Objective: To validate an automated algorithm for the measurement of lumen volumes of coronary arteries. Background: Current intravascular ultrasound systems use absolute measurements of and changes in areas and diameters for the assessment of coronary artery disease. However, the coronary artery is a three-dimensional structure of complex geometry and volume. Methods: We used a comprehensive imaging system designed to reconstruct planar intravascular ultrasound images in three dimensions. This system consisted of a 25 MHz transducer-tipped rigid probe (for in vitro studies) or a 25 MHz transducer-tipped catheter within a 3.9F monorail imaging sheath (for in vivo studies), a motorized catheter pullback device that withdrew the transducer at 0.5 mm/sec, and an image processing computer that stacked 15 image slices/mm of vessel axial length and then performed thresholding-based three dimensional image rendering and lumen volume measurement. We imaged 13 human coronary vessels (6 RCA, 6 LAD, 1 LCX) in vitro and 16 vessels (8 LAD, 6 RCA, 2 SVG) in vivo. Results: In vitro studies: Lumen volumes derived by three-dimensional intravascular ultrasound were 171 +/- 121 mm(3) acid compared very well with those derived by histology (160 +/- 109 mm(3), r = 0.97, SEE = 29 mm(3), P < 0.001) and with those derived by manual planimetry of planar intravascular ultrasound images (150 +/- 106 mm(3), r = 0.97, SEE = 30 mm(3), P < 0.001). In vivo studies: Lumen volumes derived by three-dimensional intravascular ultrasound were 74 +/- 35 mm(3) and compared well with those derived by quantitative angiography (52 +/- 20 mm(3), r = 0.71, SEE = 25 mm(3), P < 0.002). Conclusions: Three-dimensional intravascular ultrasound is a new technique that can accurately measure coronary artery lumen volumes. Further technical improvements may help to establish this technique as the new standard for lumen volume measurement. (C) 1994 Wiley-Liss, Inc.