Effects of repeated intra-articular hyaluronic acid on cartilage degeneration evaluated by T1ρ mapping in knee osteoarthritis.

OBJECTIVES: Intra-articular injection of hyaluronic acid (IAHA) has been used for the treatment of knee osteoarthritis (OA), but its effectiveness remains controversial. This study analyzed knee OA over time by magnetic resonance imaging (MRI) T1ρ mapping to objectively evaluate whether long-term repeated administration of IAHA influences cartilage degeneration. METHODS: Sixty knees of 60 patients [58.3 ± 12.5 years (mean ± standard deviation)] who had multiple T1ρ mapping images were retrospectively analyzed. We calculated the T1ρ values of the medial femorotibial cartilage and classified changes in degenerative areas over time into 3 groups: Improvement, No Change, and Deterioration. RESULTS: Average time between 2 MRI scans was 7.6 ± 1.2 months. The number of IAHA administrations was 15.5 ± 21.3, 8.39 ± 7.19, and 5.80 ± 7.49 in the Improvement, No Change, and Deterioration groups, respectively. Body mass index and number of IAHA administrations were significant factors causing change in the area of degeneration (p < .05) independent of age, sex, Kellgren-Lawrence grade, and posterior horn meniscus tears. CONCLUSION: Cartilage degeneration may be improved with a higher number of administrations of IAHA, based on T1ρ mapping results. This highlights the possibility of increased treatment effectiveness of IAHA for knee OA with repeated administrations.

Bone morphological factors influencing cartilage degeneration in the knee.

OBJECTIVES: Morphological features of the distal femur and proximal tibia associated with cartilage degeneration are unknown. This study aimed to elucidate local anatomical parameters of the knee which correlate with articular cartilage degeneration using MRI T1ρ mapping. METHODS: This study involved 200 subjects with knee pain (mean age, 48.7 years; range, 14-80 years) with no severe osteoarthritic changes on plain X-ray. T1ρ values were measured in the regions of interest on the surface layer of the cartilage on mid-coronal images of the femorotibial joint. Assessment of medial and lateral posterior tibial slope (MTS, LTS) and medial and lateral femoral condylar offset ratio (MFCOR, LFCOR) was performed using sagittal proton density-weighted imaging. Morphological assessment of posterior root and horn of menisci was also performed according to a modified Whole Organ Magnetic Resonance Imaging Score (WORMS) of the knee. RESULTS: Multiple regression analysis revealed that a decrease in MTS was associated with increased T1ρ values in the medial tibia, independent of age, osteoarthritic changes on plain X-ray, femur-tibia angle (FTA), and posterior medial meniscal lesions. CONCLUSIONS: Shallow MTS correlates with cartilage degeneration in symptomatic patients. This parameter could help in understanding the etiology of osteoarthritis in the early stage. Future kinematic studies will be needed to confirm our findings.

Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs.

BACKGROUND: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. PURPOSE: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. RESULTS: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. CONCLUSION: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. CLINICAL RELEVANCE: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.

Volume change in infrapatellar fat pad is associated not with obesity but with cartilage degeneration.

Infrapatellar fat pad has been implicated in knee osteoarthritis. We examined whether infrapatellar fat pad volume is associated with quantitative cartilage changes using magnetic resonance imaging T1ρ mapping. Fifty-eight knees of knee pain patients (19 men, 39 women, mean age 57.0 [range 29-85] years) who were conservatively managed and had >1 T1ρ mapping images taken over time were evaluated. We used three slices from the medial femoral and tibial cartilage; areas showing T1ρ values <130 ms and >50 ms were designated as having cartilage degeneration. Cases were categorized into three groups: Improvement, No Change, and Deterioration. Fat-suppressed T2-weighted sagittal magnetic resonance images were used for measuring infrapatellar fat pad volume. Percent change in infrapatellar fat pad volume was -5.01 ± 5.66%, -2.06 ± 4.92%, and 0.05 ± 6.09% in the Improvement (n = 22), No Change (n = 22), and Deterioration (n = 14) groups, respectively, demonstrating significantly reduced infrapatellar fat pad volume in the Improvement group (p < 0.05). Multivariate regression analyses revealed that the percent change in infrapatellar fat pad volume significantly affected T1ρ change category independent of age, sex, follow-up period, baseline infrapatellar fat pad volume, and Kellgren-Lawrence grade. Infrapatellar fat pad volume and obesity or body weight change showed no correlation. Infrapatellar fat pad volume was reduced in patients with improved quantitative cartilage assessment on magnetic resonance imaging T1ρ mapping. This is the first study demonstrating associations between quantitative cartilage changes and infrapatellar fat pad morphological changes, suggesting a detrimental role of infrapatellar fat pad volume in articular cartilage degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Projected Cartilage Area Ratio Determined by 3-Dimensional MRI Analysis: Validation of a Novel Technique to Evaluate Articular Cartilage.

We have developed 3-dimensional (3D) magnetic resonance imaging (MRI) analysis software that allows measurement of the projected cartilage area ratio with a particular thickness intended to allow quantitation of the cartilage in the knee. Our aims in this study were to validate the projected cartilage area ratio in both pig and human knees and to examine the ratio in patients reporting knee pain. METHODS: After 3D MRI reconstruction, the femoral cartilage was projected onto a flat surface. The projected cartilage area was determined in pig knees using our 3D MRI analysis software, and was compared with the area obtained with other software. The projected cartilage area ratio (for cartilage thickness ≥1.5 mm) at 4 segments was also validated in human knees. Finally, changes in the projected cartilage area ratio were examined in 8 patients with knee pain who had undergone 2 MR images at 3 to 21-month intervals. RESULTS: The projected cartilage areas determined with our 3D MRI analysis software were validated in pig knees. The projected cartilage area ratio at each segment in human knees had an intraclass correlation coefficient (ICC) of 0.87 to 0.99 (n = 16) between readers and 0.76 to 0.99 (n = 20) between measurements on repeat MR images. The projected cartilage area ratio (for cartilage thickness ≥1.5 mm) at the most affected segment in 8 human patients significantly decreased between the pairs of MR images obtained at intervals of 3 to 21 months. CONCLUSIONS: We proposed a novel evaluation method using 3D MRI to quantify the amount of cartilage in the knee. This method had a low measurement error in both pig and human knees. CLINICAL RELEVANCE: The projected cartilage area ratio based on a particular thickness may serve as a sensitive method for assessing changes in cartilage over time.

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017.