Isotropic imaging offers the potential of improving lesion detection and imaging efficiency by enabling orthogonal image reformations without loss of spatial resolution. However, lengthy scan times for T1-weighted isotropic data acquisitions have been an impediment to the routine clinical application of this approach. We tested the feasibility of using the improved signal-to-noise ratio at 3 Tesla to perform rapid, whole-brain T1-weighted imaging with isotropic 0.8 mm x 0.8 mm x 0.8 mm (0.51 mm3) voxels. The method was validated in healthy volunteers and patients.Eight healthy subjects were imaged pre- and postcontrast on a 3 Tesla MR system. T1-weighted, 3-dimensional spoiled gradient-echo (3D SPGR) data were acquired at 0.8-mm slice thickness and reconstructed at 2-mm thickness in 3 orthogonal orientations. Scan time was 4 minutes 42 seconds. The technique was compared with inversion recovery-prepared spoiled gradient-echo (SPGR-IR) and 2D spin-echo (SE) for comparable spatial resolution and scan time. It was then tested in comparison with 2D SE in a series of 10 patients with enhancing brain lesions.The 3D SPGR technique provided approximately twice the contrast-to-noise ratio (CNR) of SPGR-IR and 50% greater CNR than 2D SE for discriminating gray and white matter. Image quality ratings, evaluated with nonparametric analyses, were also significantly higher for 3D SPGR in both volunteers (P < 0.05) and patients with enhancing lesions (P < 0.05). Of particular note was the elimination of postcontrast vessel pulsation artifacts, which were commonly present with 2D SE, and more uniform hypointensity of cerebrospinal fluid. Lesion enhancement in patients did not differ significantly for 2D SE and 3D SPGR.Our results demonstrate the feasibility of rapid, whole-brain isotropic imaging at 3 Tesla using submillimeter voxels. Artifacts were minimal, especially compared with 2D SE, whereas CNR was 2-fold better than SPGR-IR. The capability for creating reformatted images in orthogonal orientations from a single isotropic acquisition greatly improves efficiency compared with 2D acquisitions acquired in multiple planes. Although further clinical study is needed in a larger patient cohort, these initial results suggest substantial clinical promise for the technique.