Abstract
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Objectives NaF uptake has been investigated as an in vivo biomarker of coronary artery calcification (CAC) in humans. No studies to date have investigated non-invasive early detection of microcalcification before clinically significant coronary artery disease(CAD). In this study we assessed 18F-NaF PET/CT as a diagnostic tool for early CAC in a preclinical swine model of metabolic syndrome(MetS)
Methods Eleven MetS Ossabaw swine with early-stage CAD and 3 lean swine underwent ECG-gated NaF PET/CT scans followed by intravascular ultrasound (IVUS) and histologic examinations (HCl extraction, Hematoxylin & Eosin, Von Kossa, Masson’s trichrome and Verhoff van Giesen stains to assess the myocardium and microvasculature). Global cardiac and coronary tracking techniques were used to measure NaF uptake
Results MetS swine had almost 2-fold increased NaF uptake in the coronaries(p<0.05) & 2.5-fold increased global molecular calcium score (p<0.05) compared to lean swine. A focal macroscopic calcified lesion was identified in only 1 MetS by IVUS. Agatston CT calcium score was 0 in all cases. By IVUS assessment, the MetS group had ~5-fold greater neointimal wall coverage vs to the leans (57±9% vs 12±3%, p<0.05). The wall coverage data significantly correlated with NaF uptake in right coronary artery (RCA) (p<0.05, r=0.61). HCL extraction revealed no significant difference in left ventricle calcium content from lean(1.11±0.05 μmol/g) and MetS group (1.17±0.06 μmol/g, p=0.24). Von Kossa stain of left ventricle specimens revealed no evidence of myocardial or microvascular calcification in either group, while RCA histology revealed microcalcifications in 36% of MetS. Masson’s trichrome stains showed no significant fibrosis in myocardium
Conclusions We have shown in a preclinical swine model of early CAD that NaF-PET/CT can detect CAC in early stage lesions when macroscopic evidence for calcification is not clear yet. Further studies are required to validate these findings