Audrey White

Coronary Arterial 18F-Sodium Fluoride Uptake : A Novel Marker of Plaque Biology

OBJECTIVES With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively. BACKGROUND The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation. METHODS We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0). RESULTS Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498). CONCLUSIONS 18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).

Assessment of Valvular Calcification and Inflammation by Positron Emission Tomography in Patients With Aortic Stenosis

Background— The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. Methods and Results— Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of ±0.21 (18F-NaF) and ±0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F-NaF: 2.87±0.82 versus 1.55±0.17; 18F-FDG: 1.58±0.21 versus 1.30±0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r2=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r2=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F-NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r2=0.174, P<0.001). Conclusions— Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Harmonic imaging improves estimation of left ventricular mass

Objectives: To assess the effect of tissue harmonic imaging (THI) on assessment of left ventricular mass index (LVMI) measurements by M-mode trans-thoracic echocardiography, when compared with magnetic resonance imaging (MRI). Methods: 20 hypertensive male subjects were studied. LVMI was measured in all subjects by both gradient-echo MRI (Lscelsint Prestige 1.9 T) and by transthoracic echocardiography (ATL HDI 5000). M-mode echocardiography recordings were taken for each patient, two with fundamental imaging (FI) and two using THI in a randomised order and the images unlabelled. Recordings were analysed off-line, by a blinded observer. LVMI by MRI was calculated using Simpsons rule on serial short axis slices of 8 mm thickness. Data are expressed as mean ± SD. Results: There was a difference in LVMI measurements between FI and THI (LVMI) (79 ± 20 vs. 93 ± 25 g2; p < 0.001). A lower mean difference was obtained by THI, compared to FI, when compared with MRI (2 ± 15 vs. −32 ± 22 g2; p < 0.001) suggesting that FI underestimates LVMI. Inter-observer variability was similar between THI and FI (4.5 ± 15 vs. 6.4 ± 15 g2; p = 0.46). Conclusion: In hypertensive males, M-mode echo derived from FI underestimated LVMI. These results imply that widely accepted reference ranges for LVMI using FI are not applicable when THI is used.

CORONARY ARTERIAL 18F-NAF UPTAKE: A NOVEL MARKER OF PLAQUE BIOLOGY

Results: Repeatability statistics for the measurement of the coronary 18F-NaF uptake (max TBR) were excellent (intra-class coeficient 0.99). Activity was higher in patients with coronary atherosclerosis versus controls (1.64±0.49 vs 1.23±0.24; p 1000 displayed normal uptake. Patients with increased coronary 18F-NaF (n=40) had higher rates of prior cardiovascular events (P=0.02) and angina (p=0.02) and higher Framingham risk scores (P=0.01). By contrast quantiication of coronary 18F-FDG activity was hampered by myocardial uptake and not increased in those with atherosclerosis versus controls (p=0.50). Conclusion: 18F-NaF is a promising new approach for the assessment of coronary plaque biology and appears to be a novel marker of vulnerability, recent plaque rupture and cardiovascular risk