18F-sodium Fluoride Positron Emission Research Articles

The potential advantages of 18F sodium fluoride positron emission tomography-computed tomography for clinical staging and management planning in patients with nasopharyngeal carcinoma.

The staging and treatment planning of nasopharyngeal carcinoma (NPC) face challenges due to limited sensitivity of conventional imaging. 18F-sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET/CT) offers potential advantages in detecting early bone involvement. This retrospective cohort study aimed to assess the potential advantage of 18F-NaF PET/CT for clinical staging and management planning in patients with NPC and to compare 18F-NaF PET/CT findings with those of conventional imaging modalities. We enrolled a cohort of patients with NPC who underwent 18F-NaF PET/CT at our PET/CT center between July 1, 2017, and June 30, 2021, and analyzed the findings of 18F-NaF PET/CT and conventional imaging modalities. Data from multidisciplinary team discussions on clinical staging and management planning both before and after 18F-NaF PET/CT were recorded. Additionally, any changes in clinical staging and management planning following 18F-NaF PET/CT were documented. A total of 58 patients were included in this study. After 18F-NaF PET/CT imaging, clinical tumor-node-metastasis (TNM) staging was observed to have changed in seven cases (12.1%). Among these, four cases had changes in T stage and three cases in the M stage. Additionally, changes in clinical management plans were observed in eight patients (13.8%). Changes due the results of 18F-NaF PET/CT included three cases with major modification (two cases switched from curative treatment to palliative treatment, and one case switched from palliative treatment to curative treatment) and five cases with minor changes. The minor changes involved alteration to the radiotherapy target volume (three cases with an increased target volume and one case with a reduced target area). Furthermore, one case required an alteration to the radiotherapy strategy for local bone involvement. The use of 18F-NaF PET/CT in patients newly diagnosed with NPC may offer potential advantages for clinical staging and treatment planning, enabling physicians to select a more individualized treatment approach.

Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria.

Diabetes affects the kidneys, and presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advantages in non-invasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of sub-clinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (18F-sodium fluoride positron emission tomography/computed tomography (PET/CT), plaque inflammation (64Cu- DOTATATE PET/CT) and myocardial flow reserve (82Rubidium PET/CT). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin creatinine ratio (UACR) ≥ 30 mg/g)), and 30 had normoalbuminuria (UACR < 30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particularly higher levels of microcalcifications and impaired myocardial microvascular function, however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome.

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.

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...

Comparison of the diagnostic value of 18F-NaF PET/CT and 99mTc-MDP SPECT for bone metastases: a systematic review and meta-analysis.

Bone scintigraphy, the standard tool for detecting bone metastases has some insufficiencies; thus, supplementary imaging techniques are needed. This study is a comprehensive meta-analysis of studies reporting and comparing the diagnostic efficacy of 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) and 99mTc-MDP single-photon emission computed tomography (SPECT) for bone metastases. Literature related to the diagnosis of bone metastases using 18F-NaF PET/CT and 99mTc-MDP SPECT was searched on PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang databases, and VIP. Evaluation of study quality was performed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Pooled sensitivity (SEN) and specificity (SPE) were assessed along with heterogeneity. The subject operating characteristic curve was plotted, the area under the curve (AUC) was calculated, and the pre- and post-test probabilities were compared. Finally, 11 articles, consisting of 1,085 patients and 1,782 lesions, were included. At the patient level (11 articles), the results were pooled SEN =0.92 and SPE =0.96 for PET/CT, SEN =0.80 and SPE =0.90 for SPECT. The AUC of PET/CT [0.98 (0.96-0.99)] was higher than that of SPECT [0.92 (0.89-0.94), P<0.05]. At the lesion level (6 articles), the results were pooled SEN =0.96 and SPE =0.98 for PET/CT, SEN =0.76 and SPE =0.94 for SPECT. The AUC of PET/CT [0.99 (0.98-1.00)] was higher than that of SPECT [0.94 (0.92-0.96); P<0.05]. Statistical heterogeneity existed, and meta-regression showed that, at patient-based level, the study design type, tumor character, and the selection blinding method were the main sources of heterogeneity. Furthermore, both PET/CT and SPECT had superior SEN for osteogenic metastases than non-osteogenic metastases (P=0.01). At the lesion level, tumor character was a source of heterogeneity accompanied by an increased SEN for osteogenic metastases, and the SEN for SPECT combined with CT was improved [SEN =0.87 (0.68-1.00), P=0.03]. 18F-NaF PET/CT has a higher SEN and SPE than 99mTc-MDP SPECT in diagnosing bone metastases, nevertheless, it is necessary to fully understand the primary tumor and the characteristics of the imaging protocol to choose suitable modality for individuals. Combining SPECT with CT improves the diagnostic efficacy than having SPECT alone and can be a powerful supplement to PET/CT for suspected osteogenic bone metastases.

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.

Positron emission tomography assessment of metacarpal/metatarsal condylar fractures post surgical repair: Prospective study in 14 racehorses.

To assess 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings associated with metacarpal/metatarsal condylar fractures at the time of fracture repair and through healing. Prospective descriptive study. Fourteen Thoroughbred racehorses. 18F-NaF PET was performed within 4 days of surgical metacarpal/metatarsal condylar fracture repair, on both the injured and contralateral limb. Follow-up PET scans were offered at 3- and 5-months post fracture repair. Areas of abnormal uptake were assessed using a previously validated grading system. Eight fractures were located in the parasagittal groove (PSG) (six lateral and two medial) and six fractures were located abaxial to the PSG (non-PSG) through the palmar/plantar condyle (all lateral). All horses in the latter group had uptake in the lateral palmar condyle of the contralateral limb suggestive of stress remodeling. Three horses with PSG fractures had uptake in a similar location in the contralateral limb. Horses with lateral condylar fracture only presented minimal or mild uptake in the medial condyle, which is considered atypical in the front limbs for horses in full training. Four horses developed periarticular uptake in the postoperative period suggestive of degenerative joint disease, three of these horses had persistent uptake at the fracture site. These four horses did not return to racing successfully. The findings of this study provide evidence of pre-existing lesions and specific uptake patterns in racehorses suffering from metacarpal/metatarsal condylar fractures. PET has a possible role in the prevention, diagnosis, and postoperative monitoring of metacarpal/metatarsal condylar fractures in racehorses.

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.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events

Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

#6643 MOLECULAR PATHWAYS ASSOCIATED WITH VASCULAR CALCIFICATIONS IN CHILDREN WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Patients with advanced stages of chronic disease (CKD) suffer from 30-times higher risk of cardiovascular disease (CVD) as compared to the general population, vascular calcifications are prevalent. Underlying molecular mechanisms are only partly understood. Children are devoid of life-style and aging related CVD risk factors and therefore allow for a highly sensitive and specific analyses of CKD induced pathomechanisms. Method Arteriolar tissues of 55 children with normal renal function and 29 children with CKD5 (median age 9.2 years) underwent digital histomorphometry, calcium deposits were assessed by Von Kossa staining and 18F-sodium fluoride positron emission tomography (18F-NaF PET). Gene set enrichment (GSEA) and Ingenuity pathway analysis were performed on multi-omics data sets obtained from micro-dissected omental arterioles from children with normal renal function and with CKD5 (n = 7/group; age 7.3 ± 3/6.8 ± 3 years). Based on literature review, we established a vascular calcification (VC) pathway library comprising 442 biological processes/molecular functions and extracted linked genes from Gene Ontology database. Key identified mechanisms were validated in independent patient cohorts (n = 32) and controls (n = 20) by quantitative immunostaining. Results Significant arteriolar lumen obliteration was present in CKD5 children (p = 0.001), intima and media thickness were increased (p&amp;lt;0.0001 and p = 0.02). Von Kossa staining was negative, but 18F-NaF PET revealed microcalcifications in children with CKD5. Subendothelial arteriolar inflammatory cells (CD68+ macrophages) were present in CKD5 cohort (p&amp;lt;0.0001 compared to non-CKD controls) and correlated with serum inorganic phosphorus (R2 = 0.18; p = 0.04). GSEA identified top enriched pathways including telomere extension by telomerase and chromatin histone methylation. IPA cross-omics showed suppression of actin cytoskeleton, tight junction signaling, and focal adhesion. VC pathway analysis identified 30/442 pathways related to actin cytoskeleton, Wnt signaling, extracellular matrix (ECM) organization, complement activation, apoptosis, endoplasmic reticulum stress and ossification regulation. Fibronectin-1 (FN1) was identified as Hubgene, involved in ECM regulation. In independent age-matched cohorts, complement factor C3d was higher in CKD5, vascular endothelial growth factor and endothelial cell number/µm endoluminal circumference were reduced. Arteriolar osteoglycin, a protein inducing ectopic bone formation, was increased and correlated with serum PTH (R2 = 0.61; p = 0.01). FN1 was less abundant in arterioles from CKD5 children and negatively correlated with serum creatinine levels (R2 = −0.62; p = 0.02). Conclusion Vascular disease and microcalcifications are present in young children with CKD5. We provide the first comprehensive analysis of the underlying molecular mechanisms associated with the vascular calcifications and identified specific molecular pathomechanisms, of which several represent potential therapeutic targets.

Latent Coronary Plaque Morphology From Computed Tomography Angiography, Molecular Disease Activity on Positron Emission Tomography, and Clinical Outcomes.

Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. Patients with known coronary artery disease underwent coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P=0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P=0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P=0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P=0.02). In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

18F-sodium fluoride positron emission tomography following coronary computed tomography angiography in predicting long-term coronary events: a 5-year follow-up study.

The predictive value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with coronary computed tomography (CT) angiography (CCTA) for future coronary events has attracted interest. We evaluated the potential of 18F-NaF PET/CT following CCTA to predict major coronary events (MACE) during a 5-year follow-up period. Forty patients with coronary atherosclerotic lesions detected on CCTA underwent 18F-NaF PET/CT examination. Each lesion was evaluated for luminal stenosis and high-risk plaque (HRP) with < 30 Hounsfield units and a > 1.1 remodeling index on CCTA. Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue-to-background ratio (TBRmax), and the maximum TBRmax per patient (M-TBRmax) was determined. We followed MACE (cardiac death, acute coronary syndrome, and/or coronary revascularization > 6months after 18F-NaF PET/CT) for 5years. In total, 142 coronary lesions were analyzed. Eleven patients experienced any MACE. Patients with MACE showed a higher M-TBRmax than those without (1.40 ± .19 vs. 1.18 ± .18, P = .0011), and the optimal M-TBRmax cutoff to predict MACE was 1.29. Patients with M-TBRmax of ≥ 1.29 had a higher risk of MACE than those with lower values (P = .012, log-rank test), whereas patients with obstructive stenosis and those with HRP did not. Multivariate Cox proportional analysis adjusted for age, sex, coronary risk factors, and CCTA findings showed that M-TBRmax of ≥ 1.29 remained an independent predictor of 5-year MACE (hazard ratio, 5.4; 95% confidence interval, 1.1-25.4; P = .034). 18F-NaF PET/CT following CCTA provides useful strategies to predict 5-year MACE.

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.

Serum lipoprotein(a) and bioprosthetic aortic valve degeneration.

Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.

Qualitative and Quantitative Evaluation of Morpho-Metabolic Changes in Bone Cartilage Complex of Knee Joint in Osteoarthritis Using Simultaneous 18F-NaF PET/MRI-A Pilot Study.

Background Articular cartilage (AC) loss and deterioration, as well as bone remodeling, are all symptoms of osteoarthritis (OA). As a result, an ideal imaging technique for researching OA is required, which must be sensitive to both soft tissue and bone health. Objective The aim of this study was to assess the potential of simultaneous 18F sodium fluoride (18F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI) to identify as well as classify osseous metabolic abnormalities in knee OA and to see if degenerative changes in the cartilage and bone on MRI might be correlated with subchondral 18F-NaF uptake on PET. Methods Sixteen (32 knees) volunteers with no past history of knee injury, with or without pain, were enrolled for the research from January to July 2021. The images of both knees were taken utilizing an molecular magnetic resonance (mMR) body matrix coil on a simultaneous PET/MRI biograph mMR. The acquisition was conducted after 45 minutes of intravenous infusion of 18F-NaF 185-370 MBq (5-10 mCi) over one PET bed for 40 minutes, while MRI sequences were performed simultaneously. Results All pathologies showed significantly higher maximum standardized uptake value (SUV max ) than the background. Thirty-four subchondral magic spots were identified on 18F-NaF PET without any structural alteration on MRI. Bone marrow lesions (BMLs) and osteophytes with higher MRI osteoarthritis knee score (MOAKS) score showed higher 18F-NaF uptake (grade1˂grade2˂grade3). BMLs had corresponding AC degeneration. There was discordance between grade 1 osteophytes (86.6%), sclerosis (53.7%) and grade 1 BML in cruciate ligament insertion site (91.66%); they did not have high uptake of 18F-NaF. In case of cartilage, there was significant difference between AC grades and average subchondral SUV max and T2* relaxometry (grade0˂grade1˂grade2˂grade3˂grade4). BMLs are much more metabolically active than other pathologies, while sclerosis is the least. We also found that the subchondral uptake was statistically increased in the areas of pathology: Conclusion 18F-NaF PET/MRI was able to detect knee abnormalities unseen on MRI alone and simultaneously assessed metabolic and structural markers of knee OA across multiple tissues in the joint. Thus, it is a promising tool for detection of early metabolic changes in OA.

Trans-Aortic Flow Turbulence and Aortic Valve Inflammation: A Pilot Study Using Blood Speckle Imaging and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Patients With Moderate Aortic Stenosis.

18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT) has been proven to be useful in identification of microcalcifications, which are stimulated by inflammation. Blood speckle imaging (BSI) is a new imaging technology used for tracking the flow of blood cells using transesophageal echocardiography (TEE). We evaluated the relationship between turbulent flow identified by BSI and inflammatory activity of the aortic valve (AV) as indicated by the 18F-NaF uptake index in moderate aortic stenosis (AS) patients. This study enrolled 18 moderate AS patients diagnosed within the past 6 months. BSI within the aortic root was acquired using long-axis view TEE. The duration of laminar flow and the turbulent flow area ratio were calculated by BSI to demonstrate the degree of turbulence. The maximum and mean standardized uptake values (SUVmax, SUVmean) and the total microcalcification burden (TMB) as measured by 18F-NaF PET/CT were used to demonstrate the degree of inflammatory activity in the AV region. The mean SUVmean, SUVmax, and TMB were 1.90 ± 0.79, 2.60 ± 0.98, and 4.20 ± 2.18 mL, respectively. The mean laminar flow period and the turbulent area ratio were 116.1 ± 61.5 msec and 0.48 ± 0.32. The correlation between SUVmax and turbulent flow area ratio showed the most positive and statistically significant correlation, with a Pearson's correlation coefficient (R²) of 0.658 and a p-value of 0.014. The high degree of trans-aortic turbulence measured by BSI was correlated with severe AV inflammation.

18F-sodium fluoride positron emission tomography and coronary plaque radiomics derived from computed tomography angiography for prediction of myocardial infarction

Abstract Background Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography (18F-NaF PET) and radiomics-based precision coronary plaque phenotyping derived from contrast-enhanced computed tomography (CT) have both been shown to enhance risk stratification in patients with coronary artery disease (CAD). To date, no study has investigated whether these two promising methods (which can be obtained during a single imaging session on a hybrid PET/CT scanner) are interchangeable or can provide superior predictive performance when used in combination. Purpose We sought to investigate whether the prognostic information provided by latent morphological radiomic coronary plaque features and assessments of disease activity by 18F-NaF PET are complementary in prediction of myocardial infarction. Methods Patients with known CAD underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA). We performed quantitative plaque analysis of coronary CT angiography datasets. Additionally, coronary plaque segmentations on CT angiography were used to extract 1103 radiomic features. Using weighted correlation network analysis we derived latent morphological features of coronary plaques which were aggregated to patient-level radiomic normograms to predict myocardial infarction using univariate and multivariate Cox proportional hazard models. Results The study cohort comprised of 260 patients with established CAD (age: 65±9 years; 84% men); 179 (69%) participants showed increased coronary 18F-NaF activity (CMA &amp;gt;0). Over 53 [40–59] months of follow-up 18 patients had a myocardial infarction. Using weighted correlation network analysis, from the 1103 radiomic features we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns. On univariate cox modelling 7 of these emerged as predictors of myocardial infarction (Figure). Following adjustments for calcified, noncalcified and low-density noncalcified plaque volumes and 18F-NaF CMA 4 radiomic features (related to texture and geometry) remained independent predictors of myocardial infarction (Figure). Conclusion(s) In patients with established CAD latent morphological features of coronary plaques are predictors of myocardial infarction above and beyond plaque volumes and 18F-NaF uptake. Comprehensive plaque analysis with radiomics may enhance risk stratification of CAD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH, Wellcome Trust

After Total Ankle Arthroplasty, When Does Bone Perfusion and Metabolic Activity at the Bone-Implant Interface Normalize? A PET/CT Study

Category: Ankle Arthritis Introduction/Purpose: Radionuclide bone scintigraphy in combination with computed tomography (CT) has been used to evaluate painful total hip and knee arthroplasties, and has also been used in the evaluation of the painful total ankle arthroplasty (TAA). Increased tracer uptake around implants may indicate loosening, but uptake characteristics of bone-seeking radiopharmaceuticals in asymptomatic total ankle patients have not been clarified. While findings of increased metabolic activity may prompt surgical intervention, there has been no work performed to define when postoperatively periprosthetic activity normalizes, if at all. In this study, we plan to establish normative data on 18F sodium fluoride (18F-NaF) positron emission tomography/CT (PET/CT) uptake ratios around TAA implants at various time intervals after surgery in asymptomatic TAA patients. Methods: The majority of the arthroplasty literature has investigated use of SPECT/CT performed with 99mTc-labeled bisphosphonates. However, data suggest that 18F-NaF PET/CT may be superior for this indication, with more favorable pharmacokinetics and similar sensitivity to detect aseptic loosening. In the present study, asymptomatic patients who underwent TAA with a modern fixed-bearing TAA prosthesis (either the Wright Infinity Adaptis or Exactech Vantage prosthesis) for posttraumatic arthritis were eligible for inclusion. Patients with ipsilateral hindfoot fusion and with any periprosthetic lucencies or cysts were excluded. Patients were enrolled at one of four time intervals following TAA: 6, 12, 18, or 24 months. Standard uptake values were measured at the bone-implant interface for the tibial and talar components on static PET, in regions of interest defined on axial CT scan slices. Periprosthetic bone blood flow (K1) and bone turnover (flux) were assessed at each time interval in each periprosthetic region using dynamic PET. Results: Sixteen asymptomatic patients underwent PET/CT: 4 patients at 6 months postoperatively, 6 at 12 months, and 6 at 24 months. We are currently still in data collection and at this time only 2 patients at 18 months have completed the scan, therefore their data were excluded. The average age was 65 years (range, 55 to 80) and 6 patients were female (38%), with individual patient data shown in the Table. Talar K1 and flux both appeared to increase from 6 to 12 months, and decrease between 12 and 24 months, although there was no statistically significant difference between timepoints. Overall tibial K1 and flux appeared to decrease slightly from 6 to 12 months, and stayed relatively stable between 12 and 24 months, again with no significant difference between timepoints (Figure). Conclusion: There is currently no normative data to help guide interpretation of radionuclide bone scintigraphy for the painful TAA. The present study utilizing 18F-NaF PET/CT scans demonstrates that even in asymptomatic patients, periprosthetic bone blood flow and bone turnover remain elevated up to 24 months following modern fixed-bearing TAA. Not only do these values remain elevated at 24 months, but we found that there does not appear to be any significant decrease in either measurement over time from 6 to 24 months postoperatively. Our findings suggest that radionuclide bone scintigraphy should be cautiously interpreted when performed within 2 years of TAA.

Longitudinal monitoring of fetlock lesions in Thoroughbred racehorses using standing 18F-sodium fluoride positron emission tomography.

To assess the repeatability of equine 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings, and to evaluate the ability of PET to monitor the progression of areas of increased radiopharmaceutical uptake (IRU) in the fetlocks of Thoroughbred racehorses. 25 racehorses with clinical signs related to fetlock injuries. This study is a prospective, longitudinal clinical study. Twenty-five racehorses (54 fetlocks) underwent three 18F-NaF PET scans 6 weeks apart. The first 18F-NaF PET scan was performed at the start of a 12-week period of rest from racing (lay-up). Areas of IRU in the fetlock joints were quantified using maximal standardized uptake values (SUVmax) and were graded by 2 experienced observers. Statistical comparisons were made between scans to detect changes in IRU grade and SUVmax over time. Standing PET findings were repeatable, with 131/149 (88%) areas of IRU identified on the initial scans seen again at the 6-week follow-up scan. The palmar/plantar condyles were the sites most commonly presenting with IRU, followed by the proximal sesamoid bones. Overall, 65% of fetlocks demonstrated improvement in IRU grade during the 12-week period of rest from racing. Areas of higher IRU grade took longer to resolve than the lower graded areas. Standing PET findings in the racehorse fetlock were repeatable. The SUV-based grading system may be helpful when determining appropriate lay-up duration for Thoroughbred racehorses. PET may be used to monitor areas of the fetlock involved in catastrophic breakdown injuries in Thoroughbred racehorses.

The effect of Vitamin-K1 and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial

BackgroundThere is currently no treatment for attenuating progression of arterial calcification. 18F-sodium fluoride positron emission tomography (18F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K1 or colchicine affected arterial calcification activity. Methods154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K1 [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K1 [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on 18F-NaF PET. Results149 subjects completed follow-up (vitamin-K1: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K1 nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K1. ConclusionsIn patients with type 2 diabetes, neither vitamin-K1 nor colchicine significantly decreases coronary calcification activity, as estimated by 18F-NaF PET, over a period of 3 months. Clinical trial registration: ACTRN12616000024448.