Microcalcification Activity 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

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.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

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.

Thoracic aortic microcalcification activity in combined positron emission tomography and magnetic resonance imaging

IntroductionNon-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [18F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [18F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve,MethodsThirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [18F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [18F]fluoride uptake on PET-CT and PET-MRI.ResultsAortic sodium [18F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2.ConclusionAscending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required.

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.

Global molecular calcium score: is there a link between sodium fluoride uptake and cardiovascular risk burden?

Abstract Background Sodium fluoride (18F-NaF) uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification both in atherosclerotic plaques and the aortic valve. Purpose We aimed to evaluate global cardiac microcalcification activity with 18F-NaF, as a measure of the microcalcification burden, in high cardiovascular (CV) risk patients. Additionally, as an exploratory endpoint, we evaluated the association between global cardiac microcalcification and diastolic dysfunction. Methods High CV-risk individuals without previous CV events from a single centre were prospectively scanned with 18F-NaF PET-CT. Total cardiac 18F-NaF uptake was measured as global molecular calcium score (GMCS), which was calculated by summing the product of mean standardized uptake value and volume of the region of interest on every slice within the borders of the heart. The result was then divided by the number of slices to adjust for the volume. Results We included sixty-five patients with a mean age of 64.0 ± 9.0 years and 38.5% females. There was a high rate of CV risk factors, including hypertension (95.4%), diabetes (84.6%), dyslipidemia (78.5%), obesity (58.5%), smoking (26.2%) chronic kidney disease (18.5%), and family history of premature coronary disease (9.2%). The mean 10-year risk of fatal and nonfatal cardiovascular events predicted by ASCVD risk score was 30.54 ± 18.4. Median GMCS was 221.42 [IQR 144.55-317.58]. Individuals with &amp;gt; 5 CV risk factors (46.2%) had increased overall GMCS compared to those with a lower number of CV risk factors (295.29, IQR 159.37-356.87 vs 186.16, IQR 122.57-281.78; p=0.03). Thirty-three patients underwent diastolic dysfunction evaluation by echocardiography. All patients had normal left ventricle ejection fraction, mean of 62.86 ± 3.58%. Mean E/A was 0.88 ± 0.27, mean septal e’ velocity 0.07 ± 0.02 m/s, mean lateral e’ velocity 0.08 ± 0.02 m/s, and mean average E/e’ 10.7 ± 3.3. The mean peak tricuspid regurgitation velocity was 2.14 ± 0.59 m/s and the median indexed left atrium volume was 37, IQR 29-44mL/m2. After applying the algorithm for diagnosis of diastolic dysfunction in subjects with normal ejection fraction, 21.2% had diastolic dysfunction and 36.4% had a normal diastolic function, while 42.4% were indeterminate. There was no correlation between echocardiographic variables of diastolic function and GMCS, except for indexed left atrium volume (r = 0.83, p&amp;lt;0.01). There was no association between GMCS and diastolic function categories. Conclusions In a high CV risk cohort, the global cardiac microcalcification assessed by GMCS was associated with the burden of CV risk factors. Additionally, despite a strong positive correlation between GMCS and indexed left atrium volume, we found no association between GMCS and echocardiographic variables of diastolic function.

Temporal Changes in Coronary 18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis.

Coronary 18F-sodium fluoride (18F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18F-fluoride uptake is a temporally stable marker of established and progressive disease.

The Feasibility of Peri-Coronary Fat Attenuation Analysis on Non-Contrast Cardiac CT and Association With Microcalcification Activity

The Feasibility of Peri-Coronary Fat Attenuation Analysis on Non-Contrast Cardiac CT and Association With Microcalcification Activity

Investigating Low Endothelial Shear Stress And Microcalcification Activity In Patients With Acute Coronary Syndrome

Investigating Low Endothelial Shear Stress And Microcalcification Activity In Patients With Acute Coronary Syndrome

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.

The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction

Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.

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

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[18F]F PET-CT

BackgroundFluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. Methods and ResultsThirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. ConclusionsIn a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

Quantifying sodium [18F]fluoride uptake in abdominal aortic aneurysms

BackgroundAortic microcalcification activity is a recently described method of measuring aortic sodium [18F]fluoride uptake in the thoracic aorta on positron emission tomography. In this study, we aimed to compare and to modify this method for use within the infrarenal aorta of patients with abdominal aortic aneurysms.MethodsTwenty-five patients with abdominal aortic aneurysms underwent an sodium [18F]fluoride positron emission tomography and computed tomography scan. Maximum and mean tissue-to-background ratios (TBR) and abdominal aortic microcalcification activity were determined following application of a thresholding and variable radius method to correct for vertebral sodium [18F]fluoride signal spill-over and the nonlinear changes in aortic diameter, respectively. Agreement between the methods, and repeatability of these approaches were assessed.ResultsThe aortic microcalcification activity method was much quicker to perform than the TBR method (14 versus 40 min, p < 0.001). There was moderate-to-good agreement between TBR and aortic microcalcification activity measurements for maximum (interclass correlation co-efficient, 0.67) and mean (interclass correlation co-efficient, 0.88) values. These correlations sequentially improved with the application of thresholding (intraclass correlation coefficient 0.93, 95% confidence interval 0.89–0.95) and variable diameter (intraclass correlation coefficient 0.97, 95% confidence interval 0.94–0.99) techniques. The optimised method had good intra-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.36 and limits of agreement − 0.43 to 0.43) and inter-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.47 and limits of agreement − 0.53 to 0.53) repeatability.ConclusionsAortic microcalcification activity is a quick and simple method which demonstrates good intra-observer and inter-observer repeatabilities and provides measures of sodium [18F]fluoride uptake that are comparable to established methods.

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.

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.

Bypass Grafting and Native Coronary Artery Disease Activity

ObjectivesThe aim of this study was to describe the potential of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis. MethodsPatients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.

Observer repeatability and interscan reproducibility of 18F-sodium fluoride coronary microcalcification activity

BackgroundWe aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA). MethodsPatients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level. ResultsIn 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary18F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively. ConclusionsCMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.