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Article ; Online: Longitudinal Assessment of Health and Quality of Life of COVID-19 Patients Requiring Intensive Care—An Observational Study

Johanna Erber / Johannes R. Wießner / Gregor S. Zimmermann / Petra Barthel / Egon Burian / Fabian Lohöfer / Eimo Martens / Hrvoje Mijočević / Sebastian Rasch / Roland M. Schmid / Christoph D. Spinner / Rickmer Braren / Jochen Schneider / Tobias Lahmer

Journal of Clinical Medicine, Vol 10, Iss 5469, p

2021 Volume 5469

Abstract: Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were ... ...

Abstract	Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were prospectively followed-up at a median of 36, 75.5, 122 and 222 days after discharge. The health-related quality of life (HrQoL) (36-item Short Form Health Survey and St. George’s Respiratory Questionnaire, SGRQ), cardiopulmonary function, laboratory parameters and chest imaging were assessed longitudinally. The HrQoL assessment revealed a reduced physical functioning, as well as increased SGRQ impact and symptoms scores that all improved over time but remained markedly impaired compared to the reference groups. The median radiological severity scores significantly declined; persistent abnormalities were found in 33.3% of the patients on follow-up. A reduced diffusion capacity was the most common abnormal pulmonary function parameter. The length of hospitalization correlated with role limitations due to physical problems, the SGRQ symptom and the impact score. In conclusion, in survivors of severe COVID-19, the pulmonary function and symptoms improve over time, but impairments in their physical function and diffusion capacity can persist over months. Longer follow-up studies with larger cohorts will be necessary to comprehensively characterize long-term sequelae upon severe COVID-19 and to identify patients at risk.
Keywords	COVID-19 sequelae ; SARS-CoV-2 ; pulmonary function test ; health-related quality of life ; long-term health consequences ; Medicine ; R
Subject code	360
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Elisabeth Bliemsrieder / Georgios Kaissis / Martin Grashei / Geoffrey Topping / Jennifer Altomonte / Christian Hundshammer / Fabian Lohöfer / Irina Heid / Dominik Keim / Selamawit Gebrekidan / Marija Trajkovic-Arsic / AM Winkelkotte / Katja Steiger / Roman Nawroth / Jens Siveke / Markus Schwaiger / Marcus Makowski / Franz Schilling / Rickmer Braren

Scientific Reports, Vol 11, Iss 1, Pp 1-

Hyperpolarized 13C pyruvate magnetic resonance spectroscopy for in vivo metabolic phenotyping of rat HCC

2021 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hyperpolarized 13C pyruvate magnetic resonance spectroscopy for in vivo metabolic phenotyping of rat HCC

Elisabeth Bliemsrieder / Georgios Kaissis / Martin Grashei / Geoffrey Topping / Jennifer Altomonte / Christian Hundshammer / Fabian Lohöfer / Irina Heid / Dominik Keim / Selamawit Gebrekidan / Marija Trajkovic-Arsic / Aline Winkelkotte / Katja Steiger / Roman Nawroth / Jens Siveke / Markus Schwaiger / Marcus Makowski / Franz Schilling / Rickmer Braren

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 9

Abstract: Abstract The in vivo assessment of tissue metabolism represents a novel strategy for the evaluation of oncologic disease. Hepatocellular carcinoma (HCC) is a high-prevalence, high-mortality tumor entity often discovered at a late stage. Recent evidence ... ...

Abstract	Abstract The in vivo assessment of tissue metabolism represents a novel strategy for the evaluation of oncologic disease. Hepatocellular carcinoma (HCC) is a high-prevalence, high-mortality tumor entity often discovered at a late stage. Recent evidence indicates that survival differences depend on metabolic alterations in tumor tissue, with particular focus on glucose metabolism and lactate production. Here, we present an in vivo imaging technique for metabolic tumor phenotyping in rat models of HCC. Endogenous HCC was induced in Wistar rats by oral diethyl-nitrosamine administration. Peak lactate-to-alanine signal ratios (L/A) were assessed with hyperpolarized magnetic resonance spectroscopic imaging (HPMRSI) after [1-13C]pyruvate injection. Cell lines were derived from a subset of primary tumors, re-implanted in nude rats, and assessed in vivo with dynamic hyperpolarized magnetic resonance spectroscopy (HPMRS) after [1-13C]pyruvate injection and kinetic modelling of pyruvate metabolism, taking into account systemic lactate production and recirculation. For ex vivo validation, enzyme activity and metabolite concentrations were spectroscopically quantified in cell and tumor tissue extracts. Mean peak L/A was higher in endogenous HCC compared to non-tumorous tissue. Dynamic HPMRS revealed higher pyruvate-to-lactate conversion rates (k pl ) and lactate signal in subcutaneous tumors derived from high L/A tumor cells, consistent with ex vivo measurements of higher lactate dehydrogenase (LDH) levels in these cells. In conclusion, HPMRS and HPMRSI reveal distinct tumor phenotypes corresponding to differences in glycolytic metabolism in HCC tumor tissue.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy.

Georgios Kaissis / Sebastian Ziegelmayer / Fabian Lohöfer / Katja Steiger / Hana Algül / Alexander Muckenhuber / Hsi-Yu Yen / Ernst Rummeny / Helmut Friess / Roland Schmid / Wilko Weichert / Jens T Siveke / Rickmer Braren

PLoS ONE, Vol 14, Iss 10, p e

2019 Volume 0218642

Abstract: PURPOSE:Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. METHODS:The retrospective ... ...

Abstract	PURPOSE:Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. METHODS:The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradient-boosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. RESULTS:The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. The mean±STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76±0.05 and 0.71±0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81- patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P = <0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 2.33, P = 0.037) compared to KRT81- patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 2.41, P = 0.027). Entropy was ranked as the most important radiomic feature. CONCLUSIONS:The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

Michael Köhler / Fabian Harders / Fabian Lohöfer / Philipp M. Paprottka / Benedikt M. Schaarschmidt / Jens Theysohn / Ken Herrmann / Walter Heindel / Hartmut H. Schmidt / Andreas Pascher / Lars Stegger / Kambiz Rahbar / Moritz Wildgruber

Journal of Clinical Medicine, Vol 9, Iss 1, p

2019 Volume 56

Abstract: Purpose: To evaluate factors associated with survival following transarterial 90 Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of ... ...

Abstract	Purpose: To evaluate factors associated with survival following transarterial 90 Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan−Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29−88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1−12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume ( p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90 Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
Keywords	intrahepatic cholangiocarcinoma ; radioembolization ; y-90 yttrium ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A machine learning model for the prediction of survival and tumor subtype in pancreatic ductal adenocarcinoma from preoperative diffusion-weighted imaging

Georgios Kaissis / Sebastian Ziegelmayer / Fabian Lohöfer / Hana Algül / Matthias Eiber / Wilko Weichert / Roland Schmid / Helmut Friess / Ernst Rummeny / Donna Ankerst / Jens Siveke / Rickmer Braren

European Radiology Experimental, Vol 3, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract Background To develop a supervised machine learning (ML) algorithm predicting above- versus below-median overall survival (OS) from diffusion-weighted imaging-derived radiomic features in patients with pancreatic ductal adenocarcinoma (PDAC). ... ...

Abstract	Abstract Background To develop a supervised machine learning (ML) algorithm predicting above- versus below-median overall survival (OS) from diffusion-weighted imaging-derived radiomic features in patients with pancreatic ductal adenocarcinoma (PDAC). Methods One hundred two patients with histopathologically proven PDAC were retrospectively assessed as training cohort, and 30 prospectively accrued and retrospectively enrolled patients served as independent validation cohort (IVC). Tumors were segmented on preoperative apparent diffusion coefficient (ADC) maps, and radiomic features were extracted. A random forest ML algorithm was fit to the training cohort and tested in the IVC. Histopathological subtype of tumor samples was assessed by immunohistochemistry in 21 IVC patients. Individual radiomic feature importance was evaluated by assessment of tree node Gini impurity decrease and recursive feature elimination. Fisher’s exact test, 95% confidence intervals (CI), and receiver operating characteristic area under the curve (ROC-AUC) were used. Results The ML algorithm achieved 87% sensitivity (95% IC 67.3–92.7), 80% specificity (95% CI 74.0–86.7), and ROC-AUC 90% for the prediction of above- versus below-median OS in the IVC. Heterogeneity-related features were highly ranked by the model. Of the 21 patients with determined histopathological subtype, 8/9 patients predicted to experience below-median OS exhibited the quasi-mesenchymal subtype, whilst 11/12 patients predicted to experience above-median OS exhibited a non-quasi-mesenchymal subtype (p < 0.001). Conclusion ML application to ADC radiomics allowed OS prediction with a high diagnostic accuracy in an IVC. The high overlap of clinically relevant histopathological subtypes with model predictions underlines the potential of quantitative imaging in PDAC pre-operative subtyping and prognosis.
Keywords	Machine learning ; Diffusion magnetic resonance imaging ; Pancreatic carcinoma ; Radiomics ; Survival analysis ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	610
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 3D grating-based X-ray phase-contrast computed tomography for high-resolution quantitative assessment of cartilage

Julia Herzen / Dimitrios C Karampinos / Peter Foehr / Lorenz Birnbacher / Manuel Viermetz / Rainer Burgkart / Thomas Baum / Fabian Lohoefer / Moritz Wildgruber / Franz Schilling / Marian Willner / Mathias Marschner / Peter B Noël / Ernst J Rummeny / Franz Pfeiffer / Pia M Jungmann

PLoS ONE, Vol 14, Iss 2, p e

An experimental feasibility study with 3T MRI, 7T MRI and biomechanical correlation.

2019 Volume 0212106

Abstract: Objective Aim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage. Materials and methods In an experimental setup, 12 osteochondral ... ...

Abstract	Objective Aim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage. Materials and methods In an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses. Results PCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses. Conclusion In conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mass Spectrometry Imaging of atherosclerosis-affine Gadofluorine following Magnetic Resonance Imaging

Fabian Lohöfer / Rebecca Buchholz / Almut Glinzer / Katharina Huber / Helena Haas / Georgios Kaissis / Annette Feuchtinger / Michaela Aichler / Peter B. Sporns / Carsten Höltke / Miriam Stölting / Franz Schilling / René M. Botnar / Melanie A. Kimm / Cornelius Faber / Axel K. Walch / Alma Zernecke / Uwe Karst / Moritz Wildgruber

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 9

Abstract: Abstract Molecular imaging of atherosclerosis by Magnetic Resonance Imaging (MRI) has been impaired by a lack of validation of the specific substrate responsible for the molecular imaging signal. We therefore aimed to investigate the additive value of ... ...

Abstract	Abstract Molecular imaging of atherosclerosis by Magnetic Resonance Imaging (MRI) has been impaired by a lack of validation of the specific substrate responsible for the molecular imaging signal. We therefore aimed to investigate the additive value of mass spectrometry imaging (MSI) of atherosclerosis-affine Gadofluorine P for molecular MRI of atherosclerotic plaques. Atherosclerotic Ldlr −/− mice were investigated by high-field MRI (7 T) at different time points following injection of atherosclerosis-affine Gadofluorine P as well as at different stages of atherosclerosis formation (4, 8, 16 and 20 weeks of HFD). At each imaging time point mice were immediately sacrificed after imaging and aortas were excised for mass spectrometry imaging: Matrix Assisted Laser Desorption Ionization (MALDI) Imaging and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) imaging. Mass spectrometry imaging allowed to visualize the localization and measure the concentration of the MR imaging probe Gadofluorine P in plaque tissue ex vivo with high spatial resolution and thus adds novel and more target specific information to molecular MR imaging of atherosclerosis.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular imaging of myocardial infarction with Gadofluorine P – A combined magnetic resonance and mass spectrometry imaging approach

Fabian Lohöfer / Laura Hoffmann / Rebecca Buchholz / Katharina Huber / Almut Glinzer / Katja Kosanke / Annette Feuchtinger / Michaela Aichler / Benedikt Feuerecker / Georgios Kaissis / Ernst J. Rummeny / Carsten Höltke / Cornelius Faber / Franz Schilling / René M. Botnar / Axel K. Walch / Uwe Karst / Moritz Wildgruber

Heliyon, Vol 4, Iss 4, Pp e00606- (2018)

2018

Abstract: Background: Molecular MRI is becoming increasingly important for preclinical research. Validation of targeted gadolinium probes in tissue however has been cumbersome up to now. Novel methodology to assess gadolinium distribution in tissue after in vivo ... ...

Abstract	Background: Molecular MRI is becoming increasingly important for preclinical research. Validation of targeted gadolinium probes in tissue however has been cumbersome up to now. Novel methodology to assess gadolinium distribution in tissue after in vivo application is therefore needed. Purpose: To establish combined Magnetic Resonance Imaging (MRI) and Mass Spectrometry Imaging (MSI) for improved detection and quantification of Gadofluorine P deposition in scar formation and myocardial remodeling. Materials and methods: Animal studies were performed according to institutionally approved protocols. Myocardial infarction was induced by permanent ligation of the left ascending artery (LAD) in C57BL/6J mice. MRI was performed at 7T at 1 week and 6 weeks after myocardial infarction. Gadofluorine P was used for dynamic T1 mapping of extracellular matrix synthesis during myocardial healing and compared to Gd-DTPA. After in vivo imaging contrast agent concentration as well as distribution in tissue were validated and quantified by spatially resolved Matrix-Assisted Laser Desorption Ionization (MALDI) MSI and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) imaging. Results: Both Gadofluorine P enhancement as well as local tissue content in the myocardial scar were highest at 15 minutes post injection. R1 values increased from 1 to 6 weeks after MI (1.62 s−1 vs 2.68 s−1, p = 0.059) paralleled by an increase in Gadofluorine P concentration in the infarct from 0.019 mM at 1 week to 0.028 mM at 6 weeks (p = 0.048), whereas Gd-DTPA enhancement showed no differences (3.95 s−1 vs 3.47 s−1, p = 0.701). MALDI-MSI results were corroborated by elemental LA-ICP-MS of Gadolinium in healthy and infarcted myocardium. Histology confirmed increased extracellular matrix synthesis at 6 weeks compared to 1 week. Conclusion: Adding quantitative MSI to MR imaging enables a quantitative validation of Gadofluorine P distribution in the heart after MI for molecular imaging.
Keywords	Biomedical engineering ; Cardiology ; Medical imaging ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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