Abstract
Purpose
To study the value of 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG) positron emission tomography/computed tomography (PET/CT) and [18F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) in assessing immunocompromised patients with suspected malignancy or infection.
Methods
[18F]FDG-PET/CT and [18F]FDG-PET/MRI examinations of patients who were immunocompromised after receiving lung, heart, pancreas, kidney, liver, or combined kidney-liver transplants were analyzed in this retrospective study. Patients underwent whole-body hybrid-imaging because of clinical signs of malignancy and/or infection. Findings were assessed by molecular features ([18F]FDG-uptake) and morphological changes. The final diagnosis, which was arrived at after review of clinical, laboratory, and histopathologic analyses and follow-up imaging studies, served as the reference standard.
Results
Altogether, (i) 28 contrast-enhanced [18F]FDG-PET/CT scans (CE-PET/CT), (ii) 33 non-contrast [18F]FDG-PET/CT scans (NC-PET/CT), and (iii) 18 [18F]FDG-PET/MRI scans were included. Additionally, 12/62 patients underwent follow-up PET imaging to rule out vital tumor or metabolic active inflammatory processes. CE-PET/CT exhibited 94.4% sensitivity, 80.0% specificity, 89.5% positive predictive value (PPV), 88.9% negative predictive value (NPV), and 89.3% accuracy with regard to the reference standard. NC-PET/CT exhibited 91.3% sensitivity, 80.0% specificity, 91.3% PPV, 80.0% NPV, and 87.9% accuracy. PET/MRI exhibited 88.6% sensitivity, 99.2% specificity, 99.6% PPV, 81.3% NPV, and 94.4% accuracy. Exact McNemar statistical test (one-sided) showed significant difference between the CT-/MR-component alone and the integrated PET/CT and PET/MRI for diagnosis of malignancy or infection (p value < 0.001). Radiation exposure was 4- to 7-fold higher with PET/CT than with PET/MRI.
Conclusion
For immunocompromised patients with clinically unresolved symptoms, to rule out vital tumor manifestations or metabolic active inflammation, [18F]FDG-PET/MRI, CE-[18F]FDG-PET/CT, and NC-[18F]FDG-PET/CT exhibit excellent performance in diagnosing malignancy or infection. The main strength of PET/MRI is its considerably lower level of radiation exposure than that associated with PET/CT.
Keywords: Transplant immunology, Positron emission tomography, Magnetic resonance imaging, Diagnostic imaging
Introduction
Over the past decades, patient and graft survival rates after solid organ transplantation have tremendously improved [1, 2]. However, in transplant recipients, infectious complications and malignancy remain major hazards negatively affecting post-transplant morbidity and mortality. Because of alterations in humoral and cellular immunity, patients who have undergone organ transplant are prone to serious opportunistic and complicated infections [3, 4] and to infection-related and -unrelated malignancies [2, 5]. Patterns of infection and malignancy vary according to the transplanted organ and the time after transplant [3, 4]. The synergistic effects of patient- and donor-derived predisposing factors, the intensity of immunosuppression, the individual patient’s net state of immunosuppression, as well as the epidemiologic exposures determine the risk of developing post-transplantation-related neoplasms and infection [4]. In addition, some viruses, especially herpes viruses such as cytomegalovirus, lead to an additional weakening of the immune system and thus increase the risk of secondary infections or malignancies. In immunocompromised patients, malignancies and infections may be often initially clinically unapparent or associated with atypical clinical symptoms making timely diagnosis and therapy a challenge for the treating physicians.
In such cases, advanced imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography/CT (PET/CT) may be necessary. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT is known to be a powerful imaging technique for detecting cancer or various types of infections [6–8]. It enhances the diagnostic course by simultaneously integrating metabolic and morphologic images [9, 10]. Furthermore, in recent years, new imaging techniques, such as integrated [18F]FDG PET/MRI, have emerged and promise an even better diagnostic evaluation [11, 12]. Integrated PET/MRI yields excellent results for a wide range of diagnostic imaging capabilities, from staging malignant tumors to monitoring the outcome of therapy, infection, and inflammation [10]. To our knowledge, until now, no studies have compared the benefits of contrast-enhanced [18F]FDG PET/CT (CE PET/CT), non-contrast [18F]FDG PET/CT (NC PET/CT), and [18F]FDG PET/MRI (PET/MRI) in diagnosing infection or malignancy among immunocompromised patients. Hence, the purpose of this study was to compare the benefits of the three modalities in assessing immunocompromised patients with suspected malignancy or infection and to confirm a metabolic active neoplastic or inflammatory process after solid-organ transplant.
Methods
This retrospective study was approved by the local ethics committee [19-8575-BO] on January 28, 2019. Altogether, 79 imaging studies from 62 organ-transplanted patients who were treated at the Department of Nephrology and Infectious Diseases and received PET imaging were included in the analysis. Additionally, 12 of 62 patients underwent follow-up PET-imaging to rule out vital neoplastic or metabolic active inflammatory processes. Patients with diminished renal function in terms of reduced GFR and elevated creatinine, with suspected or confirmed hyperthyroidism, autonomous thyroid function, or contrast hypersensitivity underwent non-contrast PET/CT. Younger patients were preferably examined by PET/MRI.
PET/CT Imaging
In accordance with a one-timepoint protocol, we obtained diagnostic PET/CT scans with a Biograph mCT 128 scanner (Siemens Healthcare GmbH, Erlangen, Germany), approximately 60 min after intravenous administration of a mean injected activity of 266.5 MBq [18F]FDG (range, 70–360 MBq; IQR, 230–315 MBq). The patients had a mean blood glucose level of 123.6 mg/dl (range, 67–222 mg/dl; IQR, 100–138 mg/dl). The PET/CT scan imaged the entire body, from the infraorbital sinus to the proximal thigh. Altogether, 28 CE PET/CT scans were performed 70 s after the administration of an iodinate contrast medium (mean dose, 51.5 ml; range, 0–140 ml; IQR, 0–100 ml). Patients with diminished renal function (n = 33) received no intravenous contrast medium and underwent NC PET/CT (19 at full dose, 14 at low dose).
The diagnostic CT component was set for automatic dose modulation, a mean tube voltage of 115.38 kV (median, 120 kV; IQR, 100–130 kV), a mean effective tube current time product of 154 mAs (median, 146 mAs; IQR, 100–195 mAs), and a collimation of 128 × 0.6 mm. PET scans involved five bed positions with a 256 × 256 matrix size (acquisition time, 2 min per bed position with static frames; 1, 2, 4, 6, 8, and 10 min), iterative reconstruction (3 iterations, 21 subsets), and a Gaussian filter (4 mm). The CT component was used for attenuation correction of the PET component. The effective dose of the CT component was calculated with Monte Carlo Simulation techniques, as previously described [13, 14] and as recommended by International Commission on Radiological Protection (ICRP) Publication 103 [15]. The normalized effective dose of the [18F]FDG PET component was calculated as previously described in [16].
PET/MR Imaging
In accordance with a one-timepoint protocol, we obtained whole-body PET/MRI scans with an integrated 3-Tesla PET/MRI scanner (Biograph mMR, Siemens Healthcare GmbH, Erlangen, Germany) approximately 60 min after intravenous administration of a mean injected activity of 154.6 MBq [18F]FDG (range, 50–290 MBq; IQR, 111–212 MBq). The contrast medium used was Dotarem (gadoterate meglumine). The patients had a mean blood glucose level of 103.6 mg/dl (range, 76–160 mg/dl; IQR, 94.2–107.8 mg/dl). High intensity surface coils were applied. The PET/MRI examinations covered the entire body, from the infraorbital line to the proximal thigh (technical parameters of the standardized whole-body MRI protocol are summarized in Table 1).
Table 1.
Highlighting PET/MRI protocol features: image orientation and slice thickness (mm), time of echo (TE), time of repetition (TR), field of view (FOV), and voxel size
| PET/MR acquisition | |||||
|---|---|---|---|---|---|
| Sequence | Orientation and slice thickness | Time of echo (TE) | Time of repetition (TR) | Field of view (FOVread) | Voxel size |
| 3D Dixon VIBE | Axial 3.5 mm | 1.29 ms | 4.05 ms | 380 mm | 1.2 × 1.2 × 3.5 mm |
| T1-VIBE sequence | Axial 3.5 mm | 1.52 ms | 3.75 ms | 380 mm | 1.2 × 1.2 × 3.5 mm |
| T1-FLASH sequencea | Axial 5 mm | 2.15–3.3 ms | 1510–1700 ms | 380 mm | 1.2 × 1.2 × 3.5 mm |
| T2-HASTE sequence | Axial 5 mm | 117 ms | 1500 ms | 450 mm | 2.6 × 2.6 × 5.0 mm |
| Diffusion-weighted sequencesb | Axial 5 mm | 70.0 ms | 8100 ms | 420 mm | 2.6 × 2.6 × 5.0 mm |
aPre-contrast without fat saturation, post-contrast fat saturated
bb values: 0, 500, 1000
PET data were reconstructed with an iterative reconstruction procedure (3 iterations, 21 subsets) and a Gaussian filter (4 mm). For MR-based scatter correction, PET and 3D Dixon volumetric interpolated breath-hold examination (VIBE) sequences were acquired simultaneously. The normalized effective dose of the [18F]FDG PET component was calculated as previously described [16].
Imaging and Statistical Analysis
Board-certified radiologists and nuclear medicine physicians evaluated the PET/CT and PET/MRI datasets with regard to the clinical question of concern. Findings were assessed by comparison of molecular features in terms of maximum [18F]FDG uptake and morphological changes. The final diagnosis, arrived at after review of the results of clinical, laboratory, histopathologic, bacterial culture, and imaging follow-up findings, served as the reference standard. On the basis of the final diagnosis, the results of each scan were classified as true-negative, true-positive, false-negative, or false-positive. Important diagnostic values (sensitivity, specificity, positive and negative predictive values, and accuracy) were determined for each imaging modality. Exact McNemar statistical test was used to examine diagnostic performance of the CT- and MRI-component alone compared to integrated PET/CT and PET/MRI for diagnosis of infection or malignancy. Explorative and statistical data analyses were performed with SPSS version 19.0 (IBM, New York, NY, USA).
Results
Patient Cohort
Imaging modalities were distributed as follows: CE PET/CT (n = 28), NC PET/CT (n = 33), or PET/MRI (n = 18). All 62 patients were immunocompromised, after receiving lung (11.4%), pancreas (2.5%), heart (7.6%), kidney (57.0%), liver (19.0%), or combined kidney-liver transplants (2.5%), and had a clinically suspected or known malignancy and/or infection. Median time after organ transplantation was 73.51 months (mean 88.62, IQR 13.51–134.89). Integrated PET imaging was performed either to make, support, or confirm a diagnosis (Table 2). Additionally, nine patients underwent a second PET imaging either to follow up or rule out active inflammatory or metabolic active tumor manifestations. One patient received a third PET imaging for follow-up of an adenocarcinoma of the upper lobe, and two patients had a fourth PET imaging for follow-up of PTLD-manifestations (post-transplant lymphoproliferative disorder) (mean time interval between first and second imaging 7.85 months). The mean age of patients in the PET/CT groups was 61.28 years (range, 6–89 years; interquartile range [IQR], 57–69 years), whereas the mean age of patients in the PET/MRI group was 33.22 years (range, 2–77 years; IQR, 14–56 years) (Figs. 1, 2, and 3).
Table 2.
Highlighting patient characteristics: total patient number, age (range), percentage of concurrent and often overlapping symptoms, contrast medium (interquartile range), glucose level (average, range and interquartile range), tracer activity (average, range, and interquartile range)
| Patient characteristics | ||
|---|---|---|
| PET/CT | PET/MRI | |
| Age | 61.28 years (range 6–89 years) | 33.22 years (range 2–77 years) |
| Concurrent and overlapping symptoms |
Reduced general condition (approx. 10%) Chronic fatigue (approx. 24%) Weight loss (approx. 20%) Elevated tumor markers (approx. 22%) Recurrent fever (approx. 28%); Sepsis signs (approx. 13%); Pancytopenia, leucopenia (approx. 3%); Recurrent CRP elevation, unresolved laboratory parameters of infection (13%) |
|
| Administered contrast medium | 51.5 ml (range 0–140 ml; IQR 0–100 ml) iodinate contrast medium | 6.5 ml (range 0–17 ml; IQR 0–11.25 ml) contrast medium administration (Dotarem®) |
| Glucose level | 123,6 mg/dl (range 67–222 mg/dl; IQR 100–138 mg/dl) | 103.6 mg/dl (range 76–160 mg/dl; IQR 94.2–107.8 mg/dl) |
| Administered tracer activity | 266.5 MBq 18F-FDG (range 70–360 MBq; IQR 230–315 MBq) | 154.6 MBq 18F-FDG (range 50–290 MBq; IQR 111–212 MBq) |
Fig. 1.
a–d Highlighting superinfected renal cyst of a patient with polycystic kidney disease on PET, MRI, and unenhanced CT (a–d): a upper left: contrast enhanced, subtracted T1 VIBE sequence delineating vivid enhancement of a renal cyst of the right, polycystic degenerated kidney; b lower left: aligned PET images with peripheral [18F]FDG uptake of the renal cyst; c upper right: contrast-enhanced T1 VIBE sequence without subtraction; d lower right: CT delineating loss of physiological contour of both kidneys with multiple, peripheral calcified cysts
Fig. 2.
a–d Highlighting large paragastral abscess of a patient on PET and CT (a–d): a upper left: unenhanced CT revealing a large, encapsulated fluid collection paragastric; b lower left: aligned PET images with peripheral [18F]FDG uptake of the fluid collection; c upper right: [18F]FDG activity distribution pattern revealing large enhancing formation in the upper abdomen; d lower right: integrated PET/CT confirms the paragastral abscess
Fig. 3.
a–d Highlighting superinfection of the aneurysm sack of the descending, abdominal aorta on PET and CT (a–d): a upper left: arterial phase of CT revealing a large aneurysm sack after aortic stenting; b lower left: aligned PET images with peripheral [18F]FDG uptake of the aneurysm sack; c upper right: venous phase of CT delineating vivid enhancement of the aneurysm sack; d lower right: integrated [18F]FDG PET/CT confirms superinfected aneurysm sack of the abdominal aorta
Imaging Analysis
Our comparison of the three imaging modalities (CE PET/CT, NC PET/CT, and PET/MRI) produced the following results with respect to the final diagnosis. CE PET/CT exhibited a sensitivity of 94.4%, a specificity of 80.0%, a positive predictive value (PPV) of 89.5%, a negative predictive value (NPV) of 88.9%, and an accuracy of 89.3% with regard to the reference standard. NC PET/CT exhibited a sensitivity of 91.3%, a specificity of 80.0%, a PPV of 91.3%, an NPV of 80.0%, and an accuracy of 87.9%. PET/MRI exhibited a sensitivity of 88.5%, a specificity of 99.2%, a PPV of 99.6%, an NPV of 81.3%, and an accuracy of 94.4%. Exact McNemar statistical test (one-sided) showed significant difference between the CT-/MR-component alone and the integrated PET/CT and PET/MRI for diagnosis of malignancy or infection (p value < 0.001). Table 3 summarizes findings and total lesion counts for PET/CT and PET/MRI.
Table 3.
Highlighting findings for both modalities, PET/CT and PET/MRI: acquisition time, total lesion count differentiated according to (i) infectious focus and (ii) malignancy
| PET/CT | PET/MRI | |
|---|---|---|
| Acquisition time-point after tracer injection | 76 min (60–130) | 167 min (90–250) |
| Infectious focus | ||
| Respiratory system | Pneumonia 4 | |
| Gastrointestinal system |
Ileitis terminalis 1 Parastomal abscess 1 Diverticulitis 1 |
|
| Genitourinary system | Transplant pyelonephritis 1 Superinfected renal cyst 1 | |
| Vessels | Superinfected aortic aneurysm 1 | |
| Skeletal system and soft tissue |
Osteomyelitis 2, Phlegmon 1, Spondylodiscitis 1 |
|
| Hepatobiliary system | Ischemic type biliary lesions 1 | Primary sclerosing cholangitis 1 |
| Installation | Superinfected biliary stent 1, Superinfected central venous catheter 1 | |
| Malignancy | ||
| Respiratory system |
Pulmonal metastases 4 Lung cancer 3 Pleuramesothelioma 1 |
|
| Gastrointestinal system | Stomach cancer 1 | |
| Post-transplant lymphoproliferative disorder and lymphoma | PTLD 1 | PTLD 4 |
| Hepatobiliary system | Hepatocellular carcinoma 4 | |
| Breast and genitourinary tract | Breast cancer 1 and genitourinary 3 | |
| Skeletal system and soft tissue | Osseous metastases 1 | |
| Cancer of unknown primary | Ovarian metastasis 1 | |
Radiation Exposure
Radiation exposure was 4- to 7-fold higher with PET/CT than with PET/MRI. The mean effective dose of the CT component of PET/CT was distributed as follows: full dose for CE PET/CT, 15.7 mSv (median, 13.8 mSv; IQR, 11.8–19.2 mSv); full dose for NC PET/CT, 12.5 mSv (median, 12.0 mSv; IQR, 9.2–14.6 mSv); low dose for NC PET/CT, 1.8 mSv (median, 1.7 mSv; IQR, 1.4–2.0 mSv). The mean effective dose of the PET component of PET/CT was 5.07 mSv (Table 4). Whole-body full-dose PET/CT delivered a mean effective dose ranging from 17.5 to 20.7 mSv for adults. PET/MRI delivered a mean effective dose of 4.7 mSv for 2-year-old, 2.8 mSv for 10-year-old, 2.9 mSv for a 15-year-old, and 4.0 mSv for adults.
Table 4.
Highlighting mean effective dose for adults undergoing whole body [18F]FDG PET/CT and [18F]FDG PET/MRI imaging (from left to right): [18F]FDG PET-component of the PET/CT, full dose contrast-enhanced PET/CT, full dose non-contrast-enhanced PET/CT, low dose non-contrast-enhanced PET/CT, [18F]FDG PET-component of the PET/MRI
| Whole body [18F]FDG PET/CT | [18F]FDG PET/MRI | |||||
|---|---|---|---|---|---|---|
| PET-component | Full dose CE CT-component | Full dose NC CT-component | Low dose NC CT-component | PET-component | MRI-component | |
| Mean effective dose | 5.07 mSv | 15.7 mSv | 12.5 mSv | 1.8 mSv | 4.0 mSv | Not applicable |
Discussion
In terms of inflammatory processes, operation-associated and nosocomial acquired infections represent the most frequent complications in the early postoperative phase until about 30 days after transplantation. The second phase of about 1 to 12 months after transplantation is characterized by the occurrence of opportunistic infections. More than 1 year after transplantation, assuming that the transplant functions well, the pattern of infections is more similar to that of the general population [17, 18]. The association between infectious (especially viral) complications and malignancies after transplantation is well established, for human papillomaviruses and cervical and vulvar carcinoma, for EBV and post transplantation lymphoproliferative disorder (PTLD), for hepatitis B and C virus infection and hepatocellular carcinoma, as well as for human herpes virus-8 and Kaposi’s sarcoma [19, 20]. In addition, patients with chronic renal disease display an increased risk for the development of malignancies. Tumors of the urogenital tract and in particular renal cell carcinoma are among the most frequently encountered. Under the influence of immunosuppression pre-transplantation, malignancies may relapse, thus, making close monitoring mandatory. Regarding the timeline, post transplantation lymphoproliferative disorder (PTLD) generally occurs early after transplantation whereas skin cancers occur with increasing frequency with time. The present study examined the clinical utility of CE [18F]FDG PET/CT, NC [18F]FDG PET/CT, and [18F]FDG PET/MRI in patients with suspected malignancy or infection as well as to rule out vital tumor or metabolic active inflammatory processes after solid organ transplant. Our results confirm that both CE PET/CT and NC PET/CT are robust techniques for detecting malignancy and assessing the origin of infection among immunocompromised patients after solid-organ transplant (Table 5). PET/CT combines several favorable features, such as high sensitivity and high-resolution images that can rule out serious complications. Integrated PET/MRI may further enhance the precise delineation of physiologic changes, the evaluation of a transplanted organ, and the detection of signs of rejection.
Table 5.
Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for examined modalities, contrast (CE) PET/CT, non-contrast (NC) PET/CT, and PET/MRI
| CE-PET/CT | NC-PET/CT | PET/MRI | |
|---|---|---|---|
| Sensitivity | 94.4% | 91.3% | 88.6% |
| Specificity | 80.0% | 80.0% | 99.2% |
| Positive predictive value (PPV) | 89.5% | 91.3% | 99.6% |
| Negative predictive value (NPV) | 88.9% | 80.0% | 81.3% |
| Accuracy | 89.3% | 87.9% | 94.4% |
Typically, for focus assessment, an intravenous contrast medium is used to improve diagnostic performance. Other authors have described the potential benefits of using an intravenous contrast medium for [18F]FDG PET/CT [21]. Contrast medium improves the differentiation of anatomic structures, the localization of lesions, and the characterization of those lesions [22]. However, intravenous contrast medium may be critical, in particular when renal function is diminished.
A contrast medium is a drug, and like other drugs, it involves not only desirable effects but also undesirable adverse effects [22]. The present position of the American College of Radiology (ACR) Committee on Drugs and Contrast Media is that contrast-induced nephropathy (CIN) is a rare but real entity [22]. In the past, published studies of CIN have been heavily criticized for bias and conflation [22]. Prospective studies aimed at resolving this problem are anticipated.
Our present results show that, because of the synergy of morphologic and metabolic images, diagnostic NC PET/CT may be used for patients with comprised renal function without crucial loss of key diagnostic information. Apparently, when used with NC CT, the PET component may increase diagnostic confidence and may even serve as a contrast medium. The advantage of PET/MRI is that provided by the MR component: better soft tissue contrast, principally for the delineation of pathology of the soft tissue, joints, and spine. Diagnostic PET/CT is associated with a 4- to 7-fold higher exposure to radiation than PET/MRI. Radiation exposure is important, particularly when young patients or children are undergoing scans.
This retrospective study comprises several limitations. Our low number of cases with false-positive results may be attributed to the thorough clinical examinations that preceded the imaging studies. Nonetheless, both PET/CT and PET/MRI may yield false-positive results and thus may necessitate the performance of additional and unnecessary diagnostic tests. A study by Cheng et al. has suggested that a dual-timepoint protocol may allow for better discrimination between malignancy and inflammation [23]. However, several studies have shown that [18F]FDG PET cannot differentiate between malignant and inflammatory processes on the basis of differences in metabolic rates [24, 25]. Last but not least, PET/CT and PET/MRI are not available in all regions because they require highly specific technology and many resources. The future will show us whether the benefits of PET/MRI can outweigh the challenges of attenuation correction, considerably longer examination times, low MRI sensitivity for pulmonary processes, and lack of region-wide familiarity with the technology [10].
Conclusion
For immunocompromised patients, both [18F]FDG PET/CT and [18F]FDG PET/MRI are beneficial in evaluating clinically unresolved symptoms and exhibit a high diagnostic performance in assessing malignancy or infection. Recipients of organ transplants may benefit from [18F]FDG PET/MRI because of its considerably lower level of radiation exposure than that associated with [18F]FDG PET/CT.
Acknowledgments
Acknowledgments to Prof. Bockisch.
Authors’ Contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Nika Guberina and Hana Rohn. The first draft of the manuscript was written by Nika Guberina and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of Interest
Nika Guberina, Anja Gäckler, Johannes Grueneisen, Axel Wetter, Oliver Witzke, Ken Herrmann, Christoph Rischpler, Wolfgang Fendler, Lale Umutlu, Lino Morris Sawicki, Michael Forsting and Hana Rohn declare that they have no conflict of interest. There is no source of funding.
Ethical Statement
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
Informed Consent
The institutional review board of our institute approved this retrospective study, and the requirement to obtain informed consent was waived.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Nika Guberina, Email: Nika.Guberina@uk-essen.de.
Anja Gäckler, Email: Anja.Gaeckler@uk-essen.de.
Johannes Grueneisen, Email: Johannes.Grueneisen@uk-essen.de.
Axel Wetter, Email: Axel.Wetter@uk-essen.de.
Oliver Witzke, Email: Oliver.Witzke@uk-essen.de.
Ken Herrmann, Email: Ken.Herrmann@uk-essen.de.
Christoph Rischpler, Email: Christoph.Rischpler@uk-essen.de.
Wolfgang Fendler, Email: Wolfgang.Fendler@uk-essen.de.
Lale Umutlu, Email: Lale.Umutlu@uk-essen.de.
Lino Morris Sawicki, Email: LinoMorris.Sawicki@med.uni-duesseldorf.de.
Michael Forsting, Email: Michael.Forsting@uk-essen.de.
Hana Rohn, Email: Hana.Rohn@uk-essen.de.
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