case was completely reviewed., Results: HPV ranged up to ±3.4 mm in repeated measurements under research conditions. In the clinical setting, 2,778/3,192 (87.0%) of DL-algorithm's measurements were coherent. Mean differences of paired measurements between DL-algorithm and radiologists at aortic sinus and ascending aorta were -0.45±5.52 and -0.02±3.36 mm. Detailed analysis revealed that measurements at the aortic root were over-/underestimated due to a tilted measurement plane. In total, calculated time saved by DL-algorithm was 3:10 minutes/case., Conclusions: The DL-algorithm provided coherent results to radiologists at almost 90% of measurement locations, while the majority of discrepent cases were located at the aortic root. In summary, the DL-algorithm assisted radiologists in performing AHA-compliant measurements by saving 50% of time per case., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-142). JS is an employee of Siemens Healthineers and received personal fees, RK is a consultant for Siemens Healthineers. JS and RK both helped in installation and maintance of the software but were not involved in study design, data analysis or interpretation. They report that they have a patent US2020/0160527Al pending to Siemens Healthineers. The other authors have no conflict of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objectives: Rapid communication of CT exams positive for pulmonary embolism (PE) is crucial for timely initiation of anticoagulation and patient outcome. It is unknown if deep learning automated detection of PE on CT Pulmonary Angiograms (CTPA) in combination with worklist prioritization and an electronic notification system (ENS) can improve communication times and patient turnaround in the Emergency Department (ED)., Methods: In 01/2019, an ENS allowing direct communication between radiology and ED was installed. Starting in 10/2019, CTPAs were processed by a deep learning (DL)-powered algorithm for detection of PE. CTPAs acquired between 04/2018 and 06/2020 (n = 1808) were analysed. To assess the impact of the ENS and the DL-algorithm, radiology report reading times (RRT), radiology report communication time (RCT), time to anticoagulation (TTA), and patient turnaround times (TAT) in the ED were compared for three consecutive time periods. Performance measures of the algorithm were calculated on a per exam level (sensitivity, specificity, PPV, NPV, F1-score), with written reports and exam review as ground truth., Results: Sensitivity of the algorithm was 79.6 % (95 %CI:70.8-87.2%), specificity 95.0 % (95 %CI:92.0-97.1%), PPV 82.2 % (95 %CI:73.9-88.3), and NPV 94.1 % (95 %CI:91.4-96 %). There was no statistically significant reduction of any of the observed times (RRT, RCT, TTA, TAT)., Conclusion: DL-assisted detection of PE in CTPAs and ENS-assisted communication of results to referring physicians technically work. However, the mere clinical introduction of these tools, even if they exhibit a good performance, is not sufficient to achieve significant effects on clinical performance measures., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate potential confounding factors in the quantitative assessment of liver fibrosis and cirrhosis using T1 relaxation times., Methods: The study population is based on a radiology-information-system database search for abdominal MRI performed from July 2018 to April 2019 at our institution. After applying exclusion criteria 200 (59 ± 16 yrs) remaining patients were retrospectively included. 93 patients were defined as liver-healthy, 40 patients without known fibrosis or cirrhosis, and 67 subjects had a clinically or biopsy-proven liver fibrosis or cirrhosis. T1 mapping was performed using a slice based look-locker approach. A ROI based analysis of the left and the right liver was performed. Fat fraction, R2*, liver volume, laboratory parameters, sex, and age were evaluated as potential confounding factors., Results: T1 values were significantly lower in healthy subjects without known fibrotic changes (1.5 T MRI: 575 ± 56 ms; 3 T MRI: 857 ± 128 ms) compared to patients with acute liver disease (1.5 T MRI: 657 ± 73 ms, p < 0.0001; 3 T MRI: 952 ± 37 ms, p = 0.028) or known fibrosis or cirrhosis (1.5 T MRI: 644 ± 83 ms, p < 0.0001; 3 T MRI: 995 ± 150 ms, p = 0.018). T1 values correlated moderately with the Child-Pugh stage at 1.5 T (p = 0.01, ρ = 0.35)., Conclusion: T1 mapping is a capable predictor for detection of liver fibrosis and cirrhosis. Especially age is not a confounding factor and, hence, age-independent thresholds can be defined. Acute liver diseases are confounding factors and should be ruled out before employing T1-relaxometry based thresholds to screen for patients with liver fibrosis or cirrhosis., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Machine learning offers great opportunities to streamline and improve clinical care from the perspective of cardiac imagers, patients, and the industry and is a very active scientific research field. In light of these advances, the European Society of Cardiovascular Radiology (ESCR), a non-profit medical society dedicated to advancing cardiovascular radiology, has assembled a position statement regarding the use of machine learning (ML) in cardiovascular imaging. The purpose of this statement is to provide guidance on requirements for successful development and implementation of ML applications in cardiovascular imaging. In particular, recommendations on how to adequately design ML studies and how to report and interpret their results are provided. Finally, we identify opportunities and challenges ahead. While the focus of this position statement is ML development in cardiovascular imaging, most considerations are relevant to ML in radiology in general. KEY POINTS: • Development and clinical implementation of machine learning in cardiovascular imaging is a multidisciplinary pursuit. • Based on existing study quality standard frameworks such as SPIRIT and STARD, we propose a list of quality criteria for ML studies in radiology. • The cardiovascular imaging research community should strive for the compilation of multicenter datasets for the development, evaluation, and benchmarking of ML algorithms.

Objective: To extract pulmonary and cardiovascular metrics from chest CTs of patients with coronavirus disease 2019 (COVID-19) using a fully automated deep learning-based approach and assess their potential to predict patient management., Materials and Methods: All initial chest CTs of patients who tested positive for severe acute respiratory syndrome coronavirus 2 at our emergency department between March 25 and April 25, 2020, were identified (n = 120). Three patient management groups were defined: group 1 (outpatient), group 2 (general ward), and group 3 (intensive care unit [ICU]). Multiple pulmonary and cardiovascular metrics were extracted from the chest CT images using deep learning. Additionally, six laboratory findings indicating inflammation and cellular damage were considered. Differences in CT metrics, laboratory findings, and demographics between the patient management groups were assessed. The potential of these parameters to predict patients' needs for intensive care (yes/no) was analyzed using logistic regression and receiver operating characteristic curves. Internal and external validity were assessed using 109 independent chest CT scans., Results: While demographic parameters alone (sex and age) were not sufficient to predict ICU management status, both CT metrics alone (including both pulmonary and cardiovascular metrics; area under the curve [AUC] = 0.88; 95% confidence interval [CI] = 0.79-0.97) and laboratory findings alone (C-reactive protein, lactate dehydrogenase, white blood cell count, and albumin; AUC = 0.86; 95% CI = 0.77-0.94) were good classifiers. Excellent performance was achieved by a combination of demographic parameters, CT metrics, and laboratory findings (AUC = 0.91; 95% CI = 0.85-0.98). Application of a model that combined both pulmonary CT metrics and demographic parameters on a dataset from another hospital indicated its external validity (AUC = 0.77; 95% CI = 0.66-0.88)., Conclusion: Chest CT of patients with COVID-19 contains valuable information that can be accessed using automated image analysis. These metrics are useful for the prediction of patient management., Competing Interests: Saikiran Rapaka, Sasa Grbic, Thomas Re, Shikha Chaganti and Dorin Comaniciu are employees of Siemens Healthineers and provided the pulmonary and cardiovascular algorithms, but had no influence on data analysis and final results. All other authors declare no conflict of interest., (Copyright © 2021 The Korean Society of Radiology.)

Pancreatic cystic lesions (PCL) are a frequent and underreported incidental finding on CT scans and can transform into neoplasms with devastating consequences. We developed and evaluated an algorithm based on a two-step nnU-Net architecture for automated detection of PCL on CTs. A total of 543 cysts on 221 abdominal CTs were manually segmented in 3D by a radiology resident in consensus with a board-certified radiologist specialized in abdominal radiology. This information was used to train a two-step nnU-Net for detection with the performance assessed depending on lesions' volume and location in comparison to three human readers of varying experience. Mean sensitivity was 78.8 ± 0.1%. The sensitivity was highest for large lesions with 87.8% for cysts ≥220 mm 3 and for lesions in the distal pancreas with up to 96.2%. The number of false-positive detections for cysts ≥220 mm 3 was 0.1 per case. The algorithm's performance was comparable to human readers. To conclude, automated detection of PCL on CTs is feasible. The proposed model could serve radiologists as a second reading tool. All imaging data and code used in this study are freely available online.

CT patterns of viral pneumonia are usually only qualitatively described in radiology reports. Artificial intelligence enables automated and reliable segmentation of lungs with chest CT. Based on this, the purpose of this study was to derive meaningful imaging biomarkers reflecting CT patterns of viral pneumonia and assess their potential to discriminate between healthy lungs and lungs with viral pneumonia. This study used non-enhanced and CT pulmonary angiograms (CTPAs) of healthy lungs and viral pneumonia (SARS-CoV-2, influenza A/B) identified by radiology reports and RT-PCR results. After deep learning segmentation of the lungs, histogram-based and threshold-based analyses of lung attenuation were performed and compared. The derived imaging biomarkers were correlated with parameters of clinical and biochemical severity (modified WHO severity scale; c-reactive protein). For non-enhanced CTs ( n = 526), all imaging biomarkers significantly differed between healthy lungs and lungs with viral pneumonia (all p < 0.001), a finding that was not reproduced for CTPAs ( n = 504). Standard deviation (histogram-derived) and relative high attenuation area [600-0 HU] (HU-thresholding) differed most. The strongest correlation with disease severity was found for absolute high attenuation area [600-0 HU] (r = 0.56, 95% CI = 0.46-0.64). Deep-learning segmentation-based histogram and HU threshold analysis could be deployed in chest CT evaluation for the differentiating of healthy lungs from AP lungs.

Objectives: To evaluate the performance of an AI-powered algorithm for the automatic detection of pulmonary embolism (PE) on chest computed tomography pulmonary angiograms (CTPAs) on a large dataset., Methods: We retrospectively identified all CTPAs conducted at our institution in 2017 (n = 1499). Exams with clinical questions other than PE were excluded from the analysis (n = 34). The remaining exams were classified into positive (n = 232) and negative (n = 1233) for PE based on the final written reports, which defined the reference standard. The fully anonymized 1-mm series in soft tissue reconstruction served as input for the PE detection prototype algorithm that was based on a deep convolutional neural network comprising a Resnet architecture. It was trained and validated on 28,000 CTPAs acquired at other institutions. The result series were reviewed using a web-based feedback platform. Measures of diagnostic performance were calculated on a per patient and a per finding level., Results: The algorithm correctly identified 215 of 232 exams positive for pulmonary embolism (sensitivity 92.7%; 95% confidence interval [CI] 88.3-95.5%) and 1178 of 1233 exams negative for pulmonary embolism (specificity 95.5%; 95% CI 94.2-96.6%). On a per finding level, 1174 of 1352 findings marked as embolus by the algorithm were true emboli. Most of the false positive findings were due to contrast agent-related flow artifacts, pulmonary veins, and lymph nodes., Conclusion: The AI prototype algorithm we tested has a high degree of diagnostic accuracy for the detection of PE on CTPAs. Sensitivity and specificity are balanced, which is a prerequisite for its clinical usefulness., Key Points: • An AI-based prototype algorithm showed a high degree of diagnostic accuracy for the detection of pulmonary embolism on CTPAs. • It can therefore help clinicians to automatically prioritize exams with a high suspection of pulmonary embolism and serve as secondary reading tool. • By complementing traditional ways of worklist prioritization in radiology departments, this can speed up the diagnostic and therapeutic workup of patients with pulmonary embolism and help to avoid false negative calls.

Purpose: The purpose of this retrospective study was to correlate CT patterns of fatal cases of coronavirus disease 2019 (COVID-19) with postmortem pathology observations., Materials and Methods: The study included 70 lung lobes of 14 patients who died of reverse-transcription polymerase chain reaction-confirmed COVID-19. All patients underwent antemortem CT and autopsy between March 9 and April 30, 2020. Board-certified radiologists and pathologists performed lobewise correlations of pulmonary observations. In a consensus reading, 267 radiologic and 257 histopathologic observations of the lungs were recorded and systematically graded according to severity. These observations were matched and evaluated., Results: Predominant CT observations were ground-glass opacities (GGO) (59/70 lobes examined) and areas of consolidation (33/70). The histopathologic observations were consistent with diffuse alveolar damage (70/70) and capillary dilatation and congestion (70/70), often accompanied by microthrombi (27/70), superimposed acute bronchopneumonia (17/70), and leukocytoclastic vasculitis (7/70). Four patients had pulmonary emboli. Bronchial wall thickening at CT histologically corresponded with acute bronchopneumonia. GGOs and consolidations corresponded with mixed histopathologic observations, including capillary dilatation and congestion, interstitial edema, diffuse alveolar damage, and microthrombosis. Vascular alterations were prominent observations at both CT and histopathology., Conclusion: A significant proportion of GGO correlated with the pathologic processes of diffuse alveolar damage, capillary dilatation and congestion, and microthrombosis. Our results confirm the presence and underline the importance of vascular alterations as key pathophysiologic drivers in lethal COVID-19. Supplemental material is available for this article. © RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: M.H. disclosed no relevant relationships. T.W. disclosed no relevant relationships. K.M. disclosed no relevant relationships. N.S. disclosed no relevant relationships. G.S. disclosed no relevant relationships. J.H. Activities related to the present article: disclosed grant to author’s institution from Botnar Research Centre for Child Health.no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. F.F. disclosed no relevant relationships. C.A. disclosed no relevant relationships. B.S. disclosed no relevant relationships. A.M. disclosed no relevant relationships. J.B. disclosed no relevant relationships. T.M. disclosed no relevant relationships. K.D.M. disclosed no relevant relationships. A.T. Activities related to the present article: disclosed grant to author’s institution from Botnar Research Centre for Child Health. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. A.W.S. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Purpose: During the emerging COVID-19 pandemic, radiology departments faced a substantial increase in chest CT admissions coupled with the novel demand for quantification of pulmonary opacities. This article describes how our clinic implemented an automated software solution for this purpose into an established software platform in 10 days. The underlying hypothesis was that modern academic centers in radiology are capable of developing and implementing such tools by their own efforts and fast enough to meet the rapidly increasing clinical needs in the wake of a pandemic., Method: Deep convolutional neural network algorithms for lung segmentation and opacity quantification on chest CTs were trained using semi-automatically and manually created ground-truth (N total  = 172). The performance of the in-house method was compared to an externally developed algorithm on a separate test subset (N = 66)., Results: The final algorithm was available at day 10 and achieved human-like performance (Dice coefficient = 0.97). For opacity quantification, a slight underestimation was seen both for the in-house (1.8 %) and for the external algorithm (0.9 %). In contrast to the external reference, the underestimation for the in-house algorithm showed no dependency on total opacity load, making it more suitable for follow-up., Conclusions: The combination of machine learning and a clinically embedded software development platform enabled time-efficient development, instant deployment, and rapid adoption in clinical routine. The algorithm for fully automated lung segmentation and opacity quantification that we developed in the midst of the COVID-19 pandemic was ready for clinical use within just 10 days and achieved human-level performance even in complex cases., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To assess the diagnostic performance of a deep learning-based algorithm for automated detection of acute and chronic rib fractures on whole-body trauma CT., Materials and Methods: We retrospectively identified all whole-body trauma CT scans referred from the emergency department of our hospital from January to December 2018 (n = 511). Scans were categorized as positive (n = 159) or negative (n = 352) for rib fractures according to the clinically approved written CT reports, which served as the index test. The bone kernel series (1.5-mm slice thickness) served as an input for a detection prototype algorithm trained to detect both acute and chronic rib fractures based on a deep convolutional neural network. It had previously been trained on an independent sample from eight other institutions (n = 11455)., Results: All CTs except one were successfully processed (510/511). The algorithm achieved a sensitivity of 87.4% and specificity of 91.5% on a per-examination level [per CT scan: rib fracture(s): yes/no]. There were 0.16 false-positives per examination (= 81/510). On a per-finding level, there were 587 true-positive findings (sensitivity: 65.7%) and 307 false-negatives. Furthermore, 97 true rib fractures were detected that were not mentioned in the written CT reports. A major factor associated with correct detection was displacement., Conclusion: We found good performance of a deep learning-based prototype algorithm detecting rib fractures on trauma CT on a per-examination level at a low rate of false-positives per case. A potential area for clinical application is its use as a screening tool to avoid false-negative radiology reports., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

Purpose: To design and evaluate a self-trainable natural language processing (NLP)-based procedure to classify unstructured radiology reports. The method enabling the generation of curated datasets is exemplified on CT pulmonary angiogram (CTPA) reports., Method: We extracted the impressions of CTPA reports created at our institution from 2016 to 2018 (n = 4397; language: German). The status (pulmonary embolism: yes/no) was manually labelled for all exams. Data from 2016/2017 (n = 2801) served as a ground truth to train three NLP architectures that only require a subset of reference datasets for training to be operative. The three architectures were as follows: a convolutional neural network (CNN), a support vector machine (SVM) and a random forest (RF) classifier. Impressions of 2018 (n = 1377) were kept aside and used for general performance measurements. Furthermore, we investigated the dependence of classification performance on the amount of training data with multiple simulations., Results: The classification performance of all three models was excellent (accuracies: 97 %-99 %; F1 scores 0.88-0.97; AUCs: 0.993-0.997). Highest accuracy was reached by the CNN with 99.1 % (95 % CI 98.5-99.6 %). Training with 470 labelled impressions was sufficient to reach an accuracy of > 93 % with all three NLP architectures., Conclusion: Our NLP-based approaches allow for an automated and highly accurate retrospective classification of CTPA reports with manageable effort solely using unstructured impression sections. We demonstrated that this approach is useful for the classification of radiology reports not written in English. Moreover, excellent classification performance is achieved at relatively small training set sizes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The use of artificial intelligence (AI) is a powerful tool for image analysis that is increasingly being evaluated by radiology professionals. However, due to the fact that these methods have been developed for the analysis of nonmedical image data and data structure in radiology departments is not "AI ready", implementing AI in radiology is not straightforward. The purpose of this review is to guide the reader through the pipeline of an AI project for automated image analysis in radiology and thereby encourage its implementation in radiology departments. At the same time, this review aims to enable readers to critically appraise articles on AI-based software in radiology.

Purpose: To share experience from a large, ongoing expert reading teleradiology program in Europe and Asia aiming at supporting referring centers to interpret high-resolution computed tomography (HRCT) with respect to presence of Usual Interstitial Pneumonia (UIP)-pattern in patients with suspected Idiopathic Pulmonary Fibrosis (IPF)., Method: We analyzed data from 01/2014 to 05/2019, including HRCTs from 239 medical centers in 12 European and Asian countries that were transmitted to our Picture Archiving and Communication System (PACS) via a secured internet connection. Structured reports were generated in consensus by a radiologist with over 20 years of experience in thoracic imaging and a pulmonologist with specific expertise in interstitial lung disease according to current guidelines on IPF. Reports were sent to referring physicians. We evaluated patient characteristics, technical issues, report turnaround times and frequency of diagnoses. We also conducted a survey to collect feedback from referring physicians., Results: HRCT image data from 703 patients were transmitted (53.5% male). Mean age was 63.7 years (SD:17). In 35.1% of all cases diagnosis was "UIP"/"Typical UIP". The mean report turnaround time was 1.7 days (SD:2.9). Data transmission errors occurred in 7.1%. Overall satisfaction rate among referring physicians was high (8.4 out of 10; SD:3.2)., Conclusions: This Eurasian teleradiology program demonstrates the feasibility of cross-border teleradiology for the provision of state-of-the-art reporting despite heterogeneity of referring medical centers and challenges like data transmission errors and language barriers. We also point out important factors for success like the usage of structured reporting templates., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The purpose of this study was to determine if parameters derived from diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) can help to assess early response to peptide receptor radionuclide therapy (PRRT) with 90 Y-DOTATOC in neuroendocrine hepatic metastases (NET-HM). Twenty patients (10 male; 10 female; mean age: 59.2 years) with NET-HM were prospectively enrolled in this single-center imaging study. DW-MRI and DCE-MRI studies were performed just before and 48 hours after therapy with 90 Y-DOTATOC. Abdominal SPECT/CT was performed 24 hours after therapy. This MRI imaging and therapy session was repeated after a mean interval of 10 weeks. Up to four lesions per patient were evaluated. Response to therapy was evaluated using metastasis sizes at the first and second therapy session as standard for comparison (regressive, stable, and progressive). DW-MRI analysis included the apparent diffusion coefficient (ADC) and parameters related to intravoxel incoherent motion (IVIM), namely, diffusion ( D ), perfusion fraction ( f ) and pseudo-diffusion ( D ∗ ). DCE-MRI analysis comprised K trans , v e and k ep . For statistical analysis of group differences, one-way analysis of variance (ANOVA) and appropriate post hoc testing was performed. A total of 51 lesions were evaluated. Seven of 51 lesions (14%) showed size progression, 18/51 (35%) regression, and 26/51 (51%) remained stable. The lesion-to-spleen uptake ratio in SPECT showed a decrease between the two treatment sessions that was significantly stronger in regressive lesions compared with stable ( p = 0.013) and progressive lesions ( p = 0.021). ANOVA showed significant differences in mean ADC after 48 h ( p = 0.026), with higher ADC values for regressive lesions. Regarding IVIM, highest values for D at baseline were seen in regressive lesions ( p = 0.023). In DCE-MRI, a statistically significant increase in v e after 10 weeks ( p = 0.046) was found in regressive lesions. No differences were observed for the transfer constants K trans and k ep . Diffusion restriction quantified as ADC was able to differentiate regressive from progressive NET-HMs as early as 48 hours after PRRT. DW-MRI therefore may complement scintigraphy/SPECT for early assessment of response to PRRT. Assessment of perfusion parameters using IVIM and DCE-MRI did not show an additional benefit., Competing Interests: Markus Klarhöfer is an employee of Siemens Healthcare AG (Switzerland) and declares no conflicts of interest regarding this study. All other authors declare that they have no conflicts of interest., (Copyright © 2019 Thomas Weikert et al.)

Automated detection and segmentation is a prerequisite for the deployment of image-based secondary analyses, especially for lung tumors. However, currently only applications for lung nodules ≤3 cm exist. Therefore, we tested the performance of a fully automated AI-based lung nodule algorithm for detection and 3D segmentation of primary lung tumors in the context of tumor staging using the CT component of FDG-PET/CT and including all T-categories (T1-T4). FDG-PET/CTs of 320 patients with histologically confirmed lung cancer performed between 01/2010 and 06/2016 were selected. First, the main primary lung tumor within each scan was manually segmented using the CT component of the PET/CTs as reference. Second, the CT series were transferred to a platform with AI-based algorithms trained on chest CTs for detection and segmentation of lung nodules. Detection and segmentation performance were analyzed. Factors influencing detection rates were explored with binominal logistic regression and radiomic analysis. We also processed 94 PET/CTs negative for pulmonary nodules to investigate frequency and reasons of false-positive findings. The ratio of detected tumors was best in the T1-category (90.4%) and decreased continuously: T2 (70.8%), T3 (29.4%), and T4 (8.8%). Tumor contact with the pleura was a strong predictor of misdetection. Segmentation performance was excellent for T1 tumors ( r  = 0.908, p < 0.001) and tumors without pleural contact ( r  = 0.971, p < 0.001). Volumes of larger tumors were systematically underestimated. There were 0.41 false-positive findings per exam. The algorithm tested facilitates a reliable detection and 3D segmentation of T1/T2 lung tumors on FDG-PET/CTs. The detection and segmentation of more advanced lung tumors is currently imprecise due to the conception of the algorithm for lung nodules <3 cm. Future efforts should therefore focus on this collective to facilitate segmentation of all tumor types and sizes to bridge the gap between CAD applications for screening and staging of lung cancer.

Chitosans, partially de-N-acetylated derivatives of chitin, are multifunctional biopolymers. In nature, biological activities of partially acetylated chitosan polymers are mediated in part by their oligomeric breakdown products, which are generated in situ by the action of chitosanolytic enzymes. Understanding chitosanolytic enzymes, therefore, can lead to the production of chitosan oligomers with fully defined structures that may confer specific bioactivities. To address whether defined oligomer products can be produced via chitosanolytic enzymes, we here characterized a GH8 family chitosanase from Bacillus spec. MN, determining its mode of action and product profiles. We found that the enzyme has higher activity towards polymers with lower degree of acetylation. Oligomeric products were dominated by GlcN 3 , GlcN 3 GlcNAc 1 , and GlcN 4 GlcNAc 1 . The product distribution from oligomers were GlcN 3  > GlcN 2 . Modeling and simulations show that the binding site comprises subsites ranging from (-3) to (+3), and a putative (+4) subsite, with defined preferences for GlcN or GlcNAc at each subsite. Flexible loops at the binding site facilitate enzyme-substrate interactions and form a cleft at the active site which can open and close. The detailed insight gained here will help to engineer enzyme variants to produce tailored chitosan oligomers with defined structures that can then be used to probe their specific biological activities.

Results of PET/CT examinations are communicated as text-based reports which are frequently not fully structured. Incomplete or missing staging information can be a significant source of staging and treatment errors. We compared standard text-based reports to a manual full 3D-segmentation-based approach with respect to TNM completeness and processing time. TNM information was extracted retrospectively from 395 reports. Moreover, the RIS time stamps of these reports were analyzed. 2995 lesions using a set of 41 classification labels (TNM features + location) were manually segmented on the corresponding image data. Information content and processing time of reports and segmentations were compared using descriptive statistics and modelling. The TNM/UICC stage was mentioned explicitly in only 6% ( n =22) of the text-based reports. In 22% ( n =86), information was incomplete, most frequently affecting T stage (19%, n =74), followed by N stage (6%, n =22) and M stage (2%, n =9). Full NSCLC-lesion segmentation required a median time of 13.3 min, while the median of the shortest estimator of the text-based reporting time ( R 1) was 18.1 min ( p =0.01). Tumor stage (UICC I/II: 5.2 min, UICC III/IV: 20.3 min, p < 0.001), lesion size ( p < 0.001), and lesion count ( n =1: 4.4 min, n =12: 37.2 min, p < 0.001) correlated significantly with the segmentation time, but not with the estimators of text-based reporting time. Numerous text-based reports are lacking staging information. A segmentation-based reporting approach tailored to the staging task improves report quality with manageable processing time and helps to avoid erroneous therapy decisions based on incomplete reports. Furthermore, segmented data may be used for multimedia enhancement and automatization.

Partially acetylated chitosan oligosaccharides (paCOS) have various potential applications in agriculture, biomedicine, and pharmaceutics due to their suitable bioactivities. One method to produce paCOS is partial chemical hydrolysis of chitosan polymers, but that leads to poorly defined mixtures of oligosaccharides. However, the effective production of defined paCOS is crucial for fundamental research and for developing applications. A more promising approach is enzymatic depolymerization of chitosan using chitinases or chitosanases, as the substrate specificity of the enzyme determines the composition of the oligomeric products. Protein-engineering of these enzymes to alter their substrate specificity can overcome the limitations associated with naturally occurring enzymes and expand the spectrum of specific paCOS that can be produced. Here, engineering the substrate specificity of Bacillus sp. MN chitosanase is described for the first time. Two muteins with active site substitutions can accept N-acetyl-D-glucosamine units at their subsite (-2), which is impossible for the wildtype enzyme., (© 2017 Wiley Periodicals, Inc.)

The minimum apparent diffusion coefficient (ADC min ) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUV max ) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADC min - and SUV max -voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance ( D ) between ADC min - and SUV max -voxels was 14.0 mm (average of two readers). Spatial mismatch ( D > 12 mm) between ADC min and SUV max was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUV max and ADC min was seen, while a moderate negative linear relationship ( r = -0.5) between SUV max and ADC min was observed in tumors with a spatial match ( D ≤ 12 mm). In conclusion, spatial mismatch between ADC min and SUV max is found in a considerable percentage of patients. The spatial connection of the two parameters SUV max and ADC min has a crucial influence on their numeric correlation.

Chitosanases can be used to produce partially acetylated chitosan oligosaccharides (paCOS) for different applications, provided they are thoroughly characterized. However, recent studies indicate that the established classification system for chitosanases is too simplistic. Here, we apply a highly sensitive method for quantitatively sequencing paCOS to reassess the substrate specificities of the best-characterized class I-III chitosanases. The enzymes' abilities to cleave bonds at GlcNAc residues positioned at subsite (-1) or (+1), on which the classification system is based, vary especially when the substrates have different fractions of acetylation (F A ). Conflicts with the recent classification are observed at higher F A , which were not investigated in prior specificity determinations. Initial analyses of pectin-degrading enzymes reveal that classifications of other polysaccharide-degrading enzymes should also be critically reassessed. Based on our results, we tentatively suggest a chitosanase classification system which is based on specificities and preferences of subsites (-2) to (+2).

Chitosan (CS) is a family of linear polysaccharides with diverse applications in medicine, agriculture, and industry. Its bioactive properties are determined by parameters such as the degree of acetylation (DA), but current techniques to measure the DA are laborious and require large amounts of substrate and sophisticated equipment. It is also challenging to monitor the fate of chitosan-based nanoparticles (CS-NPs) in vitro because current tools cannot measure their enzymatic or chemical degradation. We have developed a method based on the Förster resonance energy transfer (FRET) that occurs between two independent fluorescent proteins fused to a CS-binding domain, who interact with CS polymers or CS-NPs. We used this approach to calibrate a simple and rapid analytical method that can determine the DA of CS substrates. We showed unequivocally that FRET occurs on the surface of CS-NPs and that the FRET signal is quenched by enzymatic degradation of the CS substrate. Finally, we provide in vitro proof-of-concept that these approaches can be used to label CS-NPs and colocalize them following their interactions with mammalian cells.

Background: Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders. Furthermore, animal and genetic imaging studies have reported strong functional evidence for the association of CACNA1C with learning, memory, neural plasticity, and its association with the hippocampal formation. In the present study we investigated the impact of the CACNA1C SNP rs1006737 on the fractional anisotropy (FA) in the hippocampal formation as well as on verbal learning and memory in healthy individuals., Methods: 118 healthy individuals (72 males, 46 females, age 18-56years) initially underwent diffusion tensor imaging (DTI), 100 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) to examine the impact of the CACNA1C SNP rs1006737 on the hippocampal formation as predefined region of interest (ROI). Furthermore, all participants completed the Verbal Learning and Memory Test (VLMT)., Results: In the VLMT genotype was significantly associated with learning performance. Bonferroni corrected post-hoc tests indicated a diminished performance at the beginning of the learning curve in risk allele carriers compared to non-risk allele carriers. The TBSS ROI analysis revealed one cluster of reduced FA in risk allele carriers compared to non-risk allele carriers located in the right hippocampal formation. Moreover, an association between the initial learning performance and FA values was found., Discussion: These findings demonstrate that genetic variation in the CACNA1C SNP rs1006737 is associated with FA reduction in the hippocampal formation as well as with differences in learning performance in healthy individuals., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Embryonic cholinesterases are assigned important functions during morphogenesis. Here we describe the expression of butyrylcholinesterase and acetylcholinesterase, and the binding of peanut agglutinin, and relate the results to mitotic activity in chick wing and leg buds from embryonic day 4 to embryonic day 9. During early stages, butyrylcholinesterase is elevated in cells under the apical ectodermal ridge and around invading motoraxons, while acetylcholinesterase is found in the chondrogenic core, on motoraxons and along the ectoderm. Peanut agglutinin binds to the apical ectodermal ridge and most prominently to the chondrogenic core. Measurements of thymidine incorporation and enzyme activities were consistent with our histological findings. Butyrylcholinesterase is concentrated near proliferative zones and periods, while acetylcholinesterase is associated with low proliferative activity. At late stages of limb development, acetylcholinesterase is concentrated in muscles and nonexistent within bones, while butyrylcholinesterase shows an inverse pattern. Thus, as in other systems, in limb formation butyrylcholinesterase is a transmitotic marker preceding differentiation, acetylcholinesterase is found on navigating axons, while peanut agglutinin appears in non-invaded regions. These data suggest roles for cholinesterases as positive regulators and peanut-agglutinin-binding proteins as negative regulators of neural differentiation.

The HNK-1 epitope as a hallmark of many cell adhesion molecules is supposed to convey positive cellular interactions. Here, we report that in the adult chick the HNK-1 epitope is absent from active serum butyrylcholinesterases (BChE), but is strongly expressed on all inactive serum BChEs and on active brain BChE. These data further support roles of cholinesterases in cell adhesion, particularly so for their inactive forms. Moreover, we show that the HNK-1-positive BChEs belong to different types of glycoproteins.

Three different homologues of butyrylcholinesterase (BChE) with 75-, 62-, and 54-kDa subunit size are isolated from adult chicken serum, and all show very low or zero enzyme activity. Although the active BChE from serum with a subunit size of 81 kDa forms tetramers, the 75-kDa protein is isolated as a dimer. The homology of the 75-kDa protein with active BChE is shown by immunoreactivity with BChE-specific monoclonal antibodies, by coisolation with the active BChE, and by their identical first six N-terminal amino acids. By deglycosylation of these proteins and by their differential lectin binding, we show that the active BChE is an N-glycosylated protein of the triantennary type, whereas the inactive 75-kDa protein is O-glycosylated. These data show for the first time the existence of (1) multiple inactive forms of BChE, (2) secreted inactive cholinesterases, because they are found in serum, and (3) an O-glycosylated cholinesterase. Because cholinesterases can regulate neurite growth in vitro by a nonenzymatic mechanism, these data strongly support that both inactive and active forms of BChE may be involved in noncholinergic communication, possibly depending on particular glycosylation patterns.

The G4 glycoprotein is found on the earliest developing neurite tracts of the chick embryo. An ELISA is introduced here to quantify the amount of G4-expressing neurites in the picogram range. In this double-sandwich assay, an anti-G4 monoclonal antibody fixes the G4 antigen to the plastic surface, which then is detected by a polyclonal antiserum; nonspecific background is decreased by competitive displacement. The sensitivity of the assay allows us to follow quantitatively the very first neurite growth in embryonic heads, trunks, retinae, and brains. G4-based neurite growth is shown to occur earlier in heads than in trunks; in brain it is nearly 10-fold higher than in the retina by embryonic day 8. By determination of acetylcholinesterase (AChE) activities from the same homogenates, our earlier histochemical findings are verified now on a quantitative basis, again showing that AChE consistently precedes G4 antigen. Moreover, as an in vitro example, the G4 ELISA is applied to the nerve growth factor (NGF) standard bioassay on dorsal root ganglia; the half-maximal response is reached at approximately 10 ng/ml of NGF for G4-based neurite growth and at approximately 1 ng/ml of NGF for AChE expression, respectively.

Cholinesterases present homologies with some cell adhesion molecules; however, it is unclear whether and how they perform adhesive functions. Here, we provide the first direct evidence showing that neurite growth in vitro from various neuronal tissues of the chick embryo can be modified by some, but not all, anticholinesterase agents. By quantifying the neuritic G4 antigen in tectal cell cultures, the effect of anticholinesterases on neurite growth is directly compared with their cholinesterase inhibitory action. BW 284C51 and ethopropazine, inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, strongly decrease neurite growth in a dose-dependent manner. However, echothiophate which inhibits both cholinesterases, does not change neuritic growth. These quantitative data are supplemented by morphological observations in retinal explant cultures grown on striped laminin carpets, viz., defasciculation of neurite bundles by BW 284C51 and Bambuterol occurs, indicating that these drugs disturb adhesive mechanisms. These data strongly suggest that a) cholinesterases can participate in regulating axonal growth, b) both AChE and BChE can perform such a nonsynaptic function, and c) this function is not the result of the enzyme activity per se, since at least one drug was found that inhibits all cholinesterase activities but not neurite growth. Thus, a secondary site on cholinesterase molecules must be responsible for adhesive functions.

The phylo- and ontogenetically related enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are expressed consecutively at the onset of avian neuronal differentiation. In order to investigate their possible co-regulation, we have studied the effect of highly selective inhibitors on each of the cholinesterases with respect to their expression in rotary cultures of the retina (retinospheroids) and stationary cultures of the embryonic chick tectum. Adding the irreversible BChE inhibitor iso-OMPA to reaggregating retinal cells has only slight morphological effects and fully inhibits BChE expression. Unexpectedly, iso-OMPA also suppresses the expression of AChE to 35%-60% of its control activity. Histochemically, this inhibition is most pronounced in fibrous regions. The release of AChE into the media of both types of cultures is inhibited by iso-OMPA by more than 85%. Control experiments show that AChE suppression by the BChE inhibitor is only partially explainable by direct cross-inhibition of iso-OMPA on AChE. In contrast, the treatment of retinospheroids with the reversible AChE inhibitor BW284C51 first accelerates the expression of AChE and then leads to a rapid decay of the spheroids. After injection of BW284C51 into living embryos, we find that AChE is expressed prematurely in cells that normally express BChE. We conclude that the cellular expression of AChE is regulated by the amount of both active BChE and active AChE within neuronal tissues. Thus, direct interaction with classical cholinergic systems is indicated for the seemingly redundant BChE.

After approaching the outer surface of the neuroepithelium, postmitotic cell bodies abruptly start to synthesize acetylcholinesterase (AChE). Their easy histochemical detection allows us to trace sensitively spatiotemporal patterns of differentiation processes of the chicken nervous system. To investigate the relationship between postmitotic AChE production and the first formation of neurites, AChE histochemistry is combined here with immunohistochemistry using the neurite-specific G4-antibody. Spatial computer reconstructions from double-stained serial sections of whole brains of H.H. stages 10-20 demonstrate that G4-neurite expression spatio-temporally follows the expression of AChE in its complex polycentric pattern closely, the details of which have been described earlier. By comparing both differentiative steps at the single cell level reveals that a great majority (if not all) of the G4-positive neurites originate from AChE-positive cell bodies. Based on both the computer reconstructions as well as single cell analysis, including [3H]-thymidine pulse-experiments followed by autoradiography, we conclude, that AChE expression precedes formation of G4-neurites by about 15 h. In addition, the reconstructions provide the first detailed maps of G4-fiber tract formation and shows that G4-neurites form fascicles, most of which travel over long distances to targets within or without the central nervous system (CNS). This is the first demonstration for the entire young chicken brain which verifies that AChE-expressing cells, generally, are those that will establish efferents to distant targets.