Risk of cancer and serious disease in Danish patients with urgent referral for serious non-specific symptoms and signs of cancer in Funen 2014-2021.

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.

Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients.

Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.

Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Fluoride PET/CT: Correlation with Cardiovascular and Thromboembolic Risk Factors.

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (ß = 0.005, 95% CI 0.003-0.008, p < 0.01 in LCC and ß = 0.006, 95% CI 0.004-0.009, p < 0.01 in RCC), male gender (ß = -0.08, 95% CI -0.173--0.002, p = 0.04 in LCC and ß = -0.13, 95% CI -0.21--0.06, p < 0.01 in RCC), BMI (ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in LCC and ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in RCC), fibrinogen (ß = 0.006, 95% CI 0.0009-0.01, p = 0.02 in LCC and ß = 0.005, 95% CI 0.001-0.01, p = 0.01), HDL cholesterol (ß = 0.13, 95% CI 0.04-0.21, p < 0.01 in RCC only), and CRP (ß = -0.01, 95% CI -0.02-0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p < 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique's predictive value and its potential impact on clinical outcomes.

Novel technique of detecting inflammatory and osseous changes in the glenohumeral joint associated with patient age and weight using FDG- and NaF-PET imaging.

OBJECTIVE: The glenohumeral (GH) joint is a classic ball-and-socket joint of the shoulder subject to various pathologies including osteoarthritis (OA). Degenerative changes of the OA evident on traditional imaging are proceeded by molecular changes, which if detected early could enhance disease prevention and treatment. In this study, we use 18F-FluoroDeoxyGlucose (FDG) and 18F-sodium-fluoride (NaF)-PET/CT to investigate the effects limb laterality, age, and BMI on the inflammation and bone turnover of the GH shoulder joint. METHODS: FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) were analyzed with a semi-quantitative technique based on predefined region of interest. RESULTS: There was greater FDG uptake in the left side of the GH joint compared to the right in both females (left: 0.79 ± 0.17, right: 0.71 ± 0.2; P < 0.0001) and males (left: 0.76 ± 0.19, right: 0.57 ± 0.18; P < 0.0001). We also observed a strong positive association between BMI and FDG uptakes in females (left: P < 0.0001, r = 0.71, right: P < 0.0001, r = 0.58) and males (left: P < 0.0001, r = 0.56, right: P < 0.0001, r = 0.64). Association between BMI and NaF uptake were found in males as well (left: P = 0.004, r = 0.42, right: P = 0.02, r = 0.35). CONCLUSION: Our study demonstrates the varying effect of limb laterality and BMI on FDG and NaF uptake at the GH joint. Adoption of molecular imaging will require future studies that correlate tracer uptake with relevant medical and illness history as well as degenerative change evident on traditional imaging.

The Utility of 18 F-NaF-Positron Emission Tomography/Computed Tomography in Measuring the Metabolic Activity of the Aging Spine : Implications for Osteoporosis.

STUDY DESIGN: Cross-sectional; observational. OBJECTIVES: To determine whether sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) can be used to monitor decreased bone turnover with aging in the spine. BACKGROUND: Osteoporosis is characterized by structural changes in the bone such as decreased bone mineral density leading to an increased risk for fractures. An imaging modality capable of identifying molecular changes that precede these structural changes could be critical for the early diagnosis and monitoring of osteoporosis and other metabolic bone disorders. MATERIALS AND METHODS: The potential of 18 F-sodium fluoride (NaF)-PET/CT in detecting changes in bone turnover associated with aging was examined in the lumbar spine of 88 healthy volunteers (43 females, 45 males; mean age 44.6 yr). Regions of interest equal to the trabecular body of the L1 to L4 vertebrae were used to calculate the mean standardized uptake value (SUVmean) and average Hounsfield unit (HU) values. Receiver-operating characteristic curve analysis with an area under the curve using the Wilson/Brown method was generated to assess the value of NaF uptake (SUVmean) in predicting osteoporosis as defined by HU-threshold values. To determine the correlation among global SUVmean, mean HU values, and age, the Spearman correlation test was performed on images acquired at 90 minutes postinjection. RESULTS: There was a significant negative correlation between NaF SUVmean and age in females ( P < 0.0001, r = -0.59), and a weaker, but also significant correlation in males ( P = 0.03, r = -0.32). In females only, there was a significant correlation between NaF uptake and age at all acquisition time points. Measured NaF uptake increased by 10% to 15% with acquisition time in both sexes, from 45 to 90 minutes and from 90 to 180 minutes. CONCLUSIONS: NaF-PET/CT detects decreased vertebral bone turnover with aging, particularly in females. Measured NaF uptake increased with PET acquisition time after tracer injection, which must be considered in follow-up studies monitoring disease development and treatment effects.

The additive effects of nicotinamide mononucleotide and melatonin on mitochondrial biogenesis and fission/fusion, autophagy, and microRNA-499 in the aged rat heart with reperfusion injury.

The prognosis of myocardial ischemia/reperfusion (I/R) injury is poor in elderly patients. Aging increases the susceptibility of the heart to cell death from I/R injury and prevents the optimal effectiveness of cardioprotective modalities. Since the interaction of aging with cardioprotection is multifactorial, combination therapy may overcome the above-mentioned burden through correcting various components of the injury. Here, we explored the effects of nicotinamide mononucleotide (NMN)/melatonin combination therapy on mitochondrial biogenesis and fission/fusion, autophagy, and microRNA-499 in the aged rat heart with reperfusion injury. Ex vivo model of myocardial I/R injury was established by coronary occlusion and re-opening in 30 aged male Wistar rats (400-450 g, 22-24 months old). NMN (100 mg/kg/48 h, intraperitoneally) was administered over 28 days before I/R, and melatonin (50 µM) was added to the perfusion solution at early reperfusion. CK-MB release and expression of mitochondrial biogenesis genes and proteins, mitochondrial fission/fusion proteins, autophagy genes, and microRNA-499 were assessed. NMN/melatonin combination therapy concomitantly decreased CK-MB release in aged reperfused hearts (P < .001). It also upregulated SIRT1/PGC-1α/Nrf1/TFAM profiles at both gene and protein levels, Mfn2 protein, and microRNA-499 expression, and downregulated Drp1 protein and Beclin1, LC3, and p62 genes (P < .05 to P < .001). The effect of combination therapy was greater than individual ones. Co-application of NMN/melatonin within the setting of I/R injury in the aged rat heart induced noticeable cardioprotection through modulation of a coordinated network including microRNA-499 expression along with mitochondrial biogenesis associated with SIRT1/PGC-1α/Nrf1/TFAM profiles, mitochondrial fission/fusion, and autophagy, therefore, appears to prevent the burden of myocardial I/R injury in elderly patients.

Melatonin/nicotinamide mononucleotide/ubiquinol: a cocktail providing superior cardioprotection against ischemia/reperfusion injury in a common co-morbidities modelled rat.

BACKGROUND: The metabolic and intracellular abnormalities in aging and diabetes cause loss of cardioprotection by routine interventions against myocardial ischemia/reperfusion (I/R) injury. We aimed to evaluate the possible interaction of aging and type-2 diabetes mellitus with cardioprotection and the potential protective effect of a mitochondrial cocktail (melatonin/nicotinamide mononucleotide (NMN)/ubiquinol) on myocardial I/R injury in aged diabetic rats. METHODS: Male Wistar rats (n = 108, 22-24 months old, 400-450 g) received high-fat diet/low dose of streptozotocin to induce type-2 diabetes, then were randomized into 9 groups of 12 rats each with/without I/R and/or melatonin, NMN, and ubiquinol, alone or in dual or triple combinations. Myocardial I/R was induced by LAD occlusion for 30 min followed by 24 h reperfusion. NMN (100 mg/kg/48 h, intraperitoneally) was administered for 28 days before I/R operation. Melatonin (10 mg/kg, intraperitoneally) and/or ubiquinol (30 mg/kg, intravenously) were administered at early reperfusion. Finally, hemodynamic index changes, infarct size, CK-MB levels, mitochondrial functional endpoints, and expression of mitochondrial biogenesis genes (SIRT-1/PGC-1α/NRF-2/TFAM) were assessed. RESULTS: The solo and dual applications of melatonin, NMN, and ubiquinol did not exert remarkable cardioprotective impacts. However, the triple combination improved myocardial function and decreased infarct size and CK-MB levels following myocardial I/R (P < .05 to P < .01). It also improved mitochondrial function and restored mitochondrial biogenesis genes (P < .01). CONCLUSIONS: Combination therapy with melatonin, NMN, and ubiquinol exerted significant cardioprotection and improved mitochondrial function and biogenesis via upregulation of SIRT-1/PGC-1α/NRF-2/TFAM profiles in aged diabetic rats and, thus, offers a promising strategy for providing noticeable cardioprotection against I/R injury also in aged diabetic patients.

Common carotid segmentation in 18 F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based and manual method.

BACKGROUND: Carotid atherosclerosis is a major cause of stroke, traditionally diagnosed late. Positron emission tomography/computed tomography (PET/CT) with 18 F-sodium fluoride (NaF) detects arterial wall micro-calcification long before macro-calcification becomes detectable by ultrasound, CT or magnetic resonance imaging. However, manual PET/CT processing is time-consuming and requires experience. We compared a convolutional neural network (CNN) approach with manual segmentation of the common carotids. METHODS: Segmentation in NaF-PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients were compared for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, and SUVtotal). SUVmean was the average of SUVmeans within the VOI, SUVmax the highest SUV in all voxels in the VOI, and SUVtotal the SUVmean multiplied by the Vol of the VOI. Intra and Interobserver variability with manual segmentation was examined in 25 randomly selected scans. RESULTS: Bias for Vol, SUVmean, SUVmax, and SUVtotal were 1.33 ± 2.06, -0.01 ± 0.05, 0.09 ± 0.48, and 1.18 ± 1.99 in the left and 1.89 ± 1.5, -0.07 ± 0.12, 0.05 ± 0.47, and 1.61 ± 1.47, respectively, in the right common carotid artery. Manual segmentation lasted typically 20 min versus 1 min with the CNN-based approach. Mean Vol deviation at repeat manual segmentation was 14% and 27% in left and right common carotids. CONCLUSIONS: CNN-based segmentation was much faster and provided SUVmean values virtually identical to manually obtained ones, suggesting CNN-based analysis as a promising substitute of slow and cumbersome manual processing.

"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography.

The aim of this study was to assess coronary artery and aortic calcification in healthy controls, angina pectoris patients, and prostate cancer patients using 18F-sodium fluoride PET/computed tomography (NaF-PET/CT). A retrospective analysis compared 33 prostate cancer patients with 33 healthy subjects and 33 patients with angina pectoris. Increased target-to-background ratio (TBR) of the coronary arteries, ascending aorta, aortic arch, and descending aorta was observed in cancer patients compared to healthy controls but not compared to angina pectoris patients. These results demonstrate the feasibility of assessing vascular microcalcification with NaF-PET/CT, with significant differences in uptake according to comorbidities.

Inter- and Intrarater Reliability and Agreement Among Danish Head and Neck Pathologists Assessing Extranodal Extension in Lymph Node Metastases from Oropharyngeal Squamous Cell Carcinomas.

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.

Application of 18F-NaF-PET/CT in assessing age-related changes in the cervical spine.

Background: Cervical spondylosis is the degeneration of cervical spine often associated with aging and neck pain. As the degenerative changes are coupled with altered osteoblastic activity, imaging modalities sensitive to such molecular changes could be valuable for clinical assessment, disease prophylaxis, and monitoring early therapy response. In this study, we examined the role of 18F-sodium fluoride-positron emission tomography/computed tomography (18F-NaF-PET/CT) in detecting age-associated changes in the cervical spine of an adult population with broad age spectrum. Methods: In this retrospective cross-sectional study, we analyzed 18F-NaF-PET/CT scans of 88 control volunteers (43 females, 45 males) with age ranging from 21 to 75 years (mean =44.6, standard deviation, 14.0) divided into younger (21-45 years) and older (46-75 years) age groups. A semi-automated global assessment technique was used to measure 18F-NaF uptake in C2-C4 and C5-C7 vertebrae of the subjects. Furthermore, a CT-based scoring system was devised to measure the degree of structural degeneration. Results: There was a significant difference in 18F-NaF uptake of the younger and older groups at the C5-C7 vertebrae for both females (younger: mean =4.13, 95% CI: 3.72-4.55; older: mean = 4.80, 95% CI: 4.40-5.20; P=0.005) and males (younger: mean =3.66, 95% CI: 3.24-4.09; older: mean =4.22, 95% CI: 3.80-4.64; P=0.009), but not at the C2-C4 vertebrae. Furthermore, there was a positive correlation between the degree of degeneration and 18F-NaF uptake at both C2-C4 and C5-C7 spinal segments of both sexes. Conclusions: Aging is associated with increased 18F-NaF uptake in the cervical spine, which may be associated with osteoblastic activity coupled with degeneration. Our study alludes to the potential role of 18F-NaF-PET/CT in evaluating age-related degeneration and osteoarthritis of the spine.

The effects of limb laterality and age on the inflammation and bone turnover of the acromioclavicular shoulder joint: 18 F-fluorodeoxyglucose and 18 F-sodium-fluoride-PET/computed tomography study.

PURPOSE: The acromioclavicular (AC) joint is a common site of injury and degenerative changes such as osteoarthritis (OA) of the shoulder. Physical manifestations of OA are preceded by molecular changes, detection of which may enhance early prophylaxis and monitoring of disease progression. In this study, we investigate the use of 18 F-FDG and 18 F-NaF-PET/CT to assess the effects of limb laterality and age on the inflammation and bone turnover of the AC shoulder joint. METHODS: We analyzed FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) using a semiquantitative technique based on predefined ROI. RESULTS: There was a greater NaF uptake in the right side of the AC joint compared with the left in both females (left: 2.22 ± 1.00; right: 3.08 ± 1.18; P < 0.0001) and males (left: 2.57 ± 1.49; right: 2.99 ± 1.40; P = 0.003). No consistent correlation between age and NaF or FDG uptakes were found in both females and males. There was also a positive correlation between FDG and NaF uptakes in both left ( P = 0.01; r = 0.37) and right ( P = 0.0006; r = 0.53) AC joints of male subjects. CONCLUSION: Our study is the first to reveal the varying effect of right-left limb laterality and aging on FDG and NaF uptake at the AC joint. Future studies correlating the history of shoulder trauma, pain, and degenerative change with FDG and NaF-PET/CT findings will be critical in the adoption of molecular imaging in the clinical setting.

Can Target-to-Background Ratio Measurement Lead to Detection and Accurate Quantification of Atherosclerosis With FDG PET? Likely Not.

ABSTRACT: The introduction of FDG in 1976 started a new discipline and enhanced the role of molecular imaging in medicine. While the initial intent with this tracer was to determine brain function in a variety of neuropsychiatric disorders, over time, this powerful approach has made a major impact on managing many other diseases and disorders. During the past 2 decades, FDG PET has been used to detect inflammatory lesions in the atherosclerotic plaques and in other settings. However, the suboptimal spatial resolution of PET limits its ability to visualize plaques that are very small in size. Furthermore, this tracer remains in the blood for an extended period and therefore provides suboptimal results. Target-to-background ratio (TBR) has been suggested to correct for this source of error. Unfortunately, TBR values vary substantially, depending on the timing of image acquisition. Delayed imaging at later time points (3-4 hours) may obviate the need for TBR measurement, but it is impractical with conventional PET instruments. Recently, 18F-sodium fluoride (NaF) has been used for detection and quantification of molecular calcification in the plaques. This tracer is highly specific for calcification and is rapidly cleared from the circulation. In addition, global atherosclerotic burden as measured by NaF PET can be determined accurately either in the heart or major arteries throughout the body. Therefore, the role of FDG PET-based TBR measurement for detection and quantification of atherosclerotic plaques is questionable at this time.

PET/CT imaging of spinal inflammation and microcalcification in patients with low back pain: A pilot study on the quantification by artificial intelligence-based segmentation.

BACKGROUND: Current imaging modalities are often incapable of identifying nociceptive sources of low back pain (LBP). We aimed to characterize these by means of positron emission tomography/computed tomography (PET/CT) of the lumbar spine region applying tracers 18 F-fluorodeoxyglucose (FDG) and 18 F-sodium fluoride (NaF) targeting inflammation and active microcalcification, respectively. METHODS: Using artificial intelligence (AI)-based quantification, we compared PET findings in two sex- and age-matched groups, a case group of seven males and five females, mean age 45 ± 14 years, with ongoing LBP and a similar control group of 12 pain-free individuals. PET/CT scans were segmented into three distinct volumes of interest (VOIs): lumbar vertebral bodies, facet joints and intervertebral discs. Maximum, mean and total standardized uptake values (SUVmax, SUVmean and SUVtotal) for FDG and NaF uptake in the 3 VOIs were measured and compared between groups. Holm-Bonferroni correction was applied to adjust for multiple testing. RESULTS: FDG uptake was slightly higher in most locations of the LBP group including higher SUVmean in the intervertebral discs (0.96 ± 0.34 vs. 0.69 ± 0.15). All NaF uptake values were higher in cases, including higher SUVmax in the intervertebral discs (11.63 ± 3.29 vs. 9.45 ± 1.32) and facet joints (14.98 ± 6.55 vs. 10.60 ± 2.97). CONCLUSION: Observed intergroup differences suggest acute inflammation and microcalcification as possible nociceptive causes of LBP. AI-based quantification of relevant lumbar VOIs in PET/CT scans of LBP patients and controls appears to be feasible. These promising, early findings warrant further investigation and confirmation.

Preclinical cerebral cryoablation in non-tumor bearing pigs.

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.

"Global" cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison.

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.

Aortic wall segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based versus manual segmentation.

BACKGROUND: We aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans. METHODS: For segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on 18F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland-Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans. RESULTS: CNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%. CONCLUSIONS: The automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation.

PET-Based Imaging with 18F-FDG and 18F-NaF to Assess Inflammation and Microcalcification in Atherosclerosis and Other Vascular and Thrombotic Disorders.

Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) represents a method of detecting and characterizing arterial wall inflammation, with potential applications in the early assessment of vascular disorders such as atherosclerosis. By portraying early-stage molecular changes, FDG-PET findings have previously been shown to correlate with atherosclerosis progression. In addition, recent studies have suggested that microcalcification revealed by 18F-sodium fluoride (NaF) may be more sensitive at detecting atherogenic changes compared to FDG-PET. In this review, we summarize the roles of FDG and NaF in the assessment of atherosclerosis and discuss the role of global assessment in quantification of the vascular disease burden. Furthermore, we will review the emerging applications of FDG-PET in various vascular disorders, including pulmonary embolism, as well as inflammatory and infectious vascular diseases.

Diagnosis of bone metastases in breast cancer: Lesion-based sensitivity of dual-time-point FDG-PET/CT compared to low-dose CT and bone scintigraphy.

We compared lesion-based sensitivity of dual-time-point FDG-PET/CT, bone scintigraphy (BS), and low-dose CT (LDCT) for detection of various types of bone metastases in patients with metastatic breast cancer. Prospectively, we included 18 patients with recurrent breast cancer who underwent dual-time-point FDG-PET/CT with LDCT and BS within a median time interval of three days. A total of 488 bone lesions were detected on any of the modalities and were categorized by the LDCT into osteolytic, osteosclerotic, mixed morphologic, and CT-negative lesions. Lesion-based sensitivity was 98.2% (95.4-99.3) and 98.8% (96.8-99.5) for early and delayed FDG-PET/CT, respectively, compared with 79.9% (51.1-93.8) for LDCT, 76.0% (36.3-94.6) for BS, and 98.6% (95.4-99.6) for the combined BS+LDCT. BS detected only 51.2% of osteolytic lesions which was significantly lower than other metastatic types. SUVs were significantly higher for all lesion types on delayed scans than on early scans (P<0.0001). Osteolytic and mixed-type lesions had higher SUVs than osteosclerotic and CT-negative metastases at both time-points. FDG-PET/CT had significantly higher lesion-based sensitivity than LDCT and BS, while a combination of the two yielded sensitivity comparable to that of FDG-PET/CT. Therefore, FDG-PET/CT could be considered as a sensitive one-stop-shop in case of clinical suspicion of bone metastases in breast cancer patients.