Publications by authors named "Oke Gerke"

191 Publications

Quantitative Image Quality Metrics of the Low-Dose 2D/3D Slot Scanner Compared to Two Conventional Digital Radiography X-ray Imaging Systems.

Diagnostics (Basel) 2021 Sep 17;11(9). Epub 2021 Sep 17.

Department of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark.

The aim of this study was to determine the quantitative image quality metrics of the low-dose 2D/3D EOS slot scanner X-ray imaging system (LDSS) compared with conventional digital radiography (DR) X-ray imaging systems. The effective detective quantum efficiency (eDQE) and effective noise quantum equivalent (eNEQ) were measured using chest and knee protocols.

Methods: A Nationwide Evaluation of X-ray Trends (NEXT) of a chest adult phantom and a PolyMethylmethacrylate (PMMA) phantom were used for the chest and knee protocols, respectively. Quantitative image quality metrics, including effective normalised noise power spectrum (eNNPS), effective modulation transfer function (eMTF), eDQE and eNEQ of the LDSS and DR imaging systems were assessed and compared.

Results: In the chest acquisition, the LDSS imaging system achieved significantly higher eNEQ and eDQE than the DR imaging systems at lower and higher spatial frequencies (0.001 ≤ ≤ 0.044). For the knee acquisition, the LDSS imaging system also achieved significantly higher eNEQ and eDQE than the DR imaging systems at lower and higher spatial frequencies (0.001 ≤ ≤ 0.002). However, there was no significant difference in eNEQ and eDQE between DR systems 1 and 2 at lower and higher spatial frequencies (0.10 < < 1.00) for either chest or knee protocols.

Conclusion: The LDSS imaging system performed well compared to the DR systems. Thus, we have demonstrated that the LDSS imaging system has the potential to be used for clinical diagnostic purposes.
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http://dx.doi.org/10.3390/diagnostics11091699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472127PMC
September 2021

Benefits and harms of implementing [F]FDG-PET/CT for diagnosing recurrent breast cancer: a prospective clinical study.

EJNMMI Res 2021 Sep 22;11(1):93. Epub 2021 Sep 22.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

Background: [F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy.

Methods: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard.

Results: [F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively.

Conclusion: [F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.
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http://dx.doi.org/10.1186/s13550-021-00833-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458550PMC
September 2021

Alavi-Carlsen Calcification Score (ACCS): A Simple Measure of Global Cardiac Atherosclerosis Burden.

Diagnostics (Basel) 2021 Aug 5;11(8). Epub 2021 Aug 5.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense C, Denmark.

Multislice cardiac CT characterizes late stage macrocalcification in epicardial arteries as opposed to PET/CT, which mirrors early phase arterial wall changes in epicardial and transmural coronary arteries. With regard to tracer, there has been a shift from using mainly F-fluorodeoxyglucose (FDG), indicating inflammation, to applying predominantly F-sodium fluoride (NaF) due to its high affinity for arterial wall microcalcification and more consistent association with cardiovascular risk factors. To make NaF-PET/CT an indispensable adjunct to clinical assessment of cardiac atherosclerosis, the Alavi-Carlsen Calcification Score (ACCS) has been proposed. It constitutes a global assessment of cardiac atherosclerosis burden in the individual patient, supported by an artificial intelligence (AI)-based approach for fast observer-independent segmentation. Common measures for characterizing epicardial coronary atherosclerosis by NaF-PET/CT as the maximum standardized uptake value (SUV) or target-to-background ratio are more versatile, error prone, and less reproducible than the ACCS, which equals the average cardiac SUV. The AI-based approach ensures a quick and easy delineation of the entire heart in 3D to obtain the ACCS expressing ongoing global cardiac atherosclerosis, even before it gives rise to CT-detectable coronary calcification. The quantification of global cardiac atherosclerotic burden by the ACCS is suited for management triage and monitoring of disease progression with and without intervention.
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http://dx.doi.org/10.3390/diagnostics11081421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391812PMC
August 2021

Clinical Impact of FDG-PET/CT Compared with CE-CT in Response Monitoring of Metastatic Breast Cancer.

Cancers (Basel) 2021 Aug 13;13(16). Epub 2021 Aug 13.

Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.

We compared response categories and impacts on treatment decisions for metastatic breast cancer (MBC) patients that are response-monitored with contrast-enhanced computed-tomography (CE-CT) or fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). A comparative diagnostic study was performed on MBC patients undergoing response monitoring by CE-CT ( = 34) or FDG-PET/CT ( = 31) at the Odense University Hospital (Denmark). The responses were assessed visually and allocated into categories of complete response (CR/CMR), partial response (PR/PMR), stable disease (SD/SMD), and progressive disease (PD/PMD). Response categories, clinical impact, and positive predictive values (PPV) were compared for follow-up scans. A total of 286 CE-CT and 189 FDG-PET/CT response monitoring scans were performed. Response categories were distributed into CR (3.8%), PR (8.4%), SD (70.6%), PD (15%), and others (2.1%) by CE-CT and into CMR (22.2%), PMR (23.8%), SMD (31.2%), PMD (18.5%), and others (4.4%) by FDG-PET/CT, revealing a significant difference between the groups ( < 0.001). PD and PMD caused changes of treatment in 79.1% and 60%, respectively ( = 0.083). PPV for CE-CT and FDG-PET/CT was 0.85 (95% CI: 0.72-0.97) and 0.70 (95% CI: 0.53-0.87), respectively ( = 0.17). FDG-PET/CT indicated regression of disease more frequently than CE-CT, while CE-CT indicated stable disease more often. FDG-PET/CT seems to be more sensitive than CE-CT for monitoring response in metastatic breast cancer.
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http://dx.doi.org/10.3390/cancers13164080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392540PMC
August 2021

"Global" cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison.

J Nucl Cardiol 2021 Aug 12. Epub 2021 Aug 12.

Department of Nuclear Medicine, Odense University Hospital, 5000, Odense C, Denmark.

Background: Artificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden.

Methods: A trained convolutional neural network (CNN) was used for cardiac segmentation in F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans.

Results: Mean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were - 89.42 to 74.2, - 0.02 to 0.02, - 1.52 to 1.32, and - 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators.

Conclusion: The CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart.
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http://dx.doi.org/10.1007/s12350-021-02758-9DOI Listing
August 2021

Sources of error with cardiovascular PET/CT and PET/MRI and questions to be answered to achieve clinical usefulness.

J Nucl Cardiol 2021 Jul 21. Epub 2021 Jul 21.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

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http://dx.doi.org/10.1007/s12350-021-02750-3DOI Listing
July 2021

Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74-Year-Old Individuals.

J Am Coll Cardiol 2021 Jul;78(3):201-211

Elitary Research Centre CIMA, Odense University Hospital, Odense, Denmark; Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.

Background: Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered.

Objectives: The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment.

Methods: Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses.

Results: The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor.

Conclusions: Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.
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http://dx.doi.org/10.1016/j.jacc.2021.04.094DOI Listing
July 2021

Prevalence and extent of coronary artery calcification in the middle-aged and elderly population.

Eur J Prev Cardiol 2021 Jun 28. Epub 2021 Jun 28.

Department of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000 Odense C, Denmark.

Aims: Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator.

Methods And Results: All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD.

Conclusion: This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.
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http://dx.doi.org/10.1093/eurjpc/zwab111DOI Listing
June 2021

Randomized test-treatment studies with an outlook on adaptive designs.

BMC Med Res Methodol 2021 06 1;21(1):110. Epub 2021 Jun 1.

Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.

Background: Diagnostic accuracy studies aim to examine the diagnostic accuracy of a new experimental test, but do not address the actual merit of the resulting diagnostic information to a patient in clinical practice. In order to assess the impact of diagnostic information on subsequent treatment strategies regarding patient-relevant outcomes, randomized test-treatment studies were introduced. Various designs for randomized test-treatment studies, including an evaluation of biomarkers as part of randomized biomarker-guided treatment studies, are suggested in the literature, but the nomenclature is not consistent.

Methods: The aim was to provide a clear description of the different study designs within a pre-specified framework, considering their underlying assumptions, advantages as well as limitations and derivation of effect sizes required for sample size calculations. Furthermore, an outlook on adaptive designs within randomized test-treatment studies is given.

Results: The need to integrate adaptive design procedures in randomized test-treatment studies is apparent. The derivation of effect sizes induces that sample size calculation will always be based on rather vague assumptions resulting in over- or underpowered study results. Therefore, it might be advantageous to conduct a sample size re-estimation based on a nuisance parameter during the ongoing trial.

Conclusions: Due to their increased complexity, compared to common treatment trials, the implementation of randomized test-treatment studies poses practical challenges including a huge uncertainty regarding study parameters like the expected outcome in specific subgroups or disease prevalence which might affect the sample size calculation. Since research on adaptive designs within randomized test-treatment studies is limited so far, further research is recommended.
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http://dx.doi.org/10.1186/s12874-021-01293-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167391PMC
June 2021

Aortic wall segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based versus manual segmentation.

J Nucl Cardiol 2021 May 12. Epub 2021 May 12.

Department of Nuclear Medicine, Odense University Hospital, 5000, Odense, Denmark.

Background: We aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans.

Methods: For segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland-Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans.

Results: CNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%.

Conclusions: The automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation.
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http://dx.doi.org/10.1007/s12350-021-02649-zDOI Listing
May 2021

Two-year change in 18F-sodium fluoride uptake in major arteries of healthy subjects and angina pectoris patients.

Int J Cardiovasc Imaging 2021 Oct 5;37(10):3115-3126. Epub 2021 May 5.

Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.

To examine 2-year changes in carotid and aortic F-sodium fluoride (NaF) uptake in both healthy controls and angina pectoris patients. Twenty-nine healthy subjects and 20 angina pectoris patients underwent 90-min NaF-PET/CT twice 2 years apart. The carotids and three sections of the aorta (arch, thoracic, abdominal) were manually segmented. NaF uptake was expressed as the mean and total standardized uptake values without and with partial volume correction (SUVmean, SUVtotal and pvcSUVmean, pvcSUVtotal). Insignificant tendencies were higher NaF uptake in angina patients at both time points with less uptake in healthy subjects and higher uptake in angina patients after 2 years. Thus, aortic pvcSUVmean of angina patients was 1.14 ± 0.35 and 1.29 ± 0.71 at baseline and after 2 years vs. 0.99 ± 0.31 and 0.95 ± 0.28 in healthy subjects. A similar pattern was observed for the carotid pvcSUVmean. NaF uptake at baseline could not predict a change in CT-calcification after 2 years. NaF uptake in all parts of the aorta correlated positively with age. There was an insignificant, but consistent, tendency for slightly higher arterial NaF uptake in the angina group indicating more ongoing microcalcification at both time points in patients than healthy subjects. The 2-year changes were in both groups very small suggesting that the atherosclerotic process is slow, albeit with a tendency of slight decreases among healthy controls and slight increases in angina patients despite statin therapy in half of these.
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http://dx.doi.org/10.1007/s10554-021-02263-7DOI Listing
October 2021

FDG-PET/CT for Response Monitoring in Metastatic Breast Cancer: The Feasibility and Benefits of Applying PERCIST.

Diagnostics (Basel) 2021 Apr 19;11(4). Epub 2021 Apr 19.

Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense, Denmark.

Background: We aimed to examine the feasibility and potential benefit of applying PET Response Criteria in Solid Tumors (PERCIST) for response monitoring in metastatic breast cancer (MBC). Further, we introduced the nadir scan as a reference.

Methods: Response monitoring FDG-PET/CT scans in 37 women with MBC were retrospectively screened for PERCIST standardization and measurability criteria. One-lesion PERCIST based on changes in SULpeak measurements of the hottest metastatic lesion was used for response categorization. The baseline (PERCIST) and the nadir scan (PERCIST) were used as references for PERCIST analyses.

Results: Metastatic lesions were measurable according to PERCIST in 35 of 37 (94.7%) patients. PERCIST was applied in 150 follow-up scans, with progression more frequently reported by PERCIST (36%) than PERCIST (29.3%; = 0.020). Reasons for progression were (a) more than 30% increase in SUL of the hottest lesion ( = 7, 15.9%), (b) detection of new metastatic lesions ( = 28, 63.6%), or both (a) and (b) ( = 9, 20.5%).

Conclusions: PERCIST, with the introduction of PERCIST, allows a graphical interpretation of disease fluctuation that may be beneficial in clinical decision-making regarding potential earlier termination of non-effective toxic treatment. PERCIST seems feasible for response monitoring in MBC but prospective studies are needed to come this closer.
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http://dx.doi.org/10.3390/diagnostics11040723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073831PMC
April 2021

The effect of forearm rotation on radiographic measurements of the wrist: an experimental study using radiostereometric analyses on cadavers.

Eur Radiol Exp 2021 Apr 2;5(1):15. Epub 2021 Apr 2.

Department of Radiology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark.

Background: Although dorsal/palmar tilt, radial inclination (RI), and ulnar variance (UV) are measurements commonly performed in wrist radiographs, the impact of forearm rotation on those measurements during the radiographic procedure is uncertain. Our aim was to determine the impact of supination and pronation on the reliability of measurements of tilt, RI, and UV.

Methods: Tantalum markers were inserted into the distal radius of 21 unfractured cadaver forearms. The forearms were radiographed in different degrees of supination and pronation. The exact degree of rotation was calculated with radiostereometric analyses. Tilt, RI, and UV were measured by two independent readers in a random and anonymised fashion. Association between forearm rotation and radiographic measurements was examined using linear regression.

Results: Forearm rotation significantly impacted the radiographically measured tilt. One degree of supination and pronation respectively increased and decreased palmar tilt with 0.68° and 0.44°, observers 1 and 2, respectively. As opposed to observer 1, observer 2 found that RI was significantly impacted by rotation with a slope of 0.08. Ulnar variance was not significantly impacted by rotation with linear regression slopes of 0.01° (95% confidence interval [CI] - 0.02-0.05, p = 0.490) and 0.02° (95% CI - 0.02-0.07; p = 0.288), observer 1 and observer 2, respectively.

Conclusion: In unfractured forearms, the radiographically measured tilt was significantly affected by rotation. Palmar tilt increased with supination and decreased with pronation. Rotation significantly affected radial inclination, although of a magnitude that is probably not clinically relevant. No significant impact on UV was found.
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http://dx.doi.org/10.1186/s41747-021-00209-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017069PMC
April 2021

Prognostic impacts of glucocorticoid treatment in patients with polymyalgia rheumatica and giant cell arteritis.

Sci Rep 2021 03 18;11(1):6220. Epub 2021 Mar 18.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients' outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess.
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http://dx.doi.org/10.1038/s41598-021-85857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973518PMC
March 2021

An understanding of the atherosclerotic molecular calcific heterogeneity between coronary, upper limb, abdominal, and lower extremity arteries as assessed by NaF PET/CT.

Am J Nucl Med Mol Imaging 2021 15;11(1):40-45. Epub 2021 Feb 15.

Department of Radiology, University of Pennsylvania Philadelphia, United States.

We aimed to quantify the heterogeneity of atherosclerosis in upper and lower limb vessels using F-NaF-PET/CT and compare calcification in coronary arteries to peripheral arteries. 68 healthy controls (42±13.5 years, 35 females, 33 males) and 40 patients at-risk for cardiovascular disease (55±11.9 years, 22 females, 18 males) underwent PET/CT imaging 90 minutes after the injection of F-NaF (2.2 Mbq/Kg). The following arteries were examined: coronary artery (CA), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), abdominal aorta (AA), common iliac artery (CIA), external iliac artery (EIA), femoral artery (FA), popliteal artery (PA). Average SUVmean (aSUVmean) was calculated for each arterial segment. A paired t-test compared the aSUVmean between CA vs. AS, AR, DA, AA, CIA, EIA, FA, and PA. CA aSUVmean in the at-risk group was higher than the healthy control group (0.74±0.04 vs. 0.67±0.04, P=0.03). Furthermore, the F-NaF uptake in the CA was lower than in AS, AR, DA, AA, CIA, EIA, FA, and PA in both healthy (all P≤0.0001) and at-risk (all P≤0.0001). Higher F-NaF uptake in non-cardiac arteries in both healthy controls and patients at-risk suggests CA calcification is a late manifestation of atherosclerosis. This differential expression of atherosclerosis is likely due to interaction of hemodynamic parameters specific to the vascular bed and systemic factors related to the development of atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936246PMC
February 2021

Use and coverage of automated external defibrillators according to location in out-of-hospital cardiac arrest.

Resuscitation 2021 05 10;162:112-119. Epub 2021 Feb 10.

Research Unit of Cardiology, Department of Cardiology, Odense University Hospital, J.B. Winsløws Vej 4, 5000 Odense C, Denmark. Electronic address:

Aims: To evaluate 1) the relative use of automated external defibrillators (AEDs) at different types of AED locations 2) the percentage of AEDs crossing location types during OHCA before use 3) the AED coverage distance at different types of AED locations, and 4) the 30-day-survival in different subgroups.

Methods: From 2014-2018, AEDs used by bystanders during out-of-hospital cardiac arrest (OHCA) in the Region of Southern Denmark were collected. Data regarding registered AEDs was retrieved from the national AED-network. The OHCA site and AED placement was categorized into; 1) Residential; 2) Public; 3) Nursing home, 4) Company/workplace; 5) Institution; 6) Health clinic and 7) Sports facility/recreational. To evaluate 30-day-survival, groups 4-7 were pooled into one Mixed group.

Results: In total 509 OHCAs were included. There was high relative usage of AEDs from public places, nursing homes, health clinics and sports facilities, and low relative usage from companies/workplaces, residential areas and institutions. Of AEDs used during residential OHCAs 39% were collected from public places. AEDs placed in residential areas and public places had a coverage of 575 m (IQR 130-1300) and 270 m (IQR5-550), respectively. Thirty-day- survival in public, residential and mixed groups were 49%, 14% and 67%, respectively.

Conclusion: The relative use of AEDs from public places, nursing homes, sports facilities and health clinics was high, and AEDs used during OHCA in residential areas were most frequently collected from public places. AEDs placed in both residential areas and public places may have a wider coverage area than proposed in current literature.
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http://dx.doi.org/10.1016/j.resuscitation.2021.01.040DOI Listing
May 2021

How Replicates Can Inform Potential Users of a Measurement Procedure about Measurement Error: Basic Concepts and Methods.

Diagnostics (Basel) 2021 Jan 22;11(2). Epub 2021 Jan 22.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark.

Measurement procedures are not error-free. Potential users of a measurement procedure need to know the expected magnitude of the measurement error in order to justify its use, in particular in health care settings. Gold standard procedures providing exact measurements for comparisons are often lacking. Consequently, scientific investigations of the measurement error are often based on using replicates. However, a standardized terminology (and partially also methodology) for such investigations is lacking. In this paper, we explain the basic conceptual approach of such investigations with minimal reference to existing terminology and describe the link to the existing general statistical methodology. This way, some of the key measures used in such investigations can be explained in a simple manner and some light can be shed on existing terminology. We encourage clearly conceptually distinguishing between investigations of the measurement error of a single measurement procedure and the comparison between different measurement procedures or observers. We also identify an unused potential for more advanced statistical analyses in scientific investigations of the measurement error.
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http://dx.doi.org/10.3390/diagnostics11020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912560PMC
January 2021

The Utility of 18F-FDG PET/CT in Patients With Clinical Suspicion of Polymyalgia Rheumatica and Giant Cell Arteritis: A Prospective, Observational, and Cross-sectional Study.

ACR Open Rheumatol 2020 Aug 22;2(8):478-490. Epub 2020 Jul 22.

University of Southern Denmark, Odense, Denmark.

Objective: To define the proportions of agreement between fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), clinical diagnosis, and temporal artery biopsy (TAB) in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Furthermore, the association of 18F-FDG PET/CT uptake patterns and clinical presentation of newly diagnosed PMR and GCA was investigated.

Methods: Eighty patients newly suspected of having PMR, GCA, or concomitant PMR and GCA were included and followed for 40 weeks. Every patient underwent an 18F-FDG PET/CT scan before or within 3 days of initiation of steroids in case of GCA. FDG uptakes in 8 paired articular/periarticular sites and 14 arterial segments were evaluated based on a 4-point visual grading scale.

Results: Of the 80 patients (female: 50 [62.5%]; mean age ± SD: 72.0 ± 7.9), 64 (80.0%) patients were diagnosed with pure PMR, 3 (3.7%) with pure GCA, and 10 (12.5%) with concomitant PMR and GCA. Additionally, three (3.7%) patients were diagnosed with seronegative rheumatoid arthritis during the follow-up period. For the diagnosis of PMR, 18F-FDG PET/CT had a proportion of agreement of 75.3 (64.2-84.4), compared with clinical diagnosis. When comparing findings of 18F-FDG PET/CT with TAB, 18F-FDG PET/CT had a proportion of agreement of 93.0 (84.3-97.7) in all included patients and 69.2 (38.6-90.9) in the subgroup of patients with vasculitis. C-reactive protein was significantly higher in patients with PMR activity on 18F-FDG PET/CT compared with those without 18F-FDG PET/CT activity (P value = 0.006).

Conclusions: 18F-FDG PET/CT is a powerful imaging technique in PMR and GCA that was in good agreement with clinical diagnosis and TAB.
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http://dx.doi.org/10.1002/acr2.11163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437127PMC
August 2020

An Extension of the Bland-Altman Plot for Analyzing the Agreement of More than Two Raters.

Diagnostics (Basel) 2021 Jan 1;11(1). Epub 2021 Jan 1.

Department of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark.

The Bland-Altman plot is the most common method to analyze and visualize agreement between raters or methods of quantitative outcomes in health research. While very useful for studies with two raters, a limitation of the classical Bland-Altman plot is that it is specifically used for studies with two raters. We propose an extension of the Bland-Altman plot suitable for more than two raters and derive the approximate limits of agreement with 95% confidence intervals. We validated the suggested limit of agreement by a simulation study. Moreover, we offer suggestions on how to present bias, heterogeneity among raters, as well as the uncertainty of the limits of agreement. The resulting plot could be utilized to investigate and present agreement in studies with more than two raters.
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http://dx.doi.org/10.3390/diagnostics11010054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824071PMC
January 2021

Association between atherosclerotic cardiovascular disease risk score estimated by pooled cohort equation and coronary plaque burden as assessed by NaF-PET/CT.

Am J Nucl Med Mol Imaging 2020 15;10(6):312-318. Epub 2020 Dec 15.

Department of Radiology, University of Pennsylvania Philadelphia, PA, USA.

Pooled Cohort Equations (PCE) combines metabolic and non-metabolic parameters to predict the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Therefore, we hypothesize that ASCVD risk score is correlated to global cardiac microcalcification, as assessed by F-sodium fluoride-positron emission tomography/computed tomography (NaF-PET/CT). Sixty-one individuals (53.4±8.9 years, 32 females, 100% Caucasian) without known ASCVD underwent NaF-PET/CT imaging. Global cardiac average SUVmean (aSUVmean), also known as the Alavi-Carlsen Calcification Score, was calculated across manually defined regions of interest on each axial slice for each individual. The 10-year ASCVD risk score was determined for each individual using the PCE as per ACC/AHA guidelines, and then individuals were categorized into low-, borderline-, intermediate-, and high-risk groups based on their score. Linear regression analysis was applied to compare each individual's ASCVD score and aSUVmean. Global cardiac aSUVmean stratified by groups estimated by 10-year ASCVD risk score were 0.67±0.09 for low risk (n=32), 0.70±0.11 for borderline risk (n=10), 0.72±0.10 for intermediate risk (n=17), and 0.78±0.10 for high risk (n=2). ASCVD risk score was significantly correlated to aSUVmean (r=0.27, P=0.03). This is among the first studies to compare ASCVD risk scores to cardiac plaque burden as assessed by NaF-PET/CT. Large, prospective studies are needed to further investigate the potential of NaF uptake in ASCVD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724277PMC
December 2020

Utilization of NaF-PET/CT in assessing global cardiovascular calcification using CHADS and CHADS-VASc scoring systems in high risk individuals for cardiovascular disease.

Am J Nucl Med Mol Imaging 2020 15;10(6):293-300. Epub 2020 Dec 15.

Department of Radiology, University of Pennsylvania Philadelphia, United States.

CHADS and CHADS-VASc scores are used to estimate the risk of strokes in patients with atrial fibrillation. We sought to determine the global quantification of cardiovascular molecular calcification in high risk individuals by NaF-PET/CT and compare it with CHADS and CHADS-VASc scores. We identified 40 high risk individuals for cardiovascular disease from the Cardiovascular Molecular Calcification Assessed by F-NaF PET CT (CAMONA) trial and calculated CHADS and CHADS-VASc scores for each. Ninety minutes after NaF injection (2.2 Mbq/kg), PET/CT imaging was performed. CT imaging was done for attenuation correction and anatomic correlation. The global cardiac uptake was calculated from regions of interest manually drawn on axial PET/CT images made in OsirixMD. Global cardiac average SUVmean (aSUVmean) values were calculated, and linear regression analysis was employed for statistical purposes. Subjects had mean age of 55 ± 11.9 SD years, (Range: 23-73 years), female 55%. The sample consisted of subjects with a mean aSUVmax of 2.9 ± 1.4, aSUVmean was 0.8 ± 0.2, CHADS 0.9 ± 0.6 (Range: 0-3), CHADS-VASc 1.8 ± 1.3 (Range: 0-5). Based on the linear regression models, we found a direct correlation between global cardiac aSUVmean and CHADS score (r=0.58, P≤0.0001) and also between global cardiac aSUVmean and CHADS-VASc (r=0.37, P=0.01). Based on the results of our study we conclude that patients with a higher CHADS and CHADS-VASc scores had a higher atherosclerotic burden and could be at greater risk of cardiovascular events. These scoring systems can help with risk stratification for predicting future adverse atherosclerotic events.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724281PMC
December 2020

Comparison of atherosclerotic burden in non-lower extremity arteries in patients with and without peripheral artery disease using F-NaF-PET/CT imaging.

Am J Nucl Med Mol Imaging 2020 15;10(6):272-278. Epub 2020 Dec 15.

Department of Radiology, University of Pennsylvania Philadelphia, United States.

Atherosclerosis is the most common cause of peripheral artery disease (PAD). We compared the atherosclerotic burden in non-lower extremity arteries in patients with and without PAD using F-sodium fluoride (NaF)-PET/CT. We identified five individuals (61.8±6.6 years, one male, four females) with PAD and matched to five individuals without PAD based on age and gender from the unfavorable cardiovascular risk profile group of the CAMONA trial (60±7.2 years, one male, four females). Individuals underwent PET/CT imaging 90 minutes after the injection of NaF (2.2 Mbq/Kg). CT imaging was conducted to account for attenuation correction and anatomic referencing. The NaF uptake was measured by manually defining regions of interest on each axial slice on the following arteries: coronary artery (CA), carotid artery (CR), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), and abdominal aorta (AA). Average SUVmean (aSUVmean) was calculated for each segment. Wilcoxon's signed rank test was used for statistical analysis. The total aSUVmean was higher in the PAD group compared to the non-PAD group (6.54±0.9 vs. 5.03±0.45, P=0.043). Comparison revealed higher NaF uptake in CR, AS, AR, and DA in the PAD group compared to the non-PAD group (0.93±0.25 vs. 0.54±0.14, P=0.01; 1.28±0.20 vs. 0.86±1.19, P<0.01; 1.18±0.17 vs. 0.90±0.19, P=0.03; 1.32±0.24 vs. 0.91±0.15, P=0.01). The NaF uptake in CA and AA was similar between the two groups (0.77±0.04 vs. 0.71±0.05, P=0.11; 1.07±0.28 vs. 1.12±0.30, P=0.82). We found individuals with PAD had higher atherosclerotic burden in the carotid arteries and thoracic aorta compared to non-PAD subjects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724274PMC
December 2020

Global brain glucose uptake on 18F-FDG-PET/CT is influenced by chronic cardiovascular risk.

Nucl Med Commun 2021 Apr;42(4):444-450

Department of Radiology, Hospital of the University of Pennsylvania.

Purpose: The goal of this study was to assess global cerebral glucose uptake in subjects with known cardiovascular risk factors by employing a quantitative 18F-fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) technique. We hypothesized that at-risk subjects would demonstrate decreased global brain glucose uptake compared to healthy controls.

Methods: We compared 35 healthy male controls and 14 male subjects at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects were grouped into two age-matched cohorts: younger (<50 years) and older (≥50 years). The global standardized uptake value mean (Avg SUVmean) was measured by mapping regions of interest of the entire brain across the supratentorial structures and cerebellum. Wilcoxon's rank-sum test was used to assess the differences in Avg SUVmean between controls and at-risk subjects.

Results: Younger subjects demonstrated higher brain Avg SUVmean than older subjects. In addition, in both age strata, the 10-year risk for fatal CVD according to the SCORE tool was significantly greater in the at-risk groups than in healthy controls (younger: P = 0.0304; older: P = 0.0436). In the younger cohort, at-risk subjects demonstrated significantly lower brain Avg SUVmean than healthy controls (P = 0.0355). In the older cohort, at-risk subjects similarly had lower Avg SUVmean than controls (P = 0.0343).

Conclusions: Global brain glucose uptake appears to be influenced by chronic cardiovascular risk factors. Therefore, FDG-PET/CT may play a role in determining the importance of CVD on brain function and has potential for monitoring the efficacy of various therapeutic interventions.
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http://dx.doi.org/10.1097/MNM.0000000000001349DOI Listing
April 2021

Prevalence of Newly Diagnosed Malignancies in Patients with Polymyalgia Rheumatica and Giant Cell Arteritis, Comparison of 18F-FDG PET/CT Scan with Chest X-ray and Abdominal Ultrasound: Data from a 40 Week Prospective, Exploratory, Single Centre Study.

J Clin Med 2020 Dec 4;9(12). Epub 2020 Dec 4.

Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark.

The aim of the study was to identify the prevalence of newly diagnosed malignancies in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with the aid of 18F-FDG PET/CT scan compared to conventional imaging techniques: Chest X-ray (CXR) and abdominal ultrasound (US). Secondarily, to examine the relative diagnostic accuracy of these two imaging modalities for the detection of cancer. Eighty consecutive patients with newly diagnosed PMR, GCA, or concomitant PMR and GCA, were included and followed up for 40 weeks. All patients underwent an 18F-FDG PET/CT scan, CXR, and abdominal US at diagnosis. Imaging findings were dichotomously categorized into malignant or benign. Among 80 patients, three patients were diagnosed with seronegative rheumatoid arthritis and were excluded from the analysis. Of the remaining 77, 64 (83.1%) patients were diagnosed with pure PMR, 3 (3.9%) with pure GCA, and 10 (13.0%) with concomitant PMR and GCA. Five types of cancer that were more prevalent than the one-year prevalence of 1.2% among the background population were found in four (5.2%; 95%CI: 1.4-12.8%) patients. CXR/abdominal US could detect the solid cancer in one patient, whereas 18F-FDG PET/CT could identify all four solid cancers. Furthermore, four (5.2%; 95%CI: 1.4-12.8%) cases of monoclonal gammopathy of undetermined significance (MGUS) were found. An increase in C reactive protein (CRP) implicated an increased risk for cancer of 2.4% (OR: 1.024, 95%CI: 1.001-1.047; = 0.041). 18F-FDG PET/CT can reveal occult cancers at an early stage with a high negative predictive value, and it is specifically beneficial in PMR/GCA patients with nonspecific symptoms.
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http://dx.doi.org/10.3390/jcm9123940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762038PMC
December 2020

Higher Interrater Agreement of FDG-PET/CT than Bone Scintigraphy in Diagnosing Bone Recurrent Breast Cancer.

Diagnostics (Basel) 2020 Nov 28;10(12). Epub 2020 Nov 28.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark.

The purpose was to investigate the interrater agreement of FDG-PET/CT and bone scintigraphy for diagnosing bone recurrence in breast cancer patients. A total of 100 women with suspected recurrence of breast cancer underwent planar whole-body bone scintigraphy with [99mTc]DPD and FDG-PET/CT. Scans were evaluated independently by experienced nuclear medicine physicians and the results for one modality were blinded to the other. Images were visually interpreted using a 4-point assessment scale (0 = no metastases, 1 = probably no metastases, 2 = probably metastases, 3 = definite metastases). Out of 100 women, 22 (22%) were verified with distant recurrence, 18 of these had bone involvement. The proportions of agreement between readers were 93% (86.3-96.6) for bone recurrence with FDG-PET/CT and 47% (37.5-56.7) for bone recurrence with planar bone scintigraphy. The strengths of agreement between readers for diagnosing bone recurrence was 'almost perfect' with FDG-PET/CT and was 'fair' with planar bone scintigraphy according to Cohen's kappa value of 0.82 (0.70-0.95) and 0.28 (0.18-0.39), respectively. Interrater agreement yielded improved reproducibility with FDG-PET/CT versus with bone scintigraphy when diagnosing recurrence with bone metastasis in this patient cohort.
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http://dx.doi.org/10.3390/diagnostics10121021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760596PMC
November 2020

Interrater Agreement and Reliability of PERCIST and Visual Assessment When Using 18F-FDG-PET/CT for Response Monitoring of Metastatic Breast Cancer.

Diagnostics (Basel) 2020 Nov 24;10(12). Epub 2020 Nov 24.

Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.

Response evaluation at regular intervals is indicated for treatment of metastatic breast cancer (MBC). FDG-PET/CT has the potential to monitor treatment response accurately. Our purpose was to: (a) compare the interrater agreement and reliability of the semi-quantitative PERCIST criteria to qualitative visual assessment in response evaluation of MBC and (b) investigate the intrarater agreement when comparing visual assessment of each rater to their respective PERCIST assessment. We performed a retrospective study on FDG-PET/CT in women who received treatment for MBC. Three specialists in nuclear medicine categorized response evaluation by qualitative assessment and standardized one-lesion PERCIST assessment. The scans were categorized into complete metabolic response, partial metabolic response, stable metabolic disease, and progressive metabolic disease. 37 patients with 179 scans were included. Visual assessment categorization yielded moderate agreement with an overall proportion of agreement (PoA) between raters of 0.52 (95% CI 0.44-0.66) and a Fleiss kappa estimate of 0.54 (95% CI 0.46-0.62). PERCIST response categorization yielded substantial agreement with an overall PoA of 0.65 (95% CI 0.57-0.73) and a Fleiss kappa estimate of 0.68 (95% CI 0.60-0.75). The difference in PoA between overall estimates for PERCIST and visual assessment was 0.13 (95% CI 0.06-0.21; = 0.001), that of kappa was 0.14 (95% CI 0.06-0.21; < 0.001). The overall intrarater PoA was 0.80 (95% CI 0.75-0.84) with substantial agreement by a Fleiss kappa of 0.74 (95% CI 0.69-0.79). Semi-quantitative PERCIST assessment achieved significantly higher level of overall agreement and reliability compared with qualitative assessment among three raters. The achieved high levels of intrarater agreement indicated no obvious conflicting elements between the two methods. PERCIST assessment may, therefore, give more consistent interpretations between raters when using FDG-PET/CT for response evaluation in MBC.
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http://dx.doi.org/10.3390/diagnostics10121001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759893PMC
November 2020

Correlation of whole-bone marrow dual-time-point F-FDG, as measured by a CT-based method of PET/CT quantification, with response to treatment in newly diagnosed multiple myeloma patients.

Am J Nucl Med Mol Imaging 2020 15;10(5):257-264. Epub 2020 Oct 15.

Department of Radiology, Hospital of The University of Pennsylvania PA, USA.

The practical application of dual-time-point-imaging (DTPI) technique still remains controversial. One of the issues is that current parameters of DTPI quantification suffer from some deficiencies, mainly limited sampling of the diseased sites by confining measurements to specific locations. We aimed to examine the correlation between the percent change from early to delayed scans in whole-bone marrow (WBM) F-FDG uptake, as measured by a CT-based method of PET/CT quantification, and response to treatment in multiple myeloma (MM) patients. Pre-treatment F-FDG-PET/CT scans of 36 newly diagnosed MM patients were collected in a prospective study at 1 h and 3 h post tracer injection (NCT02187731). A threshold algorithm based on bone Hounsfield units on CT was applied to segment and quantify WBM F-FDG uptake. Patients were separated into two treatment groups: high-dose therapy with autologous stem cell transplant (HDT) and non-high dose therapy (non-HDT). The International Response Criteria for MM patients was used to determine each patient's response to treatment. In the HDT group, WBM F-FDG uptake increased significantly in patients that had a poor response to treatment, from a median of 1.31 (IQR: 1.13-1.64) at 1 h to a median of 1.85 (1.45-2.10) at 3 h. The median percent change was 37.77% (IQR: 23.47-46.4), with a range of 6.10-50.73 ( = 0.003). However, no significant change in uptake was observed in patients with a complete response ( = 0.24). The same trend was observed for the non-HDT group. WBM uptake of F-FDG assessed with dual-time-point imaging may have a role in predicting treatment response in MM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675111PMC
October 2020

Nonparametric Limits of Agreement in Method Comparison Studies: A Simulation Study on Extreme Quantile Estimation.

Authors:
Oke Gerke

Int J Environ Res Public Health 2020 11 11;17(22). Epub 2020 Nov 11.

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense C, Denmark.

Bland-Altman limits of agreement and the underlying plot are a well-established means in method comparison studies on quantitative outcomes. Normally distributed paired differences, a constant bias, and variance homogeneity across the measurement range are implicit assumptions to this end. Whenever these assumptions are not fully met and cannot be remedied by an appropriate transformation of the data or the application of a regression approach, the 2.5% and 97.5% quantiles of the differences have to be estimated nonparametrically. Earlier, a simple Sample Quantile (SQ) estimator (a weighted average of the observations closest to the target quantile), the Harrell-Davis estimator (HD), and estimators of the Sfakianakis-Verginis type (SV) outperformed 10 other quantile estimators in terms of mean coverage for the next observation in a simulation study, based on sample sizes between 30 and 150. Here, we investigate the variability of the coverage probability of these three and another three promising nonparametric quantile estimators with n=50(50)200,250(250)1000. The SQ estimator outperformed the HD and SV estimators for n=50 and was slightly better for n=100, whereas the SQ, HD, and SV estimators performed identically well for n≥150. The similarity of the boxplots for the SQ estimator across both distributions and sample sizes was striking.
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http://dx.doi.org/10.3390/ijerph17228330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698333PMC
November 2020

Assessment of Total-Body Atherosclerosis by PET/Computed Tomography.

PET Clin 2021 Jan 5;16(1):119-128. Epub 2020 Nov 5.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, PA 19104, USA.

Atherosclerotic burden has become the focus of cardiovascular risk assessment. PET/computed tomography (CT) imaging with the tracers 18F-fluorodeoxyglucose and 18F-sodium fluoride shows arterial wall inflammation and microcalcification, respectively. Arterial uptake of both tracers is modestly age dependent. 18F-sodium fluoride uptake is consistently associated with risk factors and more easily measured in the heart. Because of extremely high sensitivity, ultrashort acquisition, and minimal radiation to the patient, total-body PET/CT provides unique opportunities for atherosclerosis imaging: disease screening and delayed and repeat imaging with global disease scoring and parametric imaging to better characterize the atherosclerosis of individual patients.
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http://dx.doi.org/10.1016/j.cpet.2020.09.013DOI Listing
January 2021

Extent of arterial calcification by conventional vitamin K antagonist treatment.

PLoS One 2020 29;15(10):e0241450. Epub 2020 Oct 29.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Background And Aims: Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD).

Methods: We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates.

Results: The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category.

Conclusions: Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241450PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595268PMC
December 2020
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