Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations.

OBJECTIVE: Cationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography of cartilage, offer quantitative evaluation of proteoglycan (PG) content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on nanoparticle diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (PG content, collagen content and network architecture). METHODS: Osteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with micro computed tomography (µCT) imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using stress-relaxation and sinusoidal loading protocols, whereas PG content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. RESULTS: The Pmax correlates with the depth-wise distribution of PGs (bulk Spearman's ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. CONCLUSION: This study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT.

Reproducibility of T1ρ and T2 quantification in a multi-vendor multi-site study.

OBJECTIVE: To evaluate the multi-vendor multi-site reproducibility of two-dimensional (2D) multi-echo spin-echo (MESE) T2 mapping (product sequences); and to evaluate the longitudinal reproducibility of three-dimensional (3D) magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) T1ρ and T2 mapping (research sequences), and 2D MESE T2 mapping, separated by 6 months, in a multi-vendor multi-site setting. METHODS: Phantoms and volunteers (n = 5 from each site, n = 20 in total) were scanned on four 3 T magnetic resonance (MR) systems from four sites and three vendors (Siemens, General Electric, and Phillips). Two traveling volunteers (3 knees) scanned at all 4 sites at baseline and 6-month follow-up. Data was transferred to one site for centralized processing. Coefficients of variation (CVs) were calculated to evaluate reproducibility. RESULTS: For baseline 2D MESE T2 measures, average CV were 0.37-2.45% (intra-site) and 5.96% (inter-site) for phantoms, and 3.15-8.49% (intra-site) and 14.16% (inter-site) for volunteers. For longitudinal phantom data, intra-site CVs were 1.42-3.48% for 3D MAPSS T1ρ, 1.77-3.56% for 3D MAPSS T2, and 1.02-2.54% for 2D MESE T2. For the longitudinal volunteer data, the intra-site CVs were 2.60-4.86% for 3D MAPSS T1ρ, 3.33-7.25% for 3D MAPSS T2, and 3.11-8.77% for 2D MESE T2. CONCLUSION: This study demonstrated excellent intra-site reproducibility of 2D MESE T2 imaging, while its inter-site variation was slightly higher than 3D MAPSS T2 imaging (10.06% as previously reported). This study also showed excellent reproducibility of longitudinal T1ρ and T2 cartilage quantification, in a multi-vendor multi-site setting for both product 2D MESE T2 and 3D MAPSS T1p/T2 research sequences.

Machine learning to predict incident radiographic knee osteoarthritis over 8 Years using combined MR imaging features, demographics, and clinical factors: data from the Osteoarthritis Initiative.

OBJECTIVE: To develop a machine learning-based prediction model for incident radiographic osteoarthritis (OA) of the knee over 8 years using MRI-based cartilage biochemical composition and knee joint structure, demographics, and clinical predictors including muscle strength and symptoms. DESIGN: Individuals (n = 1,044) with baseline Kellgren Lawrence (KL) grade 0-1 in the right knee from the Osteoarthritis Initiative database were analyzed. 3T MRI at baseline was used to quantify knee cartilage T2, and Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone marrow. The outcome was set as true if a subject developed KL grade 2-4 OA in the right knee over 8 years (n = 183) and false if the subject remained at KL 0-1 over 8 years (n = 861). We developed and compared three models: Model 1: 112 predictors based on OA risk factors; Model 2: top ten predictors based on feature importance score from Model 1 and clinical relevance; Model 3: Model 2 without the imaging predictors. We compared the models using the area under the ROC curve derived from hold-out data. RESULTS: The 10-predictor model (Model 2, that includes cartilage and meniscus WORMS scores and cartilage T2) had a slightly lower AUC (0.772) compared to the model with 112 predictors (Model 1: AUC = 0.792, p = 0.739); and had a significantly higher AUC compared to the model without MR imaging predictors (Model 3, AUC = 0.669, p = 0.011). CONCLUSIONS: A 10-predictor model including MRI parameters coupled with demographics, symptoms, muscle, and physical activity scores provides good prediction of incident radiographic OA over 8 years.

Anterior cruciate ligament abnormalities are associated with accelerated progression of knee joint degeneration in knees with and without structural knee joint abnormalities: 96-month data from the Osteoarthritis Initiative.

OBJECTIVE: To compare progression over 8 years in knee compositional cartilage degeneration and structural joint abnormalities in knees with different types of anterior cruciate ligament (ACL) abnormalities over 8 years. METHOD: Baseline MR images of the right knees of 1899 individuals of the Osteoarthritis Initiative (OAI) with no evidence of or mild to moderate radiographic osteoarthritis were assessed for nontraumatic ACL abnormalities. The knees of 91 individuals showed nontraumatic ACL abnormalities (age 60.6 ± 9.8 y, 46 females; mucoid degeneration (MD), N = 37; complete tear (CT), N = 22; partial tear (PT), N = 32) and were frequency-matched to 91 individuals with normal ACL. MRIs were assessed for knee joint abnormalities using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and cartilage T2 mapping at baseline, 4- and 8-year follow-up. RESULTS: Over 8 years, cartilage T2 values of the medial tibia showed a significantly greater increase in individuals with MD, PT or CT compared to those with normal ACL (adjusted rate of change/year [95% confidence interval], normal ACL: 0.06 [0.01, 0.23], MD: 0.34 [0.07, 0.73], PT, 0.21 [0.02, 0.33], CT, 0.51 [0.16, 0.78]), indicating an association of ACL abnormalities and an increased progression rate of cartilage degeneration in subjects with and without knee joint degeneration. This effect was also seen in cartilage T2 values averaged over all compartments (normal ACL: 0.08 [0.05, 0.20] vs abnormal ACL: 0.27 [0.06, 0.56]). CONCLUSIONS: Over 8 years, higher progression rates of cartilage degeneration, especially in the medial tibia, were associated with ACL abnormalities compared to those with normal ACL, in subjects with and without knee joint abnormalities.

Multi-vendor multi-site T1ρ and T2 quantification of knee cartilage.

OBJECTIVE: To develop 3D T1ρ and T2 imaging based on the same sequence structure on MR systems from multiple vendors, and to evaluate intra-site repeatability and inter-site inter-vendor reproducibility of T1ρ and T2 measurements of knee cartilage. METHODS: 3D magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (3D MAPSS) were implemented on MR systems from Siemens, GE and Philips. Phantom and human subject data were collected at four sites using 3T MR systems from the three vendors with harmonized protocols. Phantom data were collected by means of different positioning of the coil. Volunteers were scanned and rescanned after repositioning. Two traveling volunteers were scanned at all sites. Data were transferred to one site for centralized processing. RESULTS: Intra-site average coefficient of variations (CVs) ranged from 1.09% to 3.05% for T1ρ and 1.78-3.30% for T2 in phantoms, and 1.60-3.93% for T1ρ and 1.44-4.08% for T2 in volunteers. Inter-site average CVs were 5.23% and 6.45% for MAPSS T1ρ and T2, respectively in phantoms, and 8.14% and 10.06% for MAPSS T1ρ and T2, respectively, In volunteers. CONCLUSION: This study showed promising results of multi-site, multi-vendor reproducibility of T1ρ and T2 values in knee cartilage. These quantitative measures may be applied in large-scale multi-site, multi-vendor trials with controlled sequence structure and scan parameters and centralized data processing.

Contrast-enhanced micro-computed tomography of articular cartilage morphology with ioversol and iomeprol.

Non-ionic, low-osmolar contrast agents (CAs) used for computed tomography, such as Optiray (ioversol) and Iomeron (iomeprol), are associated with the reduced risk of adverse reactions and toxicity in comparison with ionic CAs, such as Hexabrix. Hexabrix has previously been used for imaging articular cartilage but has been commercially discontinued. This study aimed to evaluate the efficacy of Optiray and Iomeron as alternatives for visualisation of articular cartilage in small animal joints using contrast-enhanced micro-computed tomography (CECT). For this purpose, mouse femora were immersed in different concentrations (20%-50%) of Optiray 350 or Iomeron 350 for periods of time starting at five minutes. The femoral condyles were scanned ex vivo using CECT, and regions of articular cartilage manually contoured to calculate mean attenuation at each time point and concentration. For both CAs, a 30% CA concentration produced a mean cartilage attenuation optimally distinct from both bone and background signal, whilst 5-min immersion times were sufficient for equilibration of CA absorption. Additionally, plugs of bovine articular cartilage were digested by chondroitinase ABC to produce a spectrum of glycosaminoglycan (GAG) content. These samples were immersed in CA and assessed for any correlation between mean attenuation and GAG content. No significant correlation was found between attenuation and cartilage GAG content for either CAs. In conclusion, Optiray and Iomeron enable high-resolution morphological assessment of articular cartilage in small animals using CECT; however, they are not indicative of GAG content.

Assessment of Articular Cartilage Disorders After Distal Radius Fracture Using Biochemical and Morphological Nonenhanced Magnetic Resonance Imaging.

PURPOSE: To assess radiocarpal articular cartilage after distal radius fracture, with and without intra-articular extension, compared with healthy controls using multiparametric, nonenhanced magnetic resonance imaging (MRI). METHODS: In this prospective study, multiparametric MRI of the radiocarpal articular cartilage was performed in 26 participants (16 males and 10 females; mean age, 39.5 ± 14.7 years; range, 20-70 years) using 3T MRI. The cohort consisted of 14 patients with a distal radius fracture and 12 healthy volunteers. The radiocarpal articular cartilage was assessed using morphological (Double Echo Steady-State [DESS] and True Fast Imaging With Steady-State Precession [TrueFISP]) and biochemical (T2∗) MRI sequences without an intravenous contrast agent. The modified Outerbridge classification system for morphological analyses and region-of-interest biochemical analysis were applied to assess the degree of articular cartilage damage in each patient. RESULTS: Morphological articular cartilage assessment showed no difference between the DESS sequence and the reference standard, TrueFISP. In the morphological (DESS and TrueFISP) and biochemical (T2∗) assessments, patients with intra-articular fractures did not show articular cartilage damage different from those with extra-articular fractures. Greater articular cartilage degradation was observed after distal radius fracture compared with controls. CONCLUSIONS: Posttraumatic radiocarpal articular cartilage damage did not differ between fractures with intra-articular and extra-articular extension, but patients with fractures had notably higher articular cartilage degradation compared with healthy controls. Magnetic resonance imaging using advanced multiparametric sequences may facilitate accurate, noninvasive assessment of articular cartilage changes after distal radius fracture without the need for a contrast agent. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Evaluation of equine articular cartilage degeneration after mechanical impact injury using cationic contrast-enhanced computed tomography.

OBJECTIVE: Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model. DESIGN: Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.). RESULTS: Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (Eeq) (r = 0.79, P < 0.0001) and safranin-O histological score (r = -0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = -0.44, P < 0.0001) of bone. Mean [95% CI] cationic CECT attenuation at the impact site (2215 [1987, 2443] Hounsfield Units [HUs]) was lower than site-matched controls (2836 [2490, 3182] HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), Eeq (r = 0.26, P = 0.025) and safranin-O histology score (r = -0.32, P = 0.0046). CONCLUSIONS: Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners.

Weight loss regimen in obese and overweight individuals is associated with reduced cartilage degeneration: 96-month data from the Osteoarthritis Initiative.

PURPOSE: To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL regimens are associated with these changes. METHODS: We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models. RESULTS: Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year [95% CI] between the groups: 0.24 [0.20, 0.41] ms/year; P < 0.001) and global deep layer cartilage T2 0.35 [0.20, 0.42] ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively). CONCLUSION: Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.

Type 2 diabetes patients have accelerated cartilage matrix degeneration compared to diabetes free controls: data from the Osteoarthritis Initiative.

PURPOSE: Osteoarthritis (OA) and diabetes mellitus (DM) share common risk factors with a potential underlying relationship between both diseases. The purpose of this study was to investigate the longitudinal effects of DM on cartilage deterioration over 24-months with MR-based T2 relaxation time measurements. METHODS: From the Osteoarthritis Initiative (OAI) cohort 196 diabetics were matched in small sets for age, sex, BMI and Kellgren-Lawrence score with 196 non-diabetic controls. Knee cartilage semi-automatic segmentation was performed on 2D multi-slice multi-echo spin-echo sequences. Texture of cartilage T2 maps was obtained via grey level co-occurrence matrix analysis. Linear regression analysis was used to compare cross-sectional and changes in T2 and texture parameters between the groups. RESULTS: Both study groups were similar in age (63.3 vs 63.0 years, P = 0.70), BMI (30.9 vs 31.2 kg/m2, P = 0.52), sex (female 53.6% vs 54.1%, P = 0.92) and KL score distribution (P = 0.97). In diabetics, except for the patella, all compartments showed a significantly higher increase in mean T2 values when compared to non-diabetic controls. Global T2 values increased almost twice as much; 1.77ms vs 0.98ms (0.79ms [CI: 0.39,1.19]) (P < 0.001). Additionally, global T2 values showed a significantly higher increase in the bone layer (P = 0.006), and in a separate analysis of the texture parameters, diabetics also showed consistently higher texture values (P < 0.05), indicating a more disordered cartilage composition. CONCLUSION: Cartilage T2 values in diabetics show a faster increase with a consistently more heterogeneous cartilage texture composition. DM seems to be a risk factor for developing early OA with an accelerated degeneration of the articular cartilage in the knee.

Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis.

OBJECTIVE: To assess reliability and discriminative validity of cartilage compositional magnetic resonance imaging (MRI) in knee osteoarthritis (OA). DESIGN: The study was carried out per PRISMA recommendations. We searched MEDLINE and EMBASE (1974 - present) for eligible studies. We performed qualitative synthesis of reliability data. Where data from at least two discrimination studies were available, we estimated pooled standardized mean difference (SMD) between subjects with and without OA. Discrimination analyses compared controls and subjects with mild OA (Kellgren-Lawrence (KL) grade 1-2), severe OA (KL grade 3-4) and OA not otherwise specified (NOS) where not possible to stratify. We assessed quality of the evidence using Quality Appraisal of Diagnostic Reliability (QAREL) and Quality Assessment of Diagnostic Accuracy (QUADAS-2) tools. RESULTS: Fifty-eight studies were included in the reliability analysis and 26 studies were included in the discrimination analysis, with data from a total of 2,007 knees. Intra-observer, inter-observer and test-retest reliability of compositional techniques were excellent with most intraclass correlation coefficients >0.8 and coefficients of variation <10%. T1rho and T2 relaxometry were significant discriminators between subjects with mild OA and controls, and between subjects with OA (NOS) and controls (P < 0.001). T1rho showed best discrimination for mild OA (SMD [95% CI] = 0.73 [0.40 to 1.06], P < 0.001) and OA (NOS) (0.60 [0.41 to 0.80], P < 0.001). Quality of evidence was moderate for both parts of the review. CONCLUSIONS: Cartilage compositional MRI techniques are reliable and, in the case of T1rho and T2 relaxometry, can discriminate between subjects with OA and controls.

Association of diabetes mellitus and biochemical knee cartilage composition assessed by T2 relaxation time measurements: Data from the osteoarthritis initiative.

PURPOSE: To investigate the association of the presence and severity of diabetes mellitus (DM) with articular cartilage composition, using magnetic resonance imaging (MRI)-based T2 relaxation time measurements, and structural knee abnormalities. MATERIALS AND METHODS: In the Osteoarthritis Initiative 208, participants with DM (age 63.0 ± 8.9 years; 111 females) and risk factors for osteoarthritis (OA) or mild radiographic tibiofemoral OA (Kellgren-Lawrence [KL] grade ≤2) were identified and group-matched with 208 controls without DM (age 63.3 ± 9.1 years; 111 females). Subjects with diabetes-related renal or ophthalmological complications or insulin treatment at baseline (n = 50) were defined as severe DM. 3T MR images of the right knee were assessed for articular cartilage T2 , including texture and laminar analyses derived from the patella, medial, and lateral femur and tibia and for structural abnormalities using the modified whole-organ magnetic resonance imaging score (WORMS). Clustered linear regression analyses were used to assess associations of DM with MRI findings. RESULTS: DM subjects had significantly higher cartilage T2 in the patella (mean difference 0.92 msec [95% confidence interval (CI) 0.79, 1.06]; P = 0.001) and medial femur (mean difference 0.36 msec [95% CI 0.27, 0.81]; P = 0.006) compared to controls. Averaged over all compartments, DM subjects showed significantly higher texture parameters (variance, P = 0.001; contrast, P = 0.002; entropy, P < 0.001). Subjects with severe DM additionally showed higher T2 in the medial tibial deep and superficial layers (P = 0.011 and P = 0.041) compared to controls. No significant differences in cartilage, meniscus, and overall WORMS were found between the groups (P > 0.05). CONCLUSION: In comparison to nondiabetic controls, cartilage in DM subjects showed higher and more heterogeneous cartilage T2 values, indicating increased articular cartilage degeneration. This affected even more compartments in subjects with severe DM. LEVEL OF EVIDENCE: 2 Technical Efficacy: 5 J. Magn. Reson. Imaging 2018;47:380-390.

Quantitative Assessment of Degenerative Cartilage and Subchondral Bony Lesions in a Preserved Cadaveric Knee: Propagation-Based Phase-Contrast CT Versus Conventional MRI and CT.

OBJECTIVE: The aim of this study was to quantitatively assess hyaline cartilage and subchondral bone conditions in a fully preserved cadaveric human knee joint using high-resolution x-ray propagation-based phase-contrast imaging (PBI) CT and to compare the performance of the new technique with conventional CT and MRI. MATERIALS AND METHODS: A cadaveric human knee was examined using an x-ray beam of 60 keV, a detector with a 90-mm2 FOV, and a pixel size of 46 × 46 µm2. PBI CT images were reconstructed with both the filtered back projection algorithm and the equally sloped tomography method. Conventional 3-T MRI and CT were also performed. Measurements of cartilage thickness, cartilage lesions, International Cartilage Repair Society scoring, and detection of subchondral bone changes were evaluated. Visual inspection of the specimen akin to arthroscopy was conducted and served as a standard of reference for lesion detection. RESULTS: Loss of cartilage height was visible on PBI CT and MRI. Quantification of cartilage thickness showed a strong correlation between the two modalities. Cartilage lesions appeared darker than the adjacent cartilage on PBI CT. PBI CT showed similar agreement to MRI for depicting cartilage substance defects or lesions compared with the visual inspection. The assessment of subchondral bone cysts showed moderate to strong agreement between PBI CT and CT. CONCLUSION: In contrast to the standard clinical methods of MRI and CT, PBI CT is able to simultaneously depict cartilage and bony changes at high resolution. Though still an experimental technique, PBI CT is a promising high-resolution imaging method to evaluate comprehensive changes of osteoarthritic disease in a clinical setting.

Conservatively treated knee injury is associated with knee cartilage matrix degeneration measured with MRI-based T2 relaxation times: data from the osteoarthritis initiative.

OBJECTIVE: To investigate the association of cartilage degeneration with previous knee injuries not undergoing surgery, determined by morphologic and quantitative 3-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: We performed a nested cross-sectional study of right knee MRIs from participants in the Osteoarthritis Initiative (OAI) aged 45-79 with baseline Kellgren-Lawrence score of 0-2. Cases were 142 right knees of patients with self-reported history of injury limiting the ability to walk for at least 2 days. Controls were 426 right knees without history of injury, frequency-matched to cases on age, BMI, gender, KL scores and race (1:3 ratio). Cases and controls were compared using covariate-adjusted linear regression analysis, with the outcomes of region-specific T2 mean, laminar analysis and heterogeneity measured by texture analysis to investigate early cartilage matrix abnormalities and the Whole-Organ Magnetic Resonance Imaging Score (WORMS) to investigate morphologic knee lesions. RESULTS: Compared to control subjects, we found significantly higher mean T2 values in the injury [lateral tibia (28.10 ms vs. 29.11 ms, p = 0.001), medial tibia (29.70 ms vs. 30.40 ms, p = 0.014) and global knee cartilage (32.73 ms vs. 33.29 ms, p = 0.005)]. Injury subjects also had more heterogeneous cartilage as measured by GLCM texture contrast, variance and entropy (p < 0.05 in 14 out of 18 texture parameters). WORMS gradings were not significantly different between the two groups (p > 0.05). CONCLUSION: A history of knee injury not treated surgically is associated with higher and more heterogeneous T2 values, but not with morphologic knee abnormalities. Our findings suggest that significant, conservatively treated knee injuries are associated with permanent cartilage matrix abnormalities.

Sliding enhances fluid and solute transport into buried articular cartilage contacts.

OBJECTIVE: Solutes and interstitial water are naturally transported from cartilage by load-induced interstitial fluid pressures. Fluid and solute recovery during joint articulation have been primarily attributed to passive diffusion and mechanical 'pumping' from dynamic loading. This paper tests if the sliding action of articulation is a significant and independent driver of fluid and solute transport in cartilage. DESIGN: The large osteochondral samples utilized in the present study preserve the convergent wedges necessary for physiological hydrodynamics. Following static load-induced fluid exudation and prior to sliding, a fluorescent solute (AlexaFluor 633) was added to the lubricant bath. In situ confocal microscopy was used to quantify the transport of solute from the bath into the buried stationary contact area (SCA) during sliding. RESULTS: Following static exudation, significant reductions in friction and strain during sliding at 60 mm/s were accompanied by significant solute transport into the inaccessible center of the buried contact; no such transport was detected for the 0- or 1 mm/s sliding conditions. The results suggest that external hydrodynamic pressures from sliding induced advective flows that carried solutes from the bath toward the center of contact. CONCLUSIONS: These results provide the first direct evidence that the action of sliding is a significant contributor to fluid and solute recovery by cartilage. Furthermore, they indicate that the sliding-induced transport of solutes into the buried interface was orders of magnitude greater than that attributable to diffusion alone, a result with critical implications for disease prevention and tissue engineering.

Evaluation of Chondrocalcinosis and Associated Knee Joint Degeneration Using MR Imaging: Data from the Osteoarthritis Initiative.

OBJECTIVES: To evaluate the ability of different MRI sequences to detect chondrocalcinosis within knee cartilage and menisci, and to analyze the association with joint degeneration. METHODS: Subjects with radiographic knee chondrocalcinosis (n = 90, age 67.7 ± 7.3 years, 50 women) were selected from the Osteoarthritis Initiative and matched to controls without radiographic chondrocalcinosis (n = 90). Visualization of calcium-containing crystals (CaC) was compared between 3D T1-weighted gradient-echo (T1GE), 3D dual echo steady-state (DESS), 2D intermediate-weighted (IW), and proton density (PD)-weighted fast spin-echo (FSE) sequences obtained with 3T MRI and correlated with a semiquantitative CaC score obtained from radiographs. Structural abnormalities were assessed using Whole-Organ MRI Score (WORMS) and logistic regression models were used to compare cartilage compartments with and without CaC. RESULTS: Correlations between CaC counts of MRI sequences and degree of radiographic calcifications were highest for GE (rT1GE = 0.73, P < 0.001; rDESS = 0.68, P < 0.001) compared to other sequences (P > 0.05). Meniscus WORMS was significantly higher in subjects with chondrocalcinosis compared to controls (P = 0.005). Cartilage defects were significantly more frequent in compartments with CaC than without (patella: P = 0.006; lateral tibia: P < 0.001; lateral femur condyle: P = 0.017). CONCLUSIONS: Gradient-echo sequences were most useful for the detection of chondrocalcinosis and presence of CaC was associated with higher prevalence of cartilage and meniscal damage. KEY POINTS: • Magnetic resonance imaging is useful for assessing burden of calcium-containing crystals (CaC). • Gradient-echo sequences are superior to fast spin echo sequences for CaC imaging. • Presence of CaC is associated with meniscus and cartilage degradation.

Rapid multicomponent relaxometry in steady state with correction of magnetization transfer effects.

PURPOSE: To study the effects of magnetization transfer (MT) on multicomponent T2 parameters obtained using mcDESPOT in macromolecule-rich tissues and to propose a new method called mcRISE to correct MT-induced biases. METHODS: The two-pool mcDESPOT model was modified by the addition of an exchanging macromolecule proton pool to model the MT effect in cartilage. The mcRISE acquisition scheme was developed to provide sensitivity to all pools. An incremental fitting was applied to estimate MT and relaxometry parameters with minimized coupling. The interaction between MT and relaxometry parameters, efficacy of MT correction, and feasibility of mcRISE in vivo were investigated in simulations and in healthy volunteers. RESULTS: The MT effect caused significant errors in multicomponent T1/T2 values and in fast-relaxing water fraction fF , which is consistent with previous experimental observations. fF increased significantly with macromolecule content if MT was ignored. mcRISE resulted in a multifold reduction of MT biases and yielded decoupled multicomponent T1/T2 relaxometry and quantitative MT parameters. CONCLUSION: mcRISE is an efficient approach for correcting MT biases in multicomponent relaxometry based on steady state sequences. Improved specificity of mcRISE may help to elucidate the sources of the previously described high sensitivity of noncorrected mcDESPOT parameters to disease-related changes in cartilage and the brain.

Accelerating T1ρ cartilage imaging using compressed sensing with iterative locally adapted support detection and JSENSE.

PURPOSE: To accelerate T1ρ quantification in cartilage imaging using combined compressed sensing with iterative locally adaptive support detection and JSENSE. METHODS: To reconstruct T1ρ images from accelerated acquisition at different time of spin-lock (TSLs), we propose an approach to combine an advanced compressed sensing (CS) based reconstruction technique, LAISD (locally adaptive iterative support detection), and an advanced parallel imaging technique, JSENSE. Specifically, the reconstruction process alternates iteratively among local support detection in the domain of principal component analysis, compressed sensing reconstruction of the image sequence, and sensitivity estimation with JSENSE. T1ρ quantification results from accelerated scans using the proposed method are evaluated using in vivo knee cartilage data from bilateral scans of three healthy volunteers. RESULTS: T1ρ maps obtained from accelerated scans (acceleration factors of 3 and 3.5) using the proposed method showed results comparable to conventional full scans. The T1ρ errors in all compartments are below 1%, which is well below the in vivo reproducibility of cartilage T1ρ reported from previous studies. CONCLUSION: The proposed method can significantly accelerate the acquisition process of T1ρ quantification on human cartilage imaging without sacrificing accuracy, which will greatly facilitate the clinical translation of quantitative cartilage MRI.

Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate compositional cartilage changes measured with 3T MRI-based T2 values over 48 months in overweight and obese individuals with different degrees of weight loss (WL) and to study whether WL slows knee cartilage degeneration and symptom worsening. DESIGN: We studied participants from the Osteoarthritis Initiative with risk factors or radiographic evidence of mild to moderate knee osteoarthritis with a baseline BMI ≥25 kg/m(2). We selected subjects who over 48 months lost a, moderate (BMI change, 5-10%WL, n = 180) or large amount of weight (≥10%WL, n = 78) and frequency-matched these to individuals with stable weight (<3%, n = 258). Right knee cartilage T2 maps of all compartments and grey-level co-occurrence matrix (GLCM) texture analyses were evaluated and associations with WL and clinical symptoms (WOMAC subscales for pain, stiffness and disability) were assessed using multivariable regression models. RESULTS: The amount of weight change was significantly associated with change in cartilage T2 of the medial tibia (ß 0.9 ms, 95% CI 0.4 to 1.1, P = 0.001). Increase of T2 in the medial tibia was significantly associated with increase in WOMAC pain (ß 0.5 ms, 95% CI 0.2 to 0.6, P = 0.02) and disability (ß 0.03 ms, 95% CI 0.003 to 0.05, P = 0.03). GLCM contrast and variance over all compartments showed significantly less progression in the >10%WL group compared to the stable weight group (both comparisons, P = 0.04). CONCLUSIONS: WL over 48 months is associated with slowed knee cartilage degeneration and improved knee symptoms.

Accuracy of 3D dual echo steady state (DESS) MR arthrography to quantify acetabular cartilage thickness.

PURPOSE: To deploy and quantify the accuracy of 3D dual echo steady state (DESS) MR arthrography with hip traction to image acetabular cartilage. Clinical magnetic resonance imaging (MRI) sequences used to image hip cartilage often have reduced out-of-plane resolution and may lack adequate signal-to-noise to image cartilage. MATERIALS AND METHODS: Saline was injected into four cadaver hips placed under traction. 3D DESS MRI scans were obtained before and after cores of cartilage were harvested from the acetabulum; the two MRIs were spatially aligned to reference core positions. The thickness of cartilage cores was measured under microscopy to serve as the reference standard. 3D reconstructions of cartilage and subchondral bone were generated using automatic and semiautomatic image segmentation. Cartilage thickness estimated from the 3D reconstructions was compared to physical measurements using Bland-Altman plots. RESULTS: As revealed by the automatic segmentation mask, saline imbibed the joint space throughout the articulating surface, with the exception of the posteroinferior region in two hips. Locations where air bubbles were introduced and regions of suspected low density bone disrupted an otherwise smooth automatic segmentation mask. Automatic and semiautomatic segmentation yielded a bias ± repeatability coefficient (95% limits of agreement) of 0.10 ± 0.51 mm (-0.41 to 0.61 mm) and 0.06 ± 0.43 mm (-0.37 to 0.49 mm), respectively. CONCLUSION: Cartilage thickness can be estimated to within ∼0.5 mm of the physical value with 95% confidence using 3D reconstructions of 3D DESS MR arthrography images. Manual correction of the automatic segmentation mask may improve reconstruction accuracy.