Approximately half of patients progress to radiographic knee osteoarthritis (OA) by 8-16 years after anterior cruciate ligament reconstruction (ACLR)¹. Post-ACL injury cartilage damage has been frequently observed in the lateral and posterolateral tibial plateau which suffers transchondral impaction in pivot shift injury^2,3. But post-ACLR OA more typically initiates in the medial tibiofemoral compartment possibly as a result of altered gait mechanics leading to disrupted cartilage homeostasis over time^2,4. Identification of patients likely to develop post-ACLR OA is essential to timely application of therapeutic interventions. Ultrashort TE-enhanced T2* mapping (UTE-T2*) is sensitive to short T2* signals (T2 <10ms) that are found in meniscus and deep articular cartilage and has the potential to provide prognostic indication of otherwise clinically occult early osteoarthritic changes^5,6. A previous longitudinal study of 16 ACL-injured patients, using an acquisition-weighted stack of spirals sequence, found that elevated cartilage and meniscus UTE-T2* values persisted 2 years after ACLR in some patients while resolving to levels similar to uninjured control subjects in others⁷. The goal of this study is to examine whether 3-D cones UTE-T2* maps similarly show evidence of alterations to the subsurface cartilage matrix suggestive of cartilage at risk for early OA in human subjects 2 years after ACLR.Twenty-two ACLR subjects (11F, 33.4±10.1 years, 2.24±0.23 years post-surgery), and 16 uninjured controls (6F, 30.4±8.4 years) participated in this IRB-approved protocol after providing informed consent. ACLR subjects underwent examination of both their ACLR and contralateral knees on a 3T MRI scanner (MR 750, GE Healthcare, Milwaukee, WI) with a transmit-receive 8-channel knee coil. UTE-T2* maps were calculated via mono-exponential fitting of a series of T2*-weighted MR images acquired at eight TEs (32μs -16ms, non-uniform echo spacing) using a radial out 3-D cones acquisition. The cones sequence samples MRI data starting at the center of k-space and twisting outwards along conical surfaces in 3-D while allowing for anisotropic FOV and resolution⁸. The selection of echo times was optimized to specifically assess deep articular cartilage, the portion of cartilage extending from the bone-cartilage interface through half of the articular thickness. In addition, data for mono-exponentially fit standard T2 maps were collected in 15 of the ACLR subjects’ index knees with a 2D FSE sequence (CartiGram, GE Healthcare), TR 1500, and eight TEs ranging 6-60ms. Mean UTE-T2* and T2 values were calculated in seven pre-defined regions: central and posterior medial and lateral femoral condyles (cMFC, pMFC, cLFC, pLFC), central medial and lateral tibial plateaus (cMTP, cLTP), and posterolateral tibial plateau (pLTP). Distributions of mean UTE-T2* and T2 values were checked for normality with Shapiro-Wilks tests. Paired t-tests assessed UTE-T2* differences between limbs. Standard t-tests or Mann Whitney rank sum tests, as appropriate, assessed differences between cohorts. Pearson product moment correlations assessed associations between deep UTE-T2* and T2 values.ACLR knees demonstrated higher mean UTE-T2* values to deep cMFC, pMFC and pLTP cartilage compared to uninjured control subjects (20%, 14%, 19%; p=0.02, 0.05, <0.001; Figure 1). Qualitative assessment of the spatial distribution of UTE-T2* values in ACLR maps demonstrate 3 discernable patterns: (1) those that appear “similar to uninjured” with an uninterrupted layer of low UTE-T2* values at the bone-cartilage interface, laminar UTE-T2* values increasing monotonically from the bone interface to the articular surface, and homogeneously low UTE-T2* meniscal values (n=7/22, 32%); (2) those that are “not similar to uninjured” with interruptions to, or lack of, a layer of low UTE-T2* values near the bone-cartilage interface, non-laminar UTE-T2* values and relatively high meniscal UTE-T2* (n=5/22, 23%); and (3) those whose maps have an intermediate appearance (n=10/22, 45%). Interestingly, side-to-side comparisons within ACLR subjects revealed a trend for lower (14%) UTE-T2* values in deep cMTP cartilage of ACLR knees compared to their contralateral uninjured knees (p=0.056, n=21). UTE-T2* values correlated to standard T2 values in ACLR knees in cMTP, pLFC and pLTP regions (R=0.59, 0.52, 0.68; p=0.02, 0.04, 0.005).Patients 2 years after ACLR have typically returned to work, hobbies and sports, and are generally asymptomatic or minimally symptomatic. However, elevated UTE-T2* values in regions of deep tibiofemoral cartilage and in side-to-side UTE-T2* differences, may be early indicators of cartilage at risk for accelerated OA development^7,9. Comparisons to standard T2 maps indicate that UTE-T2* provides different and complimentary information to that of standard T2. Together, these findings suggest that UTE-T2* mapping detects “pre-osteoarthritic” subsurface cartilage matrix changes that may occur following ACLR and thus can help to identify subjects at risk of developing OA.