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The aim of this study was to optimize the 3-dimensional (3D) fluid attenuated inversion recovery (FLAIR) pulse sequence for isotropic high-spatial-resolution imaging of white matter (WM) and cortical lesions at 7 T.We added a magnetization-prepared (MP) FLAIR module to a Cube 3D fast spin echo sequence and optimized the refocusing flip angle train using extended phase graph simulations, taking into account image contrast, specific absorption rate (SAR), and signal-to-noise ratio (SNR) as well as T1/T2 values of the different species of interest (WM, grey matter, lesions) at 7 T. We also effected improved preparation homogeneity at 7 T by redesigning the refocusing pulse used in the MP segments. Two sets of refocusing flip angle trains—(a) an SNR-optimal and (b) a contrast-optimal set—were derived and used to scan 7 patients with Alzheimer disease/cognitive impairment and 7 patients with multiple sclerosis. Conventional constant refocusing flip MP-FLAIR images were also acquired for comparison. Lesion SNR, contrast, and lesion count were compared between the 2 optimized and the standard FLAIR sequences.Whole brain coverage with 0.8 mm3 isotropic spatial resolution in ∼5-minute scan times was achieved using the optimized 3D FLAIR sequences at clinically acceptable SAR levels. The SNR efficiency of the SNR-optimal sequence was significantly better than that of conventional constant refocusing flip MP-FLAIR sequence, whereas the scan time was reduced more than 2-fold (∼5 vs >10 minutes). The contrast efficiency of the contrast-optimal sequence was comparable with that of the constant refocusing flip sequence. Lesion load ascertained by lesion counting was not significantly different among the sequences.Magnetization-prepared FLAIR-Cube with refocusing flip angle trains optimized for SNR and contrast can be used to characterize WM and cortical lesions at 7 T with 0.8 mm3 isotropic resolution in short scan times and without SAR penalty.