"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.

Effects of adding exercise to usual care in patients with either hypertension, type 2 diabetes or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: To assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. DESIGN: Systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. DATA SOURCES: The CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded on Web of Science and BIOSIS searched from inception to July 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in participants with either hypertension, type 2 diabetes or cardiovascular disease irrespective of setting, publication status, year and language. OUTCOME AND MEASURES: The primary outcomes were all-cause mortality, serious adverse events and quality of life. DATA EXTRACTION AND SYNTHESIS: Five independent reviewers extracted data and assessed risk of bias in pairs. Our methodology was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Grading of Recommendations Assessment, Development and Evaluation and Cochrane Risk of Bias-version 1. RESULTS: We included 950 trials, of which 248 trials randomising 21 633 participants reported on our predefined outcomes. All included trials were at high risk of bias. The major types of exercise reported were dynamic aerobic exercise (126/248 trials), dynamic resistance exercise (25/248 trials), and combined aerobic and resistance exercise (58/248 trials). The study participants were included due to cardiovascular diseases (189/248 trials), type 2 diabetes (41/248 trials) or hypertension (16/248 trials). The median intervention period was 3 months (IQR: 2-4 months) and the median follow-up period was 6 months (IQR: 3-8 months) after randomisation. Meta-analyses and trial sequential analyses showed evidence of a beneficial effect of adding exercise to usual care when assessing all-cause mortality (risk ratio (RR) 0.82; 95% CI 0.73 to 0.93; I2=0%, moderate certainty of evidence) and serious adverse events (RR 0.79; 95% CI 0.71 to 0.88; I2=0%, moderate certainty of evidence). We did not find evidence of a difference between trials from different economic regions, type of participants, type of exercise or duration of follow-up. Quality of life was assessed using several different tools, but the results generally showed that exercise improved quality of life, but the effect sizes were below our predefined minimal important difference. CONCLUSIONS: A short duration of any type of exercise seems to reduce the risk of all-cause mortality and serious adverse events in patients with either hypertension, type 2 diabetes or cardiovascular diseases. Exercise seems to have statistically significant effects on quality of life, but the effect sizes seem minimal. PROSPERO REGISTRATION NUMBER: CRD42019142313.

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.

"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.

Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

Association of baseline subject characteristics with changes in coronary calcification assessed by 18F-sodium fluoride PET/CT.

OBJECTIVE: The goal of this study was to test if changes in coronary microcalcification over a two year period assessed by fluorine-18-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) are associated with baseline subject characteristics. SUBJECTS AND METHODS: This prospective study included healthy female (N=8, age 52±10 years, body mass index(BMI) 24±1.7kg/m2) and male (N=15, age 50±10 years, BMI 27±2.9kg/m2) participants who had 18F-NaF PET/CT scans taken two years apart. Imaging was performed 90 minutes after intravenous injection of 2.2MBq of 18F-NaF per kilogram of body weight. The analysis regions were selected on CT images by drawing volumes of interest around the entire heart using a semi-automatic segmentation method.Mean standardize uptake value (SUVmean) and maximum SUV (SUVmax) were calculated in the same regions of the registered PET images. Percent change in SUV between the two time points were correlated against baseline age, BMI, cardiovascular risk factors, and blood chemistry. RESULTS: In males, percent change in SUVmean over the two year period was positively correlated with baseline BMI (r=0.85, P<0.0001) and systolic blood pressure (r=0.65, P=0.0082). These baseline values were not significantly correlated with SUVmax in either gender. CONCLUSION: High BMI is a known risk factor for atherosclerosis. Our data showed that rate of increase in coronary microcalcification over time measured by 18F-NaF PET/CT is associated with baseline BMI and some clinical risk factors in males. Lack of such associations in females could be due to low sample size (N=8). Further prospective studies are needed to determine if baseline BMI and clinical factors could be used to predict rate of increase in coronary microcalcification which could provide the basis for managing the progression of atherosclerosis in patient-specific manner.

Molecular imaging of carotid artery atherosclerosis with PET: a systematic review.

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.

End-of-life Care: Beliefs, Attitudes, and Experiences of Iranian Physicians.

CONTEXT: Most of the patients suffering from cancer are diagnosed at late stages of cancer, which curative interventions are unable to improve their quality of life. AIM: To survey Iranian physicians' attitudes and practices toward end-of-life (EOL) care. SUBJECTS AND METHODS: We conducted a cross-sectional survey among physicians participating in a national annually conducted educational seminar. RESULTS: The survey results show that 80% of physicians had between 1 and 3 EOL patients. About 72% of patients received medical care in hospitals. The difference in best setting for care of terminally ill patients was statically significant after controlling for the length of practice and physician belief. The results also showed that that the participants believed that that the level of physicians' knowledge in this field was unacceptable. CONCLUSION: Physicians of our study were interested to participating in continuing education programs focused on EOL patients.

Age related secretary pattern of growth hormone, insulin-like growth factor-I & insulin-like growth factor binding protein-3 in postmenopausal women.

BACKGROUND & OBJECTIVES: After menopause in women, loss of bone density increases rapidly with estrogen deficiency. Evidence has revealed that this deficiency may be directly correlated with growth hormone (GH) level declining with age. The present study was designed to evaluate the age dependant patterns of GH, insulin-like growth factor-1 (IGF1-1) and insulin-like growth factor binding protein-3 (IGFBP-3) endogenous secretion in postmenopausal women. METHODS: During this prospective study in a 12-month period, 150 postmenopausal women were enrolled who were referred to the densitometry unit of bone research centre of Tabriz University of Medical Sciences for assessing bone mineral density. Serum levels of basal and clonidine stimulated GH were measured using radioimmunoassay while IGF-1 and IGFBP-3 were measured by ELISA. Post stimulation over 3 to 6 fold increase in GH over the baseline level was considered normal response and less increase was considered abnormal. RESULTS: There were no significant differences in the mean levels of GH0, GH60 and GH90 in different age groups of postmenopausal women. No significant difference in the mean IGFBP-3 and IGF-1 levels was seen in different age groups of postmenopausal women. The number of postmenopausal women with abnormal response to stimulation by clonidine in 61-70 and > 70 yr age groups was higher than in other groups (P< 0.05). INTERPRETATION & CONCLUSIONS: Despite the higher rate of abnormal response to stimulation by clonidine in women aged more than 60 yr, the current study showed no significant correlation between age, and the basal and stimulated GH secretion rate and serum levels of IGF-1 and IGFBP-3 in postmenopausal women.

Effects of adding exercise to usual care on blood pressure in patients with hypertension, type 2 diabetes, or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis.

INTRODUCTION: Exercise is the most recommended lifestyle intervention in managing hypertension, type 2 diabetes, and/or cardiovascular disease; however, evidence in lowering blood pressure is still inconsistent and often underpowered. METHOD: We conducted a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials adding any form of trialist defined exercise to usual care versus usual care and its effect on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in participants with hypertension, type 2 diabetes, or cardiovascular disease searched in different databases from inception to July 2020. Our methodology was based on PRISMA and Cochrane Risk of Bias-version1. Five independent reviewers extracted data and assessed risk of bias in pairs. RESULTS: Two hundred sixty-nine trials randomizing 15 023 participants reported our predefined outcomes. The majority of exercise reported in the review was dynamic aerobic exercise (61%), dynamic resistance (11%), and combined aerobic and resistance exercise (15%). The trials included participants with hypertension (33%), type 2 diabetes (28%), or cardiovascular disease (37%). Meta-analyses and trial sequential analyses reported that adding exercise to usual care reduced SBP [mean difference (MD) MD: -4.1 mmHg; 95% confidence interval (95% CI) -4.99 to -3.14; P  < 0.01; I2  = 95.3%] and DBP (MD: -2.6 mmHg; 95% CI -3.22 to -2.07, P  < 0.01; I2  = 94%). Test of interaction showed that the reduction of SBP and DBP was almost two times higher among trials from low-and middle-income countries (LMICs) as compared to high-income countries (HICs). The exercise induced SBP reduction was also higher among participants with hypertension and type 2 diabetes compared to participants with cardiovascular disease. The very low certainty of evidence warrants a cautious interpretation of the present results. CONCLUSION: Adding any type of exercise to usual care may be a potential complementary strategy for optimal management of blood pressure for patients with hypertension, type 2 diabetes, or cardiovascular disease, especially, in LMICs.PROSPERO registration number CRD42019142313.

Effect of exercise on functional capacity and body weight for people with hypertension, type 2 diabetes, or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Hypertension, type 2 diabetes, and cardiovascular disease affect the activities of daily living at varying degree. While the effects of aerobic exercise on functional capacity are well-documented, the extent of change for different types of exercise in these chronic conditions remains unexplored. Additionally, there is conflicting evidence regarding the role of exercise in reducing body weight. METHODS: We conducted systematic review with meta-analysis and trial sequential analysis and searched various databases from inception to July 2020. We included randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in people with either hypertension, type 2 diabetes, and/or cardiovascular disease irrespective of setting, publication status, year, and language. The outcomes assessed were i) functional capacity assessed through different scales separately i.e., Maximal Oxygen Uptake (VO2max), 6-min walk test (6MWT), 10-m walk test (10MWT), and ii) body weight. RESULTS: We included 950 studies out of which 444 trials randomising 20,098 participants reported on various functional outcomes (355 trials) and body weight (169 trials). The median follow-up was 3 months (Interquartile ranges (IQR): 2.25 to 6). Exercise added to the usual care, improved VO2max (Mean Difference (MD):2.72 ml/kg/min; 95% Confidence Interval (CI) 2.38 to 3.06; p < 0.01; I2 = 96%), 6MWT (MD: 42.5 m; 95%CI 34.95 to 50.06; p < 0.01; I2 = 96%), and 10MWT (MD: 0.06 m/s; 95%CI 0.03 to 0.10; p < 0.01; I2 = 93%). Dynamic aerobic and resistance exercise showed a consistent improvement across various functional outcomes, whereas body-mind therapies (MD: 3.23 ml/kg/min; 95%CI 1.97 to 4.49, p < 0.01) seemed especially beneficial for VO2max and inspiratory muscle training (MD: 59.32 m; 95%CI 33.84 to 84.80; p < 0.01) for 6MWT. Exercise yielded significant reduction in body weight for people with hypertension (MD: -1.45 kg; 95%CI -2.47 to -0.43; p < 0.01), and type 2 diabetes (MD: -1.53 kg; 95%CI -2.19 to -0.87; p < 0.01) but not for cardiovascular disease with most pronounced for combined exercise (MD: -1.73 kg; 95%CI -3.08 to -0.39; p < 0.05). The very low certainty of evidence warrants cautious interpretations of the results. CONCLUSION: Exercise seemed to improve functional capacity for people with hypertension, type 2 diabetes, and/or cardiovascular disease but the effectiveness seems to vary with different forms of exercise. The potentially superior improvement in VO2max and 6MWT by body-mind therapies and inspiratory muscle training calls for further exploration. Additionally, prescribing exercise for the sole purpose of losing weight may be a potential strategy for people with hypertension and type 2 diabetes. The extent of improvement in functional capacity and body weight reduction differed with different exercise regimens hence personalised exercise prescriptions tailored to individual needs may be of importance. PROSPERO REGISTRATION: PROSPERO registration number: CRD42019142313.

PET/MRI in paediatric inflammatory bowel disease - a prospective accuracy study.

Cross-sectional imaging supplements endoscopy in detecting disease manifestations in inflammatory bowel diseases (IBD). This study aimed to evaluate the accuracy of PET/MRI in a paediatric population suspected of IBD. This prospective study consecutively included patients aged 8-17 years under diagnostic evaluation for IBD. Forty-three patients underwent a PET/MRI scan and subsequent ileocolonoscopy, of whom 26 patients diagnosed with IBD participated in a follow-up scan, hereof 19 with Crohn's disease (CD), five with Ulcerative colitis and two with unclassified IBD. The results of PET alone, MRI alone, and PET/MRI combined were compared to a reference standard of endoscopy and histopathology. Of the 208 intestinal segments analysed, 109 showed inflammation, and 99 had no inflammation. In the per-segment analysis PET had a sensitivity of 0.83 (95% CI 0.73-0.93), specificity of 0.59 (95% CI 0.47-0.71), and area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI 0.67-0.80). MRI had a sensitivity of 0.52 (95% CI 0.41-0.64), specificity 0.89 (95% CI 0.82-0.96), and AUROC of 0.72 (95% CI 0.66-0.77). PET/MRI had a sensitivity of 0.83 (95% CI 0.74-0.94), specificity of 0.57 (95% CI 0.44-0.69), and AUROC of 0.77 (95% CI 0.71-0.84). At follow-up, PET and MRI scores decreased, and the change in MRI was able to identify patients with a clinical response. The accuracy of the PET/MRI scan in detecting inflammation in the terminal ileum and colon was moderate and not superior to either modality alone. With technological advances and combined reading, PET/MRI may still be valuable in selected cases.

An ensemble modeling approach to predict spatial risk patches of the Persian leopard-livestock conflicts in Lorestan Province, Iran.

This study was conducted in the Lorestan Province in the west of Iran with two objectives of identifying major environmental variables in spatial risk modeling and identifying spatial risk patches of livestock predation by the Persian leopard. An ensemble approach of three models of maximum entropy (MaxEnt), generalized boosting model (GBM), and random forest (RF) were applied for spatial risk modeling. Our results revealed that livestock density, distance to villages, forest density, and human population density were the most important variables in spatial risk modeling of livestock predation by the leopard. The center of the study area had the highest probability of livestock predation by the leopard. Ten spatial risk patches of livestock predation by the leopard were identified in the study area. In order to mitigate the revenge killing of the leopards, the findings of this study highlight the imperative of implementing strategies by the Department of Environment (DoE) to effectively accompany the herds entering the wildlife habitats with shepherds and a manageable number of guarding dogs. Accordingly, the identified risk patches in this study deserve considerable attention, especially three primary patches found in the center and southeast of Lorestan Province.

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.

NaF-PET Imaging of Atherosclerosis Burden.

The method of 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) of atherosclerosis was introduced 12 years ago. This approach is particularly interesting because it demonstrates microcalcification as an incipient sign of atherosclerosis before the development of arterial wall macrocalcification detectable by CT. However, this method has not yet found its place in the clinical routine. The more exact association between NaF uptake and future arterial calcification is not fully understood, and it remains unclear to what extent NaF-PET may replace or significantly improve clinical cardiovascular risk scoring. The first 10 years of publications in the field were characterized by heterogeneity at multiple levels, and it is not clear how the method may contribute to triage and management of patients with atherosclerosis, including monitoring effects of anti-atherosclerosis intervention. The present review summarizes findings from the recent 2¾ years including the ability of NaF-PET imaging to assess disease progress and evaluate response to treatment. Despite valuable new information, pertinent questions remain unanswered, not least due to a pronounced lack of standardization within the field and of well-designed long-term studies illuminating the natural history of atherosclerosis and effects of intervention.

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.

Artificial Intelligence in Vascular-PET:: Translational and Clinical Applications.

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.

Age at Diagnosis of Breast Cancer in Iran: A Systematic Review and Meta-Analysis.

BACKGROUND: Breast cancer is responsible for up to 25% of all cancers in Iran. The age at diagnosis of Iranian breast cancer patients starts a decade earlier than most of developed countries. This study aimed to evaluate the mean age at diagnosis of Iranian breast cancer patients. METHODS: In this systematic review and meta-analysis, the mean age at diagnosis of Iranian breast cancer patients and its pattern between 2008 and 2017, were evaluated. All papers with age at diagnosis of histopathological verified breast cancer patients were considered eligible to enter to the analysis. We used databases including Medline/PubMed, Scopus, Embase, Cochrane Library, Iranmedex and SID for the search process. The meta-analysis was performed only on studies with separate data for female patients, using random-effects model, Mantel and Haenszel method and the Comprehensive Meta-analysis software. RESULTS: Finally, 92 studies with 19,784 patients (both-genders) were included. The mean age at diagnosis had increased from 47.93 (2008) to 49.91 (2016) years. The meta-analysis was done on 78 studies containing of 15,071 female patients and the mean age at diagnosis was 46.76±1.19. There was a wide range of age at diagnosis within different provinces. The mean age at Hamadan and Khuzestan provinces were the lowest and highest, respectively (42.48±7.96 vs. 51.00±11.47). The heterogeneity of studies was statistically significant (I2=99.744). CONCLUSION: Mean age at diagnosis of Iranian women with breast cancer was 46.76±1.19. There was an increasing pattern in mean age of diagnosis at breast cancer patients within the past 10 years.

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

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.

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

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.