Clinical Image Quality and Reader Variability in 3D Synthetic Brain MRI Compared with Conventional MRI

<b>Background/Objectives</b>: This study evaluated the clinical image quality of three-dimensional synthetic MRI (3D SI) compared with conventional MRI (cMRI), focusing on tissue contrast, anatomical detail, and motion sensitivity. <b>Methods</b>: Patients with nonspecific neurological symptoms were included. Both cMRI and 3D SI were acquired on single-vendor 1.5 T and 3 T scanners with slice thicknesses of 1.0-1.7 mm. Two experienced neuroradiologists and one fellow independently evaluated matched scans using a 0-100 scale. Assessed parameters included signal-to-noise ratio (SNR), gray-white matter contrast, artifacts, motion robustness, and confidence in detecting perivascular spaces, white matter lesions, and subtle pathology. Interrater agreement was measured using Krippendorff's alpha and ICC2. Multiple linear regression analyzed associations between image quality ratings and imaging method. <b>Results</b>: Images of 31 patients were analyzed. Three-dimensional SI demonstrated sufficient-to-good overall image quality and high robustness to motion. Cortical-surface-to-cerebrospinal-fluid contrast on FLAIR was rated lower for 3D SI than for cMRI. False-positive lesion detection occurred more frequently on 3D SI FLAIR, particularly among experienced readers. cMRI achieved significantly higher T1-weighted SNR than 3D SI (8.76 points, <i>p</i> < 0.001). Experienced readers consistently rated SNR and tissue contrast higher than the fellow. Vascular signal range was broader on 3D SI, reducing sensitivity to vascular abnormalities. <b>Conclusions</b>: Three-dimensional synthetic MRI provides clinically usable image quality and fulfills its primary diagnostic purpose, offering advantages in acquisition efficiency and robustness to motion. Nevertheless, limitations in cortical contrast, vascular signal characterization, and reader-dependent interpretive variability constrain its reliability for subtle or detail-critical findings.