Reproducibility of Quantitative Double-Echo Steady-State T2 Mapping of Knee Cartilage.

BACKGROUND: Cartilage T2 can detect joints at risk of developing osteoarthritis. The quantitative double-echo steady state (qDESS) sequence is attractive for knee cartilage T2 mapping because of its acquisition time of under 5 minutes. Understanding the reproducibility errors associated with qDESS T2 is essential to profiling the technical performance of this biomarker. PURPOSE: To examine the combined acquisition and segmentation reproducibility of knee cartilage qDESS T2 using two different regional analysis schemes: 1) manual segmentation of subregions loaded during common activities and 2) automatic subregional segmentation. STUDY TYPE: Prospective. SUBJECTS: 11 uninjured participants (age: 28 ± 3 years; 8 (73%) female). FIELD STRENGTH/SEQUENCE: 3-T, qDESS. ASSESSMENT: Test-retest T2 maps were acquired twice on the same day and with a 1-week interval between scans. For each acquisition, average cartilage T2 was calculated in four manually segmented regions encompassing tibiofemoral contact areas during common activities and 12 automatically segmented regions from the deep-learning open-source framework for musculoskeletal MRI analysis (DOSMA) encompassing medial and lateral anterior, central, and posterior tibiofemoral regions. Test-retest T2 values from matching regions were used to evaluate reproducibility. STATISTICAL TESTS: Coefficients of variation (%CV), root-mean-square-average-CV (%RMSA-CV), and intraclass correlation coefficients (ICCs) assessed test-retest T2 reproducibility. The median of test-retest standard deviations was used for T2 precision. Bland-Altman (BA) analyses examined test-retest biases. The smallest detectable difference (SDD) was defined as the BA limit of agreement of largest magnitude. Significance was accepted for P < 0.05. RESULTS: All cartilage regions across both segmentation schemes demonstrated intraday and interday qDESS T2 CVs and RMSA-CVs of ≤5%. T2 ICC values >0.75 were observed in the majority of regions but were more variable in interday tibial comparisons. Test-retest T2 precision was <1.3 msec. The T2 SDD was 3.8 msec. DATA CONCLUSION: Excellent CV and RMSA-CV reproducibility may suggest that qDESS T2 increases or decreases >5% (3.8 msec) could represent changes to cartilage composition. TECHNICAL EFFICACY: Stage 2.

Repeatability of ultrashort echo time-based two-component T2* measurements on cartilages in human knee at 3 T.

Repeatability of in vivo measurement of multicomponent T2* relaxation in articular cartialges in human knee is important to clinical use. This study evaluated the repeatability of two-component T2* relaxation on seven healthy human subjects. The left knee was scanned once a day in three consecutive days, on a clinical 3T MRI scanner with eight-channel knee coil and ultrashort echo time pulse sequence at 11 echo times=0.6-40 ms. The intrasubject and intersubject repeatability was evaluated via coefficient of variation (CV=standard deviation/mean) in four typical cartilage regions: patellar, anterior articular, femoral, and tibial regions. It was found that the intrasubject repeatability was good, with CV<10% for the short- and long-T2* relaxation time in the layered regions in the four cartilages (with one exception) and CV<13% for the component intensity fraction (with two exceptions). The intersubject repeatability was also good, with CV∼8% (range 1-15%) for the short- and long-T2* relaxation time and CV∼10% (range 2-20%) for the component intensity fraction. The long-T2* component showed significantly better repeatability (CV∼8%) than the short-T2* component (CV∼12%) (P<0.005). These CV values suggest that in vivo measurement of two-component T2* relaxation in the knee cartilages is repeatable on clinical scanner at 3 T, with a signal-to-noise ratio of 90.

A preliminary typology of caregivers and effects on service utilization of caregiver counseling.

OBJECTIVES: Caregivers (CGs) of older adults have unique and diverse needs for intervention. The present studies describe the characteristics of CGs and caregiving situations and how these relate to CG therapy utilization patterns in a community mental health setting. METHOD: Study 1: Through chart review, the researchers explored service utilization patterns and identified preliminary typologies of Caregiver Family Therapy (CFT) clients, N = 23. Study 2: By conducting a second chart review, the researchers sought to determine whether the categories that emerged in Study 1 applied to a second group of CFT clients, N = 36. RESULTS: Study 1: Four distinct categories of CGs emerged: High-Distress (high disorganization, high complexity), Resourceful but At-Risk (low disorganization, high complexity), Non-Committal (high disorganization, low complexity), and Model CGs (low disorganization, low complexity). Study 2: While the ability to classify CGs into category proved to have some inconsistencies, preliminary evidence suggests the ability to predict utilization once CGs were placed into category was good. In Study 2 a fifth category emerged: High Functioning but Static, which suggests CGs were on a continuum ranging from high to low on family organizational style and CG situation complexity. CONCLUSION: While caregiving situations vary widely among families and across time, this article provides a preliminary typology of CGs that may assist clinicians in tailoring CG interventions to meet the needs of their clients based on information garnered early in therapy, perhaps as early as the intake process.

Using 3D MRI Bone Shape to Predict Pre-Osteoarthritis of the Knee 2 Years After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) injury increases risks for osteoarthritis (OA), a poorly modifiable and disabling condition. Joint changes of potentially reversible pre-OA have been described just 2 years after ACL reconstruction (ACLR) when early bone shape changes have also been reported. PURPOSE: This study evaluates relationships between interlimb differences in tibiofemoral bone shape derived from statistical shape modeling (SSM) of magnetic resonance imaging (MRI) and participant factors on patient-reported outcomes 2 years after unilateral ACLR. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: SSM-derived tibiofemoral bone shape and subchondral bone area were assessed from bilateral knee MRI scans of 72 participants with unilateral ACLR (mean age, 34 ± 11 years; 32 women) and compared with a reference cohort of 398 older individuals without OA (mean age, 50 ± 3 years; 213 women). Multivariable logistic regression models examined relationships between participant and surgical factors with interlimb differences in bone shapes or subchondral bone areas. Relationships between patient-reported outcomes and the interlimb differences in bone shape and subchondral area were examined using similar models. RESULTS: Bone shape scores and subchondral bone areas were greater (more OA-like) in ACLR knees than uninjured contralateral knees in every bone metric tested (P≤ .001). Interlimb differences in femur shape scores of participants with ACLR were 65% greater (P < .001) than those of the significantly older reference cohort. Taller height, medial meniscal tears, and decreasing age were associated with larger interlimb differences in shape scores and subchondral areas (P < .05). Bone-patellar tendon-bone (BPTB) autograft recipients demonstrated greater interlimb subchondral area differences compared with allograft recipients (P < .05). Interlimb differences for hamstring autograft recipients did not differ from those with BPTB or allograft. Greater interlimb differences in medial femur subchondral areas were associated with worse patient-reported Knee injury and Osteoarthritis Outcome Score Symptoms (R = 0.27; P = .040). CONCLUSION: Even in the absence of radiographic OA, just 2 years after unilateral ACLR patients showed greater bone shape scores and subchondral areas consistent with pre-OA in their ACLR knees. Furthermore, greater medial femur bone areas were weakly associated with worse symptoms. Patients who are younger, are taller, have meniscal tears, or have BPTB grafts may be at increased risk for bony asymmetries 2 years after ACLR.

High-resolution ultrashort echo time (UTE) imaging on human knee with AWSOS sequence at 3.0 T.

PURPOSE: To demonstrate the technical feasibility of high-resolution (0.28-0.14 mm) ultrashort echo time (UTE) imaging on human knee at 3T with the acquisition-weighted stack of spirals (AWSOS) sequence. MATERIALS AND METHODS: Nine human subjects were scanned on a 3T MRI scanner with an 8-channel knee coil using the AWSOS sequence and isocenter positioning plus manual shimming. RESULTS: High-resolution UTE images were obtained on the subject knees at TE = 0.6 msec with total acquisition time of 5.12 minutes for 60 slices at an in-plane resolution of 0.28 mm and 10.24 minutes for 40 slices at an in-plane resolution of 0.14 mm. Isocenter positioning, manual shimming, and the 8-channel array coil helped minimize image distortion and achieve high signal-to-noise ratio (SNR). CONCLUSION: It is technically feasible on a clinical 3T MRI scanner to perform UTE imaging on human knee at very high spatial resolutions (0.28-0.14 mm) within reasonable scan time (5-10 min) using the AWSOS sequence.

Cartilage Matrix Degeneration Occurs within the First Year after ACLR and Is Associated with Impaired Clinical Outcome.

OBJECTIVE: Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes. DESIGN: Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values. RESULTS: Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR (P = .001-.011). T2 value increased (P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life (P = .009, ρ = -0.62). DISCUSSION: Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.

Visualizing pre-osteoarthritis: Integrating MRI UTE-T2* with mechanics and biology to combat osteoarthritis-The 2019 Elizabeth Winston Lanier Kappa Delta Award.

Osteoarthritis (OA) is a leading cause of pain and disability for which disease-modifying treatments remain lacking. This is because the symptoms and radiographic changes of OA occur after the onset of likely irreversible changes. Defining and treating earlier disease states are therefore needed to delay or to halt OA progression. Taking this concept a step further, studying OA pathogenesis before disease onset by characterizing potentially reversible markers of increased OA risk to identify a state of "pre-osteoarthritis (pre-OA)" shifts the paradigm towards OA prevention. The purpose of this review is to summarize the 42 studies comprising the 2019 Kappa Delta Elizabeth Lanier Award where conceptualization of a systems-based definition for "pre-osteoarthritis (pre-OA)" was followed by demonstration of potentially reversible markers of heightened OA risk in patients after anterior cruciate ligament (ACL) injury and reconstruction. In the process, these efforts contributed a new magnetic resonance imaging method of ultrashort echo time (UTE) enhanced T2* mapping to visualize joint tissue damage before the development of irreversible changes. The studies presented here support a transformative approach to OA that accounts for interactions between mechanical, biological, and structural markers of OA risk to develop and evaluate new treatment strategies that can delay or prevent the onset of clinical disease. This body of work was inspired by and performed for patients. Shifting the paradigm from attempting to modify symptomatic radiographic OA towards monitoring and reversing markers of "pre-OA" opens the door for transforming the clinical approach to OA from palliation to prevention.

Patient-Reported Outcomes and Knee Mechanics Correlate With Patellofemoral Deep Cartilage UTE-T2* 2 Years After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Patellofemoral joint degeneration and dysfunction after anterior cruciate ligament reconstruction (ACLR) are increasingly recognized as contributors to poor clinical outcomes. PURPOSE: To determine if greater deep cartilage matrix disruption at 2 years after ACLR, as assessed by elevated patellofemoral magnetic resonance imaging (MRI) ultrashort echo time-enhanced T2* (UTE-T2*), is correlated with (1) worse patient-reported knee function and pain and (2) gait metrics related to patellofemoral tracking and loading, such as greater external rotation of the tibia at heel strike, reduced knee flexion moment (as a surrogate of quadriceps function), and greater knee flexion angle at heel strike. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: MRI UTE-T2* relaxation times in patellar and trochlear deep cartilage were compared with patient-reported outcomes and ambulatory gait metrics in 60 patients with ACLR at 2 years after reconstruction. ACLR gait metrics were compared with those of 60 uninjured reference patients matched by age, body mass index, and sex. ACLR UTE-T2* values were compared with those of 20 uninjured reference patients. RESULTS: Higher trochlear UTE-T2* values were associated with worse Knee injury and Osteoarthritis Outcome Scores (KOOS) Sport/Recreation subscale scores (rho = -0.32; P = .015), and showed a trend for association with worse KOOS Pain subscale scores (rho = -0.26; P = .045). At 2 years after ACLR, greater external rotation of the tibia at heel strike was associated with higher patellar UTE-T2* values (R = 0.40; P = .002); greater knee flexion angle at heel strike was associated with higher trochlear UTE-T2* values (rho = 0.39; P = .002); and greater knee flexion moment showed a trend for association with higher trochlear UTE-T2* values (rho = 0.30; P = .019). Patellar cartilage UTE-T2* values, knee flexion angle at heel strike, and external rotation of the tibia at heel strike were all elevated in ACLR knees as compared with reference knees (P = .029, .001, and .044, respectively). CONCLUSION: Patellofemoral deep cartilage matrix disruption, as assessed by MRI UTE-T2*, was associated with reduced sports and recreational function and with gait metrics reflective of altered patellofemoral loading. As such, the findings provide new mechanistic information important to improving clinical outcomes related to patellofemoral dysfunction after ACLR.

Multicomponent T2* mapping of knee cartilage: technical feasibility ex vivo.

Disorganization of collagen fibers is a sign of early-stage cartilage degeneration in osteoarthritic knees. Water molecules trapped within well-organized collagen fibrils would be sensitive to collagen alterations. Multicomponent effective transverse relaxation (T2*) mapping with ultrashort echo time acquisitions is here proposed to probe short T(2) relaxations in those trapped water molecules. Six human tibial plateau explants were scanned on a 3T MRI scanner using a home-developed ultrashort echo time sequence with echo times optimized via Monte Carlo simulations. Time constants and component intensities of T2* decays were calculated at individual pixels, using the nonnegative least squares algorithm. Four T2*-decay types were found: 99% of cartilage pixels having mono-, bi-, or nonexponential decay, and 1% showing triexponential decay. Short T2* was mainly in 1-6 ms, while long T2* was ∼ 22 ms. A map of decay types presented spatial distribution of these T2* decays. These results showed the technical feasibility of multicomponent T2* mapping on human knee cartilage explants.

Quantitative MRI UTE-T2* and T2* Show Progressive and Continued Graft Maturation Over 2 Years in Human Patients After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Noninvasive quantitative magnetic resonance imaging (MRI) measures to assess anterior cruciate ligament (ACL) graft maturity are needed to help inform return to high-demand activities and to evaluate the effectiveness of new treatments to accelerate ACL graft maturation. Quantitative MRI ultrashort echo time T2* (UTE-T2*) and T2* mapping captures short T2 signals arising from collagen-associated water in dense regular connective tissues, such as tendon, ligament, and maturing grafts, which are invisible to conventional MRI. HYPOTHESIS: Quantitative MRI UTE-T2* and T2* mapping is sensitive to ACL graft changes over the first 2 years after ACL reconstruction (ACLR). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 32 patients (18 men; mean ± SD age, 30 ± 9 years) undergoing unilateral ACLR and 30 uninjured age-matched controls (18 men; age, 30 ± 9 years) underwent 3-T MRI examination. Patients who underwent ACLR were imaged at 6 weeks, 6 months, and 1 and 2 years postoperatively. Two separate ACLR cohorts were scanned with 2 MRI platforms at 2 institutions. Twelve ACLR knees were scanned with a 3-dimensional acquisition-weighted stack of spirals UTE sequence on a Siemens scanner, and 20 ACLR knees were scanned with a 3-dimensional Cones UTE sequence on a GE scanner. UTE-T2* or T2* maps were calculated for the intra-articular portion of the ACL graft. RESULTS: Mean ACL graft UTE-T2* and T2* decreased from 1 to 2 years after ACLR. ACL graft T2* increased 25% to 30% during the first 6 months (P < .013) to a level not different from that of uninjured native ACL (P > .4), stabilized between 6 months and 1 year (P ≥ .999), and then decreased 19% between 1 and 2 years after ACLR (P = .027). At 6-month follow-up, ACL graft UTE-T2* differed from that of tendon (P < .02) but not uninjured native ACL (P > .7) and showed the greatest variability among patients. CONCLUSION: UTE-T2* mapping suggested substantial changes within the graft during the first 6 months postsurgery. T2* and UTE-T2* mapping showed relatively stable graft composition from 6 months to 1 year, consistent with remodeling, followed by decreases from 1 to 2 years, suggestive of continuing maturation. MRI UTE-T2* and T2* mapping demonstrated potential clinical utility as noninvasive quantitative imaging metrics for evaluation of human ACL grafts.

MRI UTE-T2* shows high incidence of cartilage subsurface matrix changes 2 years after ACL reconstruction.

Alteration of deep cartilage matrix has been observed following anterior cruciate ligament (ACL) injury, evidenced by elevated MRI UTE-T2* values measured in small, 2-D cartilage regions of interest. This Level I diagnostic study seeks to more thoroughly evaluate deep cartilage matrix changes to medial tibiofemoral UTE-T2* maps 2 years after ACL reconstruction and examine the relative utilities of 3-D compared to 2-D assessments of cartilage UTE-T2* maps. Thirty-eight ACL-reconstructed and 20 uninjured subjects underwent MRI UTE-T2* mapping. "Small" single mid-sagittal 2-D and larger 3-D "tread mark" regions of interest were manually segmented and found to be correlated in medial cartilage (r > 0.58, p < 0.005). 3-D analyses of UTE-T2* maps showed differences to medial tibial cartilage between ACL-reconstructed and uninjured subjects (p = 0.007) that were not detected by smaller 2-D regions (p > 0.46). Quantitative comparisons show 14/38 (37%) ACL-reconstructed subjects have values >2 standard deviations higher than uninjured controls. Among a subset of ACL-reconstructed subjects with no morphologic MRI evidence of medial tibiofemoral cartilage or meniscal pathology (n = 12), elevated UTE-T2* values in "small" 2-D femoral (p = 0.011), but not larger 3-D tread mark regions of interest (p > 0.13), were observed. These data show the utility of 2-D UTE-T2* assessments of mid-sagittal weight-bearing regions of medial femoral cartilage for identifying subclinical deep cartilage matrix changes 2 years after ACLR. Clinical Significance: Mid-sagittal single slice 2-D UTE-T2* mapping may be an efficient means to assess medial femoral cartilage for subsurface matrix changes early after ACL reconstruction while 3-D assessments provide additional sensitivity to changes in the medial tibial plateau. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:370-377, 2019.

Cartilage Subsurface Changes to Magnetic Resonance Imaging UTE-T2* 2 Years After Anterior Cruciate Ligament Reconstruction Correlate With Walking Mechanics Associated With Knee Osteoarthritis.

BACKGROUND: Anterior cruciate ligament (ACL) injury increases risk for posttraumatic knee osteoarthritis (OA). Quantitative ultrashort echo time enhanced T2* (UTE-T2*) mapping shows promise for early detection of potentially reversible subsurface cartilage abnormalities after ACL reconstruction (ACLR) but needs further validation against established clinical metrics of OA risk such as knee adduction moment (KAM) and mechanical alignment. HYPOTHESIS: Elevated UTE-T2* values in medial knee cartilage 2 years after ACLR correlate with varus alignment and higher KAM during walking. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Twenty patients (mean age, 33.1 ± 10.5 years; 11 female) 2 years after ACLR underwent 3.0-T knee magnetic resonance imaging (MRI), radiography, and gait analysis, after which mechanical alignment was measured, KAM during walking was calculated, and UTE-T2* maps were generated. The mechanical axis and the first and second peaks of KAM (KAM1 and KAM2, respectively) were tested using linear regressions for correlations with deep UTE-T2* values in the central and posterior medial femoral condyle (cMFC and pMFC, respectively) and central medial tibial plateau (cMTP). UTE-T2* values from ACL-reconstructed patients were additionally compared with those of 14 uninjured participants (mean age, 30.9 ± 8.9 years; 6 female) using Mann-Whitney U and standard t tests. RESULTS: Central weightbearing medial compartment cartilage of ACL-reconstructed knees was intact on morphological MRI. Mean UTE-T2* values were elevated in both the cMFC and pMFC of ACL-reconstructed knees compared with those of uninjured knees ( P = .003 and P = .012, respectively). In ACL-reconstructed knees, UTE-T2* values of cMFC cartilage positively correlated with increasing varus alignment ( R = 0.568). Higher UTE-T2* values in cMFC and cMTP cartilage of ACL-reconstructed knees also correlated with greater KAM1 ( R = 0.452 and R = 0.463, respectively) and KAM2 ( R = 0.465 and R = 0.764, respectively) and with KAM2 in pMFC cartilage ( R = 0.602). CONCLUSION: Elevated deep UTE-T2* values of medial knee cartilage 2 years after ACLR correlate with 2 clinical markers of increased risk of medial knee OA. These results support the clinical utility of MRI UTE-T2* for early diagnosis of subsurface cartilage abnormalities. Longitudinal follow-up of larger cohorts is needed to determine the predictive and staging potential of UTE-T2* for posttraumatic OA.

Addition of Mesenchymal Stem Cells to Autologous Platelet-Enhanced Fibrin Scaffolds in Chondral Defects: Does It Enhance Repair?

BACKGROUND: The chondrogenic potential of culture-expanded bone-marrow-derived mesenchymal stem cells (BMDMSCs) is well described. Numerous studies have also shown enhanced repair when BMDMSCs, scaffolds, and growth factors are placed into chondral defects. Platelets provide a rich milieu of growth factors and, along with fibrin, are readily available for clinical use. The objective of this study was to determine if the addition of BMDMSCs to an autologous platelet-enriched fibrin (APEF) scaffold enhances chondral repair compared with APEF alone. METHODS: A 15-mm-diameter full-thickness chondral defect was created on the lateral trochlear ridge of both stifle joints of twelve adult horses. In each animal, one defect was randomly assigned to receive APEF+BMDMSCs and the contralateral defect received APEF alone. Repair tissues were evaluated one year later with arthroscopy, histological examination, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and biomechanical testing. RESULTS: The arthroscopic findings, MRI T2 map, histological scores, structural stiffness, and material stiffness were similar (p > 0.05) between the APEF and APEF+BMDMSC-treated repairs at one year. Ectopic bone was observed within the repair tissue in four of twelve APEF+BMDMSC-treated defects. Defects repaired with APEF alone had less trabecular bone edema (as seen on MRI) compared with defects repaired with APEF+BMDMSCs. Micro-CT analysis showed thinner repair tissue in defects repaired with APEF+BMDMSCs than in those treated with APEF alone (p < 0.05). CONCLUSIONS: APEF alone resulted in thicker repair tissue than was seen with APEF+BMDMSCs. The addition of BMDMSCs to APEF did not enhance cartilage repair and stimulated bone formation in some cartilage defects. CLINICAL RELEVANCE: APEF supported repair of critical-size full-thickness chondral defects in horses, which was not improved by the addition of BMDMSCs. This work supports further investigation to determine whether APEF enhances cartilage repair in humans.

Quantitative Magnetic Resonance Imaging UTE-T2* Mapping of Cartilage and Meniscus Healing After Anatomic Anterior Cruciate Ligament Reconstruction.

BACKGROUND: An anterior cruciate ligament (ACL) injury greatly increases the risk for premature knee osteoarthritis (OA). Improved diagnosis and staging of early disease are needed to develop strategies to delay or prevent disabling OA. PURPOSE: Novel magnetic resonance imaging (MRI) ultrashort echo time (UTE)-T2(*) mapping was evaluated against clinical metrics of cartilage health in cross-sectional and longitudinal studies of human participants before and after ACL reconstruction (ACLR) to show reversible deep subsurface cartilage and meniscus matrix changes. STUDY DESIGN: Cohort study (diagnosis/prognosis); Level of evidence, 2. METHODS: Forty-two participants (31 undergoing anatomic ACLR; 11 uninjured) underwent 3-T MRI inclusive of a sequence capturing short and ultrashort T2 signals. An arthroscopic examination of the medial meniscus was performed, and modified Outerbridge grades were assigned to the central and posterior medial femoral condyle (cMFC and pMFC, respectively) of ACL-reconstructed patients. Two years after ACLR, 16 patients underwent the same 3-T MRI. UTE-T2(*) maps were generated for the posterior medial meniscus (pMM), cMFC, pMFC, and medial tibial plateau (MTP). Cross-sectional evaluations of UTE-T2(*) and arthroscopic data along with longitudinal analyses of UTE-T2(*) changes were performed. RESULTS: Arthroscopic grades showed that 74% (23/31) of ACL-reconstructed patients had intact cMFC cartilage (Outerbridge grade 0 and 1) and that 90% (28/31) were Outerbridge grade 0 to 2. UTE-T2(*) values in deep cMFC and pMFC cartilage varied significantly with injury status and arthroscopic grade (Outerbridge grade 0-2: n = 39; P = .03 and .04, respectively). Pairwise comparisons showed UTE-T2(*) differences between uninjured controls (n = 11) and patients with arthroscopic Outerbridge grade 0 for the cMFC (n = 12; P = .01) and arthroscopic Outerbridge grade 1 for the pMFC (n = 11; P = .01) only and not individually between arthroscopic Outerbridge grade 0, 1, and 2 of ACL-reconstructed patients (P > .05). Before ACLR, UTE-T2(*) values of deep cMFC and pMFC cartilage of ACL-reconstructed patients were a respective 43% and 46% higher than those of uninjured controls (14.1 ± 5.5 vs 9.9 ± 2.3 milliseconds [cMFC] and 17.4 ± 7.0 vs 11.9 ± 2.4 milliseconds [pMFC], respectively; P = .02 for both). In longitudinal analyses, preoperative elevations in UTE-T2(*) values in deep pMFC cartilage and the pMM in those with clinically intact menisci decreased to levels similar to those in uninjured controls (P = .02 and .005, respectively), suggestive of healing. No decrease in UTE-T2(*) values for the MFC and new elevation in UTE-T2(*) values for the submeniscus MTP were observed in those with meniscus tears. CONCLUSION: This study shows that novel UTE-T2(*) mapping demonstrates changes in cartilage deep tissue health according to joint injury status as well as a potential for articular cartilage and menisci to heal deep tissue injuries. Further clinical studies of UTE-T2(*) mapping are needed to determine if it can be used to identify joints at risk for rapid degeneration and to monitor effects of new treatments to delay or prevent the development of OA.

Registration of Magnetic Resonance Image Series for Knee Articular Cartilage Analysis: Data from the Osteoarthritis Initiative.

OBJECTIVE: Although conventional radiography is used to assess osteoarthritis in a clinical setting, it has limitations, including an inability to stage early cartilage degeneration. There is a growing interest in using quantitative magnetic resonance imaging to identify degenerative changes in articular cartilage, including the large multicentered study, the Osteoarthritis Initiative (OAI). There is a demand for suitable image registration and segmentation software to complete this analysis. The objective of this study was to develop and validate the open source software, ImageK, that registers 3 T MRI T2 mapping and double echo steady state (DESS) knee MRI sequences acquired in the OAI protocol. METHODS: A C++ library, the insight toolkit, was used to develop open source software to register DESS and T2 mapping image MRI sequences using Mattes's Multimodality Mutual information metric. RESULTS: Registration was assessed using three separate methods. A checkerboard layout demonstrated acceptable visual alignment. Fiducial markers placed in cadaveric knees measured a registration error of 0.85 voxels. Measuring the local variation in Mattes's Mutual Information metric in the local area of the registered solution showed precision within 1 pixel. In this group, the registered solution required a transform of 56 voxels in translation and 1 degree of rotation. CONCLUSION: The software we have developed, ImageK, provides free, open source image analysis software that registers DESS and T2 mapping sequences of knee articular cartilage within 1 voxel accuracy. This image registration software facilitates quantitative MRI analyses of knee articular cartilage.

Early diagnosis to enable early treatment of pre-osteoarthritis.

Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies.