BackgroundBiomarkers for assessing osteoarthritis activity necessitate multiple MRI sequences with long acquisition times.PurposeTo perform 5‐minute simultaneous morphometry (thickness/volume measurements) and T₂ relaxometry of both cartilage and meniscus, and semiquantitative MRI Osteoarthritis Knee Scoring (MOAKS).Study TypeProspective.SubjectsFifteen healthy volunteers for morphometry and T₂ measurements, and 15 patients (five each Kellgren–Lawrence grades 0/2/3) for MOAKS assessment.Field Strength/SequenceA 5‐minute double‐echo steady‐state (DESS) sequence was evaluated for generating quantitative and semiquantitative osteoarthritis biomarkers at 3T.AssessmentFlip angle simulations evaluated tissue signals and sensitivity of T₂ measurements. Morphometry and T₂ reproducibility was compared against morphometry‐optimized and relaxometry‐optimized sequences. Repeatability was assessed by scanning five volunteers twice. MOAKS reproducibility was compared to MOAKS derived from a clinical knee MRI protocol by two readers.Statistical TestsCoefficients of variation (CVs), concordance confidence intervals (CCI), and Wilcoxon signed‐rank tests compared morphometry and relaxometry measurements with their reference standards. DESS MOAKS positive percent agreement (PPA), negative percentage agreement (NPA), and interreader agreement was calculated using the clinical protocol as a reference. Biomarker variations between Kellgren–Lawrence groups were evaluated using Wilcoxon rank‐sum tests.ResultsCartilage thickness (P = 0.65), cartilage T₂ (P = 0.69), and meniscus T₂ (P = 0.06) did not significantly differ from their reference standard (with a 20° DESS flip angle). DESS slightly overestimated meniscus volume (P < 0.001). Accuracy and repeatability CVs were <3.3%, except the meniscus T₂ accuracy (7.6%). DESS MOAKS had substantial interreader agreement and high PPA/NPA values of 87%/90%. Bone marrow lesions and menisci had slightly lower PPAs. Cartilage and meniscus T₂, and MOAKS (cartilage surface area, osteophytes, cysts, and total score) was higher in Kellgren–Lawrence groups 2 and 3 than group 0 (P < 0.05).Data ConclusionThe 5‐minute DESS sequence permits MOAKS assessment for a majority of tissues, along with repeatable and reproducible simultaneous cartilage and meniscus T₂ relaxometry and morphometry measurements.Level of Evidence: 2Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2018;47:1328–1341.