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BackgroundChallenges to cardiac PET-CT include patient motion, prolonged image acquisition and a reduction of counts due to gating. We compared two analytical tools, FusionQuant and OsiriX, for quantification of gated cardiac 18F-sodium fluoride (18F-fluoride) PET-CT imaging.MethodsTwenty-seven patients with aortic stenosis were included, 15 of whom underwent repeated imaging 4 weeks apart. Agreement between analytical tools and scan-rescan reproducibility was determined using the Bland-Altman method and Lin's concordance correlation coefficients (CCC).ResultsImage analysis was faster with FusionQuant [median time (IQR) 7:10 (6:40-8:20) minutes] compared with OsiriX [8:30 (8:00-10:10) minutes, p = .002]. Agreement of uptake measurements between programs was excellent, CCC = 0.972 (95% CI 0.949-0.995) for mean tissue-to-background ratio (TBRmean) and 0.981 (95% CI 0.965-0.997) for maximum tissue-to-background ratio (TBRmax). Mean noise decreased from 11.7% in the diastolic gate to 6.7% in motion-corrected images (p = .002); SNR increased from 25.41 to 41.13 (p = .0001). Aortic valve scan-rescan reproducibility for TBRmax was improved with FusionQuant using motion correction compared to OsiriX (error ± 36% vs ± 13%, p

BackgroundCoronary PET shows promise in the detection of high-risk atherosclerosis, but there remains a need to optimize imaging and reconstruction techniques. We investigated the impact of reconstruction parameters and cardiac motion-correction in 18F Sodium Fluoride (18F-NaF) PET.MethodsTwenty-two patients underwent 18F-NaF PET within 22 days of an acute coronary syndrome. Optimal reconstruction parameters were determined in a subgroup of six patients. Motion-correction was performed on ECG-gated data of all patients with optimal reconstruction. Tracer uptake was quantified in culprit and reference lesions by computing signal-to-noise ratio (SNR) in diastolic, summed, and motion-corrected images.ResultsReconstruction using 24 subsets, 4 iterations, point-spread-function modelling, time of flight, and 5-mm post-filtering provided the highest median SNR (31.5) compared to 4 iterations 0-mm (22.5), 8 iterations 0-mm (21.1), and 8 iterations 5-mm (25.6; all P

Aims 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. Methods and results 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. Conclusion Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration. [ABSTRACT FROM AUTHOR]

Assessment of coronary artery calcium (CAC) by computed tomographic (CT) imaging provides an accurate measure of atherosclerotic burden. CAC is also visible in computed tomographic attenuation correction (CTAC) scans, always acquired with cardiac positron emission tomographic (PET) imaging. The aim of this study was to develop a deep-learning (DL) model capable of fully automated CAC definition from PET CTAC scans. The novel DL model, originally developed for video applications, was adapted to rapidly quantify CAC. The model was trained using 9,543 expert-annotated CT scans and was tested in 4,331 patients from an external cohort undergoing PET/CT imaging with major adverse cardiac events (MACEs) (follow-up 4.3 years), including same-day paired electrocardiographically gated CAC scans available in 2,737 patients. MACE risk stratification in 4 CAC score categories (0, 1-100, 101-400, and >400) was analyzed and CAC scores derived from electrocardiographically gated CT scans (standard scores) by expert observers were compared with automatic DL scores from CTAC scans. Automatic DL scoring required <6 seconds per scan. DL CTAC scores provided stepwise increase in the risk for MACE across the CAC score categories (HR up to 3.2; P < 0.001). Net reclassification improvement of standard CAC scores over DL CTAC scores was nonsignificant (−0.02; 95% CI: −0.11 to 0.07). The negative predictive values for MACE of zero CAC with standard (85%) and DL CTAC (83%) CAC scores were similar (P = 0.19). DL CTAC scores predict cardiovascular risk similarly to standard CAC scores quantified manually by experienced operators from dedicated electrocardiographically gated CAC scans and can be obtained almost instantly, with no changes to PET/CT scanning protocol. [Display omitted] [ABSTRACT FROM AUTHOR]

Non-invasive testing plays a pivotal role in the diagnosis, assessment of progression, response to therapy, and risk stratification of coronary artery disease. Although anatomical plaque imaging by computed tomography angiography (CTA) and ischemia detection with myocardial perfusion imaging studies are current standards of care, there is a growing body of evidence that imaging of the processes which drive atherosclerotic plaque progression and rupture has the potential to further enhance risk stratification. In particular, non-invasive imaging of coronary plaque inflammation and active calcification has shown promise in this regard. Positron emission tomography (PET) with newly-adopted radiotracers provides unique insights into atheroma activity acting as a powerful independent predictor of myocardial infarctions. Similarly, by providing a quantitative measure of coronary inflammation, the pericoronary adipose tissue density (PCAT) derived from standard coronary CTA enhances cardiac risk prediction and allows re-stratification over and above current state-of-the-art assessments. In this review, we shall discuss the recent advances in the non-invasive methods of assessment of disease activity by PET and CTA, highlighting how these methods could improve risk stratification and ultimately benefit patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: Respiratory motion correction is of importance in studies of coronary plaques employing 18F‐NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test–retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four‐dimensional cine‐computed tomography (CT) by an expert observer. Purpose: To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of 18F‐NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine‐CT images. Methods: This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using 18F‐sodium fluoride (18F‐NaF). All patients underwent a 5‐s cine‐CT (4D‐CT), a coronary CT angiography (CTA), and 18F‐NaF PET. The 4D‐CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non‐contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D‐CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t‐tests. Signal‐to‐noise ratios (SNR) are reported for the single‐phase images (end‐expiratory phase) and for the motion‐corrected image‐series (employing the motion vector fields extracted during the diffeomorphic registrations). Results: In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 ± 1.5 mm, PET = 2.4 ± 3.2 mm; Y direction: 4D CT = 2.3 ± 1.9 mm, PET = 0.7 ± 2.9 mm, 3D motion: 4D CT = 6.6 ± 3.1 mm, PET = 5.7 ± 2.6 mm, all p ≥ 0.05). Significant differences in respiratory motion were observed in the systems' Z direction: 4D CT = 4.9 ± 3.4 mm, PET = 2.3 ± 3.2 mm, p = 0.04. Significantly improved SNR is reported for the motion corrected images compared to the end‐expiratory phase images (end‐expiratory phase = 6.8±4.8, motion corrected = 12.2±4.5, p = 0.001). Conclusion: Similar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images. [ABSTRACT FROM AUTHOR]

Aims Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes is unknown. Methods and results In this post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1–9 AU), low (10–99 AU), moderate (100–399 AU), high (400–999 AU), and very high (≥1000 AU). Adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation, and total plaque burden; Autoplaque) assessments. Of 1769 patients, 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high, and 8% very high CACS. Amongst patients with a zero CACS, 14% had non-obstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques, and 13% had low-attenuation plaque burden >4%. Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal, and low CACS (P  < 0.001), but there was no statistically significant difference between those with medium, high, and very high CACS. Myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS >1000 AU and low-attenuation plaque burden were the only predictors of myocardial infarction, independent of obstructive disease, and 10-year cardiovascular risk score. Conclusion In patients with stable chest pain, zero CACS is associated with a good but not perfect prognosis, and CACS cannot rule out obstructive coronary artery disease, non-obstructive plaque, or adverse plaque phenotypes, including low-attenuation plaque. [ABSTRACT FROM AUTHOR]

Background: Current 18F-NaF assessments of aortic valve microcalcification using 18F-NaF PET/CT are based on evaluations of end-diastolic or cardiac motion-corrected (ECG-MC) images, which are affected by both patient and respiratory motion. We aimed to test the impact of employing a triple motion correction technique (3 × MC), including cardiorespiratory and gross patient motion, on quantitative and qualitative measurements. Materials and methods: Fourteen patients with aortic stenosis underwent two repeat 30-min PET aortic valve scans within (29 ± 24) days. We considered three different image reconstruction protocols; an end-diastolic reconstruction protocol (standard) utilizing 25% of the acquired data, an ECG-gated (four ECG gates) reconstruction (ECG-MC), and a triple motion-corrected (3 × MC) dataset which corrects for both cardiorespiratory and patient motion. All datasets were compared to aortic valve calcification scores (AVCS), using the Agatston method, obtained from CT scans using correlation plots. We report SUVmax values measured in the aortic valve and maximum target-to-background ratios (TBRmax) values after correcting for blood pool activity. Results: Compared to standard and ECG-MC reconstructions, increases in both SUVmax and TBRmax were observed following 3 × MC (SUVmax: Standard = 2.8 ± 0.7, ECG-MC = 2.6 ± 0.6, and 3 × MC = 3.3 ± 0.9; TBRmax: Standard = 2.7 ± 0.7, ECG-MC = 2.5 ± 0.6, and 3 × MC = 3.3 ± 1.2, all p values ≤ 0.05). 3 × MC had improved correlations (R2 value) to the AVCS when compared to the standard methods (SUVmax: Standard = 0.10, ECG-MC = 0.10, and 3 × MC = 0.20; TBRmax: Standard = 0.20, ECG-MC = 0.28, and 3 × MC = 0.46). Conclusion: 3 × MC improves the correlation between the AVCS and SUVmax and TBRmax and should be considered in PET studies of aortic valves using 18F-NaF. [ABSTRACT FROM AUTHOR]

Objectives: Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT.Methods: This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight.Results: Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively).Conclusions: Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction. [ABSTRACT FROM AUTHOR]

Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR).Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol.Results: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001).Conclusions: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276. [ABSTRACT FROM AUTHOR]

This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain. Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men. Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden. Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex. Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590) [Display omitted] [ABSTRACT FROM AUTHOR]

Aims We aimed to investigate the role of aortic valve tissue composition from quantitative cardiac computed tomography angiography (CTA) in patients with severe aortic stenosis (AS) for the differentiation of disease subtypes and prognostication after transcatheter aortic valve implantation (TAVI). Methods and results Our study included 447 consecutive AS patients from six high-volume centres reporting to a prospective nationwide registry of TAVI procedures (POL-TAVI), who underwent cardiac CTA before TAVI, and 224 matched controls with normal aortic valves. Components of aortic valve tissue were identified using semi-automated software as calcific and non-calcific. Volumes of each tissue component and composition [(tissue component volume/total tissue volume) × 100%] were quantified. Relationship of aortic valve composition with clinical outcomes post-TAVI was evaluated using Valve Academic Research Consortium (VARC)-2 definitions. High-gradient (HG) AS patients had significantly higher aortic tissue volume compared to low-flow low-gradient (LFLG)-AS (1672.7 vs. 1395.3 mm3, P  < 0.001) as well as controls (509.9 mm3, P  < 0.001), but increased non-calcific tissue was observed in LFLG compared to HG patients (1063.6 vs. 860.2 mm3, P  < 0.001). Predictive value of aortic valve calcium score [area under the curve (AUC) 0.989, 95% confidence interval (CI): 0.981–0.996] for severe AS was improved after addition of non-calcific tissue volume (AUC 0.995, 95% CI: 0.991–0.999, P  = 0.011). In the multivariable analysis of clinical and quantitative computed tomography parameters of aortic valve tissue, non-calcific tissue volume [odds ratio (OR) 5.2, 95% CI 1.8–15.4, P  = 0.003] and history of stroke (OR 2.6, 95% CI 1.1–6.5, P  = 0.037) were independent predictors of 30-day major adverse cardiovascular event (MACE). Conclusion Quantitative CTA assessment of aortic valve tissue volume and composition can improve detection of severe AS, differentiation between HG and LFLG-AS in patients referred for TAVI as well as prediction of 30-day MACEs post-TAVI, over the current clinical standard. [ABSTRACT FROM AUTHOR]

Aims In patients with stable coronary artery disease (CAD) and high-risk plaques (HRPs) on coronary computed tomography angiography (CTA), we sought to define qualitative and quantitative CTA predictors of abnormal coronary 18F-sodium fluoride uptake (18F-NaF) by positron emission tomography (PET). Methods and results Patients undergoing coronary CTA were screened for HRP. Those who presented with ≥3 CTA adverse plaque features (APFs) including positive remodelling; low attenuation plaque (LAP, <30 HU), spotty calcification; obstructive coronary stenosis ≥50%; plaque volume >100 mm3 were recruited for 18F-NaF PET. In lesions with stenosis ≥25%, quantitative plaque analysis and maximum 18F-NaF target to background ratios (TBRs) were measured. Of 55 patients, 35 (64%) manifested coronary 18F-NaF uptake. Of 68 high-risk lesions 49 (70%) had increased PET tracer activity. Of the APFs, LAP had the highest sensitivity (39.4%) and specificity (98.3%) for predicting 18F-NaF uptake. TBR values were higher in lesions with LAP compared to those without [1.6 (1.3–1.8) vs. 1.1 (1.0–1.3), P  = 0.01]. On adjusted multivariable regression analysis, LAP (both qualitative and quantitative) was independently associated with plaque TBR [LAP qualitative: β  = 0.47, 95% confidence interval (CI) 0.30–0.65; P  < 0.001] and (LAP volume: β  = 0.20 per 10 mm3, 95% CI 0.13–0.27; P  < 0.001). Conclusion In stable CAD patients with HRP, LAP is predictive of 18F-NaF coronary uptake, but 18F-NaF is often seen in the absence of LAP. If 18F-NaF uptake is shown to be associated with adverse outcomes and becomes clinically used, the presence of LAP may define patients who would not benefit from the added testing. [ABSTRACT FROM AUTHOR]

Myocardial perfusion imaging (MPI) and anatomical imaging with coronary computed tomography angiography (CCTA) can play an important role in the preprocedural planning of a chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We aimed to establish the feasibility of a novel dynamic computed tomography perfusion (CTP) analysis for the assessment of myocardial perfusion before and after a successful recanalization of CTO in patients undergoing CCTA as part of a standard preprocedural workup. In a prospective observational study symptomatic patients underwent dynamic CTP on a dual-source CT scanner both before and 3 months after successful CTO PCI. Twenty-seven patients completed the study (63 ± 8 years old, 78% male). Following successful CTO PCI, there was a significant reduction in the ischemic burden (5 [5–7] versus 1 [0–2] segments, p < 0.001), and improvement in myocardial blood flow (85.3 [71.7–94.1] versus 134.6 [123.8–156.9] mL/min, p < 0.001) resulting in an increase in the relative flow reserve (0.49 [0.41–0.57] versus 0.88 [0.74–0.95], p < 0.001). CTP emerges as a robust and safe method for MPI in CTO patients. The single imaging session assessment of both coronary anatomy and perfusion with CT lends itself to precise disease phenotyping in the challenging population of CTO patients. [Display omitted] • CTP is a robust method for quantifying the extent of perfusion deficits and impaired MBF in the muscle subtended by a CTO. • CTP can be used to depict the recovery of myocardial flow and perfusion following successful CTO recanalization. • A single imaging assessment with CCTA and CTP lends itself to precise disease phenotyping in CTO patients. [ABSTRACT FROM AUTHOR]