BACKGROUND AND PURPOSE The quantification of cerebral blood flow (CBF), cerebral blood volume (CBV), and blood-brain barrier permeability in scattered lesions in the brain is a methodological challenge. We aimed to investigate the feasibility of a 3D T1-weighted dynamic contrast-enhanced (DCE) MRI acquisition in combination with a 2-compartment modeling approach for the quantification of CBF, CBV and permeability surface area product (PS) in lesions, and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS). MATERIAL AND METHODS In all, 19 MS patients (mean age 35 years, 12 female) underwent DCE-MRI with a 3D T1-weighted spoiled gradient-echo sequence on a 3T MRI scanner. A total of 44 slices (thickness 3 mm) with an in-plane resolution of 1.7 × 1.7 mm(2) (matrix size 128 × 104), providing coverage of the whole brain, were acquired every 2.1 seconds over a total measurement time of 420 s. Data postprocessing was performed using a set of 2-compartment models with automated model selection; CBF, CBV, and PS as a measure of blood-brain barrier leakage were determined in contrast-enhancing (CE) and nonenhancing lesions as well as in NAWM. RESULTS Perfusion quantification produced reasonable values in lesions as well as in NAWM. In CE lesions, CBF (22.9 (22.7) vs. 15.8 (6.7) mL/100 mL/min), CBV (1.18 (0.48) vs. 0.76 (0.19) mL/100 mL), and PS (0.98 (0.46) vs. 0.04 (0.03) mL/100 mL/min) were significantly (P < 0.001) higher than in NAWM. In nonenhancing lesions, a weakly (P < 0.05) significantly increased CBV of 1.00 (0.35) mL/100 mL, compared with NAWM, was observed. CONCLUSION Our study demonstrates the feasibility of 3D T1-weighted DCE-MRI for the quantitative assessment of CBF, CBV, and PS in NAWM as well as in multiple MS lesions scattered throughout the brain, even without previous knowledge of their location. Quantification on the region level produced reasonable values both in lesions and in NAWM, but parameter maps would benefit from an increase in contrast-to-noise ratio. The increased values of CBF, CBV, and PS in CE lesions may reflect inflammatory activity, the heterogeneity of parameter estimates suggests a potential for lesion characterization. NAWM appears hypoperfused, this is in accordance with previous studies, but requires validation with a control group.