18F-NaF Uptake Research Articles

Multimodality Imaging of Aortic Valve Calcification and Function in a Murine Model of Calcific Aortic Valve Disease and Bicuspid Aortic Valve.

Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. Dcbld2-/- mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). 18F-NaF PET/CT can detect the aortic valve calcification process in humans. However, its feasibility in preclinical models of CAVD remains to be determined. Here, we sought to validate 18F-NaF PET/CT for tracking murine aortic valve calcification and leveraged it to examine the development of calcification with aging and its interdependence with BAV and AS in Dcbld2-/- mice. Methods: Dcbld2-/- mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, 18F-NaF PET/CT (n = 34, or autoradiography (n = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (n = 12). The aortic valve signal was quantified as SUVmax on PET/CT and as percentage injected dose per square centimeter on autoradiography. The valve tissue sections were analyzed by microscopy to identify tricuspid and bicuspid aortic valves. Results: The aortic valve 18F-NaF signal on PET/CT was significantly higher at 18-24 mo (P < 0.0001) and 10-16 mo (P < 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher 18F-NaF signal than tricuspid aortic valves (P < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher 18F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson r = 0.79, P < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (P < 0.05). Transaortic valve flow velocity was significantly higher in animals with BAV at all ages. Finally, there was a significant correlation between transaortic valve flow velocity and aortic valve calcification by both PET/CT (r = 0.55, P < 0.001) and autoradiography (r = 0.45, P < 0.01). Conclusion: 18F-NaF PET/CT links valvular calcification to BAV and aging in Dcbld2-/- mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, 18F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.

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.

Establishment of a sequential dual tracer 18F‐NaF/18F‐FDG PET protocol for imaging the equine foot

The combination of 18 F-Sodium Fluoride (18 F-NaF) and 18 F-FluoroDeoxyGlucose (18 F-FDG) for positron emission tomography (PET) imaging of the equine foot is appealing for detection of both osseous and soft tissue lesions in a single scan. As the combination of tracers could lead to a loss of information, a sequential approach, consisting in imaging with one tracer prior to injecting the second tracer, might be valuable. The goals of this prospective, methods comparison, exploratory study were to establish the order of tracer injectionandtimingforimaging. Six research horses were imaged under general anesthesia with 18 F-NaF PET, 18 F-FDG PET, dual 18 F-NaF/18 F-FDG PET, and CT. Proper uptake could be identified in tendon lesions as early as 10 min after 18F-FDG injection. Bone uptake was limited when 18F-NaF was injected under general anesthesia, even at 1h after injection, when compared with 18 F-NaF injection prior to anesthesia. The sensitivity and specificity of the dual tracer scans were 0.77 (0.63 to 0.86) and 0.98 (0.96 to 0.99) respectively, to assess 18 F-NaF uptake and 0.5 (0.28 to 0.72) and 0.98 (0.95 to 0.99), respectively, for 18F-FDG uptake. These results suggest that the sequential dual tracer approach is a pertinent technique to optimize the PET data gained from a single anesthetic episode. Based on dynamics of tracer uptake, the optimal protocol consists in injecting 18F-NaF prior to anesthesia, acquire 18F-NaF data then inject 18F-FDG and start acquisition of dual tracer PET data 10 min later. This protocol should be further validated in a larger clinical study.

Vessel-by-vessel analysis of lower extremity 18F-NaF PET/CT imaging quantifies diabetes- and chronic kidney disease-induced active microcalcification in patients with peripheral arterial disease

BackgroundPositron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (18F)-sodium fluoride (NaF) provides assessment of active vascular microcalcification, but its utility for evaluating diabetes mellitus (DM)- and chronic kidney disease (CKD)-induced atherosclerosis in peripheral arterial disease (PAD) has not been comprehensively evaluated. This study sought to use 18F-NaF PET/CT to quantify and compare active microcalcification on an artery-by-artery basis in healthy subjects, PAD patients with or without DM, and PAD patients with or without CKD. Additionally, we evaluated the contributions of DM, CKD, statin use and established CT-detectable calcium to 18F-NaF uptake for each lower extremity artery.MethodsPAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18F-NaF PET/CT imaging. Fused PET/CT images guided segmentation of arteries of interest (i.e., femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal) and quantification of 18F-NaF uptake. 18F-NaF uptake was assessed for each artery and compared between subject groups. Additionally, established calcium burden was quantified for each artery using CT calcium mass score. Univariate and multivariate analyses were performed to evaluate DM, CKD, statin use, and CT calcium mass as predictors of 18F-NaF uptake in PAD.ResultsPAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18F-NaF uptake) for all arteries when compared to PAD patients without DM or CKD. Univariate and multivariate analyses revealed that concomitant DM or CKD was associated with increased microcalcification for all arteries of interest and this increased disease risk remained significant after adjusting for patient age, sex, and body mass index. Statin use was only associated with decreased microcalcification for the femoral-popliteal artery in multivariate analyses. Established CT-detectable calcium was not significantly associated with 18F-NaF uptake for 4 out of 5 arteries of interest.Conclusions18F-NaF PET/CT imaging quantifies vessel-specific active microcalcification in PAD that is increased in multiple lower extremity arteries by DM and CKD and decreased in the femoral-popliteal artery by statin use. 18F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18F-NaF PET/CT imaging may provide an approach for non-invasively quantifying vessel-specific responses to emerging anti-atherogenic therapies or CKD treatment in patients with PAD.

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

18 F-NaF PET/CT in Presumed Aseptic Pseudarthrosis after Spinal Fusion: Correlation with Findings at Revision Surgery and Intraoperative Cultures.

Background Conventional imaging is useful to assess interbody fusion by showing complete trabecular bony bridging, but has a low positive predictive value for pseudarthrosis. Because alterations of bone metabolism may precede structural anatomical changes on computed tomography (CT), we aimed to investigate the ability of fluorine 18 sodium fluoride positron emission tomography/computed tomography ( 18 F-NaF PET/CT) to identify pseudarthrosis after spinal fusion using surgical revision as the reference standard. Methods We retrospectively reviewed 18 F-NaF PET/CT scans performed between February 2019 and September 2020 in patients experiencing pain after spinal fusion. We included the 18 patients who underwent revision surgery for suspicion of pseudarthrosis. Five consecutive patients who were clearly fused on CT served as the control group. Results In the revision surgery group ( n =18), visual assessment by 18 F-NaF PET/CT revealed that all 22 cages with an increased 18 F-NaF uptake around intercorporal fusion material had mobility at revision surgery, whereas none of the fused patients ( n =5) showed uptake around cage/intervertebral disk space. Among the 18 patients with presumed aseptic pseudarthrosis, intraoperative cultures revealed surgical site infection (SSI) caused by Cutibacterium acnes ( C. acnes ) in seven patients (38.9%). There was a statistically significant difference in standardized uptake values and uptake ratios between the revision surgery and control groups ( p =5.3× 10 -6 and p =0.0002, respectively). Conclusions 18 F-NaF PET/CT imaging appeared as a useful tool to identify pseudarthrosis following spinal fusion. The unexpectedly high prevalence (38.9%) of SSI caused by C. acnes found in presumed aseptic patients supports the utility of intraoperative cultures in revision cases for pseudarthrosis, even without preoperative clinical suspicion of SSI.

Longitudinal analysis of atherosclerotic plaques evolution: an 18F-NaF PET/CT study

Purpose18F-NaF-PET/CT can detect mineral metabolism within atherosclerotic plaques. To ascertain whether their 18F-NaF uptake purports progression, this index was compared with subsequent morphologic evolution. Methods71 patients underwent two consecutive 18F-NaF-PET/CTs (PET1/PET2). In PET1, non-calcified 18F-NaF hot spots were identified in the abdominal aorta. Their mean/max HU was compared with those of a non-calcified control region (CR) and with corresponding areas in PET2. A target-to-background ratio (TBR), mean density (HU), and calcium score (CS) were calculated on calcified atherosclerotic plaques in PET1 and compared with those in PET2. A VOI including the entire abdominal aorta was drawn; mean TBR and total CS were calculated on PET1 and compared with those PET2. ResultsHot spots in PET1 (N = 179) had a greater HU than CR (48 ± 8 vs 37 ± 9, P < .01). Mean hot spots HU increased to 59 ± 12 in PET2 (P < .001). New calcifications appeared at the hot spots site in 73 cases (41%). Baseline atherosclerotic plaque’s (N = 375) TBR was proportional to percent HU and CS increase (P < .01 for both). Aortic CS increased (P < .001); the whole-aorta TBR in PET1 correlated with the CS increase between the baseline and the second PET/CT (R = .63, P < .01). Conclusions18F-NaF-PET/CT depicts the early stages of plaques development and tracks their evolution over time.

Effects of Anti-Tumor Necrosis Factor Therapy on Osteoblastic Activity at Sites of Inflammatory and Structural Lesions in Radiographic Axial Spondyloarthritis: A Prospective Proof-of-Concept Study Using Positron Emission Tomography/Magnetic Resonance Imaging of the Sacroiliac Joints and Spine.

Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF (18 F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18 F-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18 F-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). 18 F-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18 F-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18 F-NaF uptake, compared with baseline. For VCs, 18 F-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18 F-NaF uptake, compared with baseline. Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA.

18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome.

Background MRI and fluorine 18-labeled sodium fluoride (18F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between 18F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this prospective observational cohort study (October 2017 to January 2020), participants underwent 18F-NaF PET/MRI. An experienced clinician determined the culprit carotid artery based on symptoms and record review. 18F-NaF uptake was quantified using standardized uptake values and tissue-to-background ratios. Statistical significance was assessed with the Welch, χ2, Wilcoxon, or Fisher test. Multivariable models were used to evaluate the relationship between the imaging markers and the culprit versus nonculprit vessel. Results A total of 110 participants were evaluated (mean age, 68 years ± 10 [SD]; 70 men and 40 women). Of the 110, 34 (32%) had prior cerebrovascular disease, and 26 (24%) presented with amaurosis fugax, 54 (49%) with transient ischemic attack, and 30 (27%) with stroke. Compared with nonculprit carotids, culprit carotids had greater stenoses (≥50% stenosis: 30% vs 15% [P = .02]; ≥70% stenosis: 25% vs 4.5% [P < .001]) and had increased prevalence of MRI-derived adverse plaque features, including intraplaque hemorrhage (42% vs 23%; P = .004), necrotic core (36% vs 18%; P = .004), thrombus (7.3% vs 0%; P = .01), ulceration (18% vs 3.6%; P = .001), and higher 18F-NaF uptake (maximum tissue-to-background ratio, 1.38 [IQR, 1.12-1.82] vs 1.26 [IQR, 0.99-1.66], respectively; P = .04). Higher 18F-NaF uptake was positively associated with necrosis, intraplaque hemorrhage, ulceration, and calcification and inversely associated with fibrosis (P = .04 to P < .001). In multivariable analysis, carotid stenosis at or over 70% (odds ratio, 5.72 [95% CI: 2.2, 18]) and MRI-derived adverse plaque characteristics (odds ratio, 2.16 [95% CI: 1.2, 3.9]) were both associated with the culprit versus nonculprit carotid vessel. Conclusion Fluorine 18-labeled sodium fluoride PET/MRI characteristics were associated with the culprit carotid vessel in study participants with acute neurovascular syndrome. Clinical trial registration no. NCT03215550 and NCT03215563 © RSNA, 2022 Online supplemental material is available for this article.

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

BackgroundPrevious studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. Methods and resultsWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. Conclusions18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

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

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

Quantifying microcalcification activity in the thoracic aorta

BackgroundStandard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. MethodsTwenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. ResultsAortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. ConclusionsAMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

Prediction of Aortic Stenosis Progression by 18F-FDG and 18F-NaF PET/CT in Different Aortic Valve Phenotypes.

Background: Different imaging techniques, such as echocardiography (ECHO) and CT, allow to assess aortic stenosis (AS) severity and could be used to study its progression. But only PET/CT open opportunities to assess activity of valvular inflammation and calcification in vivo. The aim of this study was to assess prognostic value of valvular inflammation and calcification measured by 18F-FDG and 18F-NaF PET/CT in patients with tricuspid (TAV) and bicuspid aortic valve (BAV). Methods: The study included 71 patients aged 40–70 years with mild, moderate and severe asymptomatic calcific AS. Patients were divided into two groups according to valve morphology: with BAV and TAV. All patients underwent standard ECHO, CT calcium scoring PET/CT with 18F-NaF and 18F-FDG. All patients were evaluated during a follow-up visit with evaluation of ECHO parameters. (16.8 ± 4.2 months). Results: TAV and BAV groups were comparable in AS severity by ECHO (peak aortic jet velocity (Vmax): 2.90 [2.60; 3.50] vs. 2.96 [2.55; 3.31] m/s, p = 0.83). TBR max 18F-FDG did not vary in TAV and BAV patients (1.15 [1.06; 1.23] vs. 1.11 [1.03; 1.20], p = 0.39). Both groups did not differ in valvular calcification degree (Agatston score 1,058 [440; 1798] vs. 1,128 [533; 2,360], p = 0.55) and calcification activity assessed by 18F-NaF uptake level (TBR max 1.50 [1.30; 1.78] vs. 1.48 [1.27; 1.83], p = 0.97). 18F-NaF TBR max was associated with AS severity measured by Vmax in men and women with TAV (r = 0.54; p = 0.04 vs. r = 0.53; p = 0.03). In BAV group this relationship was true only in female patients (r = 0.1; p = 0.67 vs. r = 0.7; p = 0.0004). There was no association between Vmax and TBR max 18F-FDG was revealed in TAV and BAV groups. During follow-up period, the most important positive predictors of AS progression in TAV obtained by multinomial logistic regression analysis were Vmax, and 18F-NaF TBR. Whereas in BAV the highest predictive value showed model included age and Vmax. Conclusion: 18F-NaF PET/CT may be considered as the valuable predictor for hemodynamic progression of calcific AS in case of TAV. 18F-FDG PET/CT does not play a significant role to predict the AS progression.

Differential 18F–NaF uptake in various compartments in knee osteoarthritis: an observational study using PET/MRI

To investigate if the pattern of fluorine-18-labelled sodium fluoride (18F-NaF) uptake on integrated positron-emission tomography (PET)/magnetic resonance imaging (MRI) of bone marrow lesions (BML) and osteophytes differs between different knee compartments. Sixteen patients with no prior history of knee injury with or without pain were recruited for the study. The images of both knees were acquired on simultaneous PET/MRI. The acquisition was done after 45 minutes of intravenous injection of 18F-NaF 185-370 MBq (5-10 mCi) for 40 minutes. Each knee was divided into eight compartments patella, trochlea, medial central femur, lateral central femur, medial posterior femur, lateral posterior femur, medial tibia, lateral tibia, and cruciate ligament insertion specifically for BML. BML and osteophytes were scored using MRI Osteoarthritis Knee Score (MOAKS) criteria and their corresponding maximum standardised uptake values (SUVmax) recorded. BML and osteophytes both showed statistically significant differences among knee compartments, i.e., p-value <0.000 and<0.043 respectively. SUVmax for BML and osteophytes was greatest in the medial tibia. 18F-NaF PET/MRI showed that BML and osteophytes had differential uptake values due to bone remodelling amongst the various knee compartments and this may help to design disease-modifying osteoarthritis drugs in the future.

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease

Background18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). MethodsPatients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. Results100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. ConclusionsCoronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

Respiration-averaged CT versus standard CT attenuation map for correction of 18F-sodium fluoride uptake in coronary atherosclerotic lesions on hybrid PET/CT

BackgroundTo evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of 18F-sodium fluoride (18F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). MethodsThis study comprised 23 patients who underwent 18F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBRMAX) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. ResultsIn 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBRMAX (median [Interquartile range]): CTAC = 1.65 [1.23 to 2.38], RACTAC = 1.63 [1.23 to 2.33], p = 0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC = 0.10 [0 to 1.0], RACTAC = 0.15 [0 to 1.03], p = 0.55 with coefficient of reproducibility of 0.17 ConclusionRespiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary 18F-NaF uptake on PET/CT.

18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome

BackgroundAcute aortic syndrome is associated with aortic medial degeneration. 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity. ObjectivesIn a proof-of-concept study, this investigation aimed to establish whether 18F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome. MethodsPatients with aortic dissection or intramural hematomas and control subjects underwent 18F-NaF PET/CT angiography of the aorta. Aortic 18F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBRmax]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months. ResultsAortic 18F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased 18F-NaF uptake (TBRmax: 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). 18F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019). ConclusionsIn patients with acute aortic syndrome, 18F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. 18F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. (18F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566)