SUMMARY Objective Meniscus tear is a known risk factor for osteoarthritis (OA). Quantitative assessment of meniscus degeneration, prior to surface break-down, is important to identification of early disease potentially amenable to therapeutic interventions. This work examines the diagnostic potential of ultrashort echo time-enhanced T2* (UTE-T2*) mapping to detect human meniscus degeneration in vitro and in vivo in subjects at risk of developing OA. Design UTE-T2* maps of 16 human cadaver menisci were compared to histological evaluations of meniscal structural integrity and clinical magnetic resonance imaging (MRI) assessment by a musculoskeletal radiologist. In vivo UTE-T2* maps were compared in 10 asymptomatic subjects and 25 ACL-injured patients with and without concomitant meniscal tear. Results In vitro, UTE-T2* values tended to be lower in histologically and clinically normal meniscus tissue and higher in torn or degenerate tissue. UTE-T2* map heterogeneity reflected collagen disorganization. In vivo, asymptomatic meniscus UTE-T2* values were repeatable within 9% (root-mean-square average coefficient of variation). Posteromedial meniscus UTE-T2* values in ACL-injured subjects with clinically diagnosed medial meniscus tear (n = 10) were 87% higher than asymptomatics (n = 10, P < 0.001). Posteromedial menisci UTE-T2* values of ACL-injured subjects without concomitant medial meniscal tear (n = 15) were 33% higher than asymptomatics (P = 0.001). Posterolateral menisci UTE-T2* values also varied significantly with degree of joint pathology (P = 0.001). Conclusion Significant elevations of UTE-T2* values in the menisci of ACL-injured subjects without clinical evidence of subsurface meniscal abnormality suggest that UTE-T2* mapping is sensitive to subclinical meniscus degeneration. Further study is needed to determine whether elevated subsurface meniscus UTE-T2* values predict progression of meniscal degeneration and development of OA.
Objective To examine the sensitivity of ultra-short echo time (UTE) T2* mapping to collagen matrix degeneration in human articular cartilage. Methods MRI UTE-T2* maps and standard T2 maps were acquired on four human tibial plateau explants. Thirty-three osteochondral cores were harvested for polarized light microscopy (PLM), and composition analyses. Collagen matrix integrity was evaluated from PLM and histological images. Matrix integrity and composition was compared to standard T2 values and UTE-T2* values on a spatially registered basis. Results UTE-T2* values varied with matrix degeneration (p=0.008) and were lower in severely degraded cartilage compared to healthy tissue (p=0.012). A trend for higher UTE-T2* values in healthy tissue compared to mildly degenerate tissue (p=0.051) was detected. Standard T2 values were not found to vary with matrix degeneration (p=0.13) but tended to be higher in severely degraded cartilage compared to healthy tissue. UTE-T2* value variations were independent of type II collagen and glycosaminoglycan contents. UTE-T2* mapping of deep cartilage, adjacent to subchondral bone, was more robust than standard T2 mapping in this zone. Conclusion UTE-T2* mapping of articular cartilage is sensitive to matrix degeneration and detects short T2 signal, particularly in deep tissue, that is not well captured by standard T2 mapping. Correlation of UTE-T2* values and PLM indices supports the hypothesis that both may be sensitive to collagen microstructure. Further exploration of UTE-T2* mapping as a noninvasive tool to detect early articular cartilage degeneration is warranted.
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.
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 ident...
Objective. Delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is used to examine the distribution of glycosaminoglycan in cartilage. This study sought to characterize dGEMRIC in the evaluation of knee osteoarthritis (OA) according to various radiographically determined disease parameters, and to examine the relationship between alignment of the knee joint and the lateral:medial dGEMRIC ratio.Methods. Thirty-one patients with knee OA underwent MRI with a dGEMRIC protocol at 1.5T. Semiflexed knee radiographs and full-limb radiographs were also obtained for assessment of alignment.Results. Compartments of the knee joint without joint space narrowing had a higher dGEMRIC index than those with any level of narrowing (mean 408 msec versus 365 msec; P ؍ 0.001). In knees with 1 unnarrowed (spared) and 1 narrowed (diseased) compartment, the dGEMRIC index was greater in the spared versus the diseased compartment (mean 395 msec versus 369 msec; P ؍ 0.001). In spared compartments, there was a trend toward a lower dGEMRIC index with increasing Kellgren/Lawrence (K/L) radiographic sever- Conclusion. The biochemical information provided by dGEMRIC scans may augment radiography by improving the differentiation of disease status within a given radiographic grade, especially in early OA.
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