Changes in tissue sodium concentration and sodium relaxation times during the maturation of human knee cartilage: Ex vivo 23 Na MRI study at 10.5 T.

PURPOSE: To evaluate the influence of skeletal maturation on sodium (23 Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. METHODS: Twelve pediatric knee specimens were imaged with whole-body 10.5 T MRI using a density-adapted 3D radial projection sequence to evaluate 23 Na parameters: B1 + , T1 , biexponential T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1 + , relaxation, and water content. The literature-based TSC (TSCLB ) used previously published values for corrections, whereas the specimen-specific TSC (TSCSP ) used measurements from individual specimens. 23 Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23 Na parameters, TSCLB - TSCSP difference, biochemical content, and age were determined. RESULTS: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ ( T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ) decreased by 72%, and the signal fraction relaxing with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ( fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ ) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP . The TSCLB - TSCSP difference was significantly correlated with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). CONCLUSION: TSC and relaxation parameters measured with 23 Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years.

Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

Lower cell number, lateral defect location and milder grade are associated with improved autologous chondrocyte implantation outcome.

PURPOSE: To investigate patient demographic, injury and surgery/treatment-associated factors that can influence the patient-reported outcome (Lysholm score), following autologous chondrocyte implantation (ACI) in a large, 'real-world', nonuniform, prospective data examined retrospectively. METHODS: Knee patients treated at the Robert Jones and Agnes Hunt Orthopaedic Hospital, UK, using ACI between 1996 and 2020 were eligible. All longitudinal postoperative Lysholm scores collected between 1 and 23 years after ACI treatment and before any second major procedure (e.g., arthroplasty) were included. Multilevel longitudinal models were built investigating the association of short-term (1 year) or long-term trends in Lysholm score with baseline demographic, clinical and cell-culture variables, namely age, gender, smoker status, body mass index, baseline Lysholm score, time from surgery, defect grade, diameter and location, number of defects, previous microfracture, patch/scaffold type, associated procedure(s), number of cells implanted and their passage number. RESULTS: Following filtering, 306 of the 427 knee ACI procedures reviewed were suitable for inclusion. Factors shown to result in higher postoperative Lysholm scores in the short term were lower patient age, higher baseline Lysholm scores, fewer implanted cells and a lateral femoral defect location. The factor which was associated with higher long-term postoperative Lysholm scores was a milder defect grade. Additionally, the failure rate in this cohort was explored and it was found that 73/306 (24%) of patients experienced joint failure according to our definition. Furthermore, the outcome was not influenced by coincidental procedures in this cohort of patients. CONCLUSIONS: This study has identified a number of baseline factors associated with patient-reported outcomes following ACI and shows that treatment of associated pathology at the time of surgery potentially restores patient outcomes to a similar level as those with no associated pathologies. LEVEL OF EVIDENCE: Level IV.

Cartilage regeneration is related to superior mid-term patient-reported outcomes after open-wedge high tibial osteotomy.

PURPOSE: Medial open-wedge high tibial osteotomy (OWHTO) is related to cartilage improvement in the medial compartment. This study aimed to evaluate factors associated with cartilage improvement and patient-reported outcomes (PRO) after OWHTO. It was hypothesised that cartilage improvement is associated with favourable PRO. METHODS: This retrospective study included 94 patients who underwent OWHTO. The mean follow-up period was 5 years. The weight-bearing line ratio (WBLR) was defined as the ratio of the distance from the medial tibial edge to the tibial insertion of the weight-bearing line and the tibial width. The International Cartilage Research Society grade evaluated the medial femoral condyle (MFC) and medial tibial plateau (MTP) at initial and second-look arthroscopy, and cartilage improvement after OWHTO was assessed. Postoperative knee injury and osteoarthritis outcome scores (KOOS) were compared between the groups with improved and non-improved cartilage. Additionally, factors related to cartilage improvement and postoperative KOOS scores were analysed. RESULTS: Regarding the MFC, KOOS pain, symptoms, activities of daily living (ADL) and quality of life (QOL) were significantly higher in the cartilage-improved group than in the non-improved group (p = 0.012, 0.003, 0.001, 0.006), and cartilage improvement was significantly related to KOOS pain, ADL and QOL (p = 0.021, 0.039, 0.013). In addition, the postoperative WBLR was associated with cartilage improvement, with a cutoff value of 54.0% (p = 0.046). Regarding the MTP, KOOS ADL and QOL (p = 0.026, 0.022) were significantly higher in the cartilage-improved group than in the nonimproved group. Body mass index (BMI) was significantly related to the postoperative QOL (p = 0.018) and associated with cartilage improvement, with a cutoff value of 25.9 kg/m2 (p = 0.002). CONCLUSION: A postoperative WBLR greater than 54.0% and a preoperative BMI below 25.9 kg/m2 were associated with cartilage improvement, positively impacting PRO after OWHTO. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Multi-frame biomechanical and relaxometry analysis during in vivo loading of the human knee by spiral dualMRI and compressed sensing.

PURPOSE: Knee cartilage experiences repetitive loading during physical activities, which is altered during the pathogenesis of diseases like osteoarthritis. Analyzing the biomechanics during motion provides a clear understanding of the dynamics of cartilage deformation and may establish essential imaging biomarkers of early-stage disease. However, in vivo biomechanical analysis of cartilage during rapid motion is not well established. METHODS: We used spiral displacement encoding with stimulated echoes (DENSE) MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and used compressed sensing on the k-space data. The applied compressive load was set for each participant at 0.5 times body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1ρ , T2 ) and after (T1ρ ) varus load. RESULTS: Displacement and strain maps showed a gradual shift of displacement and strain in time. Compressive strain was observed in the medial condyle cartilage and shear strain was roughly half of the compressive strain. Male participants had more displacement in the loading direction compared to females, and T1ρ values did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25% to 40% when comparing the displacement maps and substantially lowered the noise levels. CONCLUSION: These results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies because of the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities and that could serve as biomarkers of early osteoarthritis.

Repeatability of Quantitative Knee Cartilage T1 , T2 , and T1ρ Mapping With 3D-MRI Fingerprinting.

BACKGROUND: Three-dimensional MR fingerprinting (3D-MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. PURPOSE: To assess the intra-day and inter-day repeatabilities of knee cartilage T1 , T2 , and T1ρ maps using a 3D-MRF sequence for simultaneous measurement. STUDY TYPE: Prospective. SUBJECTS: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. FIELD STRENGTH/SEQUENCE: 3 T/3D-MRF, T1 , T2 , and T1ρ maps. ASSESSMENT: The acquisition of 3D-MRF cartilage (simultaneous acquisition of T1 , T2 , and T1ρ maps) were acquired using a dictionary pattern-matching approach. Conventional cartilage T1 , T2 , and T1ρ maps were acquired using variable flip angles and a modified 3D-Turbo-Flash sequence with different echo and spin-lock times, respectively, and were fitted using mono-exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. STATISTICAL TESTS: The mean and SD for cartilage T1 , T2 , and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra-subject and inter-subject repeatabilities were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland-Altman analysis were performed to compare maps between the conventional and 3D-MRF sequences. RESULTS: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1 , T2 , and T1ρ , respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. CONCLUSION: The 3D-MRF sequence had high intra-subject and inter-subject repeatabilities for simultaneously measuring knee cartilage T1 , T2 , and T1ρ with good agreement with conventional sequences. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

A New Zn(II) Compound: Luminescent Property and Promoting Knee Cartilage Repair by Modulating Iron Death.

The hydrothermal reactions of bis{6-{5-methyl-1 H,7 H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one}}methane (L) and Zn(NO3)2·6H2O at 180 ℃ afforded a novel Zn(II) coordination polymer (CP), that is, {[Zn2(L)(µ2-O)2]·3H2O}n (1), which further characterized via Single crystal X-ray diffraction (SCXRD), elemental analysis (EA), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA). Besides, this CP reveals strong luminescence that may be caused by the charge transfer within the ligand. In biological study, the new compound was evaluated for its protective effect on chondrocytes. This compound significantly up-regulated GPX4 and down-regulated HO-1 mRNA levels, thereby inhibiting iron death in chondrocytes.

Magnetization-prepared spoiled gradient-echo snapshot imaging for efficient measurement of R2 -R1ρ in knee cartilage.

PURPOSE: To validate the potential of quantifying R2 -R1ρ using one pair of signals with T1ρ preparation and T2 preparation incorporated to magnetization-prepared angle-modulated partitioned k-space spoiled gradient-echo snapshots (MAPSS) acquisition and to find an optimal preparation time (Tprep ) for in vivo knee MRI. METHODS: Bloch equation simulations were first performed to assess the accuracy of quantifying R2 -R1ρ using T1ρ - and T2 -prepared signals with an equivalent Tprep . For validation of this technique in comparison to the conventional approach that calculates R2 -R1ρ after estimating both T2 and T1ρ , phantom experiments and in vivo validation with five healthy subjects and five osteoarthritis patients were performed at a clinical 3T scanner. RESULTS: Bloch equation simulations demonstrated that the accuracy of this efficient R2 -R1ρ quantification method and the optimal Tprep can be affected by image signal-to-noise ratio (SNR) and tissue relaxation times, but quantification can be closest to the reference with an around 25 ms Tprep for knee cartilage. Phantom experiments demonstrated that the proposed method can depict R2 -R1ρ changes with agarose gel concentration. With in vivo data, significant correlation was observed between cartilage R2 -R1ρ measured from the conventional and the proposed methods, and a Tprep of 25.6 ms provided the most agreement by Bland-Altman analysis. R2 -R1ρ was significantly lower in patients than in healthy subjects for most cartilage compartments. CONCLUSION: As a potential biomarker to indicate cartilage degeneration, R2 -R1ρ can be efficiently measured using one pair of T1ρ -prepared and T2 -prepared signals with an optimal Tprep considering cartilage relaxation times and image SNR.

T2 mapping for knee cartilage degeneration in young patients with mild symptoms.

BACKGROUND: We aimed to analyze the distribution of knee cartilage degeneration in young patients with mild symptoms using quantitative magnetic resonance imaging (MRI) T2 mapping. MATERIALS AND METHODS: This study included sixty six patients (case group) and twenty eight healthy volunteers (control group). The participants underwent 3.0 T conventional MRI plus a multi-echo sequence. The cartilage of each participant was divided into twenty eight subregions. We then calculated the T2 mean values and standard deviation or median and quartile range for each subregion according to whether the normal distribution was satisfied. Besides, we employed Kruskal-Wallis test to determine the statistical differences of each subregion in the control group while the Mann-Whitney U test was used to define the statistical difference between the case group and the control group and between the control group and subjects aged less than or equal to 35 years in the case group. RESULTS: In the case group, age of 30 male patients was 31.5 ± 9.3 and age of 36 female patients was 35.7 ± 8.3. In the two groups, the superficial central lateral femoral region exhibited relatively high T2 values (control/case group: 49.6 ± 2.7/55.9 ± 8.8), and the deep medial patellar region exhibited relatively low T2 values (control/case group: 34.2 ± 1.3/33.5(32.2, 35.5)). Comparison of the T2 values between the case and the control group demonstrated a statistically significant increase in nine subregions (P1 < 0.05) and there were five subregions in the case group with age ≤ 35 years (P2 < 0.05). In particular, the p-values for four subregions of the patellofemoral joint were all less than 0.05 (P1 = 0.002, 0.015, 0.036, 0.005). CONCLUSION: T2 values of patients were significantly different with values of healthy groups, especially in the superficial cartilage of the patellofemoral joint. It made T2 mapping helpful to early identify patients with knee cartilage degeneration.

Acute changes in knee cartilage and meniscus following long-distance running in habituate runners: a systematic review on studies using quantitative magnetic resonance imaging.

OBJECTIVE: Running is among the most popular recreational activities; nonetheless, the acute post-race changes of cartilage or meniscus have rarely been determined. The current study aimed to review the acute changes in knee cartilage and meniscus among habituate runners following long-distance running detected by using quantitative magnetic resonance imaging (MRI). MATERIALS AND METHODS: Systematic literature search was performed on those dominate clinical databases which including MEDLINE, Cochrane, Embase, ScienceDirect, and Web of Science. Included studies should be conducted on healthy marathon runners, and the participants should be examined before and after running by using MRI. Intervention studies were excluded. RESULTS: A total number of 14 studies were finally included in this review which all examined the cartilage or meniscus by using MRI functional sequences. Among them, six studies quantitatively measured the changes regarding volume of the knee cartilage or/and meniscus. Five studies found that the volume would decrease initially after running. Ten studies reported T2 (T2*) would decrease after running and returned to the baseline in a short term, while T1ρ may remain increased in months. Five studies measured subareas for T2 (T2*) value, and found that the superficial and medial subarea changed more vastly than other regions after running. CONCLUSION: Runners experience transient changes in the volume and signals of knee cartilage and meniscus after long-distance running. A liquid exchange and material interaction in cartilage and meniscus was observed after running. Superficial and medial areas of knee cartilage and meniscus might be more susceptible to mechanical loading.

An exploratory study to investigate the association between age, physical activity, femoral trochlear cartilage thickness and biomarkers of tissue metabolism in adult males.

PURPOSE: To investigate the association between age, physical activity, femoral trochlear cartilage thickness and biomarkers of tissue metabolism in a cross-sectional sample of adult males. This study utilizes several emerging biomarkers that have been associated with early joint degenerative changes; serum COMP (cartilage oligomeric matrix protein), HA (hyaluronan) and lubricin. METHODS: Eighty-one males (age: mean (range): 43(18-70) years; body mass index: 25.2 (21.0-30.6) kg/m2) volunteered. Resting serum COMP, HA and lubricin concentrations were determined via commercially available enzyme-linked immunosorbent assay (ELISA) and femoral trochlear cartilage thickness via supra-patellar ultrasound imaging. Physical activity levels were assessed using questionnaires. Statistical analyses were performed using correlation and regression analyses. RESULTS: Age was correlated with lateral trochlear cartilage thickness (r = - 0.372; p < 0.01) and serum COMP (r = 0.342; p < 0.01). 7-day physical activity was correlated with serum COMP (r = 0.357, p < 0.01), and 12-month physical activity with both lateral trochlear cartilage thickness (r = 0.340, p = 0.01) and serum HA (r = 0.296, p < 0.05). Regression analyses revealed that age significantly accounted for the variability in lateral cartilage thickness and serum COMP, following the adjustment for potential cofounders. However, the association between age and lateral trochlear cartilage thickness was not moderated by physical activity levels (all p > 0.05). CONCLUSION: This study indicates that older age may be associated with thinner lateral trochlear cartilage and higher cartilage turnover. Being physically active may also be positive for lateral trochlear cartilage thickness. However, overall, both age and physical activity level only account for a small amount of the variability in cartilage thickness and serum biomarkers.

Accuracy measures of 1.5-tesla MRI for the diagnosis of ACL, meniscus and articular knee cartilage damage and characteristics of false negative lesions: a level III prognostic study.

BACKGROUND: MRI is the most accurate imaging modality for diagnosing knee pathologies. However, there is uncertainty concerning factors predicting false negative MRI, such as meniscal tear patterns as well as patient factors. The aims of this study were to report 1.5-Tesla MRI accuracy of ACL, meniscus and articular cartilage damage and characterize false negative lesions. METHODS: Two hundred eighteen consecutive knee arthroscopies performed in our institution between 2013 and 2016 and their respective prospectively-collected MRI reports were reviewed. Inclusion criteria were age > 15 years-old, primary arthroscopy, 1.5-Tesla MRI performed at the same institution, and time interval MRI-surgery < 6 months. Exclusion criteria were revision arthroscopy and arthroscopic-assisted fracture fixation or multiligament surgery. Accuracy measures and Kappa coefficients were calculated comparing the MRI diagnosis to the arthroscopic findings. Moreover, the arthroscopic findings of false negative MRI were compared to the findings of true positive MRI using the Fisher-exact test. Pearson correlation was used for testing the correlation between MRI accuracy and patient age. RESULTS: The highest accuracy was observed in medial meniscus and in ACL findings. For the medial meniscus sensitivity, specificity, agreement, and Kappa coefficient were 77, 92, 86%, and 0.7, and for the ACL these measures were 82, 97, 87%, and 0.73. MRI accuracy was lower in the lateral meniscus and articular cartilage with Kappa coefficient 0.42 and 0.3, respectively. More specifically, short peripheral tears in the posterior horn of the medial meniscus were characteristic of false negative findings compared to true positive findings of the MRI (p <  0.01). MRI accuracy correlated negatively compared to arthroscopic findings with patient age for the medial meniscus (r = - 0.21, p = 0.002) and for articular cartilage damage (r = - 0.45, p <  0.001). CONCLUSION: 1.5-Tesla MRI will accurately diagnose ACL and medial meniscal tears and can reliably complete the diagnostic workup following physical examination, particularly in young adults. This modality however is not reliable for diagnosing short peripheral tears at the posterior horn of the medial meniscus and partial thickness articular cartilage lesion of the femoral condyles. For these lesions, definitive diagnosis may require cartilage-specific MRI sequences or direct arthroscopic evaluation. LEVEL OF EVIDENCE: Prognostic study, Level III.

Automated cartilage and meniscus segmentation of knee MRI with conditional generative adversarial networks.

PURPOSE: Fully automatic tissue segmentation is an essential step to translate quantitative MRI techniques to clinical setting. The goal of this study was to develop a novel approach based on the generative adversarial networks for fully automatic segmentation of knee cartilage and meniscus. THEORY AND METHODS: Defining proper loss function for semantic segmentation to enforce the learning of multiscale spatial constraints in an end-to-end training process is an open problem. In this work, we have used the conditional generative adversarial networks to improve segmentation performance of convolutional neural network, such as UNet alone by overcoming the problems caused by pixel-wise mapping based objective functions, and to capture cartilage features during the training of the network. Furthermore, the Dice coefficient and cross entropy losses were incorporated to the loss functions to improve the model performance. The model was trained and tested on 176, 3D DESS (double-echo steady-state) knee images from the Osteoarthritis Initiative data set. RESULTS: The proposed model provided excellent segmentation performance for cartilages with Dice coefficients ranging from 0.84 in patellar cartilage to 0.91 in lateral tibial cartilage, with an average Dice coefficient of 0.88. For meniscus segmentation, the model achieves 0.89 Dice coefficient for lateral meniscus and 0.87 Dice coefficient for medial meniscus. The results are superior to previously published automatic cartilage and meniscus segmentation methods based on deep learning models such as convolutional neural network. CONCLUSION: The proposed UNet-conditional generative adversarial networks based model demonstrated a fully automated segmentation method with high accuracy for knee cartilage and meniscus.

Cartilage damage at the time of anterior cruciate ligament reconstruction is associated with weaker quadriceps function and lower risk of future ACL injury.

PURPOSE: To determine whether articular cartilage damage noted at the time of primary anterior cruciate ligament reconstruction (ACLR) affects the likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery or risk of recurrent ACL injury. METHODS: Five hundred and eight patients underwent primary ACLR and diagnostic arthroscopy. All identified cartilage lesions were graded using the Outerbridge system. All patients underwent isokinetic strength testing. The association between cartilage Outerbridge grade and a ≥ 90% Limb Symmetry Index (LSI) and recurrent ACL injury risk at mean 38.7 month follow-up (SD 31.8) was evaluated via multivariate regression analysis. RESULTS: Grade 2 or higher damage was present in 394 (77.5%) of patients, grade 3 or higher in 143 (28.1%) and grade 4 in 83 (16.4%) at time of ACLR. Ipsilateral ACLR graft rupture occurred in 31 (6.1%) of patients. Contralateral ACL injury occurred in 19 (3.7%). Patients with grade 2 or higher damage were significantly less likely to meet an LSI goal of ≥ 90% for fast (300°/s) isokinetic extension. There was no association with slow isokinetic extension. Cartilage lesion severity at or beyond grade 2 had a similar effect on isokinetic testing results regardless of compartment involvement or performance of microfracture. Patients with grade 2-4 cartilage damage were less likely to sustain a second ipsilateral ACL injury or a contralateral native ACL injury. CONCLUSIONS: Cartilage damage seen at time of ACL reconstruction is common and associated with lower likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery. However, lower recurrent ACL injury rates are seen in patients with concurrent cartilage damage. These data may inform future clinical decisions regarding operative managment of recurrent ACL injuries. LEVEL OF EVIDENCE: III.

A unique anisotropic R2 of collagen degeneration (ARCADE) mapping as an efficient alternative to composite relaxation metric (R2 -R1ρ ) in human knee cartilage study.

PURPOSE: Anisotropic transverse R2 (1/T2 ) relaxation of water proton is sensitive to cartilage degenerative changes. The purpose is to develop an efficient method to extract this relaxation metric in clinical studies. METHODS: Anisotropic R2 can be measured inefficiently by standard R2 mapping after removing an isotropic contribution obtained from R1ρ mapping. In the proposed method, named as a unique anisotropic R2 of collagen degeneration (ARCADE) mapping, an assumed uniform isotropic R2 was estimated at magic angle locations in the deep cartilage, and an anisotropic R2 was thus isolated in a single T2W sagittal image. Five human knees from 4 volunteers were studied with standard R2 and R1ρ mappings at 3T, and anisotropic R2 derived from ARCADE on the T2W (TE = 48.8 ms) image from R2 mapping was compared with the composite relaxation (R2 - R1ρ ) using statistical analysis including Student's t-test and Pearson's correlation coefficient. RESULTS: Anisotropic R2 (1/s) from ARCADE was highly positively correlated with but not significantly different from standard R2 - R1ρ (1/s) in the segmented deep (r = 0.83 ± 0.06; 8.3 ± 2.9 vs. 7.3 ± 1.9, P = .50) and the superficial (r = 0.82 ± 0.05; 3.5 ± 2.4 vs. 4.5 ± 1.6, P = .39) zones. However, after eliminating systematic errors by the normalization in terms of zonal contrast, anisotropic R2 was significantly higher (60.2 ± 18.5% vs. 38.4 ± 16.6%, P < .01) than R2 - R1ρ as predicted. CONCLUSION: The proposed anisotropic R2 mapping could be an efficient alternative to the conventional approach, holding great promise in providing both high-resolution morphological and more sensitive transverse relaxation imaging from a single T2W scan in a clinical setting.

Patterns of cartilage degeneration in knees with medial tibiofemoral offset.

OBJECTIVE: To determine if radiographic medial tibiofemoral offset (MTFO) is associated with: (1) magnetic resonance imaging (MRI) pathology of cartilage, meniscus, and ligament; and (2) a distinct pattern of lateral cartilage degeneration on MRI. MATERIALS AND METHODS: Three hundred consecutive adult knee MRIs with anteroposterior (AP) radiographs were retrospectively reviewed, and 145 studies were included. MTFO was defined as a medial extension of the medial femoral condyle beyond the articular surface of the medial tibial plateau on weight-bearing AP radiographs. The patients were then divided into the MTFO (n = 61) or no-offset (n = 84) groups. On MRI data obtained on a 1.5-Tesla system, articular cartilage of the femoral condyle and tibial plateau were graded using a modified Outerbridge classification (36 sub-regions similar to whole-organ MRI Score (WORMS) system). In addition, MR pathology of the ACL, MCL, LCL, medial and lateral menisci, were determined. RESULTS: Significantly increased (ANOVA p < 0.007) MR grade of the ligaments, menisci, and cartilage in the MTFO group (ranging from 0.3 to 2.5) compared to the control group (0.2 to 1.1). Color maps of the cartilage grades suggested a marked difference in both severity of degeneration and regional variations between the groups. MTFO group exhibited focally increased cartilage grades in the central, non-weight regions of lateral compartment (region p = 0.07 to 0.12, interaction p = 0.05 to 0.1). CONCLUSIONS: MTFO is associated with overall degeneration of the knee and features a distinct lateral cartilage degeneration pattern, which may reflect non-physiologic contact of the cartilage between the lateral tibial eminence and lateral central femoral condyle.

Medial compartment defects progress at a more rapid rate than lateral cartilage defects in older adults with minimal to moderate knee osteoarthritis (OA): data from the OA initiative.

PURPOSE: To determine: (1) rates and risk factors for progression of lateral and medial full-thickness cartilage defect size in older adults without severe knee osteoarthritis (OA), and (2) whether risk factors for defect progression differ for knees with Kellgren-Lawrence OA grade 3 (moderate) OA versus grades 0-2 (none to mild) OA. METHODS: Three-hundred and eighty adults enrolled in the Osteoarthritis Initiative were included (43% male, mean age 63.0 SD 9.2 years). Ethical approval was obtained at all study sites prior to enrollment. All participants had full-thickness tibial or weight-bearing femoral condylar cartilage defects on baseline knee MRIs. Baseline OA grade was KL grade 3 in 71.3% and grades 0-2 in 21.7% of participants. Repeat MRIs were obtained at a minimum 2-year follow-up. Independent risk of progression in defect size due to demographic factors, knee alignment, OA grade, knee injury and surgery history, and baseline knee symptoms was determined by multivariate Cox proportional hazards and linear regression modeling. RESULTS: The average increase in defect size over 2 years for lateral defects was 0.18 cm2 (SD 0.60) and for medial defects was 0.49 cm2 (SD 1.09). Independent predictors of medical defect size progression were bipolar defects (beta 0.47 SE 0.08; p < 0.001), knee varus (per degree, beta 0.08 SE 0.03; p = 0.02) and increased weight (per kg, beta = 0.01 SE 0.004; p = 0.01). Independent predictors for lateral defect progression were larger baseline defect size (per 1.0 cm2, beta 0.14 SE 0.03; p < 0.001) and tibial sided defects (beta 0.12 SE 0.04) and degrees valgus (per degree, beta 0.04 SE 0.01; p = 0.001). CONCLUSIONS: Medial compartment full-thickness defects progress at a more rapid rate than lateral defects in older adults with minimal to moderate OA. Medial defect progression was greatest for bipolar defects in heavier adults with varus knees. Lateral defect progression was greatest for large tibial-sided defects in adults with valgus knees. LEVEL OF EVIDENCE: II.

Variation in the Thickness of Knee Cartilage. The Use of a Novel Machine Learning Algorithm for Cartilage Segmentation of Magnetic Resonance Images.

BACKGROUND: The variation in articular cartilage thickness (ACT) in healthy knees is difficult to quantify and therefore poorly documented. Our aims are to (1) define how machine learning (ML) algorithms can automate the segmentation and measurement of ACT on magnetic resonance imaging (MRI) (2) use ML to provide reference data on ACT in healthy knees, and (3) identify whether demographic variables impact these results. METHODS: Patients recruited into the Osteoarthritis Initiative with a radiographic Kellgren-Lawrence grade of 0 or 1 with 3D double-echo steady-state MRIs were included and their gender, age, and body mass index were collected. Using a validated ML algorithm, 2 orthogonal points on each femoral condyle were identified (distal and posterior) and ACT was measured on each MRI. Site-specific ACT was compared using paired t-tests, and multivariate regression was used to investigate the risk-adjusted effect of each demographic variable on ACT. RESULTS: A total of 3910 MRI were included. The average femoral ACT was 2.34 mm (standard deviation, 0.71; 95% confidence interval, 0.95-3.73). In multivariate analysis, distal-medial (-0.17 mm) and distal-lateral cartilage (-0.32 mm) were found to be thinner than posterior-lateral cartilage, while posterior-medial cartilage was found to be thicker (0.21 mm). In addition, female sex was found to negatively impact cartilage thickness (OR, -0.36; all values: P < .001). CONCLUSION: ML was effectively used to automate the segmentation and measurement of cartilage thickness on a large number of MRIs of healthy knees to provide normative data on the variation in ACT in this population. We further report patient variables that can influence ACT. Further validation will determine whether this technique represents a powerful new tool for tracking the impact of medical intervention on the progression of articular cartilage degeneration.

A robust diffusion tensor model for clinical applications of MRI to cartilage.

PURPOSE: Diffusion tensor imaging (DTI) of articular cartilage is a promising technique for the early diagnosis of osteoarthritis (OA). However, in vivo diffusion tensor (DT) measurements suffer from low signal-to-noise ratio (SNR) that can result in bias when estimating the six parameters of the full DT, thus reducing sensitivity. This study seeks to validate a simplified four-parameter DT model (zeppelin) for obtaining more robust and sensitive in vivo DTI biomarkers of cartilage. METHODS: We use simulations in a substrate to mimic changes during OA; and analytic simulations of the DT drawn from a range of fractional anisotropies (FA) measured with high-quality DT data from ex vivo human cartilage. We also use in vivo data from the knees of a healthy subject and two OA patients with Kellgren-Lawrence (KL) grades 1 and 2. RESULTS: For simulated in vivo cartilage SNR (∼25) and anisotropy levels, the estimated mean values of MD from the DT and zeppelin models were identical to the ground truth values. However, zeppelin's FA is more accurate in measuring water restriction. More specifically, the FA estimations of the DT model were additionally biased by between +2% and +48% with respect to zeppelin values. Additionally, both mean diffusivity (MD) and FA of the zeppelin had lower parameter variance compared to the full DT (F-test, P < 0.05). We observe the same trends from in vivo values of patient data. CONCLUSION: The zeppelin is more robust than the full DT for cartilage diffusion anisotropy and SNR at levels typically encountered in clinical applications of articular cartilage. Magn Reson Med 79:1157-1164, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Rapid compositional mapping of knee cartilage with compressed sensing MRI.

More than a decade after the introduction of compressed sensing (CS) in MRI, researchers are still working on ways to translate it into different research and clinical applications. The greatest advantage of CS in MRI is the reduced amount of k-space data needed to reconstruct images, which can be exploited to reduce scan time or to improve spatial resolution and volumetric coverage. Efficient data acquisition using CS is extremely important for compositional mapping of the musculoskeletal system in general and knee cartilage mapping techniques in particular. High-resolution quantitative information about tissue biochemical composition could be obtained in just a few minutes using CS MRI. However, in order to make this goal a reality, some issues still need to be addressed. In this article we review the current state of the art of CS methods for rapid compositional mapping of knee cartilage. Specifically, data acquisition strategies, image reconstruction algorithms, and data fitting models are discussed. Different CS studies for T2 and T1ρ mapping of knee cartilage are reviewed, with illustrative results. Future directions, opportunities, and challenges of rapid compositional mapping techniques are also discussed. Level of Evidence: 4 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2018;47:1185-1198.