Flow-mediated dilation (FMD) has emerged over the past 20 years as an important marker of vascular endothelial function that can be measured non-invasively. Celermajer et al. described its clinical utility in a study of children and adults who were at risk for developing atherosclerosis. 1 Endothelial dysfunction, as assessed by impaired brachial artery FMD, has been observed in almost every condition that predisposes to atherosclerosis and cardiovascular disease. 2 In addition, a recent meta-analysis indicates that impairment of brachial artery FMD is significantly associated with future cardiovascular events. 3 Unfortunately, evaluation of brachial artery FMD has not been adopted for more widespread clinical use primarily due to technical limitations that lead to poor inter-observer reproducibility of results. Multiple review papers have all noted that practical challenges, including significant test-to-test variability, have precluded widespread clinical use of this method. [4][5][6] Other than publication of guidelines to try to standardize brachial artery FMD measurement methodology, there has not been significant progress in improving the techniques for measuring brachial artery reactivity to minimize inter-observer variability.
AbstractThe object of this study was to utilize a novel feed-forward active contour (FFAC) algorithm to find a reproducible technique for analysis of brachial artery reactivity. Flow-mediated dilation (FMD) is an important marker of vascular endothelial function but has not been adopted for widespread clinical use given its technical limitations, including interobserver variability and differences in technique across clinical sites. We developed a novel FFAC algorithm with the goal of validating a more reliable standard. Forty-six healthy volunteers underwent FMD measurement according to the standard technique. Ultrasound videos lasting 5-10 seconds each were obtained pre-cuff inflation and at minutes 1 through 5 post-cuff deflation in longitudinal and transverse views. Automated segmentation using the FFAC algorithm with initial boundary definition from three different observers was used to analyze the images to measure diameter/ cross-sectional area over the cardiac cycle. The %FMD was calculated for average, minimum, and maximum diameters/ areas. Using the FFAC algorithm, the population-specific coefficient of variation (CV) at end-diastole was 3.24% for transverse compared to 9.96% for longitudinal measurements; the subject-specific CV was 15.03% compared to 57.41%, respectively. For longitudinal measurements made via the conventional method, the population-specific CV was 4.77% and subject-specific CV was 117.79%. The intraclass correlation coefficient (ICC) for transverse measurements was 0.97 (95% CI: 0.95-0.98) compared to 0.90 (95% CI: 0.84-0.94) for longitudinal measurements with FFAC and 0.72 (95% CI: 0.51-0.84) for conventional measurements. In conclusion, transverse views using the novel FFAC method provide less inter-observer variability than traditional longitudinal...