Publications by authors named "Hans-Ulrich Kauczor"

552 Publications

Effects of Lumacaftor-Ivacaftor on Lung Clearance Index, Magnetic Resonance Imaging and Airway Microbiome in Phe508del Homozygous Patients with Cystic Fibrosis.

Ann Am Thorac Soc 2021 Feb 18. Epub 2021 Feb 18.

Charité Universitätsmedizin Berlin, 14903, Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Berlin, Berlin, Germany.

Rationale: Previous studies showed that lumacaftor-ivacaftor therapy results in partial rescue of cystic fibrosis transmembrane conductance regulator (CFTR) activity and moderate improvement of spirometry in Phe508del homozygous patients with cystic fibrosis (CF). However, the effects of lumacaftor-ivacaftor on lung clearance index (LCI), lung morphology and perfusion detected by chest magnetic resonance imaging (MRI), and effects on the airway microbiome and inflammation remain unknown.

Objectives: To investigate the effects of lumacaftor-ivacaftor on LCI, lung MRI scores, and airway microbiome and inflammation.

Methods: In this prospective observational study we assessed clinical outcomes including spirometry and body mass index, LCI, lung MRI scores, sputum microbiome and pro-inflammatory cytokines in 30 Phe508del homozygous patients with CF 12 years and older before and 8-16 weeks after initiation of lumacaftor-ivacaftor therapy.

Measurements And Main Results: Lumacaftor-ivacaftor had no effects on FEV1 % predicted (1.7%, 95% confidence interval (CI) -1.0 to 4.3%; P = 0.211), but improved LCI (-1.6, 95% CI -2.6 to -0.5; P < 0.01) and MRI morphology (-1.3, 95% CI -2.3 to -0.3; P < 0.05) and perfusion score (-1.2, 95% CI -2.3 to -0.2; P < 0.05) in our study cohort. Further, lumacaftor-ivacaftor decreased the total bacterial load (-1.8, 95% CI -3.3 to -0.34; P < 0.05) and increased the Shannon diversity of the airway microbiome (0.4, 95% CI 0.1 to 0.8; P < 0.05), and reduced IL-1β levels (median change -324.2 pg/ml, 95% CI -938.7 to 290.4 pg/ml; P < 0.05) in sputum of Phe508del homozygous patients.

Conclusions: This study shows that lumacaftor-ivacaftor has beneficial effects on lung ventilation, morphology and perfusion, as well as on the airway microbiome and inflammation in Phe508del homozygous patients. Our results suggest that LCI and MRI may be more sensitive than FEV1 % predicted to detect response to CFTR modulator therapy in patients with chronic CF lung disease. Clinical trial registered with ClinicalTrials.gov (NCT02807415).
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http://dx.doi.org/10.1513/AnnalsATS.202008-1054OCDOI Listing
February 2021

Lung cancer prediction by Deep Learning to identify benign lung nodules.

Lung Cancer 2021 Jan 31;154:1-4. Epub 2021 Jan 31.

University of Groningen, Faculty of Medical Sciences, Groningen, The Netherlands. Electronic address:

Introduction: Deep Learning has been proposed as promising tool to classify malignant nodules. Our aim was to retrospectively validate our Lung Cancer Prediction Convolutional Neural Network (LCP-CNN), which was trained on US screening data, on an independent dataset of indeterminate nodules in an European multicentre trial, to rule out benign nodules maintaining a high lung cancer sensitivity.

Methods: The LCP-CNN has been trained to generate a malignancy score for each nodule using CT data from the U.S. National Lung Screening Trial (NLST), and validated on CT scans containing 2106 nodules (205 lung cancers) detected in patients from from the Early Lung Cancer Diagnosis Using Artificial Intelligence and Big Data (LUCINDA) study, recruited from three tertiary referral centers in the UK, Germany and Netherlands. We pre-defined a benign nodule rule-out test, to identify benign nodules whilst maintaining a high sensitivity, by calculating thresholds on the malignancy score that achieve at least 99 % sensitivity on the NLST data. Overall performance per validation site was evaluated using Area-Under-the-ROC-Curve analysis (AUC).

Results: The overall AUC across the European centers was 94.5 % (95 %CI 92.6-96.1). With a high sensitivity of 99.0 %, malignancy could be ruled out in 22.1 % of the nodules, enabling 18.5 % of the patients to avoid follow-up scans. The two false-negative results both represented small typical carcinoids.

Conclusion: The LCP-CNN, trained on participants with lung nodules from the US NLST dataset, showed excellent performance on identification of benign lung nodules in a multi-center external dataset, ruling out malignancy with high accuracy in about one fifth of the patients with 5-15 mm nodules.
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http://dx.doi.org/10.1016/j.lungcan.2021.01.027DOI Listing
January 2021

Assessment of tissue perfusion of pancreatic cancer as potential imaging biomarker by means of Intravoxel incoherent motion MRI and CT perfusion: correlation with histological microvessel density as ground truth.

Cancer Imaging 2021 Jan 19;21(1):13. Epub 2021 Jan 19.

Clinic for Diagnostic and Interventional Radiology (DIR), Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.

Background/objectives: The aim of this study was to compare intravoxel incoherent motion (IVIM) diffusion weighted (DW) MRI and CT perfusion to assess tumor perfusion of pancreatic ductal adenocarcinoma (PDAC).

Methods: In this prospective study, DW-MRI and CT perfusion were conducted in nineteen patients with PDAC on the day before surgery. IVIM analysis of DW-MRI was performed and the parameters perfusion fraction f, pseudodiffusion coefficient D*, and diffusion coefficient D were extracted for tumors, upstream, and downstream parenchyma. With a deconvolution-based analysis, the CT perfusion parameters blood flow (BF) and blood volume (BV) were estimated for tumors, upstream, and downstream parenchyma. In ten patients, intratumoral microvessel density (MVD) and microvessel area (MVA) were analyzed microscopically in resection specimens. Correlation coefficients between IVIM parameters, CT perfusion parameters, and histological microvessel parameters in tumors were calculated. Receiver operating characteristic (ROC) analysis was performed for differentiation of tumors and upstream parenchyma.

Results: f significantly positively correlated with BF (r = 0.668, p = 0.002) and BV (r = 0.672, p = 0.002). There were significant positive correlations between f and MVD/ MVA (r ≥ 0.770, p ≤ 0.009) as well as between BF and MVD/ MVA (r ≥ 0.697, p ≤ 0.025). Correlation coefficients between f and MVD/ MVA were not significantly different from correlation coefficients between BF and MVD/ MVA (p ≥ 0.400). Moreover, f, BF, BV, and permeability values (PEM) showed excellent performance in distinguishing tumors from upstream parenchyma (area under the ROC curve ≥0.874).

Conclusions: The study shows that IVIM derived f and CT perfusion derived BF similarly reflect vascularity of PDAC and seem to be comparably applicable for the evaluation of tumor perfusion for tumor characterization and as potential quantitative imaging biomarker.

Trial Registration: DRKS, DRKS00022227, Registered 26 June 2020, retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00022227.
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http://dx.doi.org/10.1186/s40644-021-00382-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816417PMC
January 2021

Evaluation of cross-sectional imaging features that aid in the differentiation of benign and malignant splenic lesions.

Eur J Radiol 2021 Mar 13;136:109549. Epub 2021 Jan 13.

Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.

Purpose: This study aimed to investigate the role of cross-sectional imaging in differentiating between benign and malignant splenic lesions based on various imaging features.

Methods: Database of imaging reports from January 2015 to December 2017 were searched dedicatedly for "spleen" or "splenic" terms to identify patients with splenic lesions found either on CT or MRI. The study cohort consisted of patients who had available histological reports or had follow-up imaging for a minimum of one year. Patients were categorized into the benign subcohort if they did not have a history of extra-splenic malignancy, and had a splenic lesion(s) falling into one of these categories: benign histopathology on biopsy, stable size and enhancement, or decreased size on follow-up imaging. Those who had malignant histopathology on biopsy were included in the malignant subcohort. Various morphologic features and enhancement patterns of these lesions were carefully reviewed by two radiologists who were blinded to the final histopathologic diagnosis.

Results: We identified 161 patients (54 % males, mean age ± SD = 59.7 ± 15.4) including 124 (77 %) in the benign and 37 (23 %) in the malignant subcohort. Benign lesions were more likely to be cystic (21.7 % vs 2.7 %, p < 0.001), homogenous (59.7 % vs. 29.7 %, p = 0.001) and to demonstrate well-defined borders (69.3 % vs. 29.7 % p= <0.001). Malignant lesions had significantly larger diameter (median size: 15 vs 11 mm, p = 0.03). Restricted diffusion was not seen in any of the benign lesions; however, 50 % of malignant lesions demonstrated restricted diffusion (p = 0.003). Features such as lesion distribution, presence of calcification, splenomegaly and number of lesions were not significantly different between benign and malignant lesions.

Conclusion: Smaller lesion diameter, well-defined border and homogeneity favor benign nature of splenic lesions while restricted diffusion should raise suspicion for malignancy.
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http://dx.doi.org/10.1016/j.ejrad.2021.109549DOI Listing
March 2021

Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper From the Fleischner Society.

Chest 2021 Jan 12. Epub 2021 Jan 12.

Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others.
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http://dx.doi.org/10.1016/j.chest.2020.11.027DOI Listing
January 2021

Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society.

Radiology 2021 Mar 12;298(3):550-566. Epub 2021 Jan 12.

From the Department of Radiology, Kansai Rosai Hospital, Amagasaki, Japan (T.J.); Department of Radiology, Samsung Medical Center (K.S.L., H.Y.L.) and Department of Health Sciences and Technology, SAIHST (H.Y.L.), Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea; Department of Imaging, Dana-Farber Cancer Institute, Boston, Mass (M.N.); Department of Radiology (M.N.) and Center for Pulmonary Functional Imaging (H.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (W.D.T.); Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minn (J.H.R.); Department of Medicine, University of British Columbia and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, Canada (C.J.R.); Department of Radiology, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain (T.F.); Department of Radiology, University of Massachusetts Medical Center, Worcester, Mass (A.A.B.); Departments of Medicine (K.K.B.) and Radiology (D.A.L.), National Jewish Health, Denver, Colo; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.M.G.); Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.); Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust and National Heart and Lung Institute, Imperial College, London, England (A.G.N.); Complex Operative Unit of Pneumology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy (L.R.); Department of Radiology, Meander Medical Center, Amersfoort, the Netherlands (C.M.S.P.); Department of Radiology, University Hospitals Leuven, Leuven, Belgium (J.V.); Division of Pulmonary and Critical Care Medicine, Lenox Hill Hospital, Northwell Health System, New York, NY (S.R.); Department of Radiology, Duke University School of Medicine, Durham, NC (G.D.R.); Department of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY (C.P.); and Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan (Y.I.).

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in and . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license.
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http://dx.doi.org/10.1148/radiol.2021203427DOI Listing
March 2021

Balanced steady-state free precession MRCP is a robust alternative to respiration-navigated 3D turbo-spin-echo MRCP.

BMC Med Imaging 2021 Jan 11;21(1):10. Epub 2021 Jan 11.

Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.

Background: Despite synchronization to respiration, respiration-navigated (RN) 3D turbo-spin-echo MRCP is limited by susceptibility to motion artifacts. The aim of this study was to assess the quality of pancreaticobiliary duct visualization of a non-RN MRCP alternative based on balanced steady-state free precession imaging (BSSFP) with overlapping slices compared with RN-MRCP.

Methods: This is a retrospective study on 50 patients without pancreaticobiliary duct disease receiving MRCP at 1.5 T. We performed an intraindividual comparison of coronal RN-MRCP with combined coronal and transverse BSSFP-MRCP. Image quality was scored by 3 readers for 6 pancreaticobiliary duct segments (3 pancreatic, 3 biliary) using a 6-point scale. A segment score of 3 or lower as assessed by at least 2 of 3 readers was defined as insufficient segment visualization. Nonparametric tests and interrater reliability testing were used for statistical analysis.

Results: Overall duct visualization averaged over all readers was scored with 4.5 ± 1.1 for RN-MRCP (pancreatic, 4.1 ± 0.5; biliary, 5.0 ± 0.4) and 4.9 ± 0.9 for combined coronal and transverse BSSFP-MRCP (pancreatic, 4.6 ± 0.6; biliary, 5.1 ± 0.6), respectively (p < 0.001). The number of segments visualized insufficiently was 81/300 for RN-MRCP and 43/300 for BSSFP-MRCP (p < 0.001). Segments visualized insufficiently only in RN-MRCP had a mean score of 4.4 ± 0.8 in BSSFP-MRCP. Overall interrater agreement on superiority of BSSFP-MRCP segment scores over corresponding RN-MRCP was 0.70. Mean acquisition time was 98% longer for RN-MRCP (198.0 ± 98.7 s) than for combined coronal and transverse BSSFP-MRCP (100.2 ± 0.4 s).

Conclusions: Non-RN BSSFP-MRCP with overlapping slices is a fast alternative to RN-MRCP, frequently providing sufficient duct visualization when RN-MRCP fails.
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http://dx.doi.org/10.1186/s12880-020-00532-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802244PMC
January 2021

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia.

Cancers (Basel) 2020 Dec 30;13(1). Epub 2020 Dec 30.

Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany.

Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.
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http://dx.doi.org/10.3390/cancers13010089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801953PMC
December 2020

Diagnostic accuracy of axillary staging by ultrasound in early breast cancer patients.

Eur J Radiol 2021 Feb 4;135:109468. Epub 2020 Dec 4.

Department of Obstetrics and Gynecology, Breast Unit, University Hospital of Heidelberg, Germany. Electronic address:

Background: Axillary ultrasound (AUS) is a standard procedure in the preoperative clinical identification of axillary metastatic lymph node (LN) involvement. It guides decisions about local and systemic therapy for patients with early breast cancer (EBC). But there is only weak evidence on the diagnostic criteria and standard interpretation. The aim of this study was to assess the performance of AUS in the detection and exclusion of LN metastases.

Methods: In a retrospective single-center study, 611 consecutive EBC patients with 622 axillae underwent AUS +/- core needle biopsy (CNB) plus axillary surgery, i.e. sentinel lymph node biopsy and/or axillary lymph node dissection. For all patients, AUS image documentation of at least the most suspicious LN was saved during the initial diagnostic work-up. The diagnostic outcome measures were sensitivity, specificity, accuracy, Youden-index (YI), and diagnostic odds ratio (DOR) on the basis of the daily routine interpretation and on the basis of previously recommended diagnostic criteria by two blinded examiners.

Results: On the basis of the daily routine interpretation, AUS had a sensitivity (95 % CI) of 53.3 % (46.4-60.1), a specificity (95 % CI) of 93.6 % (90.8-95.8), an accuracy (95 % CI) of 79.7 % (76.4-82.8), a YI (95 % CI) of 0.47 (0.40 - 0.54), and a DOR (95 % CI) of 16.75 (10.37-27.05). Systematic application of previously recommended diagnostic criteria did not improve the diagnostic accuracy of routinely interpreted AUS.

Conclusion: AUS performance alone is not sufficient to accurately identify or exclude axillary metastatic disease in unselected patients with EBC.
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http://dx.doi.org/10.1016/j.ejrad.2020.109468DOI Listing
February 2021

Impact of needle positioning on ablation success of irreversible electroporation: a unicentric retrospective analysis.

Sci Rep 2020 12 14;10(1):21902. Epub 2020 Dec 14.

Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.

Irreversible electroporation (IRE) is an ablation procedure in which cell death is induced by ultrashort electrical pulses. In this unicentric retrospective study we investigated the influence of needle positioning on ablation success. 15 IREs with residual tumor after ablation, detected in the first follow-up MRI, were included, and compared with 30 successful ablations. Evaluation of needle geometry revealed significantly higher values for needle divergence (NDiv, 7.0° vs. 3.7°, p = 0.02), tumor-center-to-ablation-center distance (TACD, 11.6 vs. 3.2 mm, p < 0.001), tumor-to-needle distance (4.7 vs. 1.9 mm, p = 0.04), and tumor diameter per needle (7.5 vs. 5.9 mm/needle, p = 0.01) in patients with residual tumor. The average number of needles used was higher in the group without residual tumor after ablation (3.1 vs. 2.4, p = 0.04). In many cases with residual tumor, needle depth was too short (2.1 vs. 6.8 mm tumor overlap beyond the most proximal needle tip, p < 0.01). The use of a stereotactic navigation system in 10 cases resulted in a lower NDiv value (2.1° vs. 5.6°, p < 0.01). Thus, correct needle placement seems to be a crucial factor for success and the assistance of a stereotactic navigation system might be helpful. As most important geometrical parameter TACD could be identified. Main reasons for high TACD were insufficient needle depth and a lesion location out of the needle plane.
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http://dx.doi.org/10.1038/s41598-020-78660-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736875PMC
December 2020

Impact of progressive resistance training on CT quantified muscle and adipose tissue compartments in pancreatic cancer patients.

PLoS One 2020 30;15(11):e0242785. Epub 2020 Nov 30.

Division of Physical Activity, Prevention and Cancer, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.

Objectives: Loss of body weight is often seen in pancreatic cancer and also predicts poor prognosis. Thus, maintaining muscle mass is an essential treatment goal. The primary aim was to investigate whether progressive resistance training impacts muscle and adipose tissue compartments. Furthermore, the effect of body composition on overall survival (OS) was investigated.

Methods: In the randomized SUPPORT-study, 65 patients were assigned to 6-month resistance training (2x/week) or a usual care control group. As secondary endpoint, muscle strength of the upper and lower extremities was assessed before and after the intervention period. Routine CT scans were assessed on lumbar L3/4 level for quantification of total-fat-area, visceral-fat-area, subcutaneous-fat-area, intramuscular-fat-area, visceral-to-subcutaneous fat ratio (VFR), muscle-area (MA), muscle-density and skeletal-muscle-index (SMI). OS data were retrieved.

Results: Of 65 patients, 53 had suitable CT scans at baseline and 28 completed the intervention period with suitable CT scans. There were no significant effects observed of resistance training on body composition (p>0.05; effect sizes ω2p <0.02). Significant moderate to high correlations were found between MA and muscle strength parameters (r = 0.57-0.85; p<0.001). High VFR at baseline was a predictor of poor OS (VFR≥1.3 vs. <1.3; median OS 14.6 vs. 45.3 months; p = 0.012). Loss of muscle mass was also a predictor of poor OS (loss vs. gain of SMI; median OS 24.6 vs. 50.8 months; p = 0.049).

Conclusion: There is anabolic potential in patients with resectable pancreatic cancer. A progressive resistance training may help patients to maintain their muscle mass and avoid muscle depletion. CT-quantified muscle mass at the level of L3/4 showed a good correlation to muscle strength. Therefore, maintaining muscle mass and muscle strength through structured resistance training could help patients to maintain their physical functioning. A high VFR at baseline and a high loss of muscle mass are predictors of poor OS. Registered on ClinicalTrials.gov (NCT01977066).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242785PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703876PMC
January 2021

Correlation Between Traumatic Skin and Subcutaneous Injuries and the Severity of Polytrauma Injury.

Rofo 2021 Feb 26;193(2):177-185. Epub 2020 Nov 26.

Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany.

Purpose:  To examine the relationship between superficial lesions (such as bruises, hematomas, deep abrasions, and soft tissue emphysema) and internal post-traumatic injuries, assessed using whole-body computed tomography (WBCT), and to determine if these are valid markers for internal injuries.

Methods And Materials:  250 patients who underwent WBCT emergency scans for suspected polytrauma were retrospectively analyzed after institutional review board approval of the study. The scans were carried out on patients who met the criteria for standard operating procedures for WBCT emergency scans. WBCT covering the entire head, neck, chest, and abdomen (including pelvis and proximal lower extremities) and at least one phase with intravenous contrast agent were included in the study. Initial analyses of immediate WBCT scans was carried out by a consultant radiologist and a radiological resident. The first reading focused on internal damage that needed immediate therapy. The second reading focused on a detailed analysis of the skin and subcutaneous tissue and their relation to internal injuries without the time pressure of an emergency setting, carried out by another experienced radiologist. All skin lesions and the degree of penetration and a comparison between the two readings were reported in tables.

Results:  Superficial lesion of the chest was detected in 19 patients, 17 of them had an internal injury of the thorax while only two patients, with hematoma of the chest wall, had no internal injuries. Skin and subcutaneous lesions of the chest had the strongest association with an internal injury. Skin lesions of the abdominal wall were observed in 30 patients. In only 11 cases, these lesions were correlated with internal injuries, such as fractures or active bleeding. 52 skin and subgaleal lesions of the scalp were observed. In 20 of these patients, an intracranial or internal injury was detected. In 3 patients, skin abrasions of the neck were present and in only one of them, this finding was associated with an internal injury.

Conclusion:  Trauma patients whose history and clinical presentation meet the standard operating procedures for WBCT emergency scans and who present with a cutaneous lesion, especially at the neurocranium or chest wall, should be observed for internal injuries by WBCT.

Key Points:   · Presence or lack of a superficial injury of the abdominal wall is not a reliable predictive indication of any internal abdominal injury.. · Superficial lesions of the chest and the neurocranium require a CT scan.. · Superficial injuries of the chest wall had the strongest association with internal injuries..

Citation Format: · Klempka A, Fischer C, Kauczor H et al. Correlation Between Traumatic Skin and Subcutaneous Injuries and the Severity of Trauma. Fortschr Röntgenstr 2021; 193: 177 - 185.
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http://dx.doi.org/10.1055/a-1207-0797DOI Listing
February 2021

Lung Screening Benefits and Challenges: A Review of The Data and Outline for Implementation.

J Thorac Oncol 2021 Jan 12;16(1):37-53. Epub 2020 Nov 12.

Division of Radiology, Lahey Hospital & Medical Center, Burlington, Massachusetts.

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for almost a fifth of all cancer-related deaths. Annual computed tomographic lung cancer screening (CTLS) detects lung cancer at earlier stages and reduces lung cancer-related mortality among high-risk individuals. Many medical organizations, including the U.S. Preventive Services Task Force, recommend annual CTLS in high-risk populations. However, fewer than 5% of individuals worldwide at high risk for lung cancer have undergone screening. In large part, this is owing to delayed implementation of CTLS in many countries throughout the world. Factors contributing to low uptake in countries with longstanding CTLS endorsement, such as the United States, include lack of patient and clinician awareness of current recommendations in favor of CTLS and clinician concerns about CTLS-related radiation exposure, false-positive results, overdiagnosis, and cost. This review of the literature serves to address these concerns by evaluating the potential risks and benefits of CTLS. Review of key components of a lung screening program, along with an updated shared decision aid, provides guidance for program development and optimization. Review of studies evaluating the population considered "high-risk" is included as this may affect future guidelines within the United States and other countries considering lung screening implementation.
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http://dx.doi.org/10.1016/j.jtho.2020.10.127DOI Listing
January 2021

Joint Imaging Platform for Federated Clinical Data Analytics.

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

Division of Medical Image Computing, German Cancer Research Center, 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

Gradual enhancement pattern of tracheobronchial adenoid cystic carcinoma on multiphasic dynamic computed tomography : a case series.

J Med Invest 2020 ;67(3.4):378-381

Department of Radiology, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan.

Tracheobronchial adenoid cystic carcinoma is a rare malignancy. To the best of our knowledge, its enhancement pattern on multiphasic contrast-enhanced multidetector computed tomography has not been reported. Herein, we report the computed tomography findings of three consecutive cases of tracheobronchial adenoid cystic carcinoma. All lesions presented a gradual enhancement pattern on multiphasic contrast-enhanced computed tomography. We speculate that the gradual enhancement pattern on multiphasic contrast-enhanced computed tomography could potentially serve as a characteristic imaging feature and may therefore be a clue to diagnose tracheobronchial adenoid cystic carcinoma. J. Med. Invest. 67 : 378-381, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.378DOI Listing
January 2020

Appropriateness of CT pulmonary angiograms according to current diagnostic guidelines based on risk stratification: A retrospective single-center study.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Oct 22. Epub 2020 Oct 22.

Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Germany.

Background And Aim: Assessment of appropriateness of CT pulmonary angiograms (CTPA) in patients with suspected pulmonary embolism (PE) is based on risk stratification algorithms such as simplified the Geneva Score (sGS) in combination with D-dimer blood tests. The aim of this study was to validate the diagnostic yield and appropriateness of CTPA examinations in accordance with 2014 European Society of Cardiology (ESC) guidelines.

Materials And Methods: Data from 155 outpatients who underwent CTPA for clinical suspicion of PE were gathered from the radiology information system (RIS) and the clinical information system (CIS). We assessed the presence of sGS items and D-dimer blood test results in RIS from CTPA request forms and from clinical documentation in CIS.

Results: Based on the RIS, there were 2.6% patients with high (sGS≥3) and 97.4% patients with low pre-test PE probability (sGS<3), and CTPA indication was formally comprehendible in 75.5% using sGS and D-dimer blood tests. Based on RIS and CIS data in combination, there were 41.3% patients with high and 58.7% patients with low pre-test PE probability, and CTPA indication was formally comprehendible in 88.4%. Using RIS and CIS in combination, PE probability was upgraded from low to high probability in 39.7% compared with RIS alone. In 12.9%, there was a lack of data in RIS for CTPA justification.

Conclusion: There is a high diagnostic yield when applying current diagnostic guidelines to our data. There was however a notable discrepancy between the data transferred to the CTPA request forms from the full clinical documentation, therefore not readily available for clinical decision making.
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http://dx.doi.org/10.5507/bp.2020.049DOI Listing
October 2020

Improving radiologic communication in oncology: a single-centre experience with structured reporting for cancer patients.

Insights Imaging 2020 Sep 29;11(1):106. Epub 2020 Sep 29.

Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany.

Objectives: Our aim was to develop a structured reporting concept (structured oncology report, SOR) for general follow-up assessment of cancer patients in clinical routine. Furthermore, we analysed the report quality of SOR compared to conventional reports (CR) as assessed by referring oncologists.

Methods: SOR was designed to provide standardised layout, tabulated tumour burden documentation and standardised conclusion using uniform terminology. A software application for reporting was programmed to ensure consistency of layout and vocabulary and to facilitate utilisation of SOR. Report quality was analysed for 25 SOR and 25 CR retrospectively by 6 medical oncologists using a 7-point scale (score 1 representing the best score) for 6 questionnaire items addressing different elements of report quality and overall satisfaction. A score of ≤ 3 was defined as a positive rating.

Results: In the first year after full implementation, 7471 imaging examinations were reported using SOR. The proportion of SOR in relation to all oncology reports increased from 49 to 95% within a few months. Report quality scores were better for SOR for each questionnaire item (p < 0.001 each). Averaged over all questionnaire item scores were 1.98 ± 1.22 for SOR and 3.05 ± 1.93 for CR (p < 0.001). The overall satisfaction score was 2.15 ± 1.32 for SOR and 3.39 ± 2.08 for CR (p < 0.001). The proportion of positive ratings was higher for SOR (89% versus 67%; p < 0.001).

Conclusions: Department-wide structured reporting for follow-up imaging performed for assessment of anticancer treatment efficacy is feasible using a dedicated software application. Satisfaction of referring oncologist with report quality is superior for structured reports.
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http://dx.doi.org/10.1186/s13244-020-00907-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524991PMC
September 2020

Virtual monoenergetic reconstructions of dynamic DECT acquisitions for calculation of perfusion maps of blood flow: Quantitative comparison to conventional, dynamic 80 kV CT perfusion.

Eur J Radiol 2020 Oct 31;131:109262. Epub 2020 Aug 31.

Diagnostic and Interventional Radiology (DIR), Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address:

Purpose: Investigation of potential improvements in dynamic CT perfusion measurements by exploitation of improved visualization of contrast agent in virtual monoenergetic reconstructions of images acquired with dual-energy computed tomography (DECT).

Method: For 17 patients with pancreatic carcinoma, dynamic dual-source DECT acquisitions were performed at 80kV/Sn140kV every 1.5 s over 51 s. Virtual monoenergetic images (VMI) were reconstructed for photon energies between 40 keV and 150 keV (5 keV steps). Using the maximum-slope model, perfusion maps of blood flow were calculated from VMIs and 80kV images and compared quantitatively with regard to blood flow measured in regions of interest in healthy tissue and carcinoma, standard deviation (SD), and absolute-difference-to-standard-deviation ratio (ADSDR) of measurements.

Results: On average, blood flow calculated from VMIs increased with increasing energy levels from 114.3 ± 37.2 mL/100 mL/min (healthy tissue) and 45.6 ± 25.3 mL/100 mL/min (carcinoma) for 40 keV to 128.6 ± 58.9 mL/100 mL/min (healthy tissue) and 75.5 ± 49.8 mL/100 mL/min (carcinoma) for 150 keV, compared to 114.2 ± 37.4 mL/100 mL/min (healthy tissue) and 46.5 ± 26.6 mL/100 mL/min (carcinoma) for polyenergetic 80kV. Differences in blood flow between tissue types were significant for all energies. Differences between perfusion maps calculated from VMIs and 80kV images were not significant below 110 keV. SD and ADSDR were significantly better for perfusion maps calculated from VMIs at energies between 40 keV and 55 keV than for those calculated from 80kV images. Compared to effective dose of dynamic 80kV acquisitions (4.6 ± 2.2mSv), dose of dynamic DECT/VMI acquisitions (8.0 ± 3.7mSv) was higher.

Conclusions: Perfusion maps of blood flow based on low-energy VMIs between 40 keV and 55 keV offer improved robustness and quality of quantitative measurements over those calculated from 80kV image data (reference standard), albeit at increased patient radiation exposure.
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http://dx.doi.org/10.1016/j.ejrad.2020.109262DOI Listing
October 2020

Synopsis from Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders: Fleischner Society Position Paper.

Chest 2021 Feb 14;159(2):492-495. Epub 2020 Sep 14.

Center for Pulmonary Functional Imaging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.09.075DOI Listing
February 2021

Mesopolysaccharides: The extracellular surface layer of visceral organs.

PLoS One 2020 17;15(9):e0238798. Epub 2020 Sep 17.

Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston MA, United States of America.

The mesothelium is a dynamic and specialized tissue layer that covers the somatic cavities (pleural, peritoneal, and pericardial) as well as the surface of the visceral organs such as the lung, heart, liver, bowel and tunica vaginalis testis. The potential therapeutic manipulation of visceral organs has been complicated by the carbohydrate surface layer-here, called the mesopolysaccharide (MPS)-that coats the outer layer of the mesothelium. The traditional understanding of MPS structure has relied upon fixation techniques known to degrade carbohydrates. The recent development of carbohydrate-preserving fixation for high resolution imaging techniques has provided an opportunity to re-examine the structure of both the MPS and the visceral mesothelium. In this report, we used high pressure freezing (HPF) as well as serial section transmission electron microscopy to redefine the structure of the MPS expressed on the murine lung, heart and liver surface. Tissue preserved by HPF and examined by transmission electron microscopy demonstrated a pleural MPS layer 13.01±1.1 um deep-a 100-fold increase in depth compared to previously reported data obtained with conventional fixation techniques. At the base of the MPS were microvilli 1.1±0.35 um long and 42±5 nm in diameter. Morphological evidence suggested that the MPS was anchored to the mesothelium by microvilli. In addition, membrane pits 97±17 nm in diameter were observed in the apical mesothelial membrane. The spatial proximity and surface density (29±4.5%) of the pits suggested an active process linked to the structural maintenance of the MPS. The striking magnitude and complex structure of the MPS indicates that it is an important consideration in studies of the visceral mesothelium.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238798PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498049PMC
November 2020

Overdiagnosis in lung cancer screening: Estimates from the German Lung Cancer Screening Intervention Trial.

Int J Cancer 2021 Mar 23;148(5):1097-1105. Epub 2020 Sep 23.

Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Overdiagnosis is a major potential harm of lung cancer screening; knowing its potential magnitude helps to optimize screening eligibility criteria. The German Lung Screening Intervention Trial ("LUSI") is a randomized trial among 4052 long-term smokers (2622 men), 50.3 to 71.9 years of age from the general population around Heidelberg, Germany, comparing five annual rounds of low-dose computed tomography (n = 2029) with a control arm without intervention (n = 2023). After a median follow-up of 9.77 years postrandomization and 5.73 years since last screening, 74 participants were diagnosed with lung cancer in the control arm and 90 in the screening arm: 69 during the active screening period; of which 63 screen-detected and 6 interval cancers. The excess cumulative incidence in the screening arm (N = 16) represented 25.4% (95% confidence interval: -11.3, 64.3] of screen-detected cancer cases (N = 63). Analyzed by histologic subtype, excess incidence in the screening arm appeared largely driven by adenocarcinomas. Statistical modeling yielded an estimated mean preclinical sojourn time (MPST) of 5.38 (4.76, 5.88) years and a screen-test sensitivity of 81.6 (74.4%, 88.8%) for lung cancer overall, all histologic subtypes combined. Based on modeling, we further estimated that about 48% (47.5% [43.2%, 50.7%]) of screen-detected tumors have a lead time ≥4 years, whereas about 33% (32.8% [28.4%, 36.1%]) have a lead time ≥6 years, 23% (22.6% [18.6%, 25.7%]) ≥8 years, 16% (15.6% [12.2%, 18.3%]) ≥10 years and 11% (10.7% [8.0%, 13.0%]) ≥12 years. The high proportions of tumors with relatively long lead times suggest a major risk of overdiagnosis for individuals with comparatively short remaining life expectancies.
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http://dx.doi.org/10.1002/ijc.33295DOI Listing
March 2021

Spatial Distribution of Focal Lesions in Whole-Body MRI and Influence of MRI Protocol on Staging in Patients with Smoldering Multiple Myeloma According to the New SLiM-CRAB-Criteria.

Cancers (Basel) 2020 Sep 7;12(9). Epub 2020 Sep 7.

Institute of Diagnostic and Interventional Radiology, Paediatric Radiology and Neuroradiology, University Medical Centre Rostock, Ernst-Heydemann-Str. 6, 18057 Rostock, Germany.

The purpose of this study was to assess how different MRI protocols (spinal vs. spinal plus pelvic vs. whole-body (wb)-MRI) affect staging in patients with smoldering multiple myeloma (SMM), according to the SLiM-CRAB-criterion '>1 focal lesion (FL) in MRI'. In this retrospective study, a baseline cohort of 147 SMM patients with wb-MRI at initial diagnosis was investigated, including prognostic data regarding development of CRAB-criteria. Fifty-two patients formed a follow-up cohort with a median of three wb-MRIs. The locations of all FLs were determined and it was calculated how staging decisions regarding the criterion '>1 FL in MRI' would have been made if only a limited anatomic area (spine vs. spine plus pelvis) would have been covered by the MRI protocol. Furthermore, subgroups of patients selected by different cutoff-protocol-combinations were compared regarding their prognosis for development of CRAB-criteria. With an MRI protocol limited to spine/spine plus pelvis, only 28%/64% of patients who actually had >1 FL in wb-MRI would have been rated correctly as having '>1 FL in MRI'. Fifty-four percent/36% of patients with exactly 1 FL in spine/spine plus pelvis revealed >1 FL when the entire wb-MRI was analyzed. During follow-up, four more patients developed >1 FL in wb-MRI; both limited MRI protocols would have detected only one of these four patients as having >1 FL at the correct timepoint. Having >1 FL in spine/in spine plus pelvis/in the whole body was associated with a 43%/57%/49% probability of developing CRAB-criteria within 2 years. Patients with >3 FL in spine plus pelvis and patients with >4 FL in the whole body had an 80% probability to develop CRAB-criteria within 2 years. MRI protocols limited to the spine or to spine plus pelvis lead to substantial underdiagnoses of patients who actually have >1 FL in wb-MRI at baseline and during follow-up, which influences staging and treatment decisions according to the current SLiM-CRAB criteria. However, given the spatial distribution of FLs and the analysis on clinical course of patients indicates that the cutoff for the number of FLs should be adopted according to the MRI protocol when using MRI for staging in SMM.
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http://dx.doi.org/10.3390/cancers12092537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563298PMC
September 2020

Relationship between clinical and radiological signs of bronchiectasis in COPD patients: Results from COSYCONET.

Respir Med 2020 10 22;172:106117. Epub 2020 Aug 22.

Department of Pneumology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.
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http://dx.doi.org/10.1016/j.rmed.2020.106117DOI Listing
October 2020

3-T T2 mapping magnetic resonance imaging for biochemical assessment of normal and damaged glenoid cartilage: a prospective arthroscopy-controlled study.

Sci Rep 2020 09 1;10(1):14396. Epub 2020 Sep 1.

Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.

This study evaluated the ability of T2 mapping to assess the glenoid cartilage using arthroscopy as the gold standard. Eighteen consecutive patients (mean age: 52.4 ± 14.72 years, including 12 men) with shoulder pain underwent T2 mapping at 3-T with subsequent shoulder arthroscopy. With correlation to cartilage-sensitive morphologic sequences regions-of-interest were placed in the corresponding T2 maps both in normal-appearing cartilage and focal cartilage lesions using a quadrant-wise approach. Inter-reader and intra-reader correlation coefficients (ICCs) between two independent radiologists as well as cut-off values with their sensitivities/specificities for the detection of cartilage damage were calculated. The mean T2 value for healthy cartilage was 23.0 ± 3 ms with significantly higher values in the superior quadrants compared to the inferior quadrants (p < 0.0001). In 5 patients with focal cartilage damage significantly higher T2 values of 44.7 ± 3.7 ms (P < 0.01) were observed. The maximum T2 value in normal cartilage (27.3 ms) was lower than the minimum value in damaged cartilage (40.8 ms) resulting in perfect sensitivities/specificities of 100% (95% confidence-interval 47.8-100.0) for all cut-off values between 27.3-40.8 ms. ICCs ranged between 0.63 and 0.99. In conclusion, T2 mapping can evaluate biochemical cartilage integrity and discriminates arthroscopy-proven healthy and damaged glenoid cartilage with high diagnostic performance.
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http://dx.doi.org/10.1038/s41598-020-71311-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462998PMC
September 2020

Expanding Applications of Pulmonary MRI in the Clinical Evaluation of Lung Disorders: Fleischner Society Position Paper.

Radiology 2020 Nov 1;297(2):286-301. Epub 2020 Sep 1.

From the Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115 (H.H.); Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Department of Medical Biophysics, Western University, London, Canada (G.P.); Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (B.M.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea (K.S.L.); Department of Radiology, University of Missouri, Columbia, Mo (T.A.A.); Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.); Department of Radiology, Vancouver General Hospital and University of British Colombia, Vancouver, Canada (J.R.M.); Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Section of Academic Radiology, University of Sheffield, Sheffield, England, United Kingdom (J.M.W.); Edinburgh Imaging, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom (E.J.R.v.B.); Department of Radiology, UW Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); and Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.).

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With the use of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lung parenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinical use of pulmonary MRI into three categories: suggested for current clinical use, promising but requiring further validation or regulatory approval, and appropriate for research investigations. This position paper also provides recommendations for vendors and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods.
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http://dx.doi.org/10.1148/radiol.2020201138DOI Listing
November 2020

Optimizing airway wall segmentation and quantification by reducing the influence of adjacent vessels and intravascular contrast material with a modified integral-based algorithm in quantitative computed tomography.

PLoS One 2020 19;15(8):e0237939. Epub 2020 Aug 19.

Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany.

Introduction: Quantitative analysis of multi-detector computed tomography (MDCT) plays an increasingly important role in assessing airway disease. Depending on the algorithms used, airway dimensions may be over- or underestimated, primarily if contrast material was used. Therefore, we tested a modified integral-based method (IBM) to address this problem.

Methods: Temporally resolved cine-MDCT was performed in seven ventilated pigs in breath-hold during iodinated contrast material (CM) infusion over 60s. Identical slices in non-enhanced (NE), pulmonary-arterial (PA), systemic-arterial (SA), and venous phase (VE) were subjected to an in-house software using a standard and a modified IBM. Total diameter (TD), lumen area (LA), wall area (WA), and wall thickness (WT) were measured for ten extra- and six intrapulmonary airways.

Results: The modified IBM significantly reduced TD by 7.6%, LA by 12.7%, WA by 9.7%, and WT by 3.9% compared to standard IBM on non-enhanced CT (p<0.05). Using standard IBM, CM led to a decrease of all airway parameters compared to NE. For example, LA decreased from 80.85±49.26mm2 at NE, to 75.14±47.96mm2 (-7.1%) at PA (p<0.001), 74.96±48.55mm2 (-7.3%) at SA (p<0.001), and to 78.95±48.94mm2 (-2.4%) at VE (p = 0.200). Using modified IBM, the differences were reduced to -3.1% at PA, -2.9% at SA and -0.7% at VE (p<0.001; p<0.001; p = 1.000).

Conclusions: The modified IBM can optimize airway wall segmentation and reduce the influence of CM on quantitative CT. This allows a more precise measurement as well as potentially the comparison of enhanced with non-enhanced scans in inflammatory airway disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237939PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437894PMC
October 2020

Influence of acquisition settings and radiation exposure on CT lung densitometry-An anthropomorphic ex vivo phantom study.

PLoS One 2020 14;15(8):e0237434. Epub 2020 Aug 14.

Diagnostic and Interventional Radiology (DIR), Heidelberg University Hospital, Heidelberg, Germany.

Objectives: To systematically evaluate the influence of acquisition settings in conjunction with raw-data based iterative image reconstruction (IR) on lung densitometry based on multi-row detector computed tomography (CT) in an anthropomorphic chest phantom.

Materials And Methods: Ten porcine heart-lung explants were mounted in an ex vivo chest phantom shell, six with highly and four with low attenuating chest wall. CT (Somatom Definition Flash, Siemens Healthineers) was performed at 120kVp and 80kVp, each combined with current-time products of 120, 60, 30, and 12mAs, and was reconstructed with filtered back projection (FBP) and IR (Safire, Siemens Healthineers). Mean lung density (LD), air density (AD) and noise were measured by semi-automated region-of interest (ROI) analysis, with 120kVp/120 mAs serving as the standard of reference.

Results: Using IR, noise in lung parenchyma was reduced by ~ 31% at high attenuating chest wall and by ~ 22% at low attenuating chest wall compared to FBP, respectively (p<0.05). IR induced changes in the order of ±1 HU to mean absolute LD and AD compared to corresponding FBP reconstructions which were statistically significant (p<0.05).

Conclusions: Densitometry is influenced by acquisition parameters and reconstruction algorithms to a degree that may be clinically negligible. However, in longitudinal studies and clinical research identical protocols and potentially other measures for calibration may be required.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237434PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428081PMC
October 2020

The Role of CT in the Diagnosis of COVID-19-a State of Constant Flux.

Dtsch Arztebl Int 2020 06;117(22-23):387-388

Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital; Department of Translational Pulmonology, Heidelberg University Hospital; Translational Lung Research Center Heidelberg, German Center for Lung Research (DZL); German Center for Lung Research (DZL), Hannover Medical School (MHH).

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http://dx.doi.org/10.3238/arztebl.2020.0387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465367PMC
June 2020

Use of Chest Imaging in the Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide.

Radiology 2021 02 30;298(2):E63-E69. Epub 2020 Jul 30.

From the Department of Internal Medicine (E.A.A.), Clinical Research Institute (S.Y.), Department of Emergency Medicine (E.H.), and Department of Pathology and Laboratory Medicine (R.M.), American University of Beirut, Beirut, Lebanon; Clinical Hospital Centre Zemun, Belgrade, Serbia (I.B.); Paris Descartes University, Paris, France (G.F.); Oregon Health & Science University, Portland, Ore (R.C.); Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana (J.A.A.); Department of Imaging Informatics, Virtual University of Medical Sciences, Tehran, Iran (M.F.); L. Sacco, University Hospital, Milan, Italy (N.F.); WHO Patients for Patient Safety Program Advisory Group; Fatima Jinnah Medical University, Lahore, Pakistan (H.J.); Department of Radiology, PUMC Hospital Beijing, Beijing, China (Z.Y.J.); Department of Diagnostic and Interventional Radiology; Translational Pneumology, Heidelberg University Hospital, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.); Ernest Cook Ultrasound Research and Education Institute, Kampala, Uganda (M.K.); Departments of Radiology and Internal Medicine, University of Michigan/Michigan Medicine, Ann Arbor, Mich (E.A.K.); Department of Radiology, NYU Langone Health, New York, NY (J.P.K.); Imaging, Radiation Therapy and Oncohematology Department, Ribeirao Preto, Sao Paulo, Brazil (V.M.); Radiology Department, Kenyatta National Hospital, Nairobi, Kenya (R.N.); Radiology Department, CDI Hospital Clinic, University of Barcelona, Barcelona, Spain (M.S.); Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, Calif (P.B.S.); Imaging Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina (M.U.); Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (C.Z.); Department of Environment, Climate Change and Health, Radiation and Health Unit (E.v.D., M.d.R.P.), World Health Organization, 20 ave Appia, 1211 Geneva 27, Switzerland.

The World Health Organization (WHO) undertook the development of a rapid guide on the use of chest imaging in the diagnosis and management of coronavirus disease 2019 (COVID-19). The rapid guide was developed over 2 months by using standard WHO processes, except for the use of "rapid reviews" and online meetings of the panel. The evidence review was supplemented by a survey of stakeholders regarding their views on the acceptability, feasibility, impact on equity, and resource use of the relevant chest imaging modalities (chest radiography, chest CT, and lung US). The guideline development group had broad expertise and country representation. The rapid guide includes three diagnosis recommendations and four management recommendations. The recommendations cover patients with confirmed or who are suspected of having COVID-19 with different levels of disease severity, throughout the care pathway from outpatient facility or hospital entry to home discharge. All recommendations are conditional and are based on low certainty evidence ( = 2), very low certainty evidence ( = 2), or expert opinion ( = 3). The remarks accompanying the recommendations suggest which patients are likely to benefit from chest imaging and what factors should be considered when choosing the specific imaging modality. The guidance offers considerations about implementation, monitoring, and evaluation, and also identifies research needs. Published under a CC BY 4.0 license.
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http://dx.doi.org/10.1148/radiol.2020203173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393953PMC
February 2021

Multi-omics Analysis Reveals Adipose-tumor Crosstalk in Patients with Colorectal Cancer.

Cancer Prev Res (Phila) 2020 Oct 12;13(10):817-828. Epub 2020 Jul 12.

Huntsman Cancer Institute, Salt Lake City, Utah.

Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte-colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumor-adjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma () visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling-the major signaling receptor for collagen-as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelial-to-mesenchymal transition-as in fibrosis and metastasis-and genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandin-endoperoxide synthase 2 () colorectal tumor expression is associated with a fibrotic signature in adipose-tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high expression in colorectal tumors is significantly associated with higher concentrations of serum amyloid A and glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose-tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted..
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http://dx.doi.org/10.1158/1940-6207.CAPR-19-0538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877796PMC
October 2020