16708
2018
eng
12
8
article
1
2018-08-10
--
--
Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195
Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover.
Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization.
Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.
EJNMMI Research
10.1186/s13550-018-0365-9
2191-219X
29411169
urn:nbn:de:bvb:20-opus-167081
Johns Hopkins School of Medicine
701983
EJNMMI Research (2018) 8:12 https://doi.org/10.1186/s13550-018-0365-9
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Xinyu Chen
Rudolf A. Werner
Constantin Lapa
Naoko Nose
Mitsuru Hirano
Mehrbod S. Javadi
Simon Robinson
Takahiro Higuchi
eng
uncontrolled
phaeochromocytoma
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
heart failure
eng
uncontrolled
sympathetic nervous system
eng
uncontrolled
storage vesicle turnover
eng
uncontrolled
positron emission tomography
eng
uncontrolled
18F-LMI1195
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16708/Werner Rudolf LMI1195.pdf
16699
2018
eng
article
1
2018-08-10
--
--
MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
Annals of Nuclear Medicine
0914-7187
urn:nbn:de:bvb:20-opus-166995
10.1007/s12149-018-1291-7
Johns Hopkins School of Medicine
Annals of Nuclear Medicine (2018). https://doi.org/10.1007/s12149-018-1291-7
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Ralph A. Bundschuh
Lena Bundschuh
Mehrbod S. Javadi
Takahiro Higuchi
Alexander Weich
Sara Sheikhbahaei
Kenneth J. Pienta
Andreas K. Buck
Martin G. Pomper
Michael A. Gorin
Constantin Lapa
Steven P. Rowe
eng
uncontrolled
PET
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
prostate cancer
eng
uncontrolled
neuroendocrine tumor
eng
uncontrolled
prostate-specific membrane antigen (PSMA)
eng
uncontrolled
somatostatin receptor (SSTR)
eng
uncontrolled
positron emission tomography
eng
uncontrolled
theranostics
eng
uncontrolled
standardization
eng
uncontrolled
RADS
eng
uncontrolled
reporting and data systems
eng
uncontrolled
personalized medicine
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik II
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16699/Werner_MI-RDAS_Annals_Nuclear_Medicine_2018.pdf
16791
2018
eng
article
1
2018-09-03
--
--
Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
Endocrine
1355-008X
10.1007/s12020-018-1749-3
urn:nbn:de:bvb:20-opus-167910
Johns Hopkins School of Medicine
Endocrine (2018). https://doi.org/10.1007/s12020-018-1749-3
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Ralph A. Bundschuh
Takahiro Higuchi
Mehrbod S. Javadi
Steven P. Rowe
Norbert Zsótér
Matthias Kroiss
Martin Fassnacht
Andreas K. Buck
Michael C. Kreissl
Constantin Lapa
eng
uncontrolled
personalized medicine
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
medullary thyroid carcinoma
eng
uncontrolled
tyrosine kinase inhibitor
eng
uncontrolled
TKI
eng
uncontrolled
vandetanib
eng
uncontrolled
18F-FDG
eng
uncontrolled
positron emission tomography
eng
uncontrolled
2-deoxy-2-(18F)fluoro-D-glucose
eng
uncontrolled
PET
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16791/Rudolf_Werner_VolumetricAndTextureAnalysis_Endocrine_2018.pdf
16222
2018
eng
100
Supplement No 1
59
conferenceobject
1
2018-05-27
--
--
The Impact of Ageing on [\(^{11}\)C]meta-Hydroxyephedrine Uptake in the Rat Heart
No abstract available.
Journal of Nuclear Medicine
0161-5505
http://jnm.snmjournals.org/content/59/supplement_1/100.abstract
urn:nbn:de:bvb:20-opus-162228
Johns Hopkins School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. supplement 1 100
701983
Deutsches Urheberrecht
Rudolf A. Werner
Xinyu Chen
Mitsuru Hirano
Naoko Nose
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
moycardial sympathetic innervation
deu
uncontrolled
Positronen-Emissions-Tomografie
eng
uncontrolled
positron emission tomography
eng
uncontrolled
PET
eng
uncontrolled
11C-HED
eng
uncontrolled
hydroxyephedrine
eng
uncontrolled
ageing
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16222/Werner_Rudolf_11C-HED_JNM_Kongressbeitrag_accepted_version.pdf
16362
2018
eng
article
1
2018-06-30
--
--
SPECT vs. PET in Cardiac Innervation Imaging: Clash of the Titans
Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers.
Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.
Clinical and Translational Imaging
10.1007/s40336-018-0289-4
2281-5872
urn:nbn:de:bvb:20-opus-163628
Johns Hopkins School of Medicine, Baltimore, MD, USA
National Cardiovascular and Cerebral Center, Suita, Japan
Clinical and Translational Imaging (2018) 6, 4, 293–303. https://doi.org/10.1007/s40336-018-0289-4
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Xinyu Chen
Mitsuru Hirano
Steven P. Rowe
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
eng
uncontrolled
single photon emission computed tomography: sympathetic nerve
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
18F-LMI1195
eng
uncontrolled
11C-hydroxyephedrine
eng
uncontrolled
123I-metaiodobenzylguanidine
eng
uncontrolled
positron emission tomography
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16362/Werner_2018_SPECTVsPETInCardiacInnervation.pdf
16913
2018
eng
article
1
2018-10-12
--
--
Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers
The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.
The International Journal of Cardiovascular Imaging
1569-5794
10.1007/s10554-018-1469-z
urn:nbn:de:bvb:20-opus-169134
Johns Hopkins University, Baltimore, MD, U.S.
International Journal of Cardiovascular Imaging (2019) 35: 569. https://doi.org/10.1007/s10554-018-1469-z
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Xinyu Chen
Steven P. Rowe
Constantin Lapa
Mehrbod S. Javadi
Takahiro Higuchi
eng
uncontrolled
heart failure with mid-range ejection fraction
deu
swd
Positronenemissionstomografie
eng
uncontrolled
coronary artery disease
eng
uncontrolled
precision medicine
eng
uncontrolled
positron emission tomography
eng
uncontrolled
PET
eng
uncontrolled
SPECT
eng
uncontrolled
myocardial perfusion imaging
eng
uncontrolled
MPI
eng
uncontrolled
18F-flurpiridaz
eng
uncontrolled
18FFBnTP
eng
uncontrolled
HFmrEF
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16913/Werner2018_IJCI_PETMyocardialPerfusionImaging.pdf
16125
2018
eng
article
1
2018-04-29
--
--
Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We
aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment.
Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type).
Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation.
Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance.
Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
Journal of Nuclear Medicine
10.2967/jnumed.117.199778
0161-5505
https://www.ncbi.nlm.nih.gov/pubmed/29025983
urn:nbn:de:bvb:20-opus-161256
This research was originally published in JNM. Rudolf A. Werner, Jan-Stefan Schmid, Takahiro Higuchi, Mehrbod S. Javadi, Steven P. Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K. Buck, Michael C. Kreissl, Constantin Lapa. Predictive value of 18F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. May 1, 2018;vol. 59 no. 5: 756-761. © SNMMI.
Johns Hopkins University School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. 5 756-761. doi:10.2967/jnumed.117.199778
701983
Deutsches Urheberrecht
Rudolf Werner
Jan-Stefan Schmid
Takahiro Higuchi
Mehrbod S. Javadi
Steven P. Rowe
Bruno Märkl
Christoph Aulmann
Martin Fassnacht
Matthias Kroiß
Christoph Reiners
Andreas Buck
Michael Kreissl
Constantin Lapa
eng
uncontrolled
positron emission tomography
deu
swd
Medullärer Schilddrüsenkrebs
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
medullary thyroid carcinoma
eng
uncontrolled
tyrosine kinase inhibitor
eng
uncontrolled
vandetanib
eng
uncontrolled
2- deoxy-2-(18F)fluoro-D-glucose
eng
uncontrolled
18F-FDG
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16125/Werner_Rudolf_Vandetanib_JNM_accepted_version.pdf
16560
2018
eng
1-8
article
1
2018-07-24
--
--
Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.
Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).
Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
European Heart Journal Cardiovascular Imaging
2047-2404
10.1093/ehjci/jey119
urn:nbn:de:bvb:20-opus-165601
Johns Hopkins School of Medicine
701983
European Heart Journal - Cardiovascular Imaging (2018) 0, 1–8 doi:10.1093/ehjci/jey119
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Rudolf Werner
Hiroshi Wakabayashi
Jochen Bauer
Claudia Schütz
Christina Zechmeister
Nobuyuki Hayakawa
Mehrbod S. Javadi
Constantin Lapa
Roland Jahns
Süleyman Ergün
Valerie Jahns
Takahiro Higuchi
eng
uncontrolled
positron emission tomography
deu
swd
Myokarditis
eng
uncontrolled
myocarditis
eng
uncontrolled
inflammation
eng
uncontrolled
18F-FDG
eng
uncontrolled
PET
eng
uncontrolled
personalized treatment
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16560/Werner_EHJ_Cardiovascular_Imaging_2018.pdf