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The aim of this study was to evaluate the impact of a noise-optimized virtual monochromatic imaging algorithm (VMI+) on image quality and diagnostic accuracy at dual-energy computed tomography angiography (CTA) of the lower extremity runoff.This retrospective Health Insurance Portability and Accountability Act–compliant study was approved by the local institutional review board. We evaluated dual-energy CTA studies of the lower extremity runoff in 48 patients (16 women; mean age, 63.3 ± 13.8 years) performed on a third-generation dual-source CT system. Images were reconstructed with standard linear blending (F_0.5), VMI+, and traditional monochromatic (VMI) algorithms at 40 to 120 keV in 10-keV intervals. Vascular attenuation and image noise in 18 artery segments were measured; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Five-point scales were used to subjectively evaluate vascular attenuation and image noise. In a subgroup of 21 patients who underwent additional invasive catheter angiography, diagnostic accuracy for the detection of significant stenosis (≥50% lumen restriction) of F_0.5, 50-keV VMI+, and 60-keV VMI data sets were assessed.Objective image quality metrics were highest in the 40- and 50-keV VMI+ series (SNR: 20.2 ± 10.7 and 19.0 ± 9.5, respectively; CNR: 18.5 ± 10.3 and 16.8 ± 9.1, respectively) and were significantly (all P < 0.001) higher than in the corresponding VMI data sets (SNR: 8.7 ± 4.1 and 10.8 ± 5.0; CNR: 8.0 ± 4.0 and 9.6 ± 4.9) and F_0.5 series (SNR: 10.7 ± 4.4; CNR: 8.3 ± 4.1). Subjective assessment of attenuation was highest in the 40- and 50-keV VMI and VMI+ image series (range, 4.84–4.91), superior to F_0.5 (4.07; P < 0.001). Corresponding subjective noise assessment was superior for 50-keV VMI+ (4.71; all P < 0.001) compared with VMI (2.60) and F_0.5 (4.11). Sensitivity and specificity for detection of 50% or greater stenoses were highest in VMI+ reconstructions (92% and 95%, respectively), significantly higher compared with standard F_0.5 (87% and 90%; both P ≤ 0.02).Image reconstruction using low-kiloelectron volt VMI+ improves image quality and diagnostic accuracy compared with traditional VMI technique and standard linear blending for evaluation of the lower extremity runoff using dual-energy CTA.