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Purpose: This study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment. Materials and methods: This registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT. Results: A total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7–39%) and 95% (88–98%), muscles and joints 71% (48–89%) and 83% (75–90%), intestines 100% (75–100%) and 85% (77–91%); thyroid gland 92% (62–99%) and 95% (89–98%), lungs 75% (19–99%) and 90% (83–95%), and heart 50% (13–99%) and 97% (92–99%), respectively. Conclusion: [18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports. [ABSTRACT FROM AUTHOR]

Objectives: To validate an AI system for standalone breast cancer detection on an entire screening population in comparison to first-reading breast radiologists. Materials and methods: All mammography screenings performed between August 4, 2014, and August 15, 2018, in the Region of Southern Denmark with follow-up within 24 months were eligible. Screenings were assessed as normal or abnormal by breast radiologists through double reading with arbitration. For an AI decision of normal or abnormal, two AI-score cut-off points were applied by matching at mean sensitivity (AIsens) and specificity (AIspec) of first readers. Accuracy measures were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and recall rate (RR). Results: The sample included 249,402 screenings (149,495 women) and 2033 breast cancers (72.6% screen-detected cancers, 27.4% interval cancers). AIsens had lower specificity (97.5% vs 97.7%; p < 0.0001) and PPV (17.5% vs 18.7%; p = 0.01) and a higher RR (3.0% vs 2.8%; p < 0.0001) than first readers. AIspec was comparable to first readers in terms of all accuracy measures. Both AIsens and AIspec detected significantly fewer screen-detected cancers (1166 (AIsens), 1156 (AIspec) vs 1252; p < 0.0001) but found more interval cancers compared to first readers (126 (AIsens), 117 (AIspec) vs 39; p < 0.0001) with varying types of cancers detected across multiple subgroups. Conclusion: Standalone AI can detect breast cancer at an accuracy level equivalent to the standard of first readers when the AI threshold point was matched at first reader specificity. However, AI and first readers detected a different composition of cancers. Clinical relevance statement: Replacing first readers with AI with an appropriate cut-off score could be feasible. AI-detected cancers not detected by radiologists suggest a potential increase in the number of cancers detected if AI is implemented to support double reading within screening, although the clinicopathological characteristics of detected cancers would not change significantly. Key Points: • Standalone AI cancer detection was compared to first readers in a double-read mammography screening population. • Standalone AI matched at first reader specificity showed no statistically significant difference in overall accuracy but detected different cancers. • With an appropriate threshold, AI-integrated screening can increase the number of detected cancers with similar clinicopathological characteristics. [ABSTRACT FROM AUTHOR]

Background: In 2011, as the first European country, Denmark introduced the non-organ-specific cancer patient pathway (CPP) for patients presenting with non-specific symptoms and signs of cancer (NSSC). The proportion of patients with cancer over time is unknown. Methods: A retrospective cohort study of all patients with a NSSC-CPP investigational course in the province of Funen to the Diagnostic Centre in Svendborg from 2014 to 2021 was performed to evaluate the proportion of patients with cancer and serious disease over time. Results: A total of 6698 patients were referred to the NSSC-CPP of which 20.2% had cancer. While the crude referral rate increased from 114 per 100,000 people in 2014 and stabilised to around 214 in 2017–2021, the cancer detection rate of the total yearly new cancers in Funen diagnosed through the NSSC-CPP in DC Svendborg increased from 3 to 6%. Conclusions: With now high and stable conversion and crude referral rates, the NSSC-CPP is one of the largest CPPs in Denmark as measured by the number of new cancer cases found. Similar urgent referral programmes in other countries might fill an unmet medical need for patients presenting with serious non-specific symptoms and signs of cancer in general practice. [ABSTRACT FROM AUTHOR]

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007–2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands. Procedures: The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV). Results: Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1–79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (−0.11, 95% confidence interval (95% CI): −0.29 to 0.08; −0.05, 95% CI: −0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1). Conclusions: Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery. [ABSTRACT FROM AUTHOR]

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities. Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www.ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Background: Extranodal extension (ENE) in lymph node metastases is one of the most important prognostic factors in head and neck squamous cell carcinomas. Studies have shown inconsistency among pathologists in the assessment of ENE. The aims of this study were: (1) to determine the interrater and intrarater reliability and agreement in the assessment of ENE among Danish pathologists and (2) to test if a standardized assessment method may increase interrater agreement. Methods: Four Danish head and neck pathologists assessed ENE presence or absence in 120 histological slides from lymph nodes with oropharyngeal squamous cell carcinoma metastases (first round). Subsequently, guidelines were introduced to the pathologists and a new assessment was performed (second round). Finally, two of the pathologists assessed the slides to determine intrarater reliability and agreement (third round). Results: Interrater kappa coefficients varied between 0.57 and 0.67 in the first round and between 0.59 and 0.72 in the second round. The intrarater agreement between round 2 and 3 was 0.88 for pathologist 1 and 0.92 for pathologist 2 with resulting kappa coefficients of 0.76 (95% CI 0.64–0.88) and 0.84 (95% CI 0.74–0.94), respectively. Conclusion: We found a moderate level of reliability and agreement among pathologists for ENE in lymph node metastases from oropharyngeal squamous cell carcinomas. The intrarater reliability and agreement was generally higher than interrater measures. Interrater agreement was slightly improved by standardized assessment. [ABSTRACT FROM AUTHOR]

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 18F-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. [ABSTRACT FROM AUTHOR]

Lymphedema affects 20% of women diagnosed with breast cancer. It is a pathology with no known cure. Animal models are essential to explore possible treatments to understand and potentially cure lymphedema. The rodent hindlimb lymphedema model is one of the most widely used. Different modalities have been used to measure lymphedema in the hindlimb of mice, and these are generally poorly assessed in terms of the interrater agreement; thus, there could be a risk of measuring bias and poor reproducibility. We examined the interrater agreement of µCT-scans, electronic caliper thickness of the paw and plethysmometer in the measurement of lymphedema in the hindlimb of mice. Three independent raters assessed 24 C57BL6 mice using these three modalities four times (week 1, 2, 4 and 8) with a total of 96 samples. The mean interrater differences were then calculated. The interrater agreement was highest in the µCT-scans, with an extremely low risk of measurement bias. The interrater agreement in the plethysmometer and electronic caliper was comparable with a low to moderate risk of measurement bias. The µCT-scanner should be used whenever possible. The electronic caliper should only be used if there is no µCT-scanner available. The plethysmometer should not be used in rodents of this size. [ABSTRACT FROM AUTHOR]

Background: Imaging of idiopathic inflammatory myopathies (IIMs) is challenging, and no pathognomonic signs exist. Different tracers have been tested for this purpose, mainly inflammation markers including technetium-99m-pyrophosphate (PYP). We aimed to examine the utility of fluorine-18-fluorodeoxyglucose (FDG) relative to PYP in idiopathic inflammatory myopathy (IIM). Methods: Using visual grading and CT-guided muscular segmentation and standardized uptake values (SUVs), we assessed muscular tracer uptake qualitatively and quantitatively, comparing FDG uptake in eight patients with recent-onset IIM and 24 healthy control persons and FDG and PYP uptake in seven patients. Results: Muscular FDG and PYP uptake was increased in all patients. However, uptake distribution and signal intensity differed considerably. FDG scans revealed clear involvement of certain muscle groups including core and swallowing muscles and, in addition, abnormality in diseased extra-muscular organs. PYP was mainly visible in bones, whereas muscular PYP uptake was generally discrete and primarily located in the extremities. Quantitatively, FDG uptake was significantly higher in patients than in controls; the volume-weighted SUVmean for all right-side muscles was 0.84 versus 0.60 g/ml (95% confidence interval (CI) for mean difference 0.14–0.34, p = 0.0001). FDG SUVmean values were up to four times higher than PYP mean values in upper limb muscles (95% CI for the mean ratio 2.37–3.77, p = 0.0004) and two–three times higher in lower limb muscles (95% CI for the mean ratio 2.28–2.71, p < 0.0001). Conclusions: Muscular FDG uptake was higher in treatment-naïve IIM patients than in healthy controls and more distinct than PYP uptake in patients with a potential to reveal extra-muscular IIM involvement and malignancy. Thus, FDG appears to be superior to PYP in the diagnostic evaluation of IIM. [ABSTRACT FROM AUTHOR]

Objective: The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery. Methods: We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients' medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures. Results: Incidence rate of MM recurrence was 0.27 [95% CI 0.17–0.37] per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% [86–99], 82% [78–86], 39% [29–50], and 99% [98–99], respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan. Conclusion: The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence. [ABSTRACT FROM AUTHOR]

Background: We compared overall survival for metastatic breast cancer (MBC) patients monitored with CE-CT, FDG-PET/CT or a combination of them in an observational setting.Methods: Patients with biopsy-verified (recurrent or de novo) MBC (n = 300) who were treated at Odense university hospital (Denmark) and response monitored with FDG-PET/CT (n = 83), CE-CT (n = 144), or a combination of these (n = 73) were followed until 2019. Survival was compared between the scan groups, and were adjusted for clinico-histopathological variables representing potential confounders in a Cox proportional-hazard regression model.Results: The study groups were mostly comparable regarding baseline characteristics, but liver metastases were reported more frequently in CE-CT group (38.9%) than in FDG-PET/CT group (19.3%) and combined group (24.7%). Median survival was 30.0 months for CE-CT group, 44.3 months for FDG-PET/CT group and 54.0 months for Combined group. Five-year survival rates were significantly higher for FDG-PET/CT group (41.9%) and combined group (43.3%), than for CE-CT group (15.8%). Using the CE-CT group as reference, the hazard ratio was 0.44 (95% CI: 0.29-0.68, P = 0.001) for the FDG-PET/CT group after adjusting for baseline characteristics. FDG-PET/CT detected the first progression 4.7 months earlier than CE-CT, leading to earlier treatment change.Conclusions: In this single-center, observational study, patients with metastatic breast cancer who were response monitored with FDG-PET/CT alone or in combination with CE-CT had longer overall survival than patients monitored with CE-CT alone. Confirmation of these findings by further, preferably randomised clinical trials is warranted. [ABSTRACT FROM AUTHOR]

The comparison of two quantitative measuring devices is often performed with the Limits of Agreement proposed by Bland and Altman in their seminal Lancet paper back in 1986. Sample size considerations were rare for such agreement analyses in the past, but recently several proposals have been made depending on how agreement is to be assessed and the number of replicates to be used. We have summarized recent developments and recommendations in various situations including a distinction between method comparison and observer variability studies. These include current state-of-the-art analysis of and reporting guidelines for agreement studies. General recommendations close the paper. [ABSTRACT FROM AUTHOR]

To examine 2-year changes in carotid and aortic 18F-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. [ABSTRACT FROM AUTHOR]

Background: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]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 [18F]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. [18F]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 [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results: [18F]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 [18F]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: [18F]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 [18F]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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To determine individual, expected normal diameters of the ascending aorta (AAo) and prevalence of dilations based upon an absolute cut-off point (≥ 40 mm) and individual cut-off point (≥ 25% than expected normal). Non-contrast computed tomography (CT) scans were obtained in 14,993 individuals (95.0% male, mean age 67.8 ± 3.8). A sub-group (n = 291) had AAo diameter measured by transthoracic echocardiography. A prediction formula for AAo diameters was created from multivariate linear regression analysis based upon gender, age, and body surface area. An index was made by dividing observed diameters with predicted diameters. A size-index ≥ 1.25 was defined as dilated. Prevalence of AAo dilations among males and females using 40 mm as cut-off point were 10.6% and 2.1% (p < 0.001), respectively, while 3.3% and 2.6% (p = 0.305) using the size-index ≥ 1.25, respectively. Proportion of agreement between cases of AAo dilations from the size-index and 40 mm was 93.0%. Using the size-index as 'golden standard' for dilation, the sensitivity and specificity using 40 mm as cut-off point for males were 100.0% and 92.4%, respectively, while 75.0% and 99.9%, respectively, for females. For males and females, the positive predicted values were 31.3% and 93.8%, respectively; the negative predicted values were 100.0% and 99.3%, respectively. An absolute echocardiographic size-criterion of 40 mm entails a significant number of females with missed AAo dilation, and a large number of males are mistaken to have dilated AAo. Thus, AAo diameters should be evaluated in relation to gender, age and BSA. This study provides a formula for potential clinical implementation. [ABSTRACT FROM AUTHOR]

Background: The use of hybrid PET/MRI for clinical staging is growing in several cancer forms and, consequently, PET/MRI has also gained interest in the assessment of non-small cell lung cancer (NSCLC) and lung lesions. However, lung evaluation with PET/MRI is associated with challenges related to technical issues and diagnostic image quality. We, therefore, investigated the published literature on PET/MRI for clinical staging in NSCLC or lung nodule detection specifically addressing diagnostic accuracy and technical issues. Methods: The data originates from a systematic search performed in PubMed/MEDLINE, Embase, and Cochrane Library on hybrid PET/MRI in patients with cancer for a scoping review published earlier (https://doi.org/10.1007/s00259-019-04402-8). Studies in English and German evaluating the diagnostic performance of hybrid PET/MRI for NSCLC or lung nodule detection in cancer patients were selected. Data reported in peer-reviewed journals without restrictions to year of publication were included. Results: A total of 3138 publications were identified from which 116 published 2012–2018 were included. Of these, nine studies addressed PET/MRI in NSCLC (4) or lung nodule detection (5). Overall, PET/MRI did not provide advantages in preoperative T- and N-staging in NSCLC compared to PET/CT. The data on M-staging were too few for conclusions to be drawn. The lung nodule detection rate of PET/MRI was comparable to that of PET/CT for FDG-avid nodules larger than 10 mm, but the sensitivity of PET/MRI for detection of non-FDG-avid nodules smaller than 5 mm was low. Conclusion: PET/MRI did not provide advantages in T- and N-staging of NSCLC compared to PET/CT. PET/MRI had a comparable sensitivity for detection of FDG-avid lung nodules and nodules over 10 mm, but PET/CT yielded a higher detection rate in non FDG-avid lung nodules under 5 mm. With PET/MRI, the overall detection rate for lung nodules in various cancer types remains inferior to that of PET/CT due to the lower diagnostic performance of MRI than CT in the lungs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. Methods: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. Results: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86–1.00) and 0.95 (0.88–0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). Conclusions: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning. [ABSTRACT FROM AUTHOR]

Aim: To compare the effects of high-dose therapy (HDT consisting of high-dose chemotherapy followed by autologous stem cell transplantation) and conventional-dose chemotherapy (non-HDT) on the uptake of 18F-sodium fluoride (NaF) in the whole bone, pelvis, and femoral neck of multiple myeloma (MM) patients. Method: The data of 19 MM patients who received HDT (61.5 (SD 5.6) years) and 11 MM patients who received conventional-dose chemotherapy (70.9 (SD 7.2) years) were collected in a prospective study. NaF PET/CT imaging was performed at baseline, and 8 weeks and 2 weeks after treatment for the HDT group and the non-HDT group, respectively. A CT-based algorithm was applied to segment the bones, and the global mean SUV (GSUVmean) of the whole bone and pelvis was calculated (OsiriX MD v.9.0, Pixmeo SARL; Bernex, Switzerland). In addition, regions of interest for the whole, medial, and lateral femoral neck were delineated bilaterally. Whole bone and pelvis measurements were replicated by two observers. Results: The average GSUVmean in the whole bone and pelvis of the patients who underwent HDT significantly decreased from before to after treatment (− 16.27%, p = 0.02 and − 16.54%, p = 0.01, respectively). A significant decrease in the whole and lateral femoral neck was also observed bilaterally in the HDT group. No significant decrease in average GSUVmean was observed in the non-HDT group. A high level of inter-observer reliability was found in intra-class correlation (ICC for pre-treatment whole bone 0.983, post-treatment whole bone 0.989, pre-treatment whole pelvis 0.998, post-treatment whole pelvis 0.996). Conclusion: NaF uptake significantly decreased after treatment in patients who received high-dose therapy. A high level of agreement was observed between two operators for whole bone and pelvis measurements. [ABSTRACT FROM AUTHOR]

Purpose: To conduct a systematic review of articles on PET imaging of carotid atherosclerosis with emphasis on clinical usefulness and comparison with other imaging modalities. Methods: Research articles reporting carotid artery PET imaging with different radiotracers until 30 November 2018 were systematically searched for in Medline/PubMed, Scopus, Embase, Google Scholar, and Cochrane Library. Duplicates were removed, and editorials, case studies, and investigations on feasibility or reproducibility of PET imaging and of patients with end-stage diseases or immunosuppressive medications were omitted. After quality assessment of included articles using Joanna Briggs Institute checklists, all eligible articles were reviewed. Results: Of 1718 primary hits, 53 studies comprising 4472 patients, aged 47–91 years (78.8% males), were included and grouped under the following headlines: diagnostic performance, risk factors, laboratory findings, imaging modalities, and treatment. 18F-fluorodeoxyglucose (FDG) (49/53) and 18F-sodium fluoride (NaF) (5/53) were the most utilized tracers to visualize carotid wall inflammation and microcalcification, respectively. Higher carotid FDG uptake was demonstrated in patients with than without symptomatic carotid atherosclerosis. Normal carotid arteries presented with the lowest FDG uptake. In symptomatic atherosclerosis, carotid arteries ipsilateral to a cerebrovascular event had higher FDG uptake than the contralateral carotid artery. FDG uptake was significantly associated with age, male gender, and body mass index in healthy individuals, and in addition with arterial hypertension, hypercholesterolemia, and diabetes mellitus in patients. Histological assessment indicated a strong correlation between microcalcification and NaF uptake in symptomatic patients. Histological evidence of calcification correlated inversely with FDG uptake, which was associated with increased macrophage and CD68 count, both accounting for increased local inflammatory response. Conclusion: FDG-PET visualizes the inflammatory part of carotid atherosclerosis enabling risk stratification to a certain degree, whereas NaF-PET seems to indicate long-term consequences of ongoing inflammation by demonstrating microcalcification allowing discrimination of atherosclerotic from normal arteries and suggesting clinically significant carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims: To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention. Methods and results: This retrospective study included 136 participants (ages 21–75, BMI 18–43 kg/m2): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUVmean; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUVmean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUVmax) did not differ between patients and controls. SUVmean correlated with age and BMI among females (age, partial R2 = 0.16, P = 0.001; BMI, partial R2 = 0.12, P = 0.004) and males (age, partial R2 = 0.28, P < 0.0001; BMI, partial R2 = 0.22, P < 0.0001). Conclusion: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUVmean, but were not sensitive enough to predict patient status. SUVmean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries. Trial registration: ClinicalTrials.gov (NCT01724749). [ABSTRACT FROM AUTHOR]

Purpose: To examine the diagnostic accuracy of spectral CT pulmonary angiography (S-CTPA) using ventilation-perfusions lung scintigraphy (V/Q-scan) as a reference standard in the diagnosis of acute or chronic pulmonary embolism (APE/CPE) and chronic thromboembolic pulmonary hypertension (CTEPH).Methods: PubMed, Embase, Scopus, and Web of Science were searched for the period from 1 Jan 2006 to 7 Feb 2019; eligible studies had > 10 patients over 18 years old, a diagnostic outcome of PE or CTEPH, and used V/Q scan as a reference standard. Bias and applicability were assessed using QUADAS-2 tools. Sensitivities, specificities, and predictive values were noted or calculated from available information. Meta-analysis employed a fixed-effects model of Mantel and Haenszel. Heterogeneity was assessed with I-squared statistics.Results: Four hundred ninety-three unique records were identified. Following screening by title, 53 studies were included in the abstract and full-text assessment. A total of six articles were included; four were suitable for a meta-analysis. Pooled sensitivity was 94.2% (95% CI, 88.3-100%), pooled specificity was 88.5% (95% CI, 81.3-95.6%), and positive and negative predictive values were 87.8% (95% CI, 80.3-95.4%) and 94.5% (95% CI, 89.3-99.7%), respectively.Conclusion: Data on S-CTPA for PE/CTEPH remains promising, but limited; only small studies with methodological issues are available. Evidence is best for CPE/CTEPH whereas no firm conclusions are possible for APE. There is a need for larger, prospective studies with a robust composite reference standard including state-of-the-art CTPA and V/Q-scans.Key Points: • S-CTPA has high sensitivity and specificity for perfusion defects in patients with PE or CPETH. • Methodological issues and diversity of reference standards were found in the small number of included studies. • There is a need for larger prospective studies with more robust composite reference standards. [ABSTRACT FROM AUTHOR]

Purpose: We examined the literature to elucidate the role of 18F-sodium fluoride (NaF)-PET in atherosclerosis. Methods: Following a systematic search of PubMed/MEDLINE, Embase, and Cochrane Library included articles underwent subjective quality assessment with categories low, medium, and high. Of 2811 records, 1780 remained after removal of duplicates. Screening by title and abstract left 41 potentially eligible full-text articles, of which 8 (about the aortic valve (n = 1), PET/MRI feasibility (n = 1), aortic aneurysms (n = 1), or quantification methodology (n = 5)) were dismissed, leaving 33 published 2010–2012 (n = 6), 2013–2015 (n = 11), and 2016–2018 (n = 16) for analysis. Results: They focused on coronary (n = 8), carotid (n = 7), and femoral arteries (n = 1), thoracic aorta (n = 1), and infrarenal aorta (n = 1). The remaining 15 studies examined more than one arterial segment. The literature was heterogeneous: few studies were designed to investigate atherosclerosis, 13 were retrospective, 9 applied both FDG and NaF as tracers, 24 NaF only. Subjective quality was low in one, medium in 13, and high in 19 studies. The literature indicates that NaF is a very specific tracer that mimics active arterial wall microcalcification, which is positively associated with cardiovascular risk. Arterial NaF uptake often presents before CT-calcification, tends to decrease with increasing density of CT-calcification, and appears, rather than FDG-avid foci, to progress to CT-calcification. It is mainly surface localized, increases with age with a wide scatter but without an obvious sex difference. NaF-avid microcalcification can occur in fatty streaks, but the degree of progression to CT-calcification is unknown. It remains unknown whether medical therapy influences microcalcification. The literature held no therapeutic or randomized controlled trials. Conclusion: The literature was heterogeneous and with few clear cut messages. NaF-PET is a new approach to detect and quantify microcalcification in early-stage atherosclerosis. NaF uptake correlates with cardiovascular risk factors and appears to be a good measure of the body's atherosclerotic burden, potentially suited also for assessment of anti-atherosclerotic therapy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether NaF-PET/CT or FDG-PET/CT can detect abdominal aortic molecular calcification and inflammation in patients with rheumatoid arthritis (RA).Methods: In this study, 18 RA patients (4 women, 14 men; mean age 56.0 ± 11.7) and 18 healthy controls (4 women, 14 men; mean age 55.8 ± 11.9) were included. The controls were matched to patients by sex and age (± 4 years). All subjects of this study underwent NaF-PET/CT scanning 90 min following the administration of NaF. FDG-PET/CT imaging was performed 180 min following intravenous FDG injection. Using OsiriX software, the global mean standardized uptake value (global SUVmean) in abdominal aorta was calculated for both FDG and NaF. The NaF SUVmean and FDG SUVmean were divided by the blood pool activity providing target-to-background ratios (TBR) namely, NaF-TBRmean and FDG-TBRmean. The CT calcium volume score was obtained using a growing region algorithm based on Hounsfield units.Results: The average NaF-TBRmean score among RA patients was significantly greater than that of healthy controls (median 1.61; IQR 1.49-1.88 and median 1.40; IQR 1.23-1.52, P = 0.002). The average CT calcium volume score among RA patients was also significantly greater than that of healthy controls (median 1.96 cm3; IQR 0.57-5.48 and median 0.004 cm3; IQR 0.04-0.05, P < 0.001). There was no significant difference between the average FDG-TBRmean scores in the RA patients when compared to healthy controls (median 1.29; IQR 1.13-1.52 and median 1.29; IQR 1.13-1.52, respectively, P = 0.98).Conclusion: Quantitative assessment with NaF-PET/CT identifies increased molecular calcification in the wall of the abdominal aorta among patients with RA as compared with healthy controls, while quantitative assessment with FDG-PET/CT did not identify a difference in aortic vessel wall FDG uptake between the RA and healthy control groups. [ABSTRACT FROM AUTHOR]

When studying illnesses that cause disturbance in volume such as lymphedema, reliable quantification of tissue volume is important. Lymphedema results in swelling and enlargement of extremities and can be both physically and psychologically stressful to the patient. Experiments in rodent models provide a cost-effective research platform and are important for preclinical research on lymphedema. When performing such research, it can be crucial to measure the changes in tissue volume. Researchers must ensure that the risk of measurement error, when measuring the tissue volume, is as low as possible. The main goal of this article was to perform a comprehensive examination of the intra- and interrater agreement and hereby assess the risk of measurement error when using microcomputed tomography (µCT) images to measure hindlimb volume. We examined the agreement between four raters with different levels of prior experience and found that the risk of measurement error is extremely low when using this method. The main limitation of this method is that it is relatively expensive and time-consuming. The main advantages of this method are that it is easily learned and that it has a high intra- and interrater agreement, even for raters with no prior measuring experience. [ABSTRACT FROM AUTHOR]

Positron emission tomography/x-ray computed tomography (PET/CT) has long been discussed as a promising modality for response evaluation in cancer. When designing respective clinical trials, several design issues have to be addressed, especially the number/timing of PET/CT scans, the approach for quantifying metabolic activity, and the final translation of measurements into a rule. It is unclear how well these issues have been tackled in quest of an optimised use of PET/CT in response evaluation. Medline via Ovid and Science Citation Index via Web of Science were systematically searched for articles from 2015 on cancer patients scanned with PET/CT before and during/after treatment. Reports were categorised as being either developmental or evaluative, i.e. focusing on either the establishment or the evaluation of a rule discriminating responders from non-responders. Of 124 included papers, 112 (90 %) were accuracy and/or prognostic studies; the remainder were response-curve studies. No randomised controlled trials were found. Most studies were prospective (62 %) and from single centres (85 %); median number of patients was 38.5 (range 5-354). Most (69 %) of the studies employed only one post-baseline scan. Quantification was mainly based on SUVmax (91 %), while change over time was most frequently used to combine measurements into a rule (79 %). Half of the reports were categorised as developmental, the other half evaluative. Most development studies assessed only one element (35/62, 56 %), most frequently the choice of cut-off points (25/62, 40 %). In summary, the majority of studies did not address the essential open issues in establishing PET/CT for response evaluation. Reasonably sized multicentre studies are needed to systematically compare the many different options when using PET/CT for response evaluation. [ABSTRACT FROM AUTHOR]

Purpose: PET/MRI was introduced for clinical use in 2011 and is now an established modality for the imaging of brain and certain pelvic cancers, whereas clinical use for the imaging of other forms of cancer is not yet widespread. We therefore systematically investigated what has been published on the use of PET/MRI compared to PET/CT in the imaging of cancers outside the brain, focusing on clinical areas of application related to diagnosis, staging and restaging. Methods: A systematic search of PubMed/MEDLINE, Embase and the Cochrane Library was performed. Studies evaluating the diagnostic performance of simultaneous PET/MRI in cancer patients were chosen. Results: A total of 3,138 publications were identified and 116 published during the period 2012–2018 were included and were grouped according to the major cancer forms: 13 head and neck (HNC), 9 breast (BC), 21 prostate (PC), 14 gynaecological, 13 gastrointestinal (GIC), and 46 various cancers. Data from studies comparing PET/MRI and PET/CT for staging/restaging suggested the superiority of 18F-FDG PET/MRI for the detection of tumour extension and retropharyngeal lymph node metastases in nasopharyngeal cancer, and for the detection of liver metastases and possibly bone marrow metastases in high-risk BC. FDG PET/MRI tended to be inferior for the detection of lung metastases in HNC and BC. 68Ga-PSMA-11 PET/MRI was superior to PET/CT for the detection of local PC recurrence. FDG PET/MRI was superior to FDG PET/CT for the detection of local tumour invasion in cervical cancer and had higher accuracy for the detection of liver metastases in colorectal cancer. Conclusion: The scoping review methodology resulted in the identification of a huge number of records, of which less than 5% were suitable for inclusion and only a limited number allowed conclusions on the advantages/disadvantages of PET/MRI compared to PET/CT in the oncological setting. There was evidence to support the use of FDG PET/MRI in staging of nasopharyngeal cancer and high-risk BC. Preliminary data indicate the superiority of PET/MRI for the detection of local recurrence in PC, local tumour invasion in cervical cancer, and liver metastases in colorectal cancer. These conclusions are based on small datasets and need to be further explored. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma.Methods: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging-magnetic resonance imaging (MRI) and chest X-ray (CXR)-in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer.Results: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers.Conclusions: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers. [ABSTRACT FROM AUTHOR]

Purpose: The present study is a register-based observational study of an unselected consecutive patient cohort with pulmonary arteriovenous malformations (PAVMs) from a single national hereditary hemorrhagic telangiectasia and PAVM embolization center. The aim was to investigate the frequency of re-embolizations and the clinical outcome after embolization with the use of different embolization materials further, to define which PAVM morphology and size of feeding arteries that most often were re-embolized, and to estimate the clinical outcome of the patients including those that were re-embolized.Methods: The population was included from 1996 until 2016 and was made up of a total of 136 patients with 322 PAVMs. Median follow-up was 38.3 (0.3-241 months).Results: The re-embolization rate was 9.3%. None of the PAVMs treated with detachable silicone balloons were re-embolized, while 4.5% treated with vascular plugs and 11.7% treated with coils were re-embolized (p=0.07). In total, 16/74 complex PAVMs were re-embolized compared with 14/248 simple PAVMs. In big-sized feeding arteries ≥ 6mm, 16/112 were re-embolized compared with 14/210 with smaller-sized feeding arteries. Out of the 30 re-embolized PAVMs, 23 resulted in a successful clinical outcome.Conclusions: Our results suggest that standard coils probably should not be the first choice for embolization of PAVMs, and vascular plug alone or in combination with coils might be a better primary option for embolization in these patients.Level Of Evidence: Level 3A, non-randomized case controlled cohort/follow-up study. [ABSTRACT FROM AUTHOR]

Purpose: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43–75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". Results: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43–0.99), 0.86 (range 0.64–0.98), and 0.95 (range 0.65–1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18–0.98), 0.70 (range 0.48–0.81), and 0.84 (range 0.75–0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. Conclusion: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions. [ABSTRACT FROM AUTHOR]

Purpose: Suspected serious disease (SSD) is a disease designation often given to patients with one or more non-specific symptoms of severe disease that could be due to cancer; the optimal diagnostic strategy is largely left to the clinician's discretion. Being a sensitive non-invasive whole-body imaging modality 18F-FDG-PET/CT may have a potential role in this cancer-prevalent group of patients to confirm or refute suspected malignancy. We aimed to investigate the diagnostic value of 18F-FDG-PET/CT in SSD using long-term follow-up as reference.Methods: We retrospectively studied results obtained in all SSD patients referred for 18F-FDG-PET/CT at a single institution in 2010-2011 retrieving the following clinical data in all patients: journal entries, examinations, and evaluations made from 6 months before the scan and until the latest recorded entry. A true positive PET scan was a positive scan with a subsequently biopsy-confirmed diagnosis of cancer in the same target organ, whereas a false positive scan had no subsequent cancer diagnosis. A true negative PET scan was a negative scan without a cancer diagnosis during follow-up, whereas a false negative PET scan was one with a subsequently confirmed cancer diagnosis.Results: Ninety-three patients, aged 67 years (range 25-89) were included and followed for up to 7.3 years (median 6). Of these, 21 [22.6% (95% CI 15.3-32.1)] turned out to have cancer. With 18F-FDG-PET/CT, the sensitivity was 81.0% (95% CI 60.0-92.3), specificity 76.4% (95% CI 65.4-84.7), positive predictive value 50% (95% CI 34.1-65.9), and negative predictive value 93.2% (95% CI 83.8-97.3). Five patients with negative scans were subsequently diagnosed with cancer.Conclusion: Cancer prevalence is substantial among patients with SSD. 18F-FDG-PET/CT is a promising option in this setting, in particular because a high negative predictive value equals a low incidence of cancer during follow-up. Further studies are needed to establish the role of 18F-FDG-PET/CT in SSD. [ABSTRACT FROM AUTHOR]

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89-97%) versus 76% (64-88%), p = 0.0004; positive predictive value 71% (55-86%) versus 51% (37-65%), p = 0.0001; accuracy 90% (84-95%) versus 77% (69-84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy. [ABSTRACT FROM AUTHOR]

Background: Nuclear imaging is increasingly being used in the diagnostic work-up of idiopathic inflammatory myopathy (IIM). Increased muscular uptake of technetium-99m-pyrophosphate (Tc-PYP) has hitherto been assessed qualitatively by planar scintigraphy. We set out to perform quantitative tomographic scintigraphy in IIM. Results: Ninety IIM patients and 48 control subjects underwent Tc-PYP single-photon emission computed tomography (SPECT)/CT of the upper and lower body. Scans were evaluated visually by an intensity score (1-4) and quantitatively by the mean standardized uptake value (SUV) in thigh muscles after semi-automated segmentation of these. Furthermore, a SUV gradient down along the thighs was determined by linear regression of the slice-by-slice activity. Interobserver analyses were performed on qualitative evaluations. Compared to controls, patients more often had a high intensity score ( p < 0.0001), but interobserver analyses revealed only moderate agreement. The thigh muscular Tc-PYP activity (SUV) was 60% higher in patients than in controls, p < 0.0001, albeit with a wide range. There was an activity gradient down the thigh muscle, the proximal tracer uptake being highest, and this gradient was steeper in patients than in controls; the activity decreased by 0.00024 and 0.00010 SUV mm, respectively, along the thighs. Conclusions: The muscular uptake of Tc-PYP was significantly higher in patients than in healthy controls by qualitative and quantitative assessment. The tracer uptake was higher in the proximal than in the distal part of the thigh muscle, and SUV gradients differed between groups. Hence, tomographic nuclear imaging allowing for quantification of the Tc-PYP uptake might contribute to the diagnosis of IIM, and SPECT/CT of the lower body might suffice. [ABSTRACT FROM AUTHOR]

Background: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT measurements, illuminating the possibility of early trial termination which implicates significant potential time and resource savings. Methods: Primary lesion maximum standardised uptake value (SUVmax) was determined twice from preoperative FDG-PET/CTs in 45 ovarian cancer patients. Differences in SUVmax were assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis ( N = 45) was compared with the group-sequential analysis strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. Results: When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis and the final analysis. Other partitions did not suggest early stopping after adjustment for multiple testing due to one influential outlier and our small sample size. Conclusions: Group-sequential testing may enable early stopping of a trial, allowing for potential time and resource savings. The testing strategy must, though, be defined at the planning stage, and sample sizes must be reasonably large at interim analysis to ensure robustness against single outliers. Group-sequential testing may have a place in accuracy and agreement studies. [ABSTRACT FROM AUTHOR]

Objective: Patients presenting with cystic lesions in the neck without obvious signs of malignancy constitute a diagnostic challenge since fine needle aspiration is often insufficient and a diagnosis may not be reached until surgical resection/biopsy is performed. The differential diagnosis of a cystic cervical mass comprises a variety of benign conditions, but malignancy must be ruled out. We examined the diagnostic performance of fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT to identify malignancy. Methods: We retrospectively included consecutive patients referred from the Department of ENT Head and Neck Surgery for 18F-FDG PET/CT-scans because of a solitary neck cyst. Scan results were compared to histopathology and follow-up. Results: The study comprised 58 patients. Twenty patients (34%) were diagnosed with cancer during follow-up. PET/CT suggested malignancy in 34 patients (19 true positive, 15 false positive) and showed no malignancy in 24 (23 true negative, 1 false negative). The sensitivity, specificity, accuracy, positive and negative predictive values were 95% (76-99%), 61% (45-74%), 72% (60-82%), 56% (39-71%), and 96% (80-99%), respectively (95% confidence intervals in brackets). The primary tumor was identified in 14 out of the 20 patients with confirmed cancer. Increased metabolism, as evaluated by PET, was the only imaging characteristic among several others, which associated independently with malignancy in the cystic neck lesions, odds ratio 1.27 (1.07-1.50), p = 0.006. Conclusion: 18F-FDG PET/CT could reliably rule out malignancy (NPV 96%), albeit with a high frequency of false positive scans, requiring further diagnostic work-up. Increased metabolism was the best imaging parameter to differentiate between malignant and benign lesions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed. Methods: Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase. Results: FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression. Conclusion: RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to define reference ranges for quantitative parameters in [(99m)Tc]mercaptoacetyltriglycerine ([(99m)Tc]MAG3) renography to assist interpretation in a semi-automated (Xeleris, GE) compared to a manual (Picker, Odyssey) software package.Procedures: Forty-eight subjects approved for renal donation were evaluated with [(99m)Tc]MAG3 renography using both the Xeleris and the Picker software.Results: Reference ranges for the two software were comparable regarding the relative function of the two kidneys (the split function, SF) and the residual activities (RA). The time to peak whole-kidney activities (T max whole-kidney) was more dependent on the type of software. Using Bland-Altman limits, we found good and acceptable agreement between the two methods.Conclusions: We found good correlation between renography results using the Xeleris and Picker software packages. However, software-specific reference ranges are needed. [ABSTRACT FROM AUTHOR]

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Purpose: CT angiography (CTA) can rule out significant stenoses with a very high reliability, whereas its ability to confirm significant stenoses is suboptimal. In contrast, measurements of myocardial blood flow (MBF) provide information on the haemodynamic consequences of stenoses. Therefore, a combination of the two might improve diagnostic accuracy. We conducted a head-to-head comparison of CTA, measurement of MBF by O-water PET, and hybrid PET/CTA for the detection of significant coronary artery stenoses. Methods: The study group comprised 44 outpatients scheduled for invasive coronary angiography (ICA) with an intermediate pretest likelihood of coronary artery disease. The patients underwent 64-slice CTA and baseline and hyperaemic PET before ICA with quantitative coronary angiography analysis. Results: On a per-patient basis, the negative predictive values (NPV; 95 % confidence intervals in parentheses) were 88 % (64 - 97 %) for CTA, 90 % (71 - 97%) for PET and 92 % (74 - 98%) for PET/CTA, and the positive predictive values (PPV) were 71 % (53 - 85%) for CTA, 87 % (68 - 95%) for PET and 100 % (84 - 100%) for PET/CTA. Similarly, on a per-vessel basis the NPVs (which were generally high) were 97 % (94 - 100%) for CTA, 95 % (90 - 99%) for PET and 97 % (95 - 100%) for PET/CTA, and the PPVs (which were lower, but higher with PET/CTA) were 53 % (39 - 66%) for CTA, 53 % (40 - 66%) for PET and 85 % (73 - 97%) for PET/CTA. In six patients, CTA analysis was hampered by the presence of severe calcifications. However, with the addition of the PET data, all six patients were correctly categorized. Conclusion: Cardiac quantitative hybrid PET/CTA imaging has better diagnostic accuracy than CTA alone and PET alone. CTA has a suboptimal PPV, suggesting that hybrid PET/CTA imaging should be used to assess the significance of coronary stenoses diagnosed by CTA. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of a normal myocardial perfusion scintigraphy (MPS) may be well described, but long-term follow-up data are sparse, and temporal variations in risk are insufficiently elucidated. Methods and Results: During long-term follow-up (mean 6.2 years) of 1,327 consecutive Danish patients with normal MPS, the rate of all-cause death (ACD) was 1.9%/year (differing by gender) and of cardiac death (CD)/myocardial infarction (MI) 0.8%/year (differing by coronary artery disease, CAD). Female gender (HR: 0.60), age (HR: 1.07 per-year increment), and known CAD without prior revascularization (HR: 2.17) were statistically significant factors for ACD, whereas diabetes and previous MI per se were not. Known CAD with previous revascularization carried a low risk of ACD when adjusted for gender and age (HR: 0.56). For CD/MI, risk increased with age and threefold with known CAD, previous MI, and previous percutaneous coronary intervention. Judged from smoothed hazard functions, mortality risk increased further with time for men, elderly, and diabetics and markedly further with known CAD without prior revascularization. Conclusions: Following a normal MPS, rates of death and hard cardiac events were low. Risk varied with age, gender, and disease history. Novel aspects of temporal risk variation suggested a general warranty period of 5 years, but less in risk groups. [ABSTRACT FROM AUTHOR]

Background: An experimental swine model ( n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO compatible with intact energy metabolism. Methods: ASDH was produced by infusion of 7 ml of autologous blood (infusion rate 0.5 ml/min) by a catheter placed subdurally. PbtO and microdialysis probes were placed symmetrically in the injured ('bad-side') and non-injured ('good-side') hemispheres. Intracranial pressure (ICP) was monitored in the 'good-side.' Results: ICP, cerebral perfusion pressure (CPP), PbtO, glucose, lactate, pyruvate, lactate-pyruvate ratio (LP ratio), glutamate, and glycerol were recorded at baseline (60 min) and post trauma (360 min). After the creation of the ASDH, PbtO decreased significantly in both the hemispheres ( P < 0.001). No significant difference was found between the sides post trauma. The LP ratio, glutamate, and glycerol in the 'bad-side' increased significantly over the 'good-side' where the values remained within the normal limits. A PbtO value below approximately 25 mmHg was found to be associated with disturbed energy metabolism in the 'bad-side' but not in the 'good-side.' No correlation was found between the LP ratio and PbtO in either hemisphere. Conclusions: PbtO monitoring accurately describes tissue oxygenation but does not disclose whether the oxygen delivery is sufficient for maintaining cerebral energy metabolism. Accordingly, it may not be possible to define a threshold level for PbtO below which energy failure and permanent tissue damage occurs. [ABSTRACT FROM AUTHOR]

Objectives: We report the 3-year clinical experience of a large new Danish PET/CT centre without capacity limitations in relation to national and European developments.Methods: The use of PET/CT in cancer was registered from early 2006 to early 2009 to judge the impact on patient management and to compare it with national and European trends.Results: 6056 PET/CT examinations were performed in 4327 patients. Activity increased by 86 examinations per month compared with the same month the year before. Referrals came primarily from oncology (23.0%), haematology (21.6%), surgery (12.6%), internal medicine (12.7%) and gynaecology (5.5%). Referral indications were diagnosis (31.3%), staging (22.3%), recurrence detection (21.2%), response evaluation (17.0%) and other (8.2%). Response from nearly 60% of users showed that PET/CT caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. During the study period, there was a steep increase in the national use of FDG and in the European use of PET/CT.Conclusions: We recorded a constantly increasing use of PET/CT that caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. In line with national and European trends this may suggest a shift in favour of functional rather than anatomical imaging. [ABSTRACT FROM AUTHOR]