Publications by authors named "Julien Dinkel"

69 Publications

Appearance of COVID-19 pneumonia on 1.5 T TrueFISP MRI.

Radiol Bras 2021 Jul-Aug;54(4):211-218

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Objective: To evaluate the performance of 1.5 T true fast imaging with steady state precession (TrueFISP) magnetic resonance imaging (MRI) sequences for the detection and characterization of pulmonary abnormalities caused by coronavirus disease 2019 (COVID-19).

Materials And Methods: In this retrospective single-center study, computed tomography (CT) and MRI scans of 20 patients with COVID-19 pneumonia were evaluated with regard to the distribution, opacity, and appearance of pulmonary lesions, as well as bronchial changes, pleural effusion, and thoracic lymphadenopathy. McNemar's test was used in order to compare the COVID-19-associated alterations seen on CT with those seen on MRI.

Results: Ground-glass opacities were better visualized on CT than on MRI ( = 0.031). We found no statistically significant differences between CT and MRI regarding the visualization/characterization of the following: consolidations; interlobular/intralobular septal thickening; the distribution or appearance of pulmonary abnormalities; bronchial pathologies; pleural effusion; and thoracic lymphadenopathy.

Conclusion: Pulmonary abnormalities caused by COVID-19 pneumonia can be detected on TrueFISP MRI sequences and correspond to the patterns known from CT. Especially during the current pandemic, the portions of the lungs imaged on cardiac or abdominal MRI should be carefully evaluated to promote the identification and isolation of unexpected cases of COVID-19, thereby curbing further spread of the disease.
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http://dx.doi.org/10.1590/0100-3984.2021.0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354185PMC
February 2021

Artificial Intelligence in Chest Radiography Reporting Accuracy: Added Clinical Value in the Emergency Unit Setting Without 24/7 Radiology Coverage.

Invest Radiol 2021 Aug 4. Epub 2021 Aug 4.

From the Department of Radiology, University Hospital, LMU Munich, Munich, Germany X-Ray Products, Siemens Healthineers, Forchheim, Germany Digital Technology and Innovation, Siemens Healthineers, Princeton, NJ Digital Technology and Innovation, Siemens Healthineers, Bangalore, India Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany Department of Radiology, Asklepios Fachklinik München, Gauting, Germany Department of Medicine I, University Hospital, LMU, Munich, Germany Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU, Munich, Germany Medicine II, University Hospital, LMU, Munich, Germany.

Objectives: Chest radiographs (CXRs) are commonly performed in emergency units (EUs), but the interpretation requires radiology experience. We developed an artificial intelligence (AI) system (precommercial) that aims to mimic board-certified radiologists' (BCRs') performance and can therefore support non-radiology residents (NRRs) in clinical settings lacking 24/7 radiology coverage. We validated by quantifying the clinical value of our AI system for radiology residents (RRs) and EU-experienced NRRs in a clinically representative EU setting.

Materials And Methods: A total of 563 EU CXRs were retrospectively assessed by 3 BCRs, 3 RRs, and 3 EU-experienced NRRs. Suspected pathologies (pleural effusion, pneumothorax, consolidations suspicious for pneumonia, lung lesions) were reported on a 5-step confidence scale (sum of 20,268 reported pathology suspicions [563 images × 9 readers × 4 pathologies]) separately by every involved reader. Board-certified radiologists' confidence scores were converted into 4 binary reference standards (RFSs) of different sensitivities. The RRs' and NRRs' performances were statistically compared with our AI system (trained on nonpublic data from different clinical sites) based on receiver operating characteristics (ROCs) and operating point metrics approximated to the maximum sum of sensitivity and specificity (Youden statistics).

Results: The NRRs lose diagnostic accuracy to RRs with increasingly sensitive BCRs' RFSs for all considered pathologies. Based on our external validation data set, the AI system/NRRs' consensus mimicked the most sensitive BCRs' RFSs with areas under ROC of 0.940/0.837 (pneumothorax), 0.953/0.823 (pleural effusion), and 0.883/0.747 (lung lesions), which were comparable to experienced RRs and significantly overcomes EU-experienced NRRs' diagnostic performance. For consolidation detection, the AI system performed on the NRRs' consensus level (and overcomes each individual NRR) with an area under ROC of 0.847 referenced to the BCRs' most sensitive RFS.

Conclusions: Our AI system matched RRs' performance, meanwhile significantly outperformed NRRs' diagnostic accuracy for most of considered CXR pathologies (pneumothorax, pleural effusion, and lung lesions) and therefore might serve as clinical decision support for NRRs.
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http://dx.doi.org/10.1097/RLI.0000000000000813DOI Listing
August 2021

Structured Reporting of Computed Tomography Examinations in Post-Lung Transplantation Patients.

J Comput Assist Tomogr 2021 Aug 2. Epub 2021 Aug 2.

From the Department of Radiology Department of Internal Medicine V-Pulmonology, University Hospital, LMU Munich Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), Helmholtz Center Munich Department of Radiology, Asklepios Lung Center Munich-Gauting, Munich, Germany.

Objective: The aim of this study was to evaluate the benefits and potential of structured reports (SR) for chest computed tomography after lung transplantation.

Methods: Free-text reports (FTR) and SR were generated for 49 computed tomography scans. Clinical routine reports were used as FTR. Two pulmonologists rated formal aspects, completeness, clinical utility, and overall quality. Wilcoxon and McNemar tests were used for statistical analysis.

Results: Structured reports received significantly higher ratings for all formals aspects (P < 0.001, respectively). Completeness was higher in SR with regard to evaluation of bronchiectases, bronchial anastomoses, bronchiolitic and fibrotic changes (P < 0.001, respectively), and air trapping (P = 0.012), but not signs of pneumonia (P = 0.5). Clinical utility and overall quality were rated significantly higher for SR than FTR (P < 0.001, respectively). However, report type did not influence initiation of further diagnostic or therapeutic measures (P = 0.307 and 1.0).

Conclusions: Structured reports are superior to FTR with regard to formal aspects, completeness, clinical utility, and overall satisfaction of referring pulmonologists.
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http://dx.doi.org/10.1097/RCT.0000000000001209DOI Listing
August 2021

Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity.

Infection 2021 Jul 28. Epub 2021 Jul 28.

Department of Medicine V, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Objective: Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors.

Methods: Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function.

Results: 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate-severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p < 0.001). Further risk factors for DLCO impairment were COPD (p < 0.001), SARS-CoV-2 antibody-Titer (p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course.

Conclusion: We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.
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http://dx.doi.org/10.1007/s15010-021-01669-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318328PMC
July 2021

Validation of proton dose calculation on scatter corrected 4D cone beam computed tomography using a porcine lung phantom.

Phys Med Biol 2021 08 30;66(17). Epub 2021 Aug 30.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Proton therapy treatment for lungs remains challenging as images enabling the detection of inter- and intra-fractional motion, which could be used for proton dose adaptation, are not readily available. 4D computed tomography (4DCT) provides high image quality but is rarely available in-room, while in-room 4D cone beam computed tomography (4DCBCT) suffers from image quality limitations stemming mostly from scatter detection. This study investigated the feasibility of using virtual 4D computed tomography (4DvCT) as a prior for a phase-per-phase scatter correction algorithm yielding a 4D scatter corrected cone beam computed tomography image (4DCBCT), which can be used for proton dose calculation. 4DCT and 4DCBCT scans of a porcine lung phantom, which generated reproducible ventilation, were acquired with matching breathing patterns. Diffeomorphic Morphons, a deformable image registration algorithm, was used to register the mid-position 4DCT to the mid-position 4DCBCT and yield a 4DvCT. The 4DCBCT was reconstructed using motion-aware reconstruction based on spatial and temporal regularization (MA-ROOSTER). Successively for each phase, digitally reconstructed radiographs of the 4DvCT, simulated without scatter, were exploited to correct scatter in the corresponding CBCT projections. The 4DCBCTwas then reconstructed with MA-ROOSTER using the corrected CBCT projections and the same settings and deformation vector fields as those already used for reconstructing the 4DCBCT. The 4DCBCTand the 4DvCT were evaluated phase-by-phase, performing proton dose calculations and comparison to those of a ground truth 4DCT by means of dose-volume-histograms (DVH) and gamma pass-rates (PR). For accumulated doses, DVH parameters deviated by at most 1.7% in the 4DvCT and 2.0% in the 4DCBCTcase. The gamma PR for a (2%, 2 mm) criterion with 10% threshold were at least 93.2% (4DvCT) and 94.2% (4DCBCT), respectively. The 4DCBCTtechnique enabled accurate proton dose calculation, which indicates the potential for applicability to clinical 4DCBCT scans.
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http://dx.doi.org/10.1088/1361-6560/ac16e9DOI Listing
August 2021

Percutaneous CT Fluoroscopy-Guided Core Needle Biopsy of Mediastinal Masses: Technical Outcome and Complications of 155 Procedures during a 10-Year Period.

Diagnostics (Basel) 2021 Apr 26;11(5). Epub 2021 Apr 26.

Institute for Diagnostic and Interventional Neuroradiology, University Hospital, LMU Munich, 81377 Munich, Germany.

Purpose: To evaluate technical outcome, diagnostic yield and safety of computed tomographic fluoroscopy-guided percutaneous core needle biopsies in patients with mediastinal masses.

Methods: Overall, 155 CT fluoroscopy-guided mediastinal core needle biopsies, performed from March 2010 to June 2020 were included. Size of lesion, size of needle, access path, number of success, number of biopsies per session, diagnostic yield, patient's position, effective dose, rate of complications, tumor localization, size of tumor and histopathological diagnosis were considered. Post-interventional CT was performed, and patients observed for any complications. Complications were classified per the Society of Interventional Radiology (SIR).

Results: 148 patients (age, 54.7 ± 18.2) underwent 155 CT-fluoroscopy-guided percutaneous biopsies with tumors in the anterior (114; 73.5%), middle (17; 11%) and posterior (24; 15.5%) mediastinum, of which 152 (98%) were technically successful. For placement of the biopsy needle, in 82 (52.9%) procedures a parasternal trajectory was chosen, in 36 (23.3%) a paravertebral access, in 20 (12.9%) through the lateral intercostal space and in 17 (11%) the thoracic anterior midline, respectively. A total of 136 (89.5%) of the biopsies were considered adequate for a specific histopathologic analysis. Total DLP (dose-length product) was 575.7 ± 488.8 mGy*cm. Mean lesion size was 6.0 ± 3.3 cm. Neoplastic pathology was diagnosed in 115 (75.7%) biopsies and 35 (23%) biopsy samples showed no evidence of malignancy. Minor complications were observed in 18 (11.6%) procedures and major pneumothorax requiring drainage insertion in 3 interventions (1.9%).

Conclusion: CT fluoroscopy-guided percutaneous core needle biopsy of mediastinal masses is an effective and safe procedure for the initial assessment of patients with mediastinal tumors.
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http://dx.doi.org/10.3390/diagnostics11050781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144979PMC
April 2021

Automated quantitative thin slice volumetric low dose CT analysis predicts disease severity in COVID-19 patients.

Clin Imaging 2021 Nov 21;79:96-101. Epub 2021 Apr 21.

Comprehensive Pneumology Center, Helmholtz Center Munich, Max-Lebsche-Platz 31, 81377 Munich, Germany(1); Department of Radiology, Ludwig-Maximilians-University Munich (LMU), Marchioninistr, 15, 81377 Munich, Germany; Department of Radiology, Asklepios Lung Clinic Munich-Gauting, Robert-Koch-Allee 2, 82131 Gauting, Germany.

Purpose: This study aimed to identify predictive (bio-)markers for COVID-19 severity derived from automated quantitative thin slice low dose volumetric CT analysis, clinical chemistry and lung function testing.

Methods: Seventy-four COVID-19 patients admitted between March 16th and June 3rd 2020 to the Asklepios Lung Clinic Munich-Gauting, Germany, were included in the study. Patients were categorized in a non-severe group including patients hospitalized on general wards only and in a severe group including patients requiring intensive care treatment. Fully automated quantification of CT scans was performed via IMBIO CT Lung Texture analysis™ software. Predictive biomarkers were assessed with receiver-operator-curve and likelihood analysis.

Results: Fifty-five patients (44% female) presented with non-severe COVID-19 and 19 patients (32% female) with severe disease. Five fatalities were reported in the severe group. Accurate automated CT analysis was possible with 61 CTs (82%). Disease severity was linked to lower residual normal lung (72.5% vs 87%, p = 0.003), increased ground glass opacities (GGO) (8% vs 5%, p = 0.031) and increased reticular pattern (8% vs 2%, p = 0.025). Disease severity was associated with advanced age (76 vs 59 years, p = 0.001) and elevated serum C-reactive protein (CRP, 92.2 vs 36.3 mg/L, p < 0.001), lactate dehydrogenase (LDH, 485 vs 268 IU/L, p < 0.001) and oxygen supplementation (p < 0.001) upon admission. Predictive risk factors for the development of severe COVID-19 were oxygen supplementation, LDH >313 IU/L, CRP >71 mg/L, <70% normal lung texture, >12.5% GGO and >4.5% reticular pattern.

Conclusion: Automated low dose CT analysis upon admission might be a useful tool to predict COVID-19 severity in patients.
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http://dx.doi.org/10.1016/j.clinimag.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058052PMC
November 2021

Fully Automated Segmentation of Pulmonary Fibrosis Using Different Software Tools.

Respiration 2021;100(7):580-587. Epub 2021 Apr 15.

Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany.

Objective: Evaluation of software tools for segmentation, quantification, and characterization of fibrotic pulmonary parenchyma changes will strengthen the role of CT as biomarkers of disease extent, evolution, and response to therapy in idiopathic pulmonary fibrosis (IPF) patients.

Methods: 418 nonenhanced thin-section MDCTs of 127 IPF patients and 78 MDCTs of 78 healthy individuals were analyzed through 3 fully automated, completely different software tools: YACTA, LUFIT, and IMBIO. The agreement between YACTA and LUFIT on segmented lung volume and 80th (reflecting fibrosis) and 40th (reflecting ground-glass opacity) percentile of the lung density histogram was analyzed using Bland-Altman plots. The fibrosis and ground-glass opacity segmented by IMBIO (lung texture analysis software tool) were included in specific regression analyses.

Results: In the IPF-group, LUFIT outperformed YACTA by segmenting more lung volume (mean difference 242 mL, 95% limits of agreement -54 to 539 mL), as well as quantifying higher 80th (76 HU, -6 to 158 HU) and 40th percentiles (9 HU, -73 to 90 HU). No relevant differences were revealed in the control group. The 80th/40th percentile as quantified by LUFIT correlated positively with the percentage of fibrosis/ground-glass opacity calculated by IMBIO (r = 0.78/r = 0.92).

Conclusions: In terms of segmentation of pulmonary fibrosis, LUFIT as a shape model-based segmentation software tool is superior to the threshold-based YACTA, tool, since the density of (severe) fibrosis is similar to that of the surrounding soft tissues. Therefore, shape modeling as used in LUFIT may serve as a valid tool in the quantification of IPF, since this mainly affects the subpleural space.
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http://dx.doi.org/10.1159/000515182DOI Listing
April 2021

PET/CT imaging for evaluation of multimodal treatment efficacy and toxicity in advanced NSCLC-current state and future directions.

Eur J Nucl Med Mol Imaging 2021 Mar 24. Epub 2021 Mar 24.

Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.

Purpose: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, leading to a string of approvals in recent years. Herein, a narrative review on the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the ever-evolving treatment landscape of advanced NSCLC is presented.

Methods: This comprehensive review will begin with an introduction into current treatment paradigms incorporating ICIs; the evolution of CT-based criteria; moving onto novel phenomena observed with ICIs and the current state of hybrid imaging for diagnosis, treatment planning, evaluation of treatment efficacy and toxicity in advanced NSCLC, also taking into consideration its limitations and future directions.

Conclusions: The advent of ICIs marks the dawn of a new era bringing forth new challenges particularly vis-à-vis treatment response assessment and observation of novel phenomena accompanied by novel systemic side effects. While FDG PET/CT is widely adopted for tumor volume delineation in locally advanced disease, response assessment to immunotherapy based on current criteria is of high clinical value but has its inherent limitations. In recent years, modifications of established (PET)/CT criteria have been proposed to provide more refined approaches towards response evaluation. Not only a comprehensive inclusion of PET-based response criteria in prospective randomized controlled trials, but also a general harmonization within the variety of PET-based response criteria is pertinent to strengthen clinical implementation and widespread use of hybrid imaging for response assessment in NSCLC.
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http://dx.doi.org/10.1007/s00259-021-05211-8DOI Listing
March 2021

S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis.

Respiration 2021;100(3):238-271. Epub 2021 Jan 22.

Center for Interstitial and Rare Lung Diseases, Pneumology Department, Ruhrlandklinik - University Hospital, University Duisburg-Essen, Essen, Germany.

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since the publication of the international IPF guideline in the year 2011 and the update 2018 several studies and technical advances have occurred, which made a new assessment of the diagnostic process mandatory. The goal of this guideline is to foster early, confident, and effective diagnosis of IPF. The guideline focusses on the typical clinical context of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardized questionnaires, serologic testing, and cellular analysis of bronchoalveolar lavage. High-resolution computed tomography remains crucial in the diagnostic workup. If it is necessary to obtain specimens for histology, transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom a bronchoscopic diagnosis did not provide the information needed. After all, IPF is a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.
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http://dx.doi.org/10.1159/000512315DOI Listing
January 2021

Diagnostic accuracy of magnetic resonance imaging for the detection of pulmonary nodules simulated in a dedicated porcine chest phantom.

PLoS One 2020 23;15(12):e0244382. Epub 2020 Dec 23.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Objective: CT serves as gold standard for the evaluation of pulmonary nodules. However, CT exposes patients to ionizing radiation, a concern especially in screening scenarios with repeated examinations. Due to recent technological advances, MRI emerges as a potential alternative for lung imaging using 3D steady state free precession and ultra-short echo-time sequences. Therefore, in this study we assessed the performance of three state-of-the-art MRI sequences for the evaluation of pulmonary nodules.

Methods: Lesions of variable sizes were simulated in porcine lungs placed in a dedicated chest phantom mimicking a human thorax, followed by CT and MRI examinations. Two blinded readers evaluated the acquired MR-images locating and measuring every suspect lesion. Using the CT-images as reference, logistic regression was performed to investigate the sensitivity of the tested MRI-sequences for the detection of pulmonary nodules.

Results: For nodules with a diameter of 6 mm, all three sequences achieved high sensitivity values above 0.91. However, the sensitivity dropped for smaller nodules, yielding an average of 0.83 for lesions with 4 mm in diameter and less than 0.69 for lesions with 2 mm in diameter. The positive predictive values ranged between 0.91 and 0.96, indicating a low amount of false positive findings. Furthermore, the size measurements done on the MR-images were subject to a bias ranging from 0.83 mm to -1.77 mm with standard deviations ranging from 1.40 mm to 2.11 mm. There was no statistically significant difference between the three tested sequences.

Conclusion: While showing promising sensitivity values for lesions larger than 4 mm, MRI appears to be not yet suited for lung cancer screening. Nonetheless, the three tested MRI sequences yielded high positive predictive values and accurate size measurements; therefore, MRI could potentially figure as imaging method of the chest in selected follow-up scenarios, e.g. of incidental findings subject to the Fleischner Criteria.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244382PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757901PMC
March 2021

Anthropomorphic lung phantom based validation of in-room proton therapy 4D-CBCT image correction for dose calculation.

Z Med Phys 2020 Nov 25. Epub 2020 Nov 25.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München (LMU Munich), Garching, Germany. Electronic address:

Purpose: Ventilation-induced tumour motion remains a challenge for the accuracy of proton therapy treatments in lung patients. We investigated the feasibility of using a 4D virtual CT (4D-vCT) approach based on deformable image registration (DIR) and motion-aware 4D CBCT reconstruction (MA-ROOSTER) to enable accurate daily proton dose calculation using a gantry-mounted CBCT scanner tailored to proton therapy.

Methods: Ventilation correlated data of 10 breathing phases were acquired from a porcine ex-vivo functional lung phantom using CT and CBCT. 4D-vCTs were generated by (1) DIR of the mid-position 4D-CT to the mid-position 4D-CBCT (reconstructed with the MA-ROOSTER) using a diffeomorphic Morphons algorithm and (2) subsequent propagation of the obtained mid-position vCT to the individual 4D-CBCT phases. Proton therapy treatment planning was performed to evaluate dose calculation accuracy of the 4D-vCTs. A robust treatment plan delivering a nominal dose of 60Gy was generated on the average intensity image of the 4D-CT for an approximated internal target volume (ITV). Dose distributions were then recalculated on individual phases of the 4D-CT and the 4D-vCT based on the optimized plan. Dose accumulation was performed for 4D-vCT and 4D-CT using DIR of each phase to the mid position, which was chosen as reference. Dose based on the 4D-vCT was then evaluated against the dose calculated on 4D-CT both, phase-by-phase as well as accumulated, by comparing dose volume histogram (DVH) values (D, D, D, D) for the ITV, and by a 3D-gamma index analysis (global, 3%/3mm, 5Gy, 20Gy and 30Gy dose thresholds).

Results: Good agreement was found between the 4D-CT and 4D-vCT-based ITV-DVH curves. The relative differences ((CT-vCT)/CT) between accumulated values of ITV D, D, D and D for the 4D-CT and 4D-vCT-based dose distributions were -0.2%, 0.0%, -0.1% and -0.1%, respectively. Phase specific values varied between -0.5% and 0.2%, -0.2% and 0.5%, -3.5% and 1.5%, and -5.7% and 2.3%. The relative difference of accumulated D over the lungs was 2.3% and D for the phases varied between -5.4% and 5.8%. The gamma pass-rates with 5Gy, 20Gy and 30Gy thresholds for the accumulated doses were 96.7%, 99.6% and 99.9%, respectively. Phase-by-phase comparison yielded pass-rates between 86% and 97%, 88% and 98%, and 94% and 100%.

Conclusions: Feasibility of the suggested 4D-vCT workflow using proton therapy specific imaging equipment was shown. Results indicate the potential of the method to be applied for daily 4D proton dose estimation.
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http://dx.doi.org/10.1016/j.zemedi.2020.09.004DOI Listing
November 2020

Porcine lung phantom-based validation of estimated 4D-MRI using orthogonal cine imaging for low-field MR-Linacs.

Phys Med Biol 2021 02 16;66(5):055006. Epub 2021 Feb 16.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Real-time motion monitoring of lung tumors with low-field magnetic resonance imaging-guided linear accelerators (MR-Linacs) is currently limited to sagittal 2D cine magnetic resonance imaging (MRI). To provide input data for improved intrafractional and interfractional adaptive radiotherapy, the 4D anatomy has to be inferred from data with lower dimensionality. The purpose of this study was to experimentally validate a previously proposed propagation method that provides continuous time-resolved estimated 4D-MRI based on orthogonal cine MRI for a low-field MR-Linac. Ex vivo porcine lungs were injected with artificial nodules and mounted in a dedicated phantom that allows for the simulation of periodic and reproducible breathing motion. The phantom was scanned with a research version of a commercial 0.35 T MR-Linac. Respiratory-correlated 4D-MRI were reconstructed and served as ground truth images. Series of interleaved orthogonal slices in sagittal and coronal orientation, intersecting the injected targets, were acquired at 7.3 Hz. Estimated 4D-MRI at 3.65 Hz were created in post-processing using the propagation method and compared to the ground truth 4D-MRI. Eight datasets at different breathing frequencies and motion amplitudes were acquired for three porcine lungs. The overall median (95[Formula: see text] percentile) deviation between ground truth and estimated deformation vector fields was 2.3 mm (5.7 mm), corresponding to 0.7 (1.6) times the in-plane imaging resolution (3.5 × 3.5 mm). Median (95[Formula: see text] percentile) estimated nodule position errors were 1.5 mm (3.8 mm) for nodules intersected by orthogonal slices and 2.1 mm (7.1 mm) for nodules located more than 2 cm away from either of the orthogonal slices. The estimation error depended on the breathing phase, the motion amplitude and the location of the estimated position with respect to the orthogonal slices. By using the propagation method, the 4D motion within the porcine lung phantom could be accurately and robustly estimated. The method could provide valuable information for treatment planning, real-time motion monitoring, treatment adaptation, and post-treatment evaluation of MR-guided radiotherapy treatments.
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http://dx.doi.org/10.1088/1361-6560/abc937DOI Listing
February 2021

A proof-of principal study using phase-contrast imaging for the detection of large airway pathologies after lung transplantation.

Sci Rep 2020 10 28;10(1):18444. Epub 2020 Oct 28.

Department of Radiology, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany.

In this study we aim to evaluate the assessment of bronchial pathologies in a murine model of lung transplantation with grating-based X-ray interferometry in vivo. Imaging was performed using a dedicated grating-based small-animal X-ray dark-field and phase-contrast scanner. While the contrast modality of the dark-field signal already showed several promising applications for diagnosing various types of pulmonary diseases, the phase-shifting contrast mechanism of the phase contrast has not yet been evaluated in vivo. For this purpose, qualitative analysis of phase-contrast images was performed and revealed pathologies due to previous lung transplantation, such as unilateral bronchial stenosis or bronchial truncation. Dependent lung parenchyma showed a strong loss in dark-field and absorption signal intensity, possibly caused by several post transplantational pathologies such as atelectasis, pleural effusion, or pulmonary infiltrates. With this study, we are able to show that bronchial pathologies can be visualized in vivo using conventional X-ray imaging when phase-contrast information is analysed. Absorption and dark-field images can be used to quantify the severity of lack of ventilation in the affected lung.
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http://dx.doi.org/10.1038/s41598-020-75185-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595203PMC
October 2020

Longitudinal lung function measurements in single lung transplant recipients with chronic lung allograft dysfunction.

J Heart Lung Transplant 2020 Aug 26. Epub 2020 Aug 26.

Department of Internal Medicine V, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL). Electronic address:

Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD.

Methods: A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71).

Results: Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p < 0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset.

Conclusions: Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival.
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http://dx.doi.org/10.1016/j.healun.2020.08.008DOI Listing
August 2020

Involvement of radiologists in oncologic multidisciplinary team meetings: an international survey by the European Society of Oncologic Imaging.

Eur Radiol 2021 Feb 24;31(2):983-991. Epub 2020 Aug 24.

Department of Radiological Sciences, Oncological and Pathological Sciences, University of Rome "Sapienza", Sant'Andrea University Hospital, Rome, Italy.

Objectives: Multidisciplinary tumour boards (MTBs) play an increasingly important role in managing cancer patients from diagnosis to treatment. However, many problems arise around the organisation of MTBs, both in terms of organisation-administration and time management. In this context, the European Society of Oncologic Imaging (ESOI) conducted a survey among its members, aimed at assessing the quality and amount of involvement of radiologists in MTBs, their role in it and related issues.

Methods: All members were invited to fill in a questionnaire consisting of 15 questions with both open and multiple-choice answers. Simple descriptive analyses and graphs were performed.

Results: A total of 292 ESOI members in full standing for the year 2018 joined the survey. Most respondents (89%) declared to attend MT-Bs, but only 114 respondents (43.9%) review over 70% of exams prior to MTB meetings, mainly due to lack of time due to a busy schedule for imaging and reporting (46.6%). Perceived benefits (i.e. surgical and histological feedback (86.9%), improved knowledge of cancer treatment (82.7%) and better interaction between radiologists and referring clinicians for discussing rare cases (56.9%)) and issues (i.e. attending MTB meetings during regular working hours (71.9%) and lack of accreditation with continuing medical education (CME) (85%)) are reported.

Conclusions: Despite the value and benefits of radiologists' participation in MTBs, issues like improper preparation due to a busy schedule and no counterpart in CME accreditation require efforts to improve the role of radiologists for a better patient care.

Key Points: • Most radiologists attend multidisciplinary tumour boards, but less than half of them review images in advance, mostly due to time constraints. • Feedback about radiological diagnoses, improved knowledge of cancer treatment and interaction with referring clinicians are perceived as major benefits. • Concerns were expressed about scheduling multidisciplinary tumour boards during regular working hours and lack of accreditation with continuing medical education.
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http://dx.doi.org/10.1007/s00330-020-07178-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813742PMC
February 2021

Impact of Confounding Thoracic Tubes and Pleural Dehiscence Extent on Artificial Intelligence Pneumothorax Detection in Chest Radiographs.

Invest Radiol 2020 12;55(12):792-798

From the Department of Radiology, University Hospital, LMU Munich.

Objectives: We hypothesized that published performances of algorithms for artificial intelligence (AI) pneumothorax (PTX) detection in chest radiographs (CXRs) do not sufficiently consider the influence of PTX size and confounding effects caused by thoracic tubes (TTs). Therefore, we established a radiologically annotated benchmarking cohort (n = 6446) allowing for a detailed subgroup analysis.

Materials And Methods: We retrospectively identified 6434 supine CXRs, among them 1652 PTX-positive cases and 4782 PTX-negative cases. Supine CXRs were radiologically annotated for PTX size, PTX location, and inserted TTs. The diagnostic performances of 2 AI algorithms ("AI_CheXNet" [Rajpurkar et al], "AI_1.5" [Guendel et al]), both trained on publicly available datasets with labels obtained from automatic report interpretation, were quantified. The algorithms' discriminative power for PTX detection was quantified by the area under the receiver operating characteristics (AUROC), and significance analysis was based on the corresponding 95% confidence interval. A detailed subgroup analysis was performed to quantify the influence of PTX size and the confounding effects caused by inserted TTs.

Results: Algorithm performance was quantified as follows: overall performance with AUROCs of 0.704 (AI_1.5) / 0.765 (AI_CheXNet) for unilateral PTXs, AUROCs of 0.666 (AI_1.5) / 0.722 (AI_CheXNet) for unilateral PTXs smaller than 1 cm, and AUROCs of 0.735 (AI_1.5) / 0.818 (AI_CheXNet) for unilateral PTXs larger than 2 cm. Subgroup analysis identified TTs to be strong confounders that significantly influence algorithm performance: Discriminative power is completely eliminated by analyzing PTX-positive cases without TTs referenced to control PTX-negative cases with inserted TTs. Contrarily, AUROCs increased up to 0.875 (AI_CheXNet) for large PTX-positive cases with inserted TTs referenced to control cases without TTs.

Conclusions: Our detailed subgroup analysis demonstrated that the performance of established AI algorithms for PTX detection trained on public datasets strongly depends on PTX size and is significantly biased by confounding image features, such as inserted TTS. Our established, clinically relevant and radiologically annotated benchmarking cohort might be of great benefit for ongoing algorithm development.
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http://dx.doi.org/10.1097/RLI.0000000000000707DOI Listing
December 2020

Delayed contrast dynamics as marker of regional impairment in pulmonary fibrosis using 5D MRI - a pilot study.

Br J Radiol 2020 Sep 8;93(1113):20190121. Epub 2020 Jul 8.

Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.

Objective: To analyse delayed contrast dynamics of fibrotic lesions in interstitial lung disease (ILD) using five dimensional (5D) MRI and to correlate contrast dynamics with disease severity.

Methods: 20 patients (mean age: 71 years; M:F, 13:7), with chronic fibrosing ILD: = 12 idiopathic pulmonary fibrosis (IPF) and = 8 non-IPF, underwent thin-section multislice CT as part of the standard diagnostic workup and additionally MRI of the lung. 2 min after contrast injection, a radial gradient echo sequence with golden-angle spacing was acquired during 5 min of free-breathing, followed by 5D image reconstruction. Disease was categorized as severe or non-severe according to CT morphological regional severity. For each patient, 10 lesions were analysed.

Results: IPF lesions showed later peak enhancement compared to non-IPF (severe: = 0.01, non-severe: = 0.003). Severe lesions showed later peak enhancement compared to non-severe lesions, in non-IPF ( = 0.04), but not in IPF ( = 0.35). There was a tendency towards higher accumulation and washout rates in IPF compared to non-IPF in non-severe disease. Severe lesions had lower washout rate than non-severe ones in both IPF ( = 0.003) and non-IPF ( = 0.005). Continuous contrast agent accumulation, without washout, was found only in IPF lesions.

Conclusions: Contrast agent dynamics are influenced by type and severity of pulmonary fibrosis, which might enable a more thorough characterisation of disease burden. The regional impairment is of particular interest in the context of antifibrotic treatments and was characterised using a non-invasive, non-irradiating, free-breathing method.

Advances In Knowledge: Delayed contrast enhancement patterns allow the assessment of regional lung impairment which could represent different disease stages or phenotypes in ILD.
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http://dx.doi.org/10.1259/bjr.20190121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465850PMC
September 2020

Clinical Course of Three Postoperative Symptomatic COVID-19 Cases in Patients After Lung Lobectomy.

Ann Thorac Surg 2020 12 6;110(6):e461-e463. Epub 2020 Jun 6.

Asklepios Lung Clinic Munich-Gauting, Gauting, Germany; Comprehensive Pneumology Center, Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.

The novel coronavirus disease 2019 is a highly contagious viral infection caused by the severe acute respiratory syndrome coronavirus 2 virus. Its rapid spread and severe clinical presentation influence patient management in all specialties including thoracic surgery. We report 3 cases of coronavirus disease 2019 occurring in patients shortly after thoracotomy and thoracoscopy procedures, illustrating the imminent threat of severe acute respiratory syndrome coronavirus 2 infection for thoracic surgery patients.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833962PMC
December 2020

Automated evaluation of probe-based confocal laser endomicroscopy in the lung.

PLoS One 2020 6;15(5):e0232847. Epub 2020 May 6.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Rationale: Probe-based confocal endomicroscopy provides real time videos of autoflourescent elastin structures within the alveoli. With it, multiple changes in the elastin structure due to different diffuse parenchymal lung diseases have previously been described. However, these evaluations have mainly relied on qualitative evaluation by the examiner and manually selected parts post-examination.

Objectives: To develop a fully automatic method for quantifying structural properties of the imaged alveoli elastin and to perform a preliminary assessment of their diagnostic potential.

Methods: 46 patients underwent probe-based confocal endomicroscopy, of which 38 were divided into 4 groups categorizing different diffuse parenchymal lung diseases. 8 patients were imaged in representative healthy lung areas and used as control group. Alveolar elastin structures were automatically segmented with a trained machine learning algorithm and subsequently evaluated with two methods developed for quantifying the local thickness and structural connectivity.

Measurements And Main Results: The automatic segmentation algorithm performed generally well and all 4 patient groups showed statistically significant differences with median elastin thickness, standard deviation of thickness and connectivity compared to the control group.

Conclusion: Alveoli elastin structures can be quantified based on their structural connectivity and thickness statistics with a fully-automated algorithm and initial results highlight its potential for distinguishing parenchymal lung diseases from normal alveoli.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232847PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202624PMC
August 2020

Comparison of MRI and VQ-SPECT as a Screening Test for Patients With Suspected CTEPH: CHANGE-MRI Study Design and Rationale.

Front Cardiovasc Med 2020 9;7:51. Epub 2020 Apr 9.

Sheffield Pulmonary Vascular Disease Unit, Royal Hallamhire Hospital, Sheffield, United Kingdom.

The diagnostic strategy for chronic thromboembolic pulmonary hypertension (CTEPH) is composed of two components required for a diagnosis of CTEPH: the presence of chronic pulmonary embolism and an elevated pulmonary artery pressure. The current guidelines require that ventilation-perfusion single-photon emission computed tomography (VQ-SPECT) is used for the first step diagnosis of chronic pulmonary embolism. However, VQ-SPECT exposes patients to ionizing radiation in a radiation sensitive population. The prospective, multicenter, comparative phase III diagnostic trial TEP diosis urope - MRI (CHANGE-MRI, ClinicalTrials.gov identifier ) aims to demonstrate whether functional lung MRI can serve as an equal rights alternative to VQ-SPECT in a diagnostic strategy for patients with suspected CTEPH. Positive findings are verified with catheter pulmonary angiography or computed tomography pulmonary angiography (gold standard). For comparing the imaging methods, a co-primary endpoint is used. (i) the proportion of patients with positive MRI in the group of patients who have a positive SPECT and gold standard diagnosis for chronic pulmonary embolism and (ii) the proportion of patients with positive MRI in the group of patients with negative SPECT and gold standard. The CHANGE-MRI trial will also investigate the performance of functional lung MRI without i.v. contrast agent as an index test and identify cardiac, hemodynamic, and pulmonary MRI-derived parameters to estimate pulmonary artery pressures and predict 6-12 month survival. Ultimately, this study will provide the necessary evidence for the discussion about changes in the recommendations on the diagnostic approach to CTEPH.
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http://dx.doi.org/10.3389/fcvm.2020.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161347PMC
April 2020

Real-time 4DMRI-based internal target volume definition for moving lung tumors.

Med Phys 2020 Apr 10;47(4):1431-1442. Epub 2020 Feb 10.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, 81377, Germany.

Purpose: In photon radiotherapy, respiratory-induced target motion can be accounted for by internal target volumes (ITV) or mid-ventilation target volumes (midV) defined on the basis of four-dimensional computed tomography (4D-CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient-specific ITV definition method based on real-time 4D magnetic resonance imaging (rt-4DMRI).

Methods: Three lung cancer patients underwent weekly rt-4DMRI scans. A total of 24 datasets were included in this retrospective study. The GTV was contoured on breath-hold MR images and propagated to all rt-4DMRI images by deformable image registration. Different targets were created for the first (reference) imaging sessions: ITVs encompassing all GTV positions over the complete (ITV ) or partial acquisition time ( ), ITVs including only voxels with a GTV probability-of-presence (POP) of at least 5% ( ) or 10% ( ), and the mid-ventilation GTV position. Reference planning target volumes ( ) were created by adding margins around the ITVs and midV target volumes. The geometrical overlap of the with from the six to eight subsequent imaging sessions on days n was quantified in terms of the Dice similarity coefficient (DSC), sensitivity [SE: ( )/ ] and precision [PRE: ( )/ ] as surrogates for target coverage and normal tissue sparing.

Results: Patient-specific analysis yielded a high variance of the overlap values of , when different periods within the reference imaging session were sampled. The mid-ventilation-based PTVs were smaller than the ITV-based PTVs. While the SE was high for patients with small breathing pattern variations, changes of the median breathing amplitudes in different imaging sessions led to inferior SE values for the mid-ventilation PTV for one patient. In contrast, and showed higher SE values with a higher robustness against interfractional changes, at the cost of larger target volumes.

Conclusions: The results indicate that rt-4DMRI could be valuable for the definition of target volumes based on the GTV POP to achieve a higher robustness against interfractional changes than feasible with today's 4D-CT-based target definition concepts.
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http://dx.doi.org/10.1002/mp.14023DOI Listing
April 2020

Assessment of intravoxel incoherent motion MRI with an artificial capillary network: analysis of biexponential and phase-distribution models.

Magn Reson Med 2019 10 26;82(4):1373-1384. Epub 2019 May 26.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Purpose: To systematically analyze intravoxel incoherent motion (IVIM) MRI in a perfusable capillary phantom closely matching the geometry of capillary beds in vivo and to compare the validity of the biexponential pseudo-diffusion and the recently introduced phase-distribution IVIM model.

Methods: IVIM-MRI was performed at 12 different flow rates ( ) in a capillary phantom using 4 different DW-MRI sequences (2 with monopolar and 2 with flow-compensated diffusion-gradient schemes, with up to values between and ). Resulting parameters from the assessed IVIM models were compared to results from optical microscopy.

Results: The acquired data were best described by a static and a flowing compartment modeled by the phase-distribution approach. The estimated signal fraction of the flowing compartment stayed approximately constant over the applied flow rates, with an average of in excellent agreement with optical microscopy ( ). The estimated average particle flow speeds showed a highly significant linear correlation to the applied flow. The estimated capillary segment length of approximately agreed well with optical microscopy measurements. Using the biexponential model, the signal fraction was substantially underestimated and displayed a strong dependence on the applied flow rate.

Conclusion: The constructed phantom facilitated the detailed investigation of IVIM-MRI methods. The results demonstrate that the phase-distribution method is capable of accurately characterizing fluid flow inside a capillary network. Parameters estimated using the biexponential model, specifically the perfusion fraction , showed a substantial bias because the model assumptions were not met by the underlying flow pattern.
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http://dx.doi.org/10.1002/mrm.27816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771596PMC
October 2019

Nonuniform Fourier-decomposition MRI for ventilation- and perfusion-weighted imaging of the lung.

Magn Reson Med 2019 10 20;82(4):1312-1321. Epub 2019 May 20.

Department of Radiology, University Hospital, LMU Munich, Munich, Germany.

Purpose: To improve the robustness of pulmonary ventilation- and perfusion-weighted imaging with Fourier decomposition (FD) MRI in the presence of respiratory and cardiac frequency variations by replacing the standard fast Fourier transform with the more general nonuniform Fourier transform.

Theory And Methods: Dynamic coronal single-slice MRI of the thorax was performed in 11 patients and 5 healthy volunteers on a 1.5T whole-body scanner using a 2D ultra-fast balanced steady-state free-precession sequence with temporal resolutions of 4-9 images/s. For the proposed nonuniform Fourier-decomposition (NUFD) approach, the original signal with variable physiological frequencies that was acquired with constant sampling rate was retrospectively transformed into a signal with (ventilation or perfusion) frequency-adapted sampling rate. For that purpose, frequency tracking was performed with the synchro-squeezed wavelet transform. Ventilation- and perfusion-weighted NUFD amplitude and signal delay maps were generated and quantitatively compared with regularly sampled FD maps based on their signal-to-noise ratio (SNR).

Results: Volunteers and patients showed statistically significant increases of SNR in frequency-adapted NUFD results compared to regularly sampled FD results. For ventilation data, the mean SNR increased by and in volunteers and patients, respectively; for perfusion data, SNR increased by and . Two patients showed perfusion signal in pulmonary areas with NUFD that could not be imaged with FD.

Conclusion: This study demonstrates that using nonuniform Fourier transform in combination with frequency tracking can significantly increase SNR and reduce frequency overlaps by collecting the signal intensity onto single frequency bins.
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http://dx.doi.org/10.1002/mrm.27803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767124PMC
October 2019

Feasibility of 4DCBCT-based proton dose calculation: An ex vivo porcine lung phantom study.

Z Med Phys 2019 Aug 14;29(3):249-261. Epub 2018 Nov 14.

Department of Medical Physics, Ludwig-Maximilians-Universität München (LMU Munich), Am Coulombwall 1, 85748 Garching, Germany. Electronic address:

Inter-fractional variations of breathing pattern and patient anatomy introduce dose uncertainties in proton therapy. One approach to monitor these variations is to utilize the cone-beam computed tomography (CT, CBCT) scans routinely taken for patient positioning, reconstruct them as 4DCBCTs, and generate 'virtual CTs' (vCTs), combining the accurate CT numbers of the diagnostic 4DCT and the geometry of the daily 4DCBCT by using deformable image registration (DIR). In this study different algorithms for 4DCBCT reconstruction and DIR were evaluated. For this purpose, CBCT scans of a moving ex vivo porcine lung phantom with 663 and 2350 projections respectively were acquired, accompanied by an additional 4DCT as reference. The CBCT projections were sorted in 10 phase bins with the Amsterdam-shroud method and reconstructed phase-by-phase using first a FDK reconstruction from the Reconstruction Toolkit (RTK) and again an iterative reconstruction algorithm implemented in the Gadgetron Toolkit. The resulting 4DCBCTs were corrected by DIR of the corresponding 4DCT phases, using both a morphons algorithm from REGGUI and a b-spline deformation from Plastimatch. The resulting 4DvCTs were compared to the 4DCT by visual inspection and by calculating water equivalent thickness (WET) maps from the phantom's surface to the distal edge of a target from various angles. The optimized procedure was successfully repeated with mismatched input phases and on a clinical patient dataset. Proton treatment plans were simulated on the 4DvCTs and the dose distributions compared to the reference based on the 4DCT via gamma pass rate analysis. A combination of iterative reconstruction and morphons DIR yielded the most accurate 4DvCTs, with median WET differences under 2mm and 3%/3mm gamma pass rates per phase between 89% and 99%. These results suggest that image correction of iteratively reconstructed 4DCBCTs with a morphons DIR of the planning CT may yield sufficiently accurate 4DvCTs for daily time resolved proton dose calculations.
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http://dx.doi.org/10.1016/j.zemedi.2018.10.005DOI Listing
August 2019

CT fluoroscopy-guided percutaneous osteoplasty with or without radiofrequency ablation in the treatment of painful extraspinal and spinal bone metastases: technical outcome and complications in 29 patients.

Diagn Interv Radiol 2018 May-Jun;24(3):158-165

Institute for Clinical Radiology, University Hospitals Munich - Campus Großhadern, München, Germany.

Purpose: We aimed to assess the safety and technical outcome of computed tomography (CT) fluoroscopy-guided osteoplasty with or without prior percutaneous radiofrequency ablation (RFA) in patients with painful osteolyses.

Methods: We performed a retrospective analysis of 29 patients with painful extraspinal and spinal osteolyses (16 women, 13 men; 63.1±14.4 years) who underwent CT fluoroscopy-guided osteoplasty (10-20 mAs tube current) with or without RFA (26 and 14 lesions, respectively), in 33 consecutive procedures from 2002 to 2016. Technical success was defined as at least one complete RFA cycle and subsequent polymethyl metacrylate (PMMA) bone cement injection covering ≥75% of longest diameter of extraspinal osteolysis on axial plane or of distance between vertebral endplates. Procedure-related complications within 30 days and dose-length-product (DLP) were also evaluated.

Results: Osteolyses were located in the pelvis (acetabulum, n=10; iliac bone, n=4), spine (thoracic, n=6; lumbar, n=5; sacral, n=8), long bones (femur, n=3; tibia, n=1), sternum (n=2) and glenoid (n=1). Mean size of the treated osteolysis was 4.0±1.2 cm (range, 1.9-6.9 cm). Of 40 osteolyses, 31 (77.5%) abutted neighboring risk structures (spinal canal or neuroforamen, n=18; neighboring joint, n=11; other, n=8). Mean number of RFA electrode positions and complete ablation cycles was 1.5±0.9 and 2.1±1.7, respectively. Mean PMMA filling volume was 7.7±5.7 mL (range, 2-30 mL). Small asymptomatic PMMA leakages were observed in 15 lesions (37.5%). Mean total DLP was 850±653 mGy*cm. Six minor complications were observed, without any major complications.

Conclusion: CT fluoroscopy-guided percutaneous osteoplasty with or without concomitant RFA for the treatment of painful extraspinal and spinal osteolyses can be performed with a low complication rate and high technical success.
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http://dx.doi.org/10.5152/dir.2018.17265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951205PMC
October 2018

Idiopathic Pulmonary Fibrosis Among Young Patients: Challenges in Diagnosis and Management.

Lung 2018 08 14;196(4):401-408. Epub 2018 May 14.

Department of Internal Medicine V, Comprehensive Pneumology Centre (CPC-M), Member of the German Centre for Lung Research (DZL), Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Introduction: Idiopathic pulmonary fibrosis (IPF) is considered a disease of older patients, being rare in patients ≤ 50 years. Still, IPF can occur in younger patients, but this particular patient group is not well characterised so far. The aim of this study was to compare the diagnostic certainty, clinical features, comorbidities and survival in young versus older IPF patients.

Methods: We reviewed our medical records from February 2011 until February 2015, to identify IPF patients, who were then classified as young (≤ 50 years) or older IPF (> 50 years). Radiographic and histological findings, lung function parameters, comorbidities, disease progression and survival were analysed and compared between the two groups.

Results: Of 440 patients with interstitial lung disease, 129 patients with IPF were identified, including 30 (23.3%) ≤50 years and 99 (76.7%) > 50 years. There were no differences between age groups in baseline demographics; younger patients were less likely to have a confirmed diagnosis by high-resolution computed tomography (p = 0.014), more likely to require a biopsy (p = 0.08) and less likely to have received antifibrotic therapy (p = 0.006). Despite an overall limited prognosis, younger patients had a significantly better median survival after diagnosis (p = 0.0375), with a significantly higher proportion of older patients dying due to respiratory failure (p = 0.0383).

Conclusion: IPF patients under the age of 50 years have similar features and clinical course compared to older IPF patients. These patients should be diagnosed by adopting a multidisciplinary team approach, potentially benefitting from earlier intervention with effective antifibrotic therapy.
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http://dx.doi.org/10.1007/s00408-018-0123-9DOI Listing
August 2018

Taking Another View on Lung Fibrosis.

Am J Respir Crit Care Med 2018 04;197(7):947-948

1 Asklepios Lung-Center Munich-Gauting.

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http://dx.doi.org/10.1164/rccm.201708-1683IMDOI Listing
April 2018

Detection of artificial pulmonary lung nodules in ultralow-dose CT using an ex vivo lung phantom.

PLoS One 2018 3;13(1):e0190501. Epub 2018 Jan 3.

Department of Clinical Radiology, University Hospital Munich, Ludwig-Maximilians-University, Munich, Germany.

Objectives: To assess the image quality of 3 different ultralow-dose CT protocols on pulmonary nodule depiction in a ventilated ex vivo-system.

Materials And Methods: Four porcine lungs were inflated inside a dedicated chest phantom and prepared with n = 195 artificial nodules (0.5-1 mL). The artificial chest wall was filled with water to simulate the absorption of a human chest. Images were acquired with a 2x192-row detector CT using low-dose (reference protocol with a tube voltage of 120 kV) and 3 different ULD protocols (respective effective doses: 1mSv and 0.1mSv). A different tube voltage was used for each ULD protocol: 70kV, 100kV with tin filter (100kV_Sn) and 150kV with tin filter (150kV_Sn). Nodule delineation was assessed by two observers (scores 1-5, 1 = unsure, 5 = high confidence).

Results: The diameter of the 195 detected artificial nodules ranged from 0.9-21.5 mm (mean 7.84 mm ± 5.31). The best ULD scores were achieved using 100kV_Sn and 70 kV ULD protocols (4.14 and 4.06 respectively). Both protocols were not significantly different (p = 0.244). The mean score of 3.78 in ULD 150kV_Sn was significantly lower compared to the 100kV_Sn ULD protocol (p = 0.008).

Conclusion: The results of this experiment, conducted in a realistic setting show the feasibility of ultralow-dose CT for the detection of pulmonary nodules.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190501PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752031PMC
February 2018

CT characteristics in pulmonary adenocarcinoma with epidermal growth factor receptor mutation.

PLoS One 2017 26;12(9):e0182741. Epub 2017 Sep 26.

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

Comprehensively investigate the association of CT morphology and clinical findings of adenocarcinoma with EGFR mutation status. Retrospectively included 282 patients who was pathologically proved as lung adenocarcinoma with known EGFR mutation status (mutations: 138 patients, female: 86, median age: 66 years; wildtype: 144 patients, female: 67, median age: 62 years) and their pre-treatment CT scans were analyzed. CT findings and clinical information were collected. Univariate and multivariable logistic regression analysis were performed. Adjusted for age, gender and smoking history of two groups, significantly more patients with pleural tags, pleural and liver metastases were found in the EGFR mutated group (P = 0.007, 0.004, and 0.043, respectively). Multivariable logistic regression analysis found that the model included age, gender, smoking history, air bronchogram, pleural tags, pleural and liver metastasis had a moderate predictive value for EGFR mutation status (AUC = 0.741, P < .0001). Exon-19 deletion was associated with air bronchogram which adjusted for age, gender and smoking history (P = 0.007, OR: 2.91, 95%CI: 1.25-7.79). The evidence of pleural tags, pleural and liver metastases go along with a higher probability of EGFR mutation in adenocarcinoma patients and air bronchogram is positively associated with Exon-19 deletion mutation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182741PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614426PMC
October 2017
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