Publications by authors named "Konstantin Nikolaou"

452 Publications

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease.

JACC Cardiovasc Imaging 2021 Sep 8. Epub 2021 Sep 8.

Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Cardiology, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands; Stanford University School of Medicine and Cardiovascular Institute, Stanford, California, USA. Electronic address:

Objectives: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).

Background: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies.

Methods: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics.

Results: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91-100), 72% (95% CI: 66-78), and 78% (95% CI: 73-83), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75-92) but higher specificity (89%; 95% CI: 85-93) and accuracy (88%; 95% CI: 84-92). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively.

Conclusions: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795).
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http://dx.doi.org/10.1016/j.jcmg.2021.07.021DOI Listing
September 2021

A novel approach for radiotherapy dose escalation in rectal cancer using online MR-guidance and rectal ultrasound gel filling - Rationale and First in human.

Radiother Oncol 2021 Sep 14. Epub 2021 Sep 14.

Section for Biomedical Physics. Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Germany.

Introduction: Dose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling.

Methods: A 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied.

Results: Based on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four.

Conclusion: This novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.
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http://dx.doi.org/10.1016/j.radonc.2021.09.002DOI Listing
September 2021

Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma.

NPJ Precis Oncol 2021 Sep 3;5(1):80. Epub 2021 Sep 3.

Department of Internal Medicine I, Eberhard-Karls University, Tübingen, Germany.

Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.
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http://dx.doi.org/10.1038/s41698-021-00220-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417271PMC
September 2021

Fluid-based augmentation of magnetic resonance visualization of interventional devices.

J Appl Clin Med Phys 2021 Aug 28. Epub 2021 Aug 28.

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

Purpose: To evaluate the transient artifact augmentation of microtubes in magnetic resonance imaging by fluid injection.

Methods: Twenty-one fluorinated ethylene propylene catheters (inner diameter 760 μm) were filled with three different contrast media at various concentrations (Ferucarbotran, Resovist®, Bayer Schering Pharma; Manganese dichloride, MnCl2, Sigma-Aldrich; Gadobutrol, Gadovist®, Bayer Schering Pharma). Artifact appearance was determined in an ex vivo phantom at 1.5 T using three different sequences: T1-weighted three-dimensional volume interpolated breath-hold examination, T2-weighted turbo spin echo, and T1-weighted fast low angle shot. Catheter angulation to the main magnetic field (B0) was varied. Influence of parameters on artifact diameters was assessed with a multiple linear regression similar to an analysis of variance.

Results: Artifact diameter was significantly influenced by the contrast agent (p < 0.001), concentration of the contrast agent (p < 0.001), angulation of the phantom to B0 with the largest artifact at 90° (p < 0.001), and encoding direction with a larger diameter in phase encoding direction (PED, p < 0.001). Mean artifact diameters at 90° angulation to B0 in PED were 18.5 ± 5.4 mm in 0.5 mmol/ml Ferucarbotran, 8.7 ± 2.5 mm in 1 mmol/ml Gadobutrol, and 11.6 ± 4.6 mm in 5 mmol/ml MnCl .

Conclusions: Fluid-based contrast agents might be applied to interventional devices and thus temporarily augment the artifact ensuring both visibility and safe navigation.
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http://dx.doi.org/10.1002/acm2.13407DOI Listing
August 2021

1.5 vs 3 Tesla Magnetic Resonance Imaging: A Review of Favorite Clinical Applications for Both Field Strengths-Part 2.

Invest Radiol 2021 Aug 19. Epub 2021 Aug 19.

From the Clinic for Diagnostic and Interventional Neuroradiology, University Hospital Bonn, Bonn Department of Radiology, Diagnostic and Interventional Radiology, University of Tübingen, Tübingen Clinic for Diagnostic and Interventional Radiology, University Hospital Bonn, Bonn Department of Neuroradiology, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.

Abstract: The second part of this review deals with experiences in neuroradiological and pediatric examinations using modern magnetic resonance imaging systems with 1.5 T and 3 T, with special attention paid to experiences in pediatric cardiac imaging. In addition, whole-body examinations, which are widely used for diagnostic purposes in systemic diseases, are compared with respect to the image quality obtained in different body parts at both field strengths. A systematic overview of the technical differences at 1.5 T and 3 T has been presented in part 1 of this review, as well as several organ-based magnetic resonance imaging applications including musculoskeletal imaging, abdominal imaging, and prostate diagnostics.
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http://dx.doi.org/10.1097/RLI.0000000000000818DOI Listing
August 2021

Robotic Transrectal Computed Tomographic Ultrasound with Artificial Neural Network Analysis: First Validation and Comparison with MRI-Guided Biopsies and Radical Prostatectomy.

Urol Int 2021 Aug 17:1-7. Epub 2021 Aug 17.

Department of Urology, Eberhard Karls University, Tübingen, Germany.

Introduction: There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA).

Methods: Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA.

Results: In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%).

Conclusions: The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.
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http://dx.doi.org/10.1159/000517674DOI Listing
August 2021

Diagnostic Performance of a Contrast-Enhanced Ultra-Low-Dose High-Pitch CT Protocol with Reduced Scan Range for Detection of Pulmonary Embolisms.

Diagnostics (Basel) 2021 Jul 13;11(7). Epub 2021 Jul 13.

Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, 72076 Tuebingen, Germany.

(1) Background: To evaluate the diagnostic performance of a simulated ultra-low-dose (ULD), high-pitch computed tomography pulmonary angiography (CTPA) protocol with low tube current (mAs) and reduced scan range for detection of pulmonary embolisms (PE). (2) Methods: We retrospectively included 130 consecutive patients (64 ± 16 years, 69 female) who underwent clinically indicated high-pitch CTPA examination for suspected acute PE on a 3rd generation dual-source CT scanner (SOMATOM FORCE, Siemens Healthineers, Forchheim, Germany). ULD datasets with a realistic simulation of 25% mAs, reduced scan range (aortic arch-basal pericardium), and Advanced Modeled Iterative Reconstruction (ADMIRE®, Siemens Healthineers, Forchheim, Germany) strength 5 were created. The effective radiation dose (ED) of both datasets (standard and ULD) was estimated using a dedicated dosimetry software solution. Subjective image quality and diagnostic confidence were evaluated independently by three reviewers using a 5-point Likert scale. Objective image quality was compared using noise measurements. For assessment of diagnostic accuracy, patients and pulmonary vessels were reviewed binarily for affection by PE, using standard CTPA protocol datasets as the reference standard. Percentual affection of pulmonary vessels by PE was computed for disease severity (modified Qanadli score). (3) Results: Mean ED in ULD protocol was 0.7 ± 0.3 mSv (16% of standard protocol: 4.3 ± 1.7 mSv, < 0.001, > 0.5). Comparing ULD to standard protocol, subjective image quality and diagnostic confidence were comparably good ( = 0.486, > 0.5) and image noise was significantly lower in ULD ( < 0.001, > 0.5). A total of 42 patients (32.2%) were affected by PE. ULD protocol had a segment-based false-negative rate of only 0.1%. Sensitivity for detection of any PE was 98.9% (95% CI, 97.2-99.7%), specificity was 100% (95% CI, 99.8-100%), and overall accuracy was 99.9% (95% CI, 98.6-100%). Diagnoses correlated strongly between ULD and standard protocol (Chi-square (1) = 42, < 0.001) with a decrease in disease severity of only 0.48% (T = 1.667, = 0.103). (4) Conclusions: Compared to a standard CTPA protocol, the proposed ULD protocol proved reliable in detecting and ruling out acute PE with good levels of image quality and diagnostic confidence, as well as significantly lower image noise, at 0.7 ± 0.3 mSv (84% dose reduction).
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http://dx.doi.org/10.3390/diagnostics11071251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304674PMC
July 2021

Editorial for "Histopathological Validation of Dark-Blood Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Without Additional Magnetization Preparation".

J Magn Reson Imaging 2021 Jul 27. Epub 2021 Jul 27.

Department of Radiology, University of Tübingen, Tübingen, 72076, Germany.

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http://dx.doi.org/10.1002/jmri.27855DOI Listing
July 2021

Contrast-enhanced MRI for simultaneous evaluation of renal morphology and split renal function in living kidney donor candidates.

Eur J Radiol 2021 Sep 13;142:109864. Epub 2021 Jul 13.

Department of Internal Medicine IV, Section of Nephrology and Hypertension, University of Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.

Purpose: The evaluation process of potential living kidney donors focusses on renal anatomy and split renal function. This study aimed to evaluate a magnetic resonance imaging (MRI)-based approach for simultaneous evaluation of both and its impact on clinical decision making.

Method: Over a 3-year period, 65 potential living kidney donors were consecutively enrolled. The MRI protocol was extended by MR-nephrography to measure split renal function. Standard DTPA-scintigraphy was used for functional comparison.

Results: Split renal function showed no systematic bias between the two methods (mean difference 0.3%, p = 0.08). Both methods would have yielded the same clinical decision for donor nephrectomy in 75% of the patients. In 25 % of the patients, one method indicated a relevant side difference while the other did not, and a different clinical decision could have been made based on split renal function alone.

Conclusions: MRI proved eligible for comprehensive living kidney donor evaluation and non-inferior to scintigraphy for determining split renal function. In clinical decision making, these two methods would have resulted in the same side for donor nephrectomy in a large proportion of potential donors. Whether MRN will be implemented in clinical practice depends on transplant centre infrastructure and policy.
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http://dx.doi.org/10.1016/j.ejrad.2021.109864DOI Listing
September 2021

Accelerated T2-Weighted TSE Imaging of the Prostate Using Deep Learning Image Reconstruction: A Prospective Comparison with Standard T2-Weighted TSE Imaging.

Cancers (Basel) 2021 Jul 17;13(14). Epub 2021 Jul 17.

Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Straße 3, 72076 Tuebingen, Germany.

Multiparametric MRI (mpMRI) of the prostate has become the standard of care in prostate cancer evaluation. Recently, deep learning image reconstruction (DLR) methods have been introduced with promising results regarding scan acceleration. Therefore, the aim of this study was to investigate the impact of deep learning image reconstruction (DLR) in a shortened acquisition process of T2-weighted TSE imaging, regarding the image quality and diagnostic confidence, as well as PI-RADS and T2 scoring, as compared to standard T2 TSE imaging. Sixty patients undergoing 3T mpMRI for the evaluation of prostate cancer were prospectively enrolled in this institutional review board-approved study between October 2020 and March 2021. After the acquisition of standard T2 TSE imaging (T2), the novel T2 TSE sequence with DLR (T2) was applied in three planes. Overall, the acquisition time for T2 resulted in 10:21 min versus 3:50 min for T2. The image evaluation was performed by two radiologists independently using a Likert scale ranging from 1-4 (4 best) applying the following criteria: noise levels, artifacts, overall image quality, diagnostic confidence, and lesion conspicuity. Additionally, T2 and PI-RADS scoring were performed. The mean patient age was 69 ± 9 years (range, 49-85 years). The noise levels and the extent of the artifacts were evaluated to be significantly improved in T2 versus T2 by both readers ( < 0.05). Overall image quality was also evaluated to be superior in T2 versus T2 in all three acquisition planes ( = 0.005-<0.001). Both readers evaluated the item lesion conspicuity to be superior in T2 with a median of 4 versus a median of 3 in T2 ( = 0.001 and <0.001, respectively). T2-weighted TSE imaging of the prostate in three planes with an acquisition time reduction of more than 60% including DLR is feasible with a significant improvement of image quality.
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http://dx.doi.org/10.3390/cancers13143593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303682PMC
July 2021

[Primary treatment of prostate cancer using 1.5 T MR-linear accelerator].

Radiologe 2021 Sep 23;61(9):839-845. Epub 2021 Jul 23.

Klinik für Radioonkologie und Strahlentherapie, Ludwigsburg, Deutschland.

Background: Hybrid devices of MR-scanners and linear accelerators (MR-Linacs) represent a new and promising extension of radiotherapeutic options for prostate cancer. The potential advantage of magnetic resonance imaging (MRI) over computed tomography (CT) for soft tissue contrast is well-known and leads to more consistent and smaller target volumes and improved normal tissue sparing.

Objectives: This article presents an overview of clinical experience, indications, advantages and challenges of utilizing a 1.5 T MR-Linac in the setting of radiotherapy of prostate cancer.

Results: All current indications for radiotherapy of prostate cancer can be treated with an MR-Linac. The advantages include daily MR-based imaging in treatment position and daily adaption of the treatment plan on current anatomy (adaptive radiotherapy). Additionally, functional MRI sequences might be exploited to enhance treatment individualization and response assessment. Ultimately treatment on an MR-Linac might further increase the therapeutic window. The limitations of using MR-Linac include treatment complexity and the duration of each session.

Conclusions: MR-Linacs expand the spectrum of radiotherapeutic options for prostate cancer. Increased precision can be reached with daily MRI-based target volume definition and plan adaption. Clinical studies are necessary to identify patient groups who would benefit most from radiotherapy on a MR-Linac.
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http://dx.doi.org/10.1007/s00117-021-00882-8DOI Listing
September 2021

Impact of F-FDG-PET/CT on Clinical Management in Patients with Cholangiocellular Carcinoma.

BJR Open 2021 5;3(1):20210008. Epub 2021 Jul 5.

Department of Radiology, Diagnostic and Interventional Radiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany.

Objective: To determine the impact of F-FDG-PET/CT on clinical management of patients with cholangiocellular carcinoma (CCA).

Methods: Patients with CCA undergoing clinically indicated F-FDG-PET/CT between 04/2013 and 08/2018 were prospectively included in a local PET/CT registry study. Intended clinical management ("non-treatment" such as watchful-waiting or additional diagnostic tests, and "palliative" or "curative treatment") was recorded before and after PET/CT. Changes in intended management after PET/CT were analyzed.

Results: 27 patients (mean age: 60 years, IQR: 51.5-67.5 years, 56% males) with 43 PET/CT examinations were included. Intended management changed in 35/43 cases (81.4%) following PET/CT. Major changes ( between "non-treatment" and "treatment" strategies or between a "curative" and "palliative" treatment goal) occurred in 27/43 (62.8%) cases. Before PET/CT, additional imaging and/or biopsy were intended in 21/43 (48.8%) and 9/43 (20.9%) cases, respectively. After PET/CT, further imaging was carried out in one case and imaging-targeted biopsy in eight cases. Although the absolute number of biopsies after PET/CT did not decrease, in only one of these eight cases biopsy had already been planned before PET/CT, whereas in the other eight cases, the originally planned biopsies were dispensable after PET/CT.

Conclusions: F-FDG-PET/CT significantly impacts clinical management of patients with CCA. It guides decisions on treatment strategy (especially curative palliative treatment goal) and on additional tests, particularly by helping referring clinicians to avoid unnecessary imaging and by guiding targeted biopsy.

Advances In Knowledge: Systematic implementation of F-FDG-PET/CT may enable a more appropriate and tailored treatment of patients with CCA, especially in cases of suspected recurrence.
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http://dx.doi.org/10.1259/bjro.20210008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256695PMC
July 2021

F-Fluoride PET/CT Imaging of Medication-Related Osteonecrosis of the Jaw in Conservative Treatment-A Case Report.

Front Oncol 2021 1;11:700397. Epub 2021 Jul 1.

Department of Oral and Maxillofacial Surgery, University Hospital of Tübingen, Tübingen, Germany.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect in antiresorptive treatment. Treatment of MRONJ is considered primarily conservative with oral mouth rinses and antibiotics but may demand surgery, depending on the complaints and general condition of the patient, the extent of the necrosis, and the overall prognosis with respect to the underlying disease. A 77 year old female patient with invasive ductal breast cancer and bone metastases was treated with intravenous bisphosphonate (BP) zoledronic acid. During therapy, she developed MRONJ in the mandible with severe pain. Clinical examination revealed confluent exposed bone of the lower left jaw and a fistula at the right molar region. The panoramic radiograph revealed a mandibular osseous involvement with diffuse radiopaque areas between radiolucent areas. For preoperative planning, F-fluoride positron emission tomography/computed tomography (PET/CT) of the jaw was performed, showing substantially increased F-fluoride uptake in regions 38 to 47 of the mandible with a focal gap in region 36 (area of clinically exposed bone). CT revealed medullary sclerosis and cortical thickening with confluent periosteal reaction and focal cortical erosion in the regions 37 to 42, whereas the regions 43 to 47 were only subtly sclerotic without cortical thickening. After systemic antibiotic therapy with sultamicillin following significant symptom and pain relief, F-fluoride PET/CT imaging was performed again after 5 months. No changes in either CT and PET were observed in regions 38 to 42, whereas the bony sclerosis was slightly increased in regions 43 to 47 with a slight reduction of F-fluoride uptake. F-fluoride PET/CT showed no significant changes assessing the extent of MRONJ prior and after systemic antibiotic therapy, providing no evidence that conservative treatment reduced the extent of the MRONJ-affected jawbone. The additional information of F-fluoride PET enables to identify the true extent of MRONJ which may be underestimated by CT imaging alone. Patients with MRONJ undergoing conservative treatment could benefit because additional imaging may be avoided as the pre-therapeutic F-fluoride PET/CT delivers all information needed for further treatment. Our findings support the recommendation of a surgical approach as long-term antibiotics cannot downsize the extent of MRONJ.
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http://dx.doi.org/10.3389/fonc.2021.700397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281890PMC
July 2021

Quantification of liver and muscular fat using contrast-enhanced Dual Source Dual Energy Computed Tomography compared to an established multi-echo Dixon MRI sequence.

Eur J Radiol 2021 Sep 6;142:109845. Epub 2021 Jul 6.

Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Tuebingen, Germany. Electronic address:

Purpose: To investigate the feasibility of liver fat quantification in contrast-enhanced dual source dual energy computed tomography (DECT) using multi-echo Dixon magnetic resonance imaging (MRI) as reference standard.

Method: Patients who underwent MRI of the liver including a multi-echo Dixon sequence for estimation of proton density fat fraction in 2017 as well as contrast-enhanced DECT imaging of the abdomen were included in this retrospective, monocentric IRB approved study. Furthermore, patients with a hepatic fat amount >5% who were examined in 2018 with MRI and DECT were included. The final study group consisted of 81 patients with 90 pairs of examinations. Analysis of parameter maps was performed manually using congruent regions of interest which were placed in the liver parenchyma, in the erector spinae muscles, and psoas major muscles.

Results: Mean patient age was 61 ± 13 years. Median time between MRI and DECT was 48 days. MRI liver fat quantification resulted in a median of 3.8% (IQR: 2.2-8.2%) compared to 1.8% (IQR: 0-6.3%) in DECT (p < 0.001), with a Spearman correlation of 0.73. Bland-Altman analysis resulted in a systematic underestimation of liver fat in DECT, with a mean difference of -1.7%. Fat quantification in the erector spinae muscles (p = 0.257) and the psoas major muscles (p = 0.208) was not significantly different in DECT compared to MRI.

Conclusions: Liver and muscular fat quantification in portal-venous phase DECT is feasible with good to excellent correlation compared to a multi-echo Dixon MRI sequence analysis. While there is an underestimation of the liver fat content in DECT, there are no significant differences between DECT and MRI fat quantification of the erector spinae and psoas major muscles.
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http://dx.doi.org/10.1016/j.ejrad.2021.109845DOI Listing
September 2021

Intravascular Application of Labelled Cell Spheroids: An Approach for Ischemic Peripheral Artery Disease.

Int J Mol Sci 2021 Jun 25;22(13). Epub 2021 Jun 25.

Department of Diagnostic and Interventional Radiology, University Hospital of Tübingen, D-72076 Tübingen, Germany.

Mesenchymal stem cells (MSC) are known for their vascular regeneration capacity by neoangiogenesis. Even though, several delivery approaches exist, particularly in the case of intravascular delivery, only limited number of cells reach the targeted tissue and are not able to remain on site. Applicated cells exhibit poor survival accompanied with a loss of functionality. Moreover, cell application techniques lead to cell death and impede the overall MSC function and survival. 3D cell spheroids mimic the physiological microenvironment, thus, overcoming these limitations. Therefore, in this study we aimed to evaluate and assess the feasibility of 3D MSCs spheroids for endovascular application, for treatment of ischemic peripheral vascular pathologies. Multicellular 3D MSC spheroids were generated at different cell seeding densities, labelled with ultra-small particles of iron oxide (USPIO) and investigated in vitro in terms of morphology, size distribution, mechanical stability as well as ex vivo with magnetic resonance imaging (MRI) to assess their trackability and distribution. Generated 3D spheroids were stable, viable, maintained stem cell phenotype and were easily trackable and visualized via MRI. MSC 3D spheroids are suitable candidates for endovascular delivery approaches in the context of ischemic peripheral vascular pathologies.
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http://dx.doi.org/10.3390/ijms22136831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269343PMC
June 2021

Correction to: Forensic age estimation in living adolescents with CT imaging of the clavicula-impact of low-dose scanning on readers' confidence.

Eur Radiol 2021 Jun 22. Epub 2021 Jun 22.

Department of Diagnostic and Interventional Radiology, University Hospital Tuebingen, Hoppe-Seyler-Straße 3, 72076, Tuebingen, Germany.

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http://dx.doi.org/10.1007/s00330-021-08111-5DOI Listing
June 2021

Correlation between thoracolumbar disc degeneration and anatomical spinopelvic parameters in supine position on MRI.

PLoS One 2021 9;16(6):e0252385. Epub 2021 Jun 9.

Department for Trauma and Reconstructive Surgery, BG Unfallklinik Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.

Objective: This study aims to investigate the correlation between spinopelvic parameters in supine position (pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)), disc degeneration and herniation of the thoracolumbar spine, as well as cardiovascular risk factors and back pain in a southern German cohort from the general population.

Methods: This study is a cross-sectional, case-control study drawn from a prospective cohort of the "Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg" study (KORA). In total, 374 participants (mean age 56.4 ± 9.2 years; 57.8% male) from the whole-body MRI cohort (FF4) were included. All participants underwent a standardized whole-body MRI on which disc degeneration of the thoracic and lumbar spine was evaluated using a sequence adapted Pfirrmann score. PI, PT, SS and LL were measured according to the description in the literature, using sagittal imaging. Furthermore, disc bulging and protrusion were assessed. Correlations were estimated by logistic regression models providing odds ratios.

Results: Mean PI was 54.0° ± 11.1°, PT 13.0° ± 5.8°, SS 40.2° ± 8.8° and LL 36.2° ± 9.6°. SS was greater in men (p<0.05) and lumbar lordosis in women (p<0.001). PT increased by 0.09° per age-year with rising age. Age was not associated with PI, SS and LL. Neither BMI, hypertension, cholesterol, lipid levels, nor physical activity were associated with PI, PT, SS or LL. Diabetes mellitus negatively correlated with SS (β = -4.19; 95%CI -7.31-1.06, p<0.01). Smaller spinopelvic parameters (PI, SS and LL) where significantly (p<0.05) correlated with an increased frequency of disc bulging, as well as a local clustering in the lumbar, but not the thoracic spine.

Conclusion: In conclusion, spinopelvic parameters, measured in supine position, are significantly correlated with disc bulging alone; there is no significant correlation between supine spinopelvic parameters and disc degeneration, back pain or cardiovascular risk factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252385PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189447PMC
June 2021

Prevalence of pathological FFR values without coronary artery stenosis in an asymptomatic marathon runner cohort.

Eur Radiol 2021 May 26. Epub 2021 May 26.

Department of Diagnostic and Interventional Radiology, University of Tuebingen, Tübingen, Germany.

Objectives: To evaluate computed tomography fractional flow reserve (FFR) values in distal parts of the coronaries in an asymptomatic cohort of marathon runners without any coronary stenosis for potentially false-positive values.

Methods: Ninety-eight asymptomatic male marathon runners (age 53 ± 7 years) were enrolled in a prospective monocentric study and underwent coronary computed tomography angiography (CCTA). CCTA data were analyzed for visual coronary artery stenosis. FFR was evaluated in 59 participants without coronary artery stenosis in proximal, mid, and distal coronary sections using an on-site software prototype.

Results: In participants without coronary artery stenosis, abnormal FFR values ≤ 0.8 in distal segments were found in 22 participants (37%); in 19 participants in the LAD; in 5 participants in the LCX; and in 4 participants in the RCA. Vessel diameters in participants with FFR values > 0.80 compared to ≤ 0.80 were 1.6 ± 0.3 mm versus 1.5 ± 0.3 mm for distal LAD (p = 0.025), 1.8 ± 0.3 mm versus 1.6 ± 0.5 mm for distal LCX (p = 0.183), and 2.0 ± 0.4 mm versus 1.5 ± 0.2 mm for distal RCA (p < 0.001).

Conclusions: Abnormal FFR values of ≤ 0.8 frequently occurred in distal coronary segments in subjects without any anatomical coronary artery stenosis. This effect is only to some degree explainable by small distal vessel diameters. Therefore, the validity of hemodynamic relevance evaluation using FFR in distal coronary artery segment stenosis is reduced.

Key Points: • Abnormal FFR values (≤ 0.8) occurred in over a third of the subjects in the distal LAD despite the absence of coronary artery stenosis.. • Therefore, the validity of hemodynamic relevance evaluation in distal coronary artery segment stenosis is reduced. • Decision-making based on abnormal FFR values in distal vessel sections should be performed with caution and only in combination with visual assessment of the grade of stenosis..
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http://dx.doi.org/10.1007/s00330-021-08027-0DOI Listing
May 2021

Efficacy and tolerability of chemosaturation in patients with hepatic metastases from uveal melanoma.

Acta Radiol 2021 May 25:2841851211019808. Epub 2021 May 25.

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

Background: Patients with hepatic metastatic uveal melanoma still have a poor outcome.

Purpose: To evaluate overall survival (OS), progression-free survival (PFS), and response predictors in these patients treated with chemosaturation by percutaneous hepatic perfusion with melphalan (CS-PHP).

Material And Methods: Between June 2015 and March 2020, a total of 29 patients (median age 69.7 years; age range 30-81 years; 60% women; median BMI 25.7 kg/m; range 18.7-35.3kg/m; 1-6 procedures per patient) were treated with 53 CS-PHPs. All patients received cross-sectional imaging for initial and follow-up examinations. Baseline tumor load, extrahepatic tumor load, tumor response, PFS, and OS were assessed. Non-parametric statistics were used.

Results: After the initial CS-PHP, a partial response was observed in 11 patients (41%), stable disease in 12 patients (44%) and progressive disease in 4 patients (15%); two patients died before the response was evaluated. After initial CS-PHP, median OS was 12.9 ± 7.4 months and median PFS was 7.1 ± 7.4 months. OS after one year was 50%. After the second CS-PHP, median PFS was 7.9 ± 5.7 months. Seven patients had a liver tumor burden >25%, associated with a significantly shorter OS (6.0 ± 2.4 vs. 14.1 ± 12.7 months;  = 0.008). At the time of first CS-PHP, 41% (12/29) of the patients had extrahepatic metastases that did not affect OS (11.1 ± 8.4 months vs. 12.9 ± 13.6 months;  = 0.66).

Conclusion: CS-PHP is a safe and effective treatment for the hepatic metastatic uveal melanoma, especially for patients with a hepatic tumor burden <25%.
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http://dx.doi.org/10.1177/02841851211019808DOI Listing
May 2021

Transarterial Chemoembolization of Hepatocellular Carcinoma Using Radiopaque Drug-Eluting Embolics: Impact of Embolic Density and Residual Tumor Perfusion on Tumor Recurrence and Survival.

Cardiovasc Intervent Radiol 2021 Sep 21;44(9):1403-1413. Epub 2021 May 21.

Department of Diagnostic and Interventional Radiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany.

Purpose: To evaluate the value of dual-phase parenchymal blood volume (PBV) C-arm mounted cone-beam-CT (CBCT) to enable assessment of radiopaque, doxorubicin-loaded drug-eluting embolics (rDEE) based on the visual degree of embolization, embolic density and residual tumor perfusion as early predictors for tumor recurrence after transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC).

Material And Methods: Thirty patients (50 HCCs) were prospectively enrolled, underwent cross-sectional imaging before and after TACE using 100-300 µm rDEE and had regular follow-up examinations. Directly before and after the TACE procedure, PBV-CBCT was acquired. The response was evaluated and compared to visual degree of embolization (DE) and embolic density (ED) of rDEE deposits, as well as the presence of residual tumor perfusion (RTP) derived from PBV-CBCT. Outcome was assessed by mid-term tumor response applying mRECIST and patient survival after 12 months.

Results: RTP was detected in 16 HCCs and correlated negatively with DE (p = .03*) and ED (p = .0009*). The absence of RTP significantly improved lesion-based mid-term response rates regarding complete response (CR, 30/34 (88%) vs 2/16 (12.5%), p = .0002*), lesion-based complete response rate was 75% (21/28) for DE ≥ 50% vs. 50% (11/22) for DE < 50% (p =  .08) and 82% (27/33) for ED ≥ 2 vs. 29% for ED < 2 (5/17), p =  .005*). Thirteen patients were treated with re-TACE within 12 months, 11 of which had shown RTP. 12-month survival rate was 93%.

Conclusion: Residual tumor perfusions as assessed by PBV-CBCT during rDEE-TACE proved to be the best parameter to predict mid-term response. "Level of Evidence: Level 3".
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http://dx.doi.org/10.1007/s00270-021-02858-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382629PMC
September 2021

Intraprocedural cone-beam CT with parenchymal blood volume assessment for transarterial chemoembolization guidance: Impact on the effectiveness of the individual TACE sessions compared to DSA guidance alone.

Eur J Radiol 2021 Jul 8;140:109768. Epub 2021 May 8.

Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. Electronic address:

Purpose: The objective of this retrospective single centre study was to evaluate the impact of intraprocedural cone-beam CT with parenchymal blood volume assessment (PBV-CBCT) for guidance of transarterial chemoembolization with drug-eluting beads (DEB-TACE) in HCC patients on the effectiveness (local tumour response, survival and number of individual TACE sessions) compared to guidance solely by digital subtraction angiography (DSA).

Method: n = 179 HCC patients (mean age, 77.4 y) undergoing DEB-TACE, with (n = 28) and without (n = 151) PBV-CBCT, using 100-300 μm microspheres loaded with epirubicin were retrospectively analysed. Tumour response according to mRECIST, overall survival and number of TACE interventions as well as laboratory parameters for liver function and inflammation were recorded. The analysis of the influence of intraprocedural PBV-CBCT was based on matched pair analysis (CBCT n = 28 vs. DSA n = 28). Gender, tumour number, tumour size and HCC risk factors were equally distributed between both groups.

Results: Response rates according to mRECIST:CBCT: PD: 7%, SD: 28 %, PR: 46 %, CR: 18 %; DSA: PD: 7 %, SD: 32 %, PR: 39 %, CR: 21 % (p = 0.174). Median OS: CBCT: 44.1 months; DSA: 28.8 months (p = 0.815). Median TACE number: CBCT: 2.0; DSA: 3.0 (p = 0.046).

Conclusions: The use of intraprocedural PBV-CBCT for TACE guidance reduced the number of re-interventions, with no negative effects on tumour response and overall survival. The study findings support the use of PBV-CBCT for DEB-TACE guidance as the improved immediate feedback leads to a considerable increase of the treatment efficiency and helps to avoid unnecessary re-interventions.
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http://dx.doi.org/10.1016/j.ejrad.2021.109768DOI Listing
July 2021

Development and Evaluation of Deep Learning-Accelerated Single-Breath-Hold Abdominal HASTE at 3 T Using Variable Refocusing Flip Angles.

Invest Radiol 2021 Oct;56(10):645-652

From the Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Tuebingen.

Objective: Deep learning (DL) reconstruction enables substantial acceleration of image acquisition while maintaining diagnostic image quality. The aims of this study were to overcome the drawback of specific absorption rate (SAR)-related limitations at 3 T and to develop a DL-accelerated single-breath-hold half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence for 2-dimesional T2-weighted fat-suppressed magnetic resonance imaging of the abdomen at 3 T using a variable flip angle (FA) evolution for the refocusing radiofrequency pulses, as well as to evaluate its feasibility and image quality in comparison to state-of-the-art T2-weighted fat-suppressed imaging technique (BLADE).

Materials And Methods: First, a suitable FA evolution with low cardiac motion-related signal loss (CRSL) and low SAR was determined through a prospective volunteer study with 11 participants. Image quality and diagnostic confidence with 5 different FA evolutions of a HASTEDL were assessed to identify the most suitable FA evolution. Second, the identified FA evolution was implemented clinically and evaluated in 51 patients undergoing a clinically indicated liver magnetic resonance imaging at 3 T. Two radiologists assessed the HASTEDL and standard sequences regarding overall image quality, noise, contrast, sharpness, artifacts, CRSL, and diagnostic confidence using a Likert scale ranging from 1 to 4, with 4 being the best. Comparative analyses were conducted to assess the differences between HASTEDL (acquisition time, 21 seconds; single breath-hold) and the routinely used T2-weighted BLADE sequence (acquisition time, 4 minutes; respiratory triggering).

Results: From the volunteer study, the FA evolution characterized by the control points 130-90-110-130 degrees (HASTEDL) was identified as optimal among the 5 evolutions evaluated and was implemented in our clinical protocol. In all 51 patients, HASTEDL was successfully acquired at 3 T and showed excellent image quality (median, 4; interquartile range, 3-4). Although BLADE was rated significantly higher for overall image quality, noise, contrast, sharpness, artifacts, CRSL, and diagnostic confidence than HASTEDL, no differences were found concerning the number (n = 102) and measured diameter of the detected hepatic lesions between the 2 sequences BLADE and HASTEDL.

Conclusions: The proposed single-breath-hold abdominal HASTEDL with variable refocusing FAs is feasible at 3 T within SAR limits and yields high image quality and diagnostic confidence as compared with a standard T2-weighted acquisition technique, at a 10th of the acquisition time.
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http://dx.doi.org/10.1097/RLI.0000000000000785DOI Listing
October 2021

Fully Automated and Standardized Segmentation of Adipose Tissue Compartments via Deep Learning in 3D Whole-Body MRI of Epidemiologic Cohort Studies.

Radiol Artif Intell 2020 Nov 28;2(6):e200010. Epub 2020 Oct 28.

Department of Diagnostic and Interventional Radiology, Medical Image and Data Analysis, University Hospital Tübingen, Hoppe-Seyler-Str 3, 72076 Tübingen, Germany (T.K., T.H., M.F., K.N., S.G.); Department of Signal Processing and System Theory, University of Stuttgart, Stuttgart, Germany (T.K., M.F., M.S., B.Y.); School of Biomedical Engineering & Imaging Sciences, King's College London, St Thomas' Hospital, London, England (T.K.); Department of Empirical Inference, Max-Planck Institute for Intelligent Systems, Tübingen, Germany (T.H.); Department of Diagnostic and Interventional Radiology, Section of Experimental Radiology, University Hospital Tübingen, Tübingen, Germany (M.F., M.S., F.S., J.M.); Department of Internal Medicine IV, Eberhard Karls University, Tübingen, Germany (A.F.); Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München, University of Tübingen, Tübingen, Germany (A.F., F.S., J.M.); German Center for Diabetes Research (DZD), Tübingen, Germany (A.F., H.U.H., F.S., J.M.); and Department of Diagnostic and Interventional Radiology, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany (F.B.).

Purpose: To enable fast and reliable assessment of subcutaneous and visceral adipose tissue compartments derived from whole-body MRI.

Materials And Methods: Quantification and localization of different adipose tissue compartments derived from whole-body MR images is of high interest in research concerning metabolic conditions. For correct identification and phenotyping of individuals at increased risk for metabolic diseases, a reliable automated segmentation of adipose tissue into subcutaneous and visceral adipose tissue is required. In this work, a three-dimensional (3D) densely connected convolutional neural network (DCNet) is proposed to provide robust and objective segmentation. In this retrospective study, 1000 cases (average age, 66 years ± 13 [standard deviation]; 523 women) from the Tuebingen Family Study database and the German Center for Diabetes research database and 300 cases (average age, 53 years ± 11; 152 women) from the German National Cohort (NAKO) database were collected for model training, validation, and testing, with transfer learning between the cohorts. These datasets included variable imaging sequences, imaging contrasts, receiver coil arrangements, scanners, and imaging field strengths. The proposed DCNet was compared to a similar 3D U-Net segmentation in terms of sensitivity, specificity, precision, accuracy, and Dice overlap.

Results: Fast (range, 5-7 seconds) and reliable adipose tissue segmentation can be performed with high Dice overlap (0.94), sensitivity (96.6%), specificity (95.1%), precision (92.1%), and accuracy (98.4%) from 3D whole-body MRI datasets (field of view coverage, 450 × 450 × 2000 mm). Segmentation masks and adipose tissue profiles are automatically reported back to the referring physician.

Conclusion: Automated adipose tissue segmentation is feasible in 3D whole-body MRI datasets and is generalizable to different epidemiologic cohort studies with the proposed DCNet.© RSNA, 2020.
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http://dx.doi.org/10.1148/ryai.2020200010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082356PMC
November 2020

Distribution patterns of intramyocellular and extramyocellular fat by magnetic resonance imaging in subjects with diabetes, prediabetes and normoglycaemic controls.

Diabetes Obes Metab 2021 08 17;23(8):1868-1878. Epub 2021 May 17.

Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Aim: To evaluate the distribution of intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) as well as total fat content in abdominal skeletal muscle by magnetic resonance imaging (MRI) using a dedicated segmentation algorithm in subjects with type 2 diabetes (T2D), prediabetes and normoglycaemic controls.

Materials And Methods: Subjects from a population-based cohort were classified with T2D, prediabetes or as normoglycaemic controls. Total myosteatosis, IMCLs and EMCLs were quantified by multiecho Dixon MRI as proton-density fat-fraction (in %) in abdominal skeletal muscle.

Results: Among 337 included subjects (median age 56.0 [IQR: 49.0-64.0] years, 56.4% males, median body mass index [BMI]: 27.2 kg/m ), 129 (38.3%) were classified with an impaired glucose metabolism (T2D: 49 [14.5%]; prediabetes: 80 [23.7%]). IMCLs were significantly higher than EMCLs in subjects without obesity (5.7% [IQR: 4.8%-7.0%] vs. 4.1% [IQR: 2.7%-5.8%], P < .001), whereas the amounts of IMCLs and EMCLs were shown to be equal and significantly higher in subjects with obesity (both 6.7%, P < .001). Subjects with prediabetes and T2D had significantly higher amounts of IMCLs and EMCLs compared with normoglycaemic controls (P < .001). In univariable analysis, prediabetes and T2D were significantly associated with both IMCLs (prediabetes: β: 0.76, 95% CI: 0.28-1.24, P = .002; T2D: β: 1.56, 95% CI: 0.66-2.47, P < .001) and EMCLs (prediabetes: β: 1.54, 95% CI: 0.56-2.51, P = .002; T2D: β: 2.15, 95% CI: 1.33-2.96, P < .001). After adjustment for age and gender, the association of IMCLs with prediabetes attenuated (P = 0.06), whereas for T2D, both IMCLs and EMCLs remained significantly and positively associated (P < .02).

Conclusion: There are significant differences in the amount and distribution ratio of IMCLs and EMCLs between subjects with T2D, prediabetes and normoglycaemic controls. Therefore, these patterns of intramuscular fat distribution by MRI might serve as imaging biomarkers in both normal and impaired glucose metabolism.
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http://dx.doi.org/10.1111/dom.14413DOI Listing
August 2021

Association between cardiovascular risk factors and degenerative disc disease of the thoracolumbar spine in the general population: results from the KORA MRI Study.

Acta Radiol 2021 Apr 20:2841851211010391. Epub 2021 Apr 20.

Department for Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, University Hospital Tuebingen, Tübingen, Germany.

Background: Little is known about the associations between cardiovascular risk factors (CRF) and disc degeneration (DD).

Purpose: To evaluate the potential association between CRFs and intervertebral DD in a population-based sample.

Methods: A total of 400 participants from the community-based KORA-study were assessed in terms of CRFs, specifically obesity, hypertension, diabetes, elevated LDL-c, low HDL-c, elevated triglycerides, smoking status, and alcohol consumption. The patients additionally underwent whole-body magnetic resonance imaging (MRI) using T2-weighted single-shot fast-spin-echo and T1 dual-echo gradient-echo Dixon pulse sequences. Thoracic and lumbar DD were assessed using the Pfirrmann score and for the presence of disc bulging/protrusion. Cross-sectional associations between CRFs and MR-based Pfirrmann score were then analyzed.

Results: A total of 385 individuals (58.2% men; mean age 56.3 ± 9.2 years) were included. Prevalence of DD was 76.4%. Older age (β = 0.18; 95% CI 0.12-0.25;  < 0.001) and higher body mass index (BMI) (β = 0.19; 95% CI 0.06-0.30;  = 0.003) were significantly associated with DD of the thoracolumbar spine. Diabetes was significantly associated with DD at T7/8 ( = 0.029) and L3/4 ( = 0.017). Hypertension correlated significantly with DD in univariate analysis, but the association did not persist using multivariate analysis (β = 0.53; 95% CI -0.74 to 1.81;  = 0.41). None of the other CRFs ( ≥ 0.11) were associated with advanced DD. Disc bulging was independently associated with hypertension (β = 0.47; 95% CI 0.27-0.81;  = 0.01).

Conclusion: A significant independent association exists between age, BMI, and intervertebral DD. In contrast, there is no significant association between cardiovascular risk factors and DD. Providing strong evidence that the pathologic process undergirding DD is mechanical, rather than microvascular, in nature.
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http://dx.doi.org/10.1177/02841851211010391DOI Listing
April 2021

A reporting and analysis framework for structured evaluation of COVID-19 clinical and imaging data.

NPJ Digit Med 2021 Apr 12;4(1):69. Epub 2021 Apr 12.

Computational Radiology, Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

The COVID-19 pandemic has worldwide individual and socioeconomic consequences. Chest computed tomography has been found to support diagnostics and disease monitoring. A standardized approach to generate, collect, analyze, and share clinical and imaging information in the highest quality possible is urgently needed. We developed systematic, computer-assisted and context-guided electronic data capture on the FDA-approved mint Lesion software platform to enable cloud-based data collection and real-time analysis. The acquisition and annotation include radiological findings and radiomics performed directly on primary imaging data together with information from the patient history and clinical data. As proof of concept, anonymized data of 283 patients with either suspected or confirmed SARS-CoV-2 infection from eight European medical centers were aggregated in data analysis dashboards. Aggregated data were compared to key findings of landmark research literature. This concept has been chosen for use in the national COVID-19 response of the radiological departments of all university hospitals in Germany.
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http://dx.doi.org/10.1038/s41746-021-00439-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041811PMC
April 2021

Prospective Image Quality and Lesion Assessment in the Setting of MR-Guided Radiation Therapy of Prostate Cancer on an MR-Linac at 1.5 T: A Comparison to a Standard 3 T MRI.

Cancers (Basel) 2021 Mar 26;13(7). Epub 2021 Mar 26.

Department of Radiation Oncology, Eberhard-Karls University, 72076 Tuebingen, Germany.

The objective of this study is to conduct a qualitative and a quantitative image quality and lesion evaluation in patients undergoing MR-guided radiation therapy (MRgRT) for prostate cancer on a hybrid magnetic resonance imaging and linear accelerator system (MR-Linac or MRL) at 1.5 Tesla. This prospective study was approved by the institutional review board. A total of 13 consecutive patients with biopsy-confirmed prostate cancer and an indication for MRgRT were included. Prior to radiation therapy, each patient underwent an MR-examination on an MRL and on a standard MRI scanner at 3 Tesla (MRI). Three readers (two radiologists and a radiation oncologist) conducted an independent qualitative and quantitative analysis of T2-weighted (T2w) and diffusion-weighted images (DWI). Qualitative outcome measures were as follows: zonal anatomy, capsule demarcation, resolution, visibility of the seminal vesicles, geometric distortion, artifacts, overall image quality, lesion conspicuity, and diagnostic confidence. All ratings were performed on an ordinal 4-point Likert scale. Lesion conspicuity and diagnostic confidence were firstly analyzed only on MRL. Afterwards, these outcome parameters were analyzed in consensus with the MRI. Quantitative outcome measures were as follows: anteroposterior and right left diameter of the prostate, lesion size, PI-RADS score (Prostate Imaging-Reporting and Data System) and apparent diffusion coefficient (ADC) of the lesions. Intergroup comparisons were computed using the Wilcoxon-sign rank test and tests. A post-hoc regression analysis was computed for lesion evaluation. Finally, inter-/intra-reader agreement was analyzed using the Fleiss kappa and intraclass correlation coefficient. For T2w images, the MRL showed good results across all quality criteria (median 3 and 4). Furthermore, there were no significant differences between MRL and MRI regarding capsule demarcation or geometric distortion. For the DWI, the MRL performed significantly less than MRI across most image quality criteria with a median ranging between 2 and 3. However, there were no significant differences between MRL and MRI regarding geometric distortion. In terms of lesion conspicuity and diagnostic confidence, inter-reader agreement was fair for MRL alone (Kappa = 0.42) and good for MRL in consensus with MRI (Kappa = 0.708). Thus, lesion conspicuity and diagnostic confidence could be significantly improved when reading MRL images in consensus with MRI (Odds ratio: 9- to 11-fold for the T2w images and 5- to 8-fold for the DWI) ( < 0.001). For measures of lesion size, anterior-posterior and right-left prostate diameter, inter-reader and intersequence agreement were excellent (ICC > 0.90) and there were no significant differences between MRL and MRI among all three readers. In terms of Prostate Imaging Reporting and Data System (PIRADS) scoring, no significant differences were observed between MRL and MRI. Finally, there was a significant positive linear relationship between lesion ADC measurements (r = 0.76, < 0.01) between the ADC values measured on both systems. In conclusion, image quality for T2w was comparable and diagnostic even without administration of spasmolytic- or contrast agents, while DWI images did not reach diagnostic level and need to be optimized for further exploitation in the setting of MRgRT. Diagnostic confidence and lesion conspicuity were significantly improved by reading MRL in consensus with MRI which would be advisable for a safe planning and treatment workflow. Finally, ADC measurements of lesions on both systems were comparable indicating that, lesion ADC as measured on the MRL could be used as a biomarker for evaluation of treatment response, similar to examinations using MRI.
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http://dx.doi.org/10.3390/cancers13071533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036991PMC
March 2021

Sonographic findings in coronavirus disease-19 associated liver damage.

PLoS One 2021 19;16(2):e0244781. Epub 2021 Feb 19.

Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Tübingen, Germany.

Purpose: This study was conducted to evaluate the role of liver sonography in patients with coronavirus disease 2019 (COVID-19) and elevated liver enzymes.

Materials And Methods: In this retrospective study, patients tested positive for SARS-CoV-2 in our emergency ward between January 01 and April 24, 2020 and elevated liver enzymes were included (Cohort 1). Additionally, the local radiology information system was screened for sonographies in COVID-19 patients at the intensive care unit in the same period (Cohort 2). Liver sonographies and histologic specimen were reviewed and suspicious findings recorded. Medical records were reviewed for clinical data. Ultrasound findings and clinical data were correlated with severity of liver enzyme elevation.

Results: Cohort 1: 126 patients were evaluated, of which 47 (37.3%) had elevated liver enzymes. Severity of liver enzyme elevation was associated with death (p<0.001). 8 patients (6.3%) had suspicious ultrasound findings, including signs of acute hepatitis (n = 5, e.g. thickening of gall bladder wall, hepatomegaly, decreased echogenicity of liver parenchyma) and vascular complications (n = 4). Cohort 2: 39 patients were evaluated, of which 14 are also included in Cohort 1. 19 patients (48.7%) had suspicious ultrasound findings, of which 13 patients had signs of acute hepatitis and 6 had vascular complications. Pathology was performed in 6 patients. Predominant findings were severe cholestasis and macrophage activation.

Conclusion: For most hospitalized COVID-19 patients, elevated liver enzymes cause little concern as they are only mild to moderate. However, in severely ill patients bedside sonography is a powerful tool to reveal different patterns of vascular, cholestatic or inflammatory complications in the liver, which are associated with high mortality. In addition, macrophage activation as histopathologic correlate for a hyperinflammatory syndrome seems to be a frequent complication in COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894893PMC
March 2021

Lymph Node Staging with a Combined Protocol of F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma.

J Nucl Med 2021 Aug 28;62(8):1062-1067. Epub 2021 Jan 28.

Department of Nuclear Medicine and Clinical Molecular Imaging, University Hospital Tuebingen, Tuebingen, Germany;

Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Forty-two women with an initial diagnosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IA-IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of Tc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%-100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%-60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.
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http://dx.doi.org/10.2967/jnumed.120.255919DOI Listing
August 2021
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