Search

Purpose: We aimed provide overview of the current literature regarding the diagnostic accuracy of 2-[18F]FDG-PET/CT in detecting immune-related adverse events (irAEs) in patients with metastatic melanoma or non-small cell lung cancer (NSCLC), receiving treatment with immune checkpoint inhibitors (ICIs). Methods: Following PRISMA guidelines for scoping reviews, we first performed a comprehensive literature search in Medline (PubMed), Embase, and Scopus. After applying inclusion/exclusion criteria and abstract/full-text review, 7 articles with 478 patients with melanoma and 2 with 155 patients with NSCLC were included. The reference standard was irAE, corroborated clinically, biochemically, histologically, or on other imaging modalities. Results: Melanoma:Five studies reported the sensitivity of 2-[18F]FDG-PET/CT, while two reported the prevalence of irAEs detected only by 2-[18F]FDG-PET/CT (without other verification of irAEs). The clinically reported prevalence of irAEs ranged from 1 to 18% for thyroiditis, 4–19% for colitis, and 3–9% for pneumonitis. The sensitivity of 2-[18F]FDG-PET/CT was 89–100% for thyroiditis, and 100% for colitis, pneumonitis, and sarcoid reaction in mediastinal lymph nodes. Only one study reported specificity and found a value of 49% for colitis, 96% for pneumonitis, and 81% for thyroiditis. NSCLC: The prevalence of 2-[18F]FDG-PET/CT detected irAEs 9–33% for thyroiditis, 34–40% for colitis, and 17–20% for pneumonitis. A sensitivity of 67% was found for thyroiditis. Results regarding specificity were lacking. Conclusion: Studies suggested that 2-[18F]FDG-PET/CT is a valuable, non-invasive tool for detecting adverse events to anticancer treatment with ICIs. Sensitivity for the most commonly investigated irAEs, including thyroiditis, colitis, and pneumonitis, was generally high. Specificity was more varying and poorly reported. Prospective studies exploring the clinical impact are needed to determine the role and optimal timing of 2-[18F]FDG-PET/CT in identifying irAEs.

Purpose: To evaluate the potential benefit of adding a low frequency vascular probe to the conventional pre-operative ultrasound examination of patients with primary hyperparathyroidism. Methods: A prospective cohort of 136 patients with primary hyperparathyroidism underwent a conventional ultrasound examination of the neck with a high frequency ( > 10 MHz) linear ultrasound probe, followed by an add-on examination with a low frequency vascular probe. For each ultrasound probe, and for every potential parathyroid lesion, the presence of a feeding vessel, a polar placement of the feeding vessel, and the presence of a vascular arch was recorded. Results: A total of 146 ultrasound lesions were evaluated for vascularity by each probe. For both ultrasound probes, the odds of a hyperfunctioning parathyroid gland being correctly identified increased with the number of visible vascular features. The vascular probe identified a significantly higher number of vascular features among ultrasound true positive glands compared with the conventional probe (p< 0.0001). Among histopathologically verified pathological parathyroid glands, the vascular probe identified 20% more feeding vessels, 27% more polar placements of the feeding vessel, and 65% more vascular arches than the high frequency probe. However, the diagnostic confidence score for true positive glands did not differ significantly between the probes (p= 0.11). Conclusion: The addition of a low frequency vascular probe increases the number of visible vascular features in hyperfunctioning parathyroid glands, which facilitates their preoperative detection. Whether or not this can increase the diagnostic confidence of ultrasound examiners has yet to be substantiated.

IMPORTANCE: Scintigraphy and ultrasonography are common imaging modalities for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism. When comparing the 2 modalities, the benefits of ultrasonography in terms of convenience, patient comfort, duration, cost, and lack of radiation should be taken into account. OBJECTIVE: To investigate whether surgeon-performed ultrasonography, with or without contrast-enhanced ultrasonography (CEUS), is noninferior to scintigraphy for localizing pathological parathyroid glands in patients with primary hyperparathyroidism. DESIGN, SETTING, AND PARTICIPANTS: Prospective, paired, noninferiority cohort study performed at a high-volume tertiary referral center for parathyroidectomy with blinded examiners and a 6-month follow-up. Participants were adults (age ≥18 years) referred for parathyroidectomy due to primary hyperparathyroidism. Of 207 eligible patients, 35 were excluded, leaving 172 enrolled in the study. Inclusion lasted from September 2019 until February 2021. Follow-up ended in December 2021. EXPOSURES: 99mTechnetium-pertechnetate/99mtechnetium-sestamibi subtraction scintigraphy with 99mtechnetium-sestamibi single-photon emission computed tomography/computed tomography, followed by surgeon-performed ultrasonography and CEUS. MAIN OUTCOMES AND MEASURES: The sensitivity of each imaging modality in localizing pathological parathyroid glands, calculated on a per-quadrant and a per-patient basis, respectively. The a priori noninferiority margin was a lower 95% confidence limit for the difference in sensitivity not falling below −10%. RESULTS: Out of 172 participants, 139 (80.8%) were women, the median (range) age was 65 (24-87) years, and the median (IQR) follow-up was 200.5 (181-280.25) days. Quadrant sensitivity (95% CI) was 70.9% (63.2%-78.5%) for ultrasonography, 68.4% (60.4%-76.5%) for ultrasonography plus CEUS, and 67.0% (60.0%-74.0%) for scintigraphy. The sensitivity difference (95% CI) compared with scintigraphy was 3.9% (−4.1% to 11.8%) for ultrasonography and 1.5% (−6.4% to 9.3%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Per-patient sensitivity was 81.4% (74.8%-86.9%) for ultrasonography and 79.1% (72.2%-84.9%) for both scintigraphy and ultrasonography plus CEUS. The sensitivity difference compared with scintigraphy was 2.3% (−6.8% to 11.4%) for ultrasonography and 0.0% (−9.1% to 9.1%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. CONCLUSIONS AND RELEVANCE: In this cohort study, conventional ultrasonography by an experienced parathyroid surgeon-sonographer was noninferior to scintigraphy and may constitute a valid first-line imaging modality in patients with primary hyperparathyroidism, even without the addition of CEUS. Further imaging should be reserved for cases that are equivocal or nonlocalizing on ultrasonography.

As the number of interventional treatments for aortic stenosis (AS) with transcatheter aortic valve implantation (TAVI) continues to increase in younger and low-risk patients [1], an important question arises: Which clinical factors should we consider when making shared, informed treatment decisions for these patients? Several randomized controlled trials in low-risk patients with short follow-up have demonstrated that TAVI is superior or non-inferior to surgical aortic valve replacement (SAVR) in terms of all-cause death [2–5], stroke [3–5] and atrial fibrillation [6].

This prospective study tested the diagnostic accuracy, and absolute agreement with MRI of a low-dose CT protocol for left ventricular ejection fraction (LVEF) measurement. Furthermore we assessed its potential for combining it with Chest-Abdomen-Pelvis CT (CAP-CT) for a one-stop examination.

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.

Purpose: To review published evidence of possible links between Alzheimer’s disease (AD) and type-2 diabetes mellitus revealed by positron emission tomography (PET). Methods: We searched online databases with keywords diabetes mellitus (DM), AD, and PET. We assessed the studies in terms of purpose, methodology, materials, and relationships between AD and DM suggested by PET imaging. Results: After removal of 142 duplicates, 227 hits yielded no more than 15 full-length publications, from which we excluded six for specific reasons. The remaining nine studies were not directly comparable because of differences of purpose, study design, material, and methods. Individual subject materials consisted of 4–154 patients in case–control (4), observational (4), and longitudinal (1) studies, the last including only four DM patients. Mean patient age was 76.4 years (range 45–90). In five studies, researchers examined regional cerebral glucose metabolism with 18F-fluorodeoxyglucose (FDG), in three studies, researchers imaged amyloid with PET, and in one study, they measured both glucose metabolism and amyloid deposition. All four studies of amyloid tracers led to the conclusion that amyloid deposition was unaffected by DM status. Evidence of insulin resistance and increased blood glucose was associated with decreased FDG accumulation in AD signature regions in DM patients. Conclusion: The relationships between DM and AD identified by PET appear to be independent of amyloid deposition and predominantly highlighted by reduced glucose metabolism, as suggested by four of the five glucose metabolism studies.

Background: Artificial intelligence (AI) systems are proposed as a replacement of the first reader in double reading within mammography screening. We aimed to assess cancer detection accuracy of an AI system in a Danish screening population. Methods: We retrieved a consecutive screening cohort from the Region of Southern Denmark including all participating women between Aug 4, 2014, and August 15, 2018. Screening mammograms were processed by a commercial AI system and detection accuracy was evaluated in two scenarios, Standalone AI and AI-integrated screening replacing first reader, with first reader and double reading with arbitration (combined reading) as comparators, respectively. Two AI-score cut-off points were applied by matching at mean first reader sensitivity (AIsens) and specificity (AIspec). Reference standard was histopathology-proven breast cancer or cancer-free follow-up within 24 months. Coprimary endpoints were sensitivity and specificity, and secondary endpoints were positive predictive value (PPV), negative predictive value (NPV), recall rate, and arbitration rate. Accuracy estimates were calculated using McNemar’s test or exact binomial test. Results: Out of 272,008 screening mammograms from 158,732 women, 257,671 (94.7%) with adequate image data were included in the final analyses. Sensitivity and specificity were 63.7% (95% CI 61.6%-65.8%) and 97.8% (97.7-97.8%) for first reader, and 73.9% (72.0-75.8%) and 97.9% (97.9-98.0%) for combined reading, respectively. Standalone AIsensshowed a lower specificity (-1.3%) and PPV (-6.1%), and a higher recall rate (+ 1.3%) compared to first reader (p< 0.0001 for all), while Standalone AIspechad a lower sensitivity (-5.1%; p < 0.0001), PPV (-1.3%; p = 0.01) and NPV (-0.04%; p = 0.0002). Compared to combined reading, Integrated AIsensachieved higher sensitivity (+ 2.3%; p = 0.0004), but lower specificity (-0.6%) and PPV (-3.9%) as well as higher recall rate (+ 0.6%) and arbitration rate (+ 2.2%; p < 0.0001 for all). Integrated AIspecshowed no significant difference in any outcome measures apart from a slightly higher arbitration rate (p< 0.0001). Subgroup analyses showed higher detection of interval cancers by Standalone AI and Integrated AI at both thresholds (p< 0.0001 for all) with a varying composition of detected cancers across multiple subgroups of tumour characteristics. Conclusions: Replacing first reader in double reading with an AI could be feasible but choosing an appropriate AI threshold is crucial to maintaining cancer detection accuracy and workload.

The use of molecular imaging in staging of prostate cancer (PC) is debated. In patients with newly diagnosed PC we investigated the diagnostic value of 18F-flouromethylcholine positron emission tomography/computed tomography (18F-FCH-PET/CT) for the detection of bone and lymph node metastases compared to whole-body bone scintigraphy (WBS) with technetium-99-methylene diphosphonate (99mTc-MDP) and results of extended pelvic lymph node dissection, respectively.

Vascular graft infection (VGI) in central grafts is a rare but dreaded complication with a high mortality. Several imaging modalities are employed, all with pros and cons. Computed tomography is the standard, but lacks sensitivity for low-grade infections. There is still no consensus regarding the diagnostic modality of choice. The study objective was to assess the role of combined positron emission tomography and computed tomography with fluorodeoxyglucose (FDG-PET/CT) in the diagnostic workup of VGI in central grafts. A systematic review was conducted according to the PRISMA guidelines through a search in Embase, PubMed, and Cochrane databases. Meta-analysis on accuracy measures was carried out with random effects models for three parameters: focal uptake, visual grading scale (VGS), and maximum standardized uptake value (SUVmax). Heterogeneity among studies was assessed with the I-squared test. A total of 307 studies were identified and 9 were eligible for inclusion. The pooled estimates for sensitivity and specificity for focal uptake were 90.6% (95% CI 81.7–99.4%) and 82.8% (95% CI 71.3–94.3%), respectively, for VGS 86.8% (95% CI 59.3–100%) and 69.4% (95% CI 39.9–98.9%), respectively, for SUVmax92.8% (95% CI 83.2–100%) and 69.7% (95% CI 52.4–86.9%), respectively. A single study employed tissue-to-background ratio (TBR) and found sensitivity and specificity of 71.8% (95% CI 54.6–84.4%) and 70.4% (95% CI 51.5–84.2%), respectively. According to this systematic review and meta-analysis, FDG-PET/CT performs well especially when using focal versus diffuse FDG uptake to diagnose VGI.

Cardiovascular molecular imaging has focused on assessing myocardial perfusion and ventricular ejection fraction. These modalities target late downstream effects of the atherosclerotic disease process; this calls for a change of focus toward methods that can detect early arterial wall changes before macrocalcifications become visible on computed tomography angiography and provide a better understanding of the disease process. We summarize current knowledge on PET in atherosclerosis and highlight pertinent questions relating to the early detection of atherosclerosis. The future of PET in atherosclerosis may be early individualized quantification of the arteriosclerotic disease burden rather than exploration of features of individual arterial plaques.

Venous thromboembolism (VTE) is common; deep venous thrombosis (DVT) and pulmonary embolism (PE) are the most common presentations. VTE may arise from anywhere in the entire venous bed and the diagnosis may be difficult. VTE is a dynamic disease, inflammation is key, and 18F-Fluorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) has been proposed in the evaluation of VTE to detect thrombi in any anatomic location, to differentiate acute from chronic VTE, and to differentiate bland VTE from tumor thrombosis. The aim of this systematic review was to assess if the potential uses of FDG-PET/CT in VTE are described and documented in the literature and to appraise the literature. PubMed and Embase databases were searched. Duplicates and papers in other languages than English and Scandinavian were removed. Remaining papers were screened by title and abstract. Eligible papers were assessed in full text. The master search yielded 3897 hits; 316 papers were eligible for full-text assessment. Ten papers were included: six on diagnostic performance of PET/CT in VTE, and four on the ability of PET/CT to differentiate bland VTE from tumor thrombosis. Three papers were prospective; seven were retrospective. The available literature is too sparse to draw firm conclusions; however, FDG-PET/CT may have a role in diagnosing early DVT, but not PE, in discriminating acute from chronic VTE, in demonstrating recurrent VTE, and possibly for screening for occult malignancy.

Background Coronary artery calcium is important in cardiovascular risk stratification, but this knowledge is based on studies with a significant selection bias. This study aims to evaluate the external validity of a screening programme including coronary artery calcium examination, and the association between coronary artery calcium and cardiovascular events.Design Multi-centre population based study.Methods Randomly selected middle-aged men and women (N= 1751) free of cardiovascular disease were invited to the examination during 2009–2010. Participation rate in the examination was 70%. Participants (n= 1227) and non-participants (n= 524) were compared regarding: cardiovascular medical treatment, Charlson comorbidity index and socioeconomic status (evaluated by cohabitation, gross income and education). Study endpoints were cardiovascular events and mortality.Results Non-participants had a significant higher comorbidity (p= 0.003) and a lower socioeconomic status (p< 0.0001), while cardiovascular medical treatment was alike. Over a median follow-up time of 6.5 years the cardiovascular event and mortality rates were equal (6.7% vs. 6.4%, p= 0.80 and 0.4% vs. 0.5%, p= 0.76, respectively). Adjusted hazard ratio was 0.90 (95% confidence interval (CI) 0.63–1.37). Among participants, the extent of coronary artery calcium was significantly associated with increased risk of cardiovascular events (hazard ratio 1.92, 95% CI 1.03–3.54, hazard ratio 3.66, 95% CI 1.82–7.32, hazard ratio 6.51, 95% CI 3.17–13.36 for coronary artery calcium scores 1–99, 100–399, ≥400 AU, respectively).Conclusions Non-participants had a higher comorbidity index and a lower socioeconomic status, but the cardiovascular event and mortality rates were equal to those of participants. Thus, a screening programme including a coronary artery calcium examination had a high external validity regarding cardiovascular risk, but also a significant social imbalance.

Supplemental Digital Content is available in the text.

Tuberculosis (TB) is an infectious disease with a high global incidence and substantial disease burden. Monitoring disease activity and evaluating treatment response with conventional methods such as culture or chest x-ray is time-consuming and non-specific. Active TB lesions are typically highly FDG-avid and may be assessed on whole-body 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). We hypothesized that FDG-PET or FDG-PET/CT is useful for evaluation of treatment response and outcome in TB-infected patients undergoing anti-tuberculosis therapy (ATT). PubMed and Embase databases were searched and original studies with humans infected with Mycobacterium tuberculosisreceiving ATT and a minimum of one FDGPET/CT or FDG-PET scan were included. Percentage change in maximum standardized uptake value (SUVmax) from baseline was assessed with a fixed-effects model using the inverse variance method supplemented by a Forest Plot. Publication bias and heterogeneity between studies was assessed with a Funnel plot and the Isquared statistic, respectively. A total of 2048 articles were identified and nine were included in the review. Four studies were included in the meta-analysis. The estimated overall percentage change in SUVmax was − 54.38% (95% confidence interval − 57.81 to − 50.96) and the heterogeneity between studies was high (I2= 90.1%). Study design, protocol, sample size and ATT varied between studies. Despite high heterogeneity there was a trend towards the usefulness of FDG-PET or FDG-PET/CT for evaluation of ATT response. Impending research is needed to further clarify the predictive value of FDG-PET/CT in tuberculous disease.

The development of clinical diagnostic procedures comprises early-phase and late-phase studies to elucidate diagnostic accuracy and patient outcome. Economic assessments of new diagnostic procedures compared with established work-ups indicate additional cost for 1 additional unit of effectiveness measure by means of incremental cost-effectiveness ratios when considering the replacement of the standard regimen by a new diagnostic procedure. This article discusses economic assessments of PET and PET/computed tomography reported until mid-July 2014. Forty-seven studies on cancer and noncancer indications were identified but, because of the widely varying scope of the analyses, a substantial amount of work remains to be done.

Coronary atherosclerosis is a leading cause of mortality. New technological developments in computed tomography (CT), including dual energy, iterative reconstructions and high definition scanning, could significantly improve the non-invasive identification of atherosclerosis plaques. Here, a new method for optimising cardiac coronary CT with optical coherence tomography (OCT) and histopathology is presented.

To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophystrain have been shown to provide independent prognostic information. In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification.

Objectives: The aim was to examine and compare the impact of HeartScore and coronary artery calcification (CAC) score on subsequent changes in the use of medication.Methods: A total of 1156 healthy men and women, aged 50 or 60, had a baseline medical examination and a coronary artery CT-scan as a part of a screening programme. Using the European HeartScore, the total 10-year cardiovascular mortality risk was estimated (≥5% risk was considered as high). Risk factors and CAC scores were reported to both the patients and their general practitioner. Six months after the screening, follow-up questionnaires addressing current medication were mailed to the participants.Results: A completed questionnaire was returned by 1075 (93%) subjects. At follow up, the overall use of prophylactic medication was significantly increased. Of those with CAC (n = 462) or high HeartScore (n = 233), 21 and 19%, respectively, received lipid-lowering treatment, while 25 and 32%, respectively, received antihypertensive treatment. In multivariate logistic regression analyses, the presence of CAC was associated with an increased use of lipid-lowering treatment (OR 2.2; 95% CI 1.2–4.0), while the presence of a high HeartScore was associated with an increased use of lipid-lowering (OR 2.9; 95% CI 1.6–5.5) and antihypertensive medication (OR 3.4; 95% CI 1.9–6.0).Conclusion: Knowledge of present cardiovascular risk factors like high HeartScore and/or CAC leads to beneficial changes in medication. However, at follow up only a minority of high-risk subjects did received prophylactic treatment. CAC score was not superior to HeartScore regarding these motivational outcomes.

Background: Coronary artery calcification (CAC) is an independent and incremental risk marker. This marker has previously not been compared to the HeartScore risk model. Design: A random sample of 1825 citizens (men and women, 50 or 60 years of age) was invited for screening. Methods: Using the HeartScore model, the 10-year risk of fatal cardiovascular events based on gender, age, smoking, systolic blood pressure, and total cholesterol was estimated. A low risk was defined as <5%. The CAC score was calculated from a non-contrast enhanced cardiac-CT scan and given in Agatston U. Results: A total of 1257 (69%) of the invited subjects were interested in the screening. Due to previous cardiovascular disease or diabetes mellitus, 101 were excluded. Of the remaining 1156, 47% were men and 53% women; one half were 50 years old and the other half 60 years old. A low HeartScore was found in 901 of which 334 (37%) had CAC. A high HeartScore was recorded in 251 of which 80 (32%) did not have any CAC. High HeartScores and CAC were significantly more common in males than females. Conclusions: CAC is common in healthy middle-aged Danes with a low HeartScore, and, on the contrary, high-risk subjects very frequently do not have CAC. The therapeutic and prognostic implications of these observations remain to be clarified.

Detection of coronary artery calcification (CAC) has been proposed for population screening. It remains unknown whether such a strategy would result in unnecessary concern among participants. Therefore, we set out to assess whether CAC screening affects the psychological well-being of screening participants.

Although type 2 diabetes mellitus is a risk factor for developing congestive heart failure, the mechanism leading to heart failure is unclear. We examined the prevalence of left ventricular (LV) systolic and diastolic dysfunction in patients with type 2 diabetes mellitus in relation to vascular function and myocardial perfusion.

In this paper statistical tests with fuzzily formulated hypotheses are discussed, i.e., hypotheses H0and H1are fuzzy sets. The classical criteria of the errors of type I and type II are generalized, and this approach is applied to the linear hypothesis in the linear regression model. A sufficient condition to control both generalized criteria simultaneously is presented even in case of testing H0against the omnibus alternative H1: -H0. This is completely different from the classical case of testing crisp complementary hypotheses.

Positron emission tomography (PET) offers an incredible wealth of diverse research applications in vascular disease, providing a depth of molecular, functional, structural, and spatial information. Despite this, vascular PET imaging has not yet assumed the same clinical use as vascular ultrasound, CT, and MR imaging which provides information about late-onset, structural tissue changes. The current clinical utility of PET relies heavily on visual inspection and suboptimal parameters such as SUVmax; emerging applications have begun to harness the tool of whole-body PET to better understand the disease. Even still, without automation, this is a time-consuming and variable process. This review summarizes PET applications in vascular disorders, highlights emerging AI methods, and discusses the unlocked potential of AI in the clinical space.

Supplemental Digital Content is available in the text