Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon.This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA.Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*).QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.