Fluoride Positron Emission Tomography Research Articles

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography

Abstract Background There are sex differences in the extent, severity, and outcomes of coronary artery disease. Purpose To assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p=0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p=0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p=0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n=80) and 48.3% (n=73); p=0.42), or CMA values >1.56 (21.8% (n=33) and 21.8% (n=33); p=1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n=10) and 7.8% of men (n=66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p=0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p<0.001). Conclusions Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.Sex differences in CAD activityCase examples

18F-NaF uptake on vascular PET imaging in symptomatic versus asymptomatic atherosclerotic disease: A meta-analysis.

18F-sodium fluoride (NaF) positron-emission tomography (PET) is increasingly being used to measure microcalcification in atherosclerotic disease in vivo. Correlations have been drawn between sodium fluoride uptake and the presence of high-risk plaque features, as well as its association with clinical atherosclerotic sequelae. The aim of this study was to perform a meta-analysis of NaF uptake on PET imaging and its relation to symptomatic and asymptomatic disease. A systematic review was performed according to PRISMA guidelines, via searching the Ovid MEDLINE, Ovid Embase, Cochrane Library, PubMed, Scopus, and Web of Science Core Collection databases up to May 2024. The search strategy included the terms 'NaF', 'PET', and 'plaque', and all studies with data regarding the degree of microcalcification, as measured by 18F-NaF uptake in symptomatic and asymptomatic atherosclerotic plaques, were included. Analysis involved calculating mean differences between uptake values and comparison using a random-effects model. A total of 16 articles, involving 423 participants, were included in the meta-analysis (10 carotid artery studies, five coronary artery studies, and one in peripheral vascular disease). Comparing 18F-NaF uptake in symptomatic versus asymptomatic atherosclerotic plaques, a mean difference of 0.43 (95% CI 0.29 to 0.57; p < 0.0001, I2 = 65%) was noted in studies comparing symptomatic and asymptomatic plaques in the same participant, with a significant difference in effect based on arterial territory studied (χ2 = 12.68, p = 0.0018). In studies of participants with and without symptomatic disease, there was no significant difference between symptomatic and asymptomatic plaques (mean difference 0.27, 95% CI -0.26 to 0.80, p = 0.28, I2 = 85%). PET imaging using 18F-NaF can detect differences in microcalcification between symptomatic and asymptomatic atherosclerotic plaques within, but not between, individuals, and thus, is a marker of symptomatic disease. The standardization of 18F-NaF PET imaging protocols, and its future use as a risk stratification tool or outcome measure, requires further study. (PROSPERO Registration ID: CRD42023451363).

Comparison of PET/CT versus CT only in the assessment of new heterotopic ossification bone lesions in patients with fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder characterized by the deposition of bone in soft tissues, known as heterotopic ossification (HO). This post hoc analysis compared the performance of two imaging modalities for the detection and volumetric measurement of new HO lesions. LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP. From baseline through to week 28, 18F-labeled sodium fluoride positron emission tomography (PET)/X-ray computed tomography (CT) and CT-only scans prospectively acquired during the initial placebo-controlled period of the study were independently reviewed by two sets of fixed blinded readers plus an adjudicator for the presence and volume of new HO lesions. The number of patients with new lesions was 14/44 (31.8 %) and 12/44 (27.3 %) as detected by PET/CT and CT only, respectively. The aggregate number/volume of new lesions were very similar both for the placebo and the garetosmab group between PET/CT (27/245.0 cm3 and 3/21.3 cm3, respectively) and CT only (37/261.8 cm3 and 1/0.1 cm3, respectively). The mean (standard deviation) number of new lesions per patient by PET/CT through week 28 was 0.68 (1.57) versus 0.86 (1.95) as detected by CT only. Through week 28, the mean (standard deviation) volume of new lesions per patient detected by PET/CT was 6.05 (14.88) cm3 versus 5.94 (21.13) cm3 by CT only. Moderate agreement between PET/CT and CT-only detection was observed when identifying patients with new lesions, with a kappa coefficient of 0.46 (standard error, 0.146; 95 % confidence interval, 0.17–0.74). CT-only imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions. CT-only imaging therefore is a viable option for the assessment of therapies on new HO in patients with FOP.

Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Using accelerometers to identify a high risk of catastrophic musculoskeletal injury in three racing Thoroughbreds.

To describe the process whereby the screening of racing Thoroughbreds with accelerometer-based inertial measurement unit (IMU) sensors followed by clinical evaluation and advanced imaging identified potentially catastrophic musculoskeletal injuries in 3 horses. 3 Thoroughbred racehorses. All cases demonstrated an abnormal stride pattern either during racing (cases 1 and 2) or while breezing (case 3) and were identified as being at very high risk of catastrophic musculoskeletal injury by an algorithm derived from IMU sensor files from > 20,000 horses' race starts. Veterinary examination and 18F-sodium fluoride (18F-NaF) positron emission tomography were performed within 10 days of the respective race or breeze in each of the cases. The intensity and location of the 18F-NaF uptake in the condyles of the third metacarpal bone in cases 1 and 2 identified them as at potential increased risk of condylar fracture. The pattern and intensity of the 18F-NaF uptake in case 3 indicated that the third carpal bone was likely responsible for the horse's lameness, with an impending slab fracture subsequently identified on radiographs. Following periods of convalescence, cases 1 and 2 returned to racing and were identified by the sensor system as no longer being at high risk of catastrophic musculoskeletal injury. Case 3 returned to training but has yet to return to racing. When worn by Thoroughbreds while racing or breezing, these IMU sensors can identify horses at high risk of catastrophic musculoskeletal injury, allowing for veterinary intervention and the potential avoidance of such injuries.

Dissecting the heterogeneity of craniofacial lesions in patients with fibrous dysplasia/McCune–Albright Syndrome

Fibrous dysplasia/McCune–Albright Syndrome (FD/MAS) frequently involves the craniofacial skeleton. Craniofacial fibrous dysplasia lesions exhibit diverse imaging characteristics on multimodality evaluation, utilizing radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-sodium fluoride positron emission tomography (18F-NaF PET). A multimodal imaging classification of craniofacial fibrous dysplasia lesions may offer clinical insights into the types of lesions that are (1) prone to progression, (2) amenable to intervention (i.e., pharmacological or surgical), or (3) associated with symptoms such as pain. In this prospective, preliminary single site study of 15 patients with FD/MAS, the heterogeneity of craniofacial lesions (N = 35) was assessed using a combination of 18F-NaF PET, MRI, and CT. A k-means clustering algorithm was used to categorize lesions based on imaging characteristics. Clustering analysis revealed three types of lesion based on the magnitude of the regional 18F-NaF standardized uptake values (SUV), signal intensities on T1-weighted and fluid-sensitive sequences, and appearance on CT (lucent, sclerotic, and/or ground glass). This preliminary study provides a foundation for future longitudinal natural history or treatment studies, where the prognostic value of baseline craniofacial fibrous dysplasia imaging characteristics and clinical symptomatology can be further evaluated.

Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: A pilot study.

Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events. Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase). Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

Metabolic bone imaging and its relationship with biomechanics

ObjectiveThis mini review delves into the mechanisms of [18F]Sodium Fluoride positron emission tomography ([18F]NaF PET), which, by interrogating areas of newly mineralizing bone, provides a valuable tool to study the joint response to loading and areas of altered whole-joint function in osteoarthritis (OA). DesignThe review consolidates and discusses findings from both preclinical and clinical studies that utilize [18F]NaF PET to evaluate the bone response to various loading paradigms. It also briefly reviews technical considerations for PET imaging and discusses its strong potential as a tool in the quest to understand bone metabolism in the context of loading and osteoarthritis. ResultsWhile considering previous studies, technical considerations and potential new applications of this methodology are also discussed. [18F]NaF PET/MRI reveals localized, load-related bone responses after exercise, providing insights into early OA progression. In human studies, significant increases in tracer uptake are observed in areas affected by OA pathology, driven by bone perfusion and blood volume. Future work to examine the relationship between metabolic bone response to exercise and the bone loading environment is needed. ConclusionsIntegrating [18F]NaF PET/MRI with advanced biomechanical modeling holds promise for guiding clinical management of OA, primarily by examining the relationship between bone, soft tissues of the joint, and loading forces.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Abstract 2021: 18 F-Sodium Fluoride Positron Emission Tomography To Assess Thoracic Aortopathy In Bicuspid Aortic Valve Disease

Background: Bicuspid aortic valve is associated with thoracic aortopathy with many patients suffering aortic dissection below the aortic diameter threshold for prophylactic aortic replacement surgery. In aortopathy, the aortic wall media initially undergoes increasing microcalcification due to elastin fibre fragmentation but with disease progression, elastin fibre degradation leads to loss of aortic microcalcification. 18 F-Sodium fluoride positron emission tomography (PET) is a non-invasive method of detecting arterial microcalcification that has been successfully used in cardiovascular disease risk stratification. Aims: To determine if aortic 18 F-sodium fluoride imaging can identify aortopathy and predict subsequent disease progression in patients with bicuspid aortic valve disease. Methods: In this prospective cohort study, 77 patients with bicuspid aortic valve from clinical sites across Scotland and 18 healthy volunteers, underwent 18 F-sodium fluoride PET-computed tomography (PET-CT) followed immediately by PET-magnetic resonance imaging (PET-MRI). Maximum standardised uptake values (SUVmax) were determined in the ascending aorta. Aortic diameters were measured in aortic axial CINE MRI sequences. Patients were followed-up at 24 months with a further PET-MRI. Annualised change in aortic size index (mm/m 2 /year) and annualised change in SUVmax stratified in tertiles were calculated. Results: Patients with bicuspid aortic valve disease had higher SUVmax than control subjects, especially in those with aortic dilatation. Baseline SUVmax was associated with annualised aortic expansion rate independent of baseline aortic size (β=0.45, p=0.001). Patients in tertile 1 (loss of SUVmax over time) exhibited greater aortic growth (0.60±0.50 mm/m 2 /year) than those with stable SUVmax (tertile 2, 0.26±0.36 mm/m 2 /year) or increasing SUVmax (tertile 3, 0.24±0.36 mm/m 2 /year; p=0.01). Conclusion: Aortic microcalcification activity is increased in aortopathy of patients with bicuspid aortic valve. Loss of aortic microcalcification is associated with more rapid disease progression and represents a promising new approach to the identification of patients at higher risk of aortic complications.

Preoperative Assessment of Medication-Related Osteonecrosis of the Jaw Using [18F]fluoride Positron Emission Tomography (PET)/CT and [18F]fluorodeoxyglucose PET/MRI in Correlation with Histomorphometry and Micro-CT-A Prospective Comparative Study.

The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis. CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas. In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake.

Temporal changes in biomarker levels and their association with the early degeneration stage of transcatheter aortic valves in 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography studies.

As transcatheter aortic valve implantation (TAVI) indications expand, understanding the valve degeneration process and potential influencing biomarkers becomes increasingly important. To investigate temporal changes in biomarker levels and their potential association with 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) uptake, assessed using positron emission tomography/computed tomography (PET/CT) studies as markers for native aortic annulus calcifications and early-stage TAVI valve degeneration. A total of 71 TAVI patients underwent blood sampling and transthoracic echocardiography at baseline (pre-TAVI) and 6, 12, 18, and 24 months after the procedure. PET/CT using 18F-NaF and 18F-FDG was performed at 6 and 24 months. Serum levels of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9), and osteopontin (OPN) were measured. In addition, plasma levels of osteoprotegerin (OPG), lipoprotein a (Lp(a)), and oxidized LDL (ox-LDL) were assessed. Finally, 31 patients (median age: 84.0 years) completed the study. Valve function improved after TAVI and remained stable during follow-up. Over 24 months, OPN levels decreased (p = 0.010), while MMP-3 and MMP-9 levels increased (p = 0.046 and p = 0.041). MMP-3 and MMP-9 showed multiple positive correlations across time points. OPN, ox-LDL, and OPG demonstrated significant negative correlations with follow-up effective orifice area index and effective orifice area (EOA). No significant correlations were found between biomarkers and PET/CT uptake. Significant biomarker changes over 24 months and negative correlations with EOA suggest potential roles in aortic valve function. However, no correlations between biomarkers and PET/CT results were observed.

Fragility fracture as the first presentation of Cushing’s disease

ABSTRACT Cushing’s syndrome (CS) is a state of glucocorticoid excess with its effect on all the systems of the body. Steroids are known to affect bone health, leading to altered bone microarchitecture. Patients of CS are at increased risk for the development of fracture but fracture as the initial presentation of CS is relatively uncommon. Here, we describe a 31-year-old female who presented with pain in the bilateral hip joint and was found to have a fracture in the right neck of the femur. Though she did not have the classical features of CS, she had striae in the bilateral thigh region. On evaluation, she had a pituitary microadenoma with cortisol dynamics suggestive of Cushing’s disease. The F-18 Fluoride positron emission tomography scan was done, which showed multiple areas of uptake suggestive of fracture. She underwent transsphenoidal surgery and later gamma knife radiotherapy due to the persistence of the disease even after surgery.

18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography imaging in assessing early stages of aortic valve degeneration after transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, primarily in elderly patients. With an increasing number of procedures and younger patients, understanding the valve degeneration and its risk factors becomes crucial. We aimed to utilize 18F‑sodium fluoride (18F‑NaF) and 18F‑fluorodeoxyglucose (18F‑FDG) positron emission tomography/computed tomography (PET/CT) to evaluate early TAVI valve degeneration. In this prospective study with a prespecified follow‑up protocol, 71 TAVI patients underwent baseline transthoracic and transesophageal echocardiography, and PET/CT with 18F‑NaF and 18F‑FDG. Of these, 31 patients completed 24‑month control examinations, while the others were lost to mortality and the COVID‑19 pandemic. We measured PET tracer activity and compared 18F‑NaF and 18F‑FDG PET/CT uptake at baseline and 24‑month follow‑up. PET/CT and echocardiography data were analyzed for 31 of the 71 enrolled TAVI patients at a median age of 84 years (interquartile range, 80-86). After TAVI, an improvement in the valve function was observed. During follow‑up, the valve function remained stable. PET/CT demonstrated an increase in 18F‑FDG maximal uptake in the inner (tissue‑to‑background ratio, P = 0.009) and outer (P = 0.01) sides of the TAVI valve stent, but no difference in 18F‑NaF maximal activity (inner, P = 0.17; outer, P = 0.57). Twenty‑four months post‑TAVI, an increase in 18F‑FDG uptake, indicative of inflammation, was observed in the valve, while the uptake of the calcification marker (18F‑NaF) remained stable. Theseobservations might suggest early stages of TAVI valve degeneration, although further investigation is required to confirm this interpretation.

Bioprosthetic aortic valve degeneration evaluated by 18F-fluoride PET-TC

Abstract Background Implantation of bioprosthetic aortic valves (BPHV) is increasing owing to the aging population and the emergence of transcatheter aortic valve implantation. Along with the increase in life expectancy, BPHV degeneration is therefore becoming an increasing problem. 18F-fluoride positron emission tomography (PET) has emerged as a method that could identify early subclinical BPHV degeneration. Purpose We aimed to compare early PET parameters of fluorid uptake with echocardiographic hemodynamic parameters at three years after the implantation of a bioprosthetic aortic valve. Methods Sub-analysis of the ANTIPRO clinical trial. Patients undergoing aortic valve replacement (AVR) for porcine bioprosthesis were recruited at two surgical centers between 01/01/2019 and 02/13/2020, and were randomized in two groups (acetylsalicylic acid (ASA) vs ASA and oral anticoagulation for 3 months). Clinical and echocardiographic controls were performed one year and three years after AVR. Bioprosthetic valve deterioration (BVD) was defined according to the Valve Academic Research Consortium 3. 43 subjects were randomly selected from the whole cohort to undergo 18F-sodium fluoride PET with CT angiography (PET-CT) at follow-up. 18F-fluoride uptake in the valve (SUVavV) and right atrium (SUVavA) was measured, creating the SUVavV/SUVavA ratio or target-to-background ratio (TBR). PET findings were categorized as "high uptake" if TBR &amp;gt; 1.3 and "low uptake" if TBR ≤1.3. TBR was compared with the mean and maximum gradients at three years. Survival between high and low uptake groups was calculated using Kaplan-Meier and compared with log-rank test. The project was approved by the national ethics committee and patients consented the procedure. Results 18F-sodium fluoride PET-CT was performed on 43 subjects, with a mean time of 22.7±8.4 months after AVR. The echocardiogram at three years was performed in a mean time of 39.9±3.0 months after AVR. Mean time between PET-CT and echocardiogram was 17.2±9.9 months. The mean TBR was 1.25±0.30. Low uptake was found in 27 patients (62.8%) and high uptake in 15 patients (34.9%). Uptake could not be quantified in one patient due to technical problems. Baseline characteristics were similar between both groups (Table 1). Mean gradient at three years was 19.6±10.3 and peak gradient 33.7±16.7. Mean gradient was similar between the high uptake and low uptake groups (17.5±11.7 vs 21.6±9.3 p=0.296). Peak gradient was also similar between the high uptake and low uptake groups (30.6±18.5 vs 36.3±15.6 p=0.362). Five patients experienced BVD, of which 4 had low uptake and 1 had high uptake (p=0.523). Survival analysis did not demonstrate statistically different survival rates between the high uptake and low uptake groups (Figure 1). Conclusion Fluorid uptake with early PET after AVR was not associated with trans-prosthetic gradients nor BVD after a mean of 17 months from the PET scan.Table 1:Baseline characteristicsFigure 1:Kaplan-Meier survival curve

Aortic valve perivascular adipose tissue computed tomography attenuation in patients with aortic stenosis

ObjectiveAortic stenosis (AS) shares pathophysiological similarities with atherosclerosis including active inflammation. CT attenuation of perivascular adipose tissue provides a measure of vascular inflammation that is linked to prognosis and has...

18F-sodium fluoride positron emission tomography provides pertinent additional information to computed tomography for assessment and management of tarsal pain in horses.

To assess the value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) for imaging the tarsus and proximal metatarsus and compare it with CT and lameness evaluation. 25 horses with lameness localized to the tarsal and proximal metatarsal regions that underwent 18F-NaF PET/CT between 2016 and 2021. 18F-NaF PET and CT images were retrospectively independently evaluated by 3 observers. Standardized uptake values (SUV) were used to characterize 18F-NaF uptake. Correlation between PET and CT findings with subjective and objective maximum (Max-D) and minimum pelvic height lameness data was estimated. The inter-observer Kappa-weighted value (κ) was higher for PET (κ = 0.66) than CT (κ = 0.6). CT and PET scores were fairly correlated (R = 0.49; P < 0.05). PET SUVratio (SUV of the main lesion/SUV talus) had the highest correlation with Max-D (R = 0.71; P < .05). PET and CT scores for the plantar region were significantly higher in Quarter Horses (P < .05) and showed consistently higher correlation with objective lameness data (CT plantar grade - Max-D [R = 0.6; P < .05], PET plantar grade - Max-D [R = 0.47; P = .04]) than other regions of the distal tarsal joints. Three Warmbloods presented marked uptake at the medial cochlea of the distal tibia. PET had a moderate correlation with CT for assessment of tarsal lesions. The degree of PET uptake can help differentiate active versus inactive lesions. Specific location of the uptake is important in determining clinical relevance.

Comparison of 18F-sodium fluoride positron emission tomography and computed tomography for imaging of the fetlock in 25 nonracehorses.

18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has been validated as a useful imaging technique in the racehorse fetlock. The use of 18F-NaF PET in the nonracehorse fetlock has not been reported. To describe 18F-NaF PET findings in nonracehorse fetlocks, to compare with computed tomography (CT) findings and to compare PET findings between horses with and without fetlock pain. Retrospective observational study. All horses undergoing 18F-NaF PET and CT imaging of the fetlock between October 2016 and March 2021 were included in the study. Medical records were reviewed for associated lameness information. Thirty-six fetlocks (33 front and 3 hind) from 25 horses were included. The interobserver agreement for PET [0.62 (95% confidence interval [CI] 0.59-0.65)] was higher than for CT [0.47 (95% CI 0.43-0.51)]. Increased 18F-NaF uptake was most common in the medial subchondral bone of the proximal phalanx (23/36), the dorsomedial (20/36) and dorsosagittal (16/36) metacarpal/metatarsal distal subchondral bone, whereas sclerosis was identified on CT in these areas in 22 of 36 (p > 0.9), 33 of 36 (p = 0.001) and 23 of 36 (p = 0.15), respectively. Significant correlations were found between PET grades and both subchondral sclerosis and resorption CT grades (p < 0.001, Spearman r = 0.19 and 0.21, respectively). Abnormal 18F-NaF uptake in the proximal sesamoid bones (PSBs) was identified in 12 of 36 of the fetlocks, which was more common than CT abnormalities (3/36, p = 0.02). Periarticular increased uptake was seen in 7 of 36 fetlocks, whereas osteophytosis was recognised on CT in 20 of 36 (p = 0.1). Maximal standardised uptake values (SUVmax) were significantly higher in painful than in nonpainful fetlocks (22.0 and 11.9, respectively, p = 0.038). Retrospective study and limited sample size. Overall PET and CT findings follow a similar distribution in their location. PET identified more abnormalities in the PSBs than CT. SUVmax is a pertinent factor to take into consideration for the assessment of the clinical significance of findings.

Quantitative Analysis of Serial Positron Emission Tomography Imaging in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide

BackgroundThe emergence of positron emission tomography (PET) in prostate cancer is impacting clinical practice, but little is known about PET imaging as a tool to determine treatment failure in metastatic castration-resistant prostate cancer (mCRPC). ObjectiveTo evaluate PET imaging dynamics in mCRPC patients on enzalutamide with stable computed tomography (CT) and technetium-99m (Tc99) bone scans. Design, setting, and participantsAll patients were on treatment with enzalutamide for first-line mCRPC in a clinical trial at the National Cancer Institute (Bethesda, MD, USA). A volunteer sample had serial 18F-sodium fluoride (NaF) PET in parallel with CT and Tc99. Regions of interest (ROIs) on NaF were analyzed quantitatively for response. InterventionPatients were randomized to enzalutamide with/without a cancer immunotherapy, Prostvac. Outcome measurements and statistical analysisA post hoc, descriptive analysis was performed comparing the changes seen on CT and Tc99 as per RECIST 1.1 with NaF PET scans including the use of a quantitative analysis. Results and limitationsEighteen mCRPC patients had 67 NaF scans. A total of 233 ROIs resolved after treatment, 52 (22%) of which eventually retuned while on therapy. In all, 394 new ROIs were seen, but 112(28%) resolved subsequently. Of 18 patients, 14 had new ROIs that ultimately resolved after appearing. Many patients experienced progression in a minority of lesions, and one patient with radiation intervention to oligoprogression had a remarkable response. This study is limited by its small number of patients and post hoc nature. ConclusionsThese data highlight the dynamic nature of NaF PET in mCRPC patients treated with enzalutamide, where not all new findings were ultimately related to disease progression. This analysis also provides a potential strategy to identify and intervene in oligoprogression in prostate cancer. Patient summaryIn this small analysis of patients with prostate cancer on enzalutamide, changes on 18F-sodium fluoride positron emission tomography (PET) imaging were not always associated with treatment failure. Caution may be indicated when using PET imaging to determine whether new therapy is needed.

Quantitative analysis of aortic Na[18F]F uptake in macrocalcifications and microcalcifications in PET/CT scans.

Currently, computed tomography (CT) is used for risk profiling of (asymptomatic) individuals by calculating coronary artery calcium scores. Although this score is a strong predictor of major adverse cardiovascular events, this method has limitations. Sodium [18F]fluoride (Na[18F]F) positron emission tomography (PET) has shown promise as an early marker for atherosclerotic progression. However, evidence on Na[18F]F as a marker for high-risk plaques is limited, particularly on its presentation in clinical PET/CT. Besides, the relationship between microcalcifications visualized by Na[18F]F PET and macrocalcifications detectable on CT is unknown. To establish a match/mismatch score in the aorta between macrocalcified plaque content on CT and microcalcification Na[18F]F PET uptake. Na[18F]F-PET/CT scans acquired in our centre in 2019-2020 were retrospectively collected. The aorta of each low-dose CT was manually segmented. Background measurements were placed in the superior vena cava. The vertebrae were automatically segmented using an open-source convolutional neural network, dilated with 10mm, and subtracted from the aortic mask. Per patient, calcium and Na[18F]F-hotspot masks were retrieved using an in-house developed algorithm. Three match/mismatch analyses were performed: a population analysis, a per slice analysis, and an overlap score. To generate a population image of calcium and Na[18F]F hotspot distribution, all aortic masks were aligned. Then, a heatmap of calcium HU and Na[18F]F-uptake on the surface was obtained by outward projection of HU and uptake values from the centerline. In each slice of the aortic wall of each patient, the calcium mass score and target-to-bloodpool ratios (TBR) were calculated within the calcium masks, in the aortic wall except the calcium masks, and in the aortic wall in slices without calcium. For the overlap score, three volumes were identified in the calcium and Na[18F]F masks: volume of PET (PET+/CT-), volume of CT (PET-/CT+), and overlapping volumes (PET+/CT+). A Spearman's correlation analysis with Bonferroni correction was performed on the population image, assessing the correlation between all HU and Na[18F]F vertex values. In the per slice analysis, a paired Wilcoxon signed-rank test was used to compare TBR values within each slice, while an ANOVA with post-hoc Kruskal-Wallis test was employed to compare TBR values between slices. p-values<0.05 were considered significant. In total, 186 Na[18F]F-PET/CT scans were included. A moderate positive exponential correlation was observed between total aortic calcium mass and total aortic TBR (r=0.68, p<0.001). A strong positive correlation (r=0.77, p<0.0001) was observed between CT values and Na[18F]F values on the population image. Significantly higher TBR values were found outside calcium masks than inside calcium masks (p<0.0001). TBR values in slices where no calcium was present, were significantly lower compared with outside calcium and inside calcium (both p<0.0001). On average, only 3.7% of the mask volumes were overlapping. Na[18F]F-uptake in the aorta behaves similarly to macrocalcification detectable on CT. Na[18F]F-uptake values are also moderately correlated to calcium mass scores (match). Higher uptake values were found just outside macrocalcification masks instead of inside the macrocalcification masks (mismatch). Also, only a small percentage of the Na[18F]F-uptake volumes overlapped with the calcium volumes (mismatch).