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Morphological and Quantitative Parametric MRI Follow-up of Cartilage Changes Before and After Intra-articular Injection Therapy in Patients With Mild to Moderate Knee Osteoarthritis: A Randomized, Placebo-Controlled Trial
Abstract
Background
Intra-articular injections are routinely used for conservative treatment of knee osteoarthritis (OA). The detailed comparative therapeutic effects of these injections on cartilage tissue are still unclear.
Objective
The aim of this study was to detect and compare knee cartilage changes after intra-articular injection of glucocorticoid, hyaluronic acid, or platelet-rich plasma (PRP) to placebo using quantitative (T2 and T2* mapping) and morphological magnetic resonance imaging parameters in patients with mild or moderate osteoarthritis.
Materials and Methods
In a double-blinded, placebo-controlled, single-center trial, knees with mild or moderate osteoarthritis (Kellgren-Lawrence grade 1–3) were randomly assigned to an intra-articular injection with 1 of these substances: glucocorticoid, hyaluronic acid, PRP, or placebo. Cartilage degeneration on baseline and follow-up magnetic resonance imaging scans (after 3 and 12 months) was assessed by 2 readers using quantitative T2 and T2* times (milliseconds) and morphological parameters (modified Outerbridge grading, subchondral bone marrow edema, subchondral cysts, osteophytes).
Results
One hundred twenty knees (30 knees per treatment group) were analyzed with a median patient age of 60 years (interquartile range, 54.0–68.0 years). Interreader reliability was good for T2 (ICC, 0.76; IQR, 0.68–0.83) and T2* (ICC, 0.83; IQR, 0.76–0.88) measurements. Morphological parameters showed no significant changes between all groups after 3 and 12 months. T2 mapping after 12 months showed the following significant ( P = 0.001–0.03) changes between groups in 6 of 14 compartments: values after PRP injection decreased compared with glucocorticoid in 4 compartments (complete medial femoral condyle and central part of lateral condyle) and compared with placebo in 2 compartments (anterior and central part of medial tibial plateau); values after glucocorticoid injection decreased compared with placebo in 1 compartment (central part of medial tibial plateau). No significant changes were seen for T2 and T2* times after 3 months and T2* times after 12 months. No correlation was found between T2/T2* times and Kellgren-Lawrence grade, age, body mass index, or pain (Spearman ρ, −0.23 to 0.18).
Conclusions
Platelet-rich plasma injection has a positive long-term effect on cartilage quality in the medial femoral compartment compared to glucocorticoid, resulting in significantly improved T2 values after 12 months. For morphological cartilage parameters, injections with glucocorticoid, PRP, or hyaluronic acid showed no better effect in the short or long term compared with placebo.
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Background:
Intra-articular injections are widely used for conservative treatment of knee osteoarthritis (OA). However, rigorous data are lacking regarding the comparative therapeutic effectiveness of these injections.
Purpose:
The aim of this study was to compare clinical outcomes after intra-articular injections of glucocorticoid, hyaluronic acid, platelet-rich plasma (PRP), or placebo in patients with mild or moderate OA of the knee.
Materials and methods:
In a double-blinded, placebo-controlled, single-center trial, we randomly assigned knees with early- to middle-stage knee OA (Kellgren-Lawrence grade 1-3) to an intra-articular injection with one of these substances: glucocorticoid, hyaluronic acid, PRP, or placebo. Primary outcome was pain reduction within 6 months after the injection, assessed with the numeric rating scale (NRS; range, 0-100). Secondary outcome parameters included WOMAC scores, Tegner Activity Scale, knee mobility, and adverse events. Finally, a linear mixed-effects model was calculated and corrected for possible patient and covariate effects.
Results:
One hundred twenty knees (30 knees per treatment group) in 95 patients (41 female) were included in the final analysis. The median age of patients was 60 years (interquartile range, 54.0-68.0). There was no evidence that the drug effects of primary and secondary outcome parameters differed over time. The median pain at baseline was 32.5 (interquartile range, 15.00-50.00) on NRS. The changes in pain level during the first 6 months compared with baseline were small (within ±5 points on NRS), whereas the intrapatient variability was large between -20 and +20 points. Secondary outcome parameters did not differ significantly among the groups. Kellgren-Lawrence grade did not have a statistically significant effect on pain reduction (P = 0.61).
Conclusions:
There is no evidence that knee injections with glucocorticoid, PRP, or hyaluronic acid have superior short- or long-term effects in patients with low pain level at baseline and early- to middle-stage knee OA when compared with placebo.
Knee osteoarthritis is one of the leading causes of chronic disability worldwide and is a significant social and economic burden on healthcare systems; hence it has become essential to develop methods to identify patients at risk for developing knee osteoarthritis at an early stage. Standard morphological MRI sequences are focused mostly on alterations seen in advanced stages of osteoarthritis. However, they possess low sensitivity for early, subtle, and potentially reversible changes of the degenerative process. In this review, we have summarized the state of the art with regard to innovative quantitative MRI techniques that exploit objective and quantifiable biomarkers to identify subtle alterations that occur in early stages of osteoarthritis in knee cartilage before any morphological alteration occurs and to capture potential effects on the brain. These novel MRI imaging tools are believed to have great potential for improving the current standard of care, but further research is needed to address limitations before these compositional techniques can be robustly applied in research and clinical settings.
Background
The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.
Methods
MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.
Results
Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m ² . The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).
Conclusions
A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA.
Trial Registration
Clinicaltrials.gov identification: NCT03883568.
Objective
To assess the effect of PRP on knee articular cartilage content (thickness/volume) and examine the correlation between cartilage changes and clinical outcomes in patients with knee OA.
Method
A systematic literature search was performed using the Cochrane methodology in four online databases. Studies were included if they reported on cartilage content with cross-sectional imaging pre- and post-injection. A random-effects model meta-analysis was performed. Correlation with clinical outcomes was evaluated.
Results
14 studies (n = 1099 patients) from 1452 records met the inclusion criteria: seven RCTs (n = 688), one prospective (n = 50), one retrospective (n = 68), and four case-series (n = 224). The PRP preparation process and treatment protocol varied widely (follow-up 6–12 months). In meta-analysis, PRP treatment was not associated with a significant increase in cartilage thickness (4 studies, n = 187, standardized mean difference: Hedges g: 0.079; 95%CI: 0.358 - 0.516; p = 0.723). Meta-analysis of 3 RCTs (n = 112) showed no significant difference in the change of overall knee cartilage content with PRP injections compared with no PRP (Hedges’ g: 0.217; 95%CI: 0.177 – 0.611; P = 0.281).
Conclusion
The current literature does not support the PRP as chondrogenic in treatment of knee OA. However, there is substantial heterogeneity in the evaluated studies which limits the robustness of any conclusion. An adequately powered RCT, with a standardized PRP regime and standardized high-resolution MRI is needed to definitely define any effect of PRP on knee cartilage content and its relation to clinical outcomes. Until such high-quality evidence becomes available, we recommend that PRP is not administered with the intention of promoting chondrogenesis.
Purpose:
This study intends to establish a study protocol for the quantitative magnetic resonance imaging (qMRI) measurement of biochemical changes in knee cartilage induced by mechanical stress during alpine skiing with the implementation of new spring-loaded ski binding.
Methods:
The MRI-knee-scans (T2*-mapping) of four skiers using a conventional and a spring-loaded ski binding system, alternately, were acquired before and after 1 h/4 h of exposure to alpine skiing. Intrachondral T2* analysis on 60 defined regions of interest in the femorotibial knee joint (FTJ) was conducted. Intra- and interobserver variability and relative changes in the cartilage T2* signal and thickness were calculated.
Results:
A relevant decrease in the T2* time after 4 h of alpine skiing could be detected at the majority of measurement times. After overnight recovery, the T2* time increased above baseline. Although, the total T2* signal in the superficial cartilage layers was higher than that in the lower ones, no differences between the layers in the T2* changes could be detected. The central and posterior cartilage zones of the FTJ responded with a stronger T2* alteration than the anterior zones.
Conclusions:
For the first time, a quantitative MRI study setting could be established to detect early knee cartilage reaction due to alpine skiing. Relevant changes in the T2* time and thus in the intrachondral collagen microstructure and the free water content were observed.
This study evaluated the ability of T2 mapping magnetic resonance imaging at 3 T, in addition to morphological sequences, to assess efficacy of platelet-rich plasma (PRP) injections, characterizing qualitatively and quantitatively the grade of knee cartilage repair in patients with patellofemoral chondropathy. We retrospectively studied 34 patients (22 men, 12 women, mean age 41.8 years, including 22 men) with patellofemoral knee chondropathy, who underwent intra-articular PRP injections and completed a clinical and instrumental follow-up. As control group, we evaluated 34 patients who underwent non-operative therapy. All patients were submitted to clinical (using VAS and WOMAC index) and imaging studies with 3 T magnetic resonance with cartilage analysis with T2 mapping sequences for cartilage analysis before and after treatment. In the study group, mean pre-treatment T2 relaxation time values were 44.2 ± 2.5 ms, considering all articular cartilage compartments, with significant reduction at the follow-up ( p < 0.001). At the index compartment, mean pre-treatment T2 relaxation times values were 47.8 ± 3.6 ms, with statistically significant reduction at the follow-up ( p < 0.001). Evaluation of focal cartilage lesions reported pre-treatment mean T2 value of 70.1 ± 13.0 ms and post-treatment mean value of 59.9 ± 4.6 ms ( p < 0.001). From a clinical point of view, the pre-treatment WOMAC and VAS scores were 18.3 ± 4.5 and 7 (IQR:6–7.2), respectively; the post-treatment values were 7.3 ± 3.2 and 2 (IQR: 1.7–3.0), respectively ( p < 0.001). In the control group, despite clinical improvement, we didn’t find significant T2 values change during the follow-up period. In conclusion, T2 mapping is a valuable indicator for chondropathy and treatment-related changes over time.
Objective
The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP’s efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2* in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection.
Design
A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT+NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP.
Results
Compared to the sham-control group, the ACLT+NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (–0.030: –0.055, –0.005) from week 4; lower permeability kep from week 18 (–0.954: –1.339, –0.569); higher cartilage T2* values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2* decreased from week 10. Histological results confirmed and were correlated with the MRI findings.
Conclusion
Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2* values.
Background and purpose — Quantitative T2 mapping MRI of cartilage has proven value for the assessment of early osteoarthritis changes in research. We evaluated knee cartilage T2 relaxation times in a clinical population with knee complaints and its association with patients and disease characteristics and clinical symptoms.
Patients and methods — In this cross-sectional study, T2 mapping knee scans of 109 patients with knee pain who were referred for an MRI by an orthopedic surgeon were collected. T2 relaxation times were calculated in 6 femoral and tibial regions of interest of full-thickness tibiofemoral cartilage. Its associations with age, sex, BMI, duration of complaints, disease onset (acute/chronic), and clinical symptoms were assessed with multivariate regression analysis. Subgroups were created of patients with abnormalities expected to cause predominantly medial or lateral tibiofemoral cartilage changes.
Results — T2 relaxation times increased statistically significantly with higher age and BMI. In patients with expected medial cartilage damage, the medial femoral T2 values were significantly higher than the lateral; in patients with expected lateral cartilage damage the lateral tibial T2 values were significantly higher. A traumatic onset of knee complaints was associated with an acute elevation. No significant association was found with clinical symptoms.
Interpretation — Our study demonstrates age, BMI, and type of injury-dependent T2 relaxation times and emphasizes the importance of acknowledging these variations when performing T2 mapping in a clinical population.
Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called ‘stem’ cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks.
Objective:
To evaluate and characterize the appearance of articular cartilage in the tibiofemoral joint of young professional soccer players using T2-relaxation time evaluation on magnetic resonance imaging (MRI).
Design:
In this study, we included 57 male adolescents from the youth academy of a professional soccer team. The MRI scans were acquired of the knee joint of the supporting leg. An "early unloading" (minute 0) and "late unloading" (minute 28) T2-sequence was included in the set of images. Quantitative T2-analysis was performed in the femorotibial joint cartilage in 4 slices with each 10 regions of interest (ROIs). Statistical evaluation, using Wilcoxon signed-rank tests, was primarily performed to compare the T2 values of the "early unloading" and "late unloading."
Results:
When comparing "early unloading" with "late unloading," our findings showed a significant increase of T2-relaxation times in the weightbearing femoral cartilage of the medial (P < 0.001) and lateral (P < 0.001) compartment of the knee and in the tibial cartilage of the medial compartment (P < 0.001).
Conclusion:
In this study, alterations of the cartilage were found with a maximum in the medial condyle where the biomechanical load of the knee joint is highest, as well as where most of the chronic cartilage lesions occur. To avoid chronic damage, special focus should be laid on this region.
High tibial osteotomy (HTO) is a surgical procedure used to correct abnormal mechanical loading of the knee joint; additionally, intra-articular hyaluronic acid injections have been shown to restore the viscoelastic properties of synovial fluid and balance abnormal biochemical processes. It was hypothesized that combining HTO with intra-articular hyaluronic acid injections would have benefit to improve the cartilage volume of knee joints.
Forty patients with medial compartment knee osteoarthritis (OA) were randomly placed into 1 of 2 groups. The study group (n = 20) received 2 cycles (at 6-month intervals) of 5 weekly intra-articular hyaluronic acid injections after HTO operation. The control group (n = 20) did not receive any intra-articular injections after HTO surgery. Cartilage volume (primary outcome) was assessed by magnetic resonance imaging (MRI) pre-operatively and 1 year post-operatively. Treatment efficacy (secondary outcomes) was evaluated with the Western Ontario and McMaster Universities OA Index (WOMAC) and by the comparison of the total rescue medication (paracetamol/diclofenac) used (weeks 6, 12, 24, 48).
MRI studies showed a significant increase in total cartilage volume (p = 0.033), lateral femoral cartilage volume (p = 0.044) and lateral tibial cartilage volume (p = 0.027) in the study group. Cartilage volume loss was detected at the lateral tibial plateau in the control group. There were significant improvements after surgery in both groups for all subscales of WOMAC scores (p < 0.001) compared to the baseline. However, no difference was found between the two groups. The study group had significantly lower amounts of diclofenac consumption (p = 0.017).
Based on the findings of the present study, intra-articular hyaluronic acid injections may be beneficial for increasing total cartilage volume and preventing the loss of lateral tibiofemoral joint cartilage after HTO.
Therapeutic study, Level I.
The purpose of this study was to analyze the longitudinal association between physical activity levels and early degenerative cartilage changes in the knee, measured using T2 relaxation times over a period of 4 years in individuals without clinical or radiographic evidence of OA.
Cartilage T2 was measured at baseline and after 2 and 4 years in 205 subjects aged 45-60 years from the Osteoarthritis Initiative incidence and normal cohorts with no knee pain (WOMAC score of zero), and a Kellgren-Lawrence score of < 2 at baseline, Physical activity was scored using the Physical Activity Scale for the Elderly (PASE) questionnaire, which was obtained yearly over 4 years. The relationship between physical activity and T2 was studied using a mixed model linear regression, including random effects, and adjusted for age, sex, and BMI.
T2 values for all PASE tertiles progressed over the 4-year period. T2 progression was increased in the highest tertile of physical activity compared to the mid-tertile at the medial tibia (P=0.041), patella (P=0.019), and average T2 of all knee compartments combined (P=0.033). Subjects with the lowest 15% PASE scores showed significantly higher T2 progression compared to the mid-level physical activity group at the lateral femur (P=0.025), lateral tibia (P=0.043), medial femur (P=0.044), tibiofemoral compartment (P=0.017), patellofemoral compartment (P=0.016), lateral compartments (P=0.003), and average of all compartments (P=0.043).
High and very low PASE scores were associated with greater progression of cartilage T2 measurements in asymptomatic, middle-aged individuals, suggesting accelerated cartilage matrix biochemical degeneration over time.
The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella.
Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1-3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Student's t-test).
T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time.
T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.
Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vivo if changes in the water content of patellar cartilage typically occurring in early OA can be detected using T(2) mapping MRI methods.
Twenty healthy volunteers performed 60 knee bends in order to compress their patellar cartilage thereby reducing its water content. MR images of the patellar cartilage were acquired immediately following exercise and after 45 min of rest. Patellar cartilage thickness and T(2) maps were determined and their difference between the time points evaluated.
Cartilage thickness increased by 5.4+/-1.5% from 2.94+/-0.15 mm to 3.10+/-0.15 mm (P< 0.001) following 45 min of rest, while T(2) increased by 2.6+/-1.0% from 23.1+/-0.5 ms to 23.7+/-0.6 ms (P< 0.05).
Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI. The proposed T(2)-mapping method, together with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA.
To describe a semi-quantitative scoring method for multi-feature, whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic resonance imaging (MRI) findings. To determine the inter-observer agreement of this scoring method. To examine associations among the features included in the scoring method.
Nineteen knees of 19 patients with knee OA were imaged with MRI using conventional pulse sequences and a clinical 1.5 T MRI system. Images were independently analyzed by two musculoskeletal radiologists using a whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular cartilage integrity, subarticular bone marrow abnormality, subarticular cysts, subarticular bone attrition, marginal osteophytes, medial and lateral meniscal integrity, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, synovitis/effusion, intraarticular loose bodies, and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were determined for each feature as a measure of inter-observer agreement. Associations among the scores for different features were expressed as Spearman Rho.
All knees showed structural abnormalities with MRI. Cartilage loss and osteophytes were the most prevalent features (98% and 92%, respectively). One of the least common features was ligament abnormality (8%). Inter-observer agreement for WORMS scores was high (most ICC values were >0.80). The individual features showed strong inter-associations.
The WORMS method described in this report provides multi-feature, whole-organ assessment of the knee in OA using conventional MR images, and shows high inter-observer agreement among trained readers. This method may be useful in epidemiological studies and clinical trials of OA.
Purpose:
To use T1ρ and T2 magnetic resonance imaging to evaluate the effect of leukocyte-poor platelet-rich plasma (LP-PRP) injections on knee cartilage health and to correlate structural changes with patient-reported outcome measurements.
Methods:
Ten patients with symptomatic unilateral mild-to-moderate knee osteoarthritis (Kellgren-Lawrence Grade 1-2) underwent T1ρ and T2 magnetic resonance imaging of both the symptomatic and contralateral knee before injection and 6 months after injection with LP-PRP. Patient-reported outcome questionnaires (Knee Osteoarthritis Outcome Score and International Knee Documentation Committee) that evaluate the domains of pain, symptoms, activities of daily living, sports function, and quality of life were completed at baseline, 3 months, 6 months, and 12 months after injection. T1ρ and T2 relaxation times, which are correlated with the proteoglycan and collagen concentration of cartilage, were measured in compartments with and without chondral lesions.
Results:
Ten patients were prospectively enrolled (9 female, 1 male) with a mean age of 52.9 years (range, 42-68) years and mean body mass index of 23.2 ± 1.9. Significant increases in Knee Osteoarthritis Outcome Score for all subscales and International Knee Documentation Committee scores were observed 3 months after injection and the improvements were sustained at 12 months. T1ρ and T2 values of compartments with chondral lesions were observed to significantly decrease by 6.0% (P = .036) and 7.1% (P = .017) 6 months after LP-PRP injection, respectively. No significant associations between T1ρ and T2 relaxation times and improvement in patient-reported outcomes were observed.
Conclusions:
Patients undergoing LP-PRP injections for the treatment of mild-to-moderate knee osteoarthritis had increased proteoglycan and collagen deposition in the cartilage of affected compartments by 6 months after injection. Patient-reported outcomes scores improved 3 months after injection and were sustained through 1 year after injection, but these improvements were not associated with the changes in proteoglycan and collagen deposition in knee cartilage.
Level of evidence:
Level II, prospective cohort study.
Osteoarthritis (OA) is a widely occurring degenerative joint disease that is severely debilitating and causes significant socioeconomic burdens to society. Magnetic resonance imaging (MRI) is the preferred imaging modality for the morphological evaluation of cartilage due to its excellent soft tissue contrast and high spatial resolution. However, its utilization typically involves subjective qualitative assessment of cartilage. Compositional MRI, which refers to the quantitative characterization of cartilage using a variety of MRI methods, can provide important information regarding underlying compositional and ultrastructural changes that occur during early OA. Cartilage compositional MRI could serve as early imaging biomarkers for the objective evaluation of cartilage and help drive diagnostics, disease characterization, and response to novel therapies. This review will summarize current and ongoing state‐of‐the‐art cartilage compositional MRI techniques and highlight emerging methods for cartilage compositional MRI including MR fingerprinting, compressed sensing, multiexponential relaxometry, improved and robust radio‐frequency pulse sequences, and deep learning‐based acquisition, reconstruction, and segmentation. The review will also briefly discuss the current challenges and future directions for adopting these emerging cartilage compositional MRI techniques for use in clinical practice and translational OA research studies.
Evidence Level
2
Technical Efficacy
Stage 2.
Background:
Magnetic resonance fingerprinting (MRF) techniques have been recently described for simultaneous multiparameter cartilage mapping of the knee although investigation of their ability to detect early cartilage degeneration remains limited.
Purpose:
To investigate age-dependent changes in knee cartilage T1 , T2 , and T1p relaxation times measured using a three-dimensional (3D) MRF sequence in healthy volunteers.
Study type:
Prospective.
Subjects:
The study group consisted of 24 healthy asymptomatic human volunteers (15 males with mean age 34.9 ± 14.4 years and 9 females with mean age 44.5 ± 13.1 years).
Field strength/sequence:
A 3.0 T gradient-echo-based 3D-MRF sequence was used to simultaneously create proton density-weighted images and T1 , T2 , and T1p maps of knee cartilage.
Assessment:
Mean global cartilage and regional cartilage (lateral femur, lateral tibia, medial femur, medial tibia, and patella) T1 , T2 , and T1ρ relaxation times of the knee were measured.
Statistical tests:
Kruskal-Wallis tests were used to compared cartilage T1 , T2 , and T1ρ relaxation times between different age groups, while Spearman correlation coefficients was used to determine the association between age and cartilage T1 , T2 , and T1ρ relaxation times. The value of P < 0.05 was considered statistically significant.
Results:
Higher age groups showed higher global and regional cartilage T1 , T2 , and T1ρ . There was a significant difference between age groups in global cartilage T2 and T1ρ but no significant difference (P = 0.13) in global cartilage T1. Significant difference was also present between age groups in cartilage T2 and T1ρ for medial femur cartilage and medial tibia cartilage. There were significant moderate correlations between age and T2 and T1ρ for global cartilage (R2 = 0.63-0.64), medial femur cartilage (R2 = 0.50-0.56), and medial tibia cartilage (R2 = 0.54-0.66).
Conclusion:
Cartilage T2 and T1p relaxation times simultaneously measured using a 3D-MRF sequence in healthy volunteers showed age-dependent changes in knee cartilage, primarily within the medial compartment.
Magnetic resonance imaging (MRI) is a valuable tool for evaluating musculoskeletal disease as it offers a range of image contrasts that are sensitive to underlying tissue biochemical composition and microstructure. Although MRI has the ability to provide high-resolution, information-rich images suitable for musculoskeletal applications, most MRI utilization remains in qualitative evaluation. Quantitative MRI (qMRI) provides additional value beyond qualitative assessment via objective metrics that can support disease characterization, disease progression monitoring, or therapy response. In this review, musculoskeletal qMRI techniques are summarized with a focus on techniques developed for osteoarthritis evaluation. Cartilage compositional MRI methods are described with a detailed discussion on relaxometric mapping (T2, T2*, T1ρ) without contrast agents. Methods to assess inflammation are described, including perfusion imaging, volume and signal changes, contrast-enhanced T1 mapping, and semiquantitative scoring systems. Quantitative characterization of structure and function by bone shape modeling and joint kinematics are described. Muscle evaluation by qMRI is discussed, including size (area, volume), relaxometric mapping (T1, T2, T1ρ), fat fraction quantification, diffusion imaging, and metabolic assessment by 31P-MR and creatine chemical exchange saturation transfer. Other notable technologies to support qMRI in musculoskeletal evaluation are described, including magnetic resonance fingerprinting, ultrashort echo time imaging, ultrahigh-field MRI, and hybrid MRI-positron emission tomography. Challenges for adopting and using qMRI in musculoskeletal evaluation are discussed, including the need for metal artifact suppression and qMRI standardization.
Importance
Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.
Objective
To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.
Design, Setting, and Participants
This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.
Interventions
Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).
Main Outcomes and Measures
The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.
Results
Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 points, respectively (difference, −0.4 [95% CI, −0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was −1.4% vs −1.2%, respectively (difference, −0.2% [95% CI, −1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.
Conclusions and Relevance
Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.
Trial Registration
Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347
Knee osteoarthritis is highly prevalent among older adults. Treatments include exercise, weight management, training in self-efficacy and pain-coping skills, and medications (commonly topical or oral NSAIDs, the latter often with a proton-pump inhibitor).
Osteoarthritis (OA) is a highly prevalent chronic condition with marked implications for affected individuals and public health care. There are available treatments to manage pain and symptoms but no effective treatment for OA. In the past 10 years, joint imaging, particularly MRI, has evolved rapidly due to technical advances and their application to clinical research, which has led to abundant evidence regarding the natural history of the disease. Radiography remains the primary imaging modality in clinical practice for the diagnosis and follow-up of OA. The many developments in MRI techniques capable of assessing cartilage morphologic features and the methods for evaluating its biochemical composition will be discussed. Advances in quantitative morphologic cartilage assessment and semiquantitative whole-organ assessment will be reviewed, as will other modalities such as US, CT and CT arthrography, and nuclear medicine techniques that play a complementary role. Various therapeutic approaches and ongoing developments, including the impact of artificial intelligence on the field of OA imaging, will also be discussed.
OBJECTIVE. Cartilage loss on preoperative knee MRI is a predictor of poor outcomes after arthroscopic partial meniscectomy. The purpose of this study was to compare the ability to predict outcomes after arthroscopic partial meniscectomy with a clinically used modified Outerbridge system versus a semiquantitative MRI Osteoarthritis Knee Score system for grading cartilage loss. MATERIALS AND METHODS. Patients who underwent preoperative knee MRI within 6 months of arthroscopic partial meniscectomy and who had outcomes available from the time of surgery and 1 year later were eligible for inclusion. Cases were evaluated by two radiologists and one radiology fellow with the use of both grading systems. The accuracy of each system in discriminating between surgical success and failure was estimated using the ROC curve (AUC) with 95% CIs. A Wald test was used to assess noninferiority of the clinical grading system. Interreader agreement regarding the accuracy of the grading systems in predicting outcomes was also compared. RESULTS. A total of 78 patients (38 women and 40 men; mean age, 56.6 years) were included in the study. A prediction model using clinical grading (AUC = 0.695; 95% CI, 0.566-0.824) was noninferior (p = 0.047) to a model using MRI Osteoarthritis Knee Score grading (AUC = 0.683; 95% CI, 0.539-0.827). Both MRI prediction models performed better than a model using demographic characteristics only (AUC = 0.667; 95% CI, 0.522-0.812). Inter-reader agreement with clinical grading (80.8%) was higher than that with MRI Osteoarthritis Knee Score grading (65.0%; p = 0.012). CONCLUSION. A clinically used system to grade cartilage loss on MRI is as effective as a semiquantitative system for predicting outcomes after arthroscopic partial meniscectomy, while also offering improved interreader agreement.
Osteoarthritis is a leading cause of disability and source of societal cost in older adults. With an ageing and increasingly obese population, this syndrome is becoming even more prevalent than in previous decades. In recent years, we have gained important insights into the cause and pathogenesis of pain in osteoarthritis. The diagnosis of osteoarthritis is clinically based despite the widespread overuse of imaging methods. Management should be tailored to the presenting individual and focus on core treatments, including self-management and education, exercise, and weight loss as relevant. Surgery should be reserved for those that have not responded appropriately to less invasive methods. Prevention and disease modification are areas being targeted by various research endeavours, which have indicated great potential thus far. This narrative Seminar provides an update on the pathogenesis, diagnosis, management, and future research on osteoarthritis for a clinical audience.
Objectives
Our aim was to investigate the role of age, sex, and location on MR T2* values of the knee cartilage in asymptomatic controls and patients with osteoarthritis (OA).
Methods
A total of 100 participants, including 40 with OA and 60 asymptomatic controls, were enrolled in this study. Patients with OA were compared to age- (≥ 41 years old) and sex-matched controls. Controls were divided by age (aged 21–40 years, 41–60, ≥ 61). T2* values were acquired using a T2*-weighted fast gradient-echo sequence and a 1.5-T MRI scanner. T2* values of the femoral and tibial cartilages at the weight-bearing areas were obtained for comparisons.
Results
The T2* values significantly increased with age and were significantly higher in the medial femoral cartilage (35.96 ± 4.06 and 31.85 ± 2.44 ms), medial tibial cartilage (30.95 ± 2.87 and 28.24 ± 1.74 ms), and lateral femoral cartilage (33.90 ± 3.15 and 31.51 ± 2.28 ms) in OA patients versus age- and sex-matched controls. Among OA patients, the T2* values for women exceed those in men in the medial femoral cartilage (37.59 ± 4.43 and 34.16 ± 2.63 ms) and medial tibial cartilage (32.17 ± 2.59 and 29.62 ± 2.53 ms; p < 0.01). Correlations were found between the Lequesne index and the T2* values for the medial femoral cartilage (r = 0.636, p < 0.001) and the medial tibial cartilage (r = 0.433, p = 0.005).
Conclusion
Cartilage T2* values tend to increase with age and are useful in assessing cartilage degeneration in early OA.
Key Points
• Age, sex, and location have important effects on cartilage T2* values at the knee.
• MR T2* measurements are useful toward assessing cartilage degeneration.
• The medial femoral and tibial cartilage T2* values correlate well with disease severity.
Background:
Platelet-rich plasma (PRP) has proven to be a very safe therapeutic option in the treatment of tendon, muscle, bone, and cartilage injuries. Currently, several commercial separation systems are available for the preparation of PRP. The concentrations of blood components in PRP among these separation systems vary substantially.
Purpose:
To systematically review and evaluate the differences between the concentrations of blood components in PRP produced by various PRP separation systems.
Study design:
Systematic review.
Methods:
MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched for studies that compared the concentrations of blood components and growth factors in PRP between various separation systems and studies that reported on the concentrations of blood components and growth factors of single separation systems. The primary outcomes were platelet count, leukocyte count, and concentration of growth factors (eg, platelet-derived growth factor-AB [PDGF-AB], transforming growth factor-β1 [TGF-β1], and vascular endothelial growth factor [VEGF]). Furthermore, the preparation protocols and prices of the systems were compared.
Results:
There were 1079 studies found, of which 19 studies were selected for inclusion in this review. The concentrations of platelets and leukocytes in PRP differed largely between, and to a lesser extent within, the studied PRP separation systems. Additionally, large differences both between and within the studied PRP separation systems were found for all the growth factors. Furthermore, preparation protocols and prices varied widely between systems.
Conclusion:
There is a large heterogeneity between PRP separation systems regarding concentrations of platelets, leukocytes, and growth factors in PRP. The choice for the most appropriate type of PRP should be based on the specific clinical field of application. As the ideal concentrations of blood components and growth factors for the specific fields of application are yet to be determined for most of the fields, future research should focus on which type of PRP is most suitable for the specific field.
Objectives:
We used T2 mapping to quantify the effect of intra-articular hyaluronic acid administration (IAHAA) on cartilage with correlation to clinical symptoms.
Methods:
One hundred two patients with clinical and MRI diagnosis of hip or knee grade I-III chondropathy were prospectively included. All patients received a standard MRI examination of the affected hip/knee (one joint/patient) and T2-mapping multiecho sequence for cartilage evaluation. T2 values of all slices were averaged and used for analysis. One month after MR evaluation 72 patients (38 males; mean age 51±10 years) underwent IAHAA. As a control group, 30 subjects (15 males; 51 ± 9 years) were not treated. MR and WOMAC evaluation was performed at baseline and after 3, 9, and 15 months in all patients.
Results:
T2 mapping in hyaluronic acid (HA) patients showed a significant increase in T2 relaxation times from baseline to the first time point after therapy in knees (40.7 ± 9.8 ms vs. 45.8 ± 8.6 ms) and hips (40.9 ± 9.7 ms; 45.9 ± 9.5 ms) (p < 0.001). At the 9- and 15-month evaluations, T2 relaxation dropped to values similar to the baseline ones (p < 0.001 vs. 3 month). The correlation between T2 increase and pain reduction after IAHAA was statistically significant (r = 0.54, p < 0.01) in patients with grade III chondropathy.
Conclusions:
T2 mapping can be used to evaluate the effect over time of IAHAA in patients with hip and knee chondropathy.
Key points:
• T2 relaxation times change over time after hyaluronic acid intra-articular administration • T2 relaxation times of the medial femoral condyle correlate with WOMAC variation • T2 relaxation times are different between Outerbridge I and II-III.
Objective:
The aim of this study was to compare T2 relaxation times of knee cartilage with intraoperative results for the assessment of early osteoarthritis (OA) and to define T2 values for the differentiation between healthy and degenerated cartilage.
Design:
Twenty-one patients with cartilage lesions or moderate OA were examined using 3T MRI. In this prospective study, a total of 882 regions of interest (ROIs) were examined by a sagittal, multi-echo, spin-echo T2 sequence and a morphological high-resolution three-dimensional, fat-saturated proton-density space sequence. Cartilage lesions were identified arthroscopically, graded by the International Cartilage Repair Society (ICRS) score in 42 defined ROIs per patient and consecutively compared with mean T2 values using analysis of variance and Spearman's rank correlation test. Receiver operating characteristics (ROC) curves were developed to identify threshold T2 values to differentiate between the ICRS grades.
Results:
A total of 882 ROIs were examined and graduated in ICRS score 0 (67.3%), 1 (25.2%), 2 (6.2%) and the merged ICRS 3 and 4 (1.0%). T2 values increased with increasing grade of cartilage damage with a statistically significant positive correlation between T2 values and ICRS scores. A T2 value threshold of 47.6 ms was identified to differentiate between ICRS score 0 (normal) and all other grades (ROC curve analysis).
Conclusion:
T2 mapping might provide a diagnostic tool for the detection of early knee-joint cartilage damage and for the non-invasive differentiation between ICRS grades by MRI in clinical practice.
Importance
Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone.
Objective
To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain.
Design, Setting, and Participants
Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015.
Interventions
Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years.
Main Outcomes and Measures
Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94).
Results
Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm (between-group difference, −0.11 mm; 95% CI, −0.20 to −0.03 mm); and no significant difference in pain (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, −0.2%; 95% CI, −0.5% to −0.007%).
Conclusions and Relevance
Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.
Trial Registration
ClinicalTrials.gov Identifier: NCT01230424
Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware.
Level of Evidence: 5
J. Magn. Reson. Imaging 2017;45:949–965
Osteoarthritis is a chronic disorder of synovial joints in which there is progressive softening and
disintegration of articular cartilage accompanied by the growth of osteophytes. Treatment designed for
osteoarthritis should aim at reducing pain, improve joint mobility, and limit functional impairment. It
can be achieved by pharmacological and non-pharmacological means. Non-operative treatment of OA is
useful for patients with KL grade 1–3, which are early stages of OA. However, in an advanced stage of OA
(KL grade 4), surgical treatment is needed as definitive treatment.
The purpose of this study was 1) to establish a gender- and BMI-specific reference database of cartilage T2 values, and 2) to assess the associations between cartilage T2 values and gender, age, and BMI in knees without radiographic osteoarthritis or MRI-based (WORMS 0/1) evidence of cartilage degeneration.
481 subjects between the ages of 45-65 years with Kellgren-Lawrence Scores 0/1 in the study knee were selected from the Osteoarthritis Initiative database. Baseline morphologic cartilage 3T MRI readings (WORMS scoring) and T2 measurements (resolution=0.313mmx0.446mm) were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. In order to create a reference database, a logarithmic transformation was applied to the data to obtain the 5(th)-95(th) percentile values for T2.
Significant differences in mean cartilage T2 values were observed between joint compartments. Although females had slightly higher T2 values than males in a majority of compartments, the differences were only significant in the medial femur (p<0.0001). A weak positive association was seen between age and T2 in all compartments, and was most pronounced in the patella (3.27% increase in median T2/10 years, p=0.009). Significant associations between BMI and T2 were observed, and were most pronounced in the lateral tibia (5.33% increase in median T2/5 kg/m(2) increase in BMI, p<0.0001), and medial tibia (4.81% increase in median T2/5 kg/m(2) increase in BMI, p<0.0001).
This study established the first reference database of T2 values in a large sample of morphologically normal cartilage plates in knees without radiographic knee osteoarthritis. While cartilage T2 values were weakly associated with age and gender, they had the highest correlations with BMI.
Copyright © 2015. Published by Elsevier Ltd.
Objective:
Cartilage spin-spin magnetic resonance imaging (MRI) relaxation time (T2) represents a promising imaging biomarker of "early" osteoarthritis (OA) known to be associated with cartilage composition (collagen integrity, orientation, and hydration). However, no longitudinal imaging studies have been conducted to examine cartilage maturation in healthy subjects thus far. Therefore, we explore T2 change in the deep and superficial cartilage layers at the end of adolescence.
Methods:
Twenty adolescent and 20 mature volleyball athletes were studied (each 10 men and 10 women). Multi-echo spin-echo (MESE) images were acquired at baseline and 2-year follow-up. After segmentation, cartilage T2 was calculated in the deep and superficial cartilage layers of the medial tibial (MT) and the central, weight-bearing part of the medial femoral condyle (cMF), using five echoes (TE 19.4-58.2 ms).
Results:
16 adolescent (6 men, 10 women, baseline age 15.8 ± 0.5 years) and 17 mature (nine men, eight women, age 46.5 ± 5.2 years) athletes had complete baseline and follow-up images of sufficient quality to compute T2. In adolescents, a longitudinal decrease in T2 was observed in the deep layers of MT (-2.0 ms; 95% confidence interval (CI): [-3.4, -0.6] ms; P < 0.01) and cMF (-1.3 ms; [-2.4, -0.3] ms; P < 0.05), without obvious differences between males and females. No significant change was observed in the superficial layers, or in the deep or superficial layers of the mature athletes.
Conclusion:
In this first pilot study on quantitative imaging of cartilage maturation in healthy, athletic subjects, we find evidence of cartilage compositional change in deep cartilage layers of the medial femorotibial compartment in adolescents, most likely related to organizational changes in the collagen matrix.
With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation-without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented.
T2* mapping is a relatively new method for the compositional assessment of the articular cartilage. Typically, a multigradient echo or an ultrashort echo time imaging technique with a range of short and very short echo times is used. In most studies, imaging is performed at a high field strength, that is, 3 and 7 T. Postprocessing includes exponential fitting of relaxation decay and manual region-of-interest-based measurements of T2* times on T2* maps. Detailed analyses of T2* times of articular cartilage have shown distinct T2* components with shorter and longer T2* times. Moreover, there is a zonal distribution with a significant depthwise gradient of T2*, with relatively short times near the osteochondral junction and relatively long times at the cartilage's surface. T2* times of normal articular cartilage at the knee are, when averaged over the whole cartilage thickness and using monoexponential fitting, approximately 20 milliseconds. The results of recent studies have shown a good test-retest as well as interreader and intrareader reliabilities for T2* mapping. This article provides a descriptive review of the current literature, briefly discusses the technique itself, and provides an outlook on future research questions and possible clinical applications.
Understanding the acute response of healthy knee cartilage to running may provide valuable insight into functional properties. In recent years, quantitative magnetic resonance (MR) imaging techniques (T1(ρ) and T2 relaxation measurement) have shown tremendous potential and unique ability to noninvasively and quantitatively determine cartilage response to physiologic levels of loading occurring with physiologic levels of exercise.
To measure the short-term changes in MR T1(ρ) and T2 relaxation times of knee articular cartilage and meniscus in healthy individuals immediately after 30 minutes of running.
Descriptive laboratory study.
Twenty young healthy volunteers, aged 22 to 35 years, underwent 3T MR imaging of the knee before and immediately after 30 minutes of running. Quantitative assessment of the cartilage and menisci was performed using MR images with a T1(ρ) and T2 mapping technique. After adjusting for age, sex, and body mass index, repeated-measures analysis of variance was used to determine the effects of running on MR relaxation times.
The post-run T1(ρ) and T2 measurement showed significant reduction in all regions of cartilage except the lateral tibia when compared with the pre-run condition. The medial tibiofemoral (T1(ρ): 9.4%, P < .0001; T2: 5.4%, P = .0049) and patellofemoral (T1(ρ): 12.5%, P < .0001; T2: 5.7%, P = .0007) compartments experienced the greatest reduction after running. The superficial layer of the articular cartilage showed significantly higher change in relaxation times than the deep layer (T1(ρ): 9.6% vs 8.2%, P = .050; T2: 6.0% vs 3.5%, P = .069). The anterior and posterior horns of the medial meniscus (9.7%, P = .016 and 11.4%, P = .001) were the only meniscal subregions with significant changes in T1(ρ) after running.
Shorter T1(ρ) and T2 values after running suggest alteration in the water content and collagen fiber orientation of the articular cartilage. Greater changes in relaxation times of the medial compartment and patellofemoral joint cartilage indicate greater load sharing by these areas during running.
The aim of this study was to identify the pattern of T2* values in acetabular and femoral head cartilage in morphologically normal and abnormal zones at 3 T.
Twenty-nine patients (mean [SD] age, 30.8 [8.8] years) with symptomatic femoroacetabular impingement and suspected cartilage damage (study group) and 35 healthy, asymptomatic volunteers (mean [SD] age, 24.9 [2.1] years) with no obvious history of hip diseases or abnormalities (control group) were included. Magnetic resonance imaging was performed at 3 T using a 3-dimensional (3D) double-echo steady-state sequence for grading cartilage morphologically and a 3D multiecho data image combination sequence for T2* assessment. Statistical assessment included the Student t test to reveal differences between mean T2* values of the study group and the control group. One-way analysis of variance was used to identify any statistically significant differences between the T2* values in various grades (modified Outerbridge score system) of cartilage damage within the study group.
Significant differences were noted between the T2* values in the study group and the control group (P < 0.001). We also noted a significant drop in T2* in accordance with the morphologic damage in the study group (P < 0.001). The largest drop in T2* was found between morphologically normal-appearing cartilage (grade 0; T2*, 25.2 milliseconds) and grade I changes (T2*, 18.1 milliseconds) (P < 0.001).
In combination with a 3-T system, T2* mapping offers unique advantages such as high image resolution and the ability of 3D biochemically sensitive cartilage evaluation in the hip joint without the need for contrast medium. Given these advantages, we believe that T2* mapping is another welcome addition to the rapidly evolving era of hip cartilage biochemical imaging. Further studies are necessary that involve a diagnostic histological analysis as gold standard for comparison.
To evaluate T2* values in various histological severities of osteoarthritis (OA).
Magnetic resonance imaging (MRI) and T2* mapping including a three-dimensional (3D) double-echo steady-state (DESS) sequence for morphological cartilage assessment and a 3D multiecho data image combination (MEDIC) sequence for T2* mapping were conducted in 21 human femoral head specimens with varying severities of OA. Subsequently, histological assessment was undertaken in all specimens to correlate the observations of T2* mapping with histological analyses. According to the Mankin score, four grades of histological changes were determined: grade 0 (Mankin scores of 0-4), grade I (scores of 5-8), grade II (scores of 9-10), and grade III (scores of 11-14). For reliability assessment, cartilage T2* measurements were repeated after 4 weeks in 10 randomly selected femoral head specimens.
T2* values decreased significantly with increasing cartilage degeneration (total P-values <0.001) ranging from 36.3 ± 4.3 ms in grade 0 regions to 22.8 ± 4.3 ms in regions with grade III changes. Pearson correlation analysis proved a fair correlation between T2* values and Mankin score (correlation coefficient = -0.362) that was statistically significant (P-value <0.001). Intra-class correlation (ICC) analysis demonstrated high intra-observer reproducibility for the T2* measurement (ICC: 0.949, P < 0.001).
Given the advantages of the T2* mapping technique with no need for contrast medium, high image resolution and ability to perform 3D biochemically sensitive imaging, T2* mapping may be a strong addition to the currently evolving era of cartilage biochemical imaging.
To measure reproducibility, longitudinal and cross-sectional differences in T2* maps at 3 Tesla (T) in the articular cartilage of the knee in subjects with osteoarthritis (OA) and healthy matched controls.
MRI data and standing radiographs were acquired from 33 subjects with OA and 21 healthy controls matched for age and gender. Reproducibility was determined by two sessions in the same day, while longitudinal and cross-sectional group differences used visits at baseline, 3 and 6 months. Each visit contained symptomological assessments and an MRI session consisting of high resolution three-dimensional double-echo-steady-state (DESS) and co-registered T2* maps of the most diseased knee. A blinded reader delineated the articular cartilage on the DESS images and median T2* values were reported.
T2* values showed an intra-visit reproducibility of 2.0% over the whole cartilage. No longitudinal effects were measured in either group over 6 months. T2* maps revealed a 5.8% longer T2* in the medial tibial cartilage and 7.6% and 6.5% shorter T2* in the patellar and lateral tibial cartilage, respectively, in OA subjects versus controls (P < 0.02).
T2* mapping is a repeatable process that showed differences between the OA subject and control groups.
Treatment options for rheumatoid arthritis range from symptomatic approaches to modern molecular interventions such as inhibition of inflammatory mediators. Inhibition of inflammation by platelet-rich plasma (PRP) has been proposed as a treatment for tendinitis and osteoarthritis. The present study was undertaken to investigate the effect of PRP on antigen-induced arthritis (AIA) of the knee joint in a large animal model.
Six-month-old pigs (n = 10) were systemically immunized by bovine serum albumin (BSA) injection, and arthritis was induced by intraarticular BSA injection. PRP was injected into the knee joints of 5 of the animals after 2 weeks. An additional 5 animals received no systemic immunization (controls). Signs of arthritis were documented by plain histologic analysis, Safranin O staining, and immunohistochemistry analysis for type II collagen (CII), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Interleukin-1β (IL-1β), IL-6, tumor necrosis factor α (TNFα), VEGF, and insulin-like growth factor 1 (IGF-1) protein content was measured by Luminex assay.
In the pigs with AIA, plain histologic analysis revealed severe arthritic changes in the synovium. Safranin O and CII staining showed decreased proteoglycan and CII content in cartilage. Immunohistochemistry analysis revealed increased levels of IL-6 and VEGF in synovium and cartilage, and protein concentrations of IL-6, VEGF, IL-1β, and IGF-1 in synovium and cartilage were elevated as well; in addition, TNFα protein was increased in cartilage. Treatment with PRP led to attenuation of these arthritic changes in the synovium and cartilage.
We have described a porcine model of AIA. Experiments using this model demonstrated that PRP can attenuate arthritic changes as assessed histologically and based on protein synthesis of typical inflammatory mediators in the synovial membrane and cartilage.
The purpose of this study was to investigate whether the effect of treatment with hyaluronic acid (HA) on cartilage in osteoarthritis (OA) can be determined by measuring the magnetic resonance (MR) T2 value of cartilage in an anterior cruciate ligament transection (ACLX) animal model.
Eighteen male Sprague Dawley rats were separated randomly into three groups (n=6 for each group). Group 1 was given ACLX and intra-articular (IA) normal saline (NS) injection (ACLX+NS), group 2 was given ACLX and IA HA injection (ACLX+HA), and group 3 was the sham control. The ACLX+NS and ACLX+HA groups received ACLX on the right knee at 8 weeks of age and were then treated with IA NS or HA injection once a week, respectively, for 4 weeks starting at 13 weeks of age. In the sham-control group, the right knee joint was opened surgically but ACLX was not performed at 8 weeks of age. MR T2 measurements were obtained on all rats at 8, 12, and 21 weeks of age, and histological Mankin scoring was performed at 21 weeks of age.
Five weeks after the 4-week treatment, the MR T2 value of the ACLX right knee cartilage was significantly lower in ACLX+HA (29.58+/-1.12ms) than in ACLX+NS (32.04+/-1.39ms) (P<0.05). Five weeks after the 4-week treatment, the Mankin score of the ACLX right knee was significantly lower in ACLX+HA (3.3+/-0.81) than in ACLX+NS (7.3+/-1.03) (P<0.001). The T2 value was significantly and positively correlated with the Mankin score in the ACLX+NS (rho=0.77, P<0.05) and ACLX+HA (rho=0.69, P<0.05) groups.
This study demonstrates the feasibility of quantitative MR T2 measurement in the early assessment of HA treatment efficiency in a cartilage degeneration model.
To assess the normal topographical variation of T2 relaxation time of articular cartilage in different compartments of the knee joint and at different tissue depths in young healthy adults.
Twenty asymptomatic young adult volunteers (age range, 21-27 years; mean age, 22.5 years), were studied at 1.5T. Both axial and sagittal multi-slice multi-echo spin echo measurements were performed to determine the T2 relaxation time of cartilage in the femoral, tibial and patellar compartments. The cartilage surfaces were divided into 24 segments and each segment was divided into deep and superficial regions-of-interest (ROIs) of equal thickness. The reproducibility for ROI analysis was assessed for five patients by determining the interclass correlation coefficient (ICC) and the root-mean-square coefficient of variation (CV(RMS)).
Cartilage T2 was significantly dependent on joint topography, compartment and tissue depth. For all joint surfaces, superficial T2 values were systematically higher as compared to deep tissue. The data showed a trend toward higher T2 values at the load bearing area of the femoral condyles. The interobserver error varied significantly among different locations and showed mostly good reproducibility with mean ICC of 0.70 and a CV(RMS) of 5.0%.
The normal variation in cartilage T2 within a joint is significant and should be acknowledged when pathology-related T2 changes are investigated. The knowledge on normal variation can be used for power and sample size calculations in further studies, and the T2 values as control data in future patient studies.
The objective of this study was to review all the published articles in the English literature about the systemic effects of intra-articular corticosteroid injection (IACI) in humans. Reports were searched through Pubmed using the terms intraarticular or intra-articular and steroids, corticosteroids, or glucocorticosteroids up and including the year 2007. Reports were also located through references of articles. Only objective findings outside the injected joint were included. The overwhelming majority of the studies was done at the knee joint and in rheumatoid arthritis/juvenile idiopathic arthritis patients. Many of the studies were done on the hypothalamic-pituitary-adrenal axis. Serum cortisol decreased within hours with a nadir after usually 24-48 h following the IACI. Recovery to baseline takes 1-4 weeks and sometimes longer depending on the type and dose of IACI and on the number of injected joints. Serum cortisol levels were blunted following adrenocorticotropic hormone stimulation in a small proportion of patients following methylprednisolone acetate injection and more common following other preparations. IACI resulted in a transient increase in blood glucose levels over few days in controlled diabetic patients with knee osteoarthritis. Peak levels are around 300 mg%. IACIs are associated with reduction in inflammatory markers like C-reactive protein and erythrocyte sedimentation rate that start few days following the IACI and could last for months. The effect on inflammatory cytokines is immediate with significant decrease within hours. IACI may induce remission also in patients with oligo-/polyarthritis and/or in patients with extra-articular manifestations. Other metabolic, hematologic, vascular, allergic, visual, psychologic, and other effects were also reported.
To evaluate differences in T2 values in femoral and tibial cartilage at magnetic resonance (MR) imaging in patients with varying degrees of osteoarthritis (OA) compared with healthy subjects and to develop a mapping and display method based on calculation of T2 z scores for visual grading and assessment of cartilage heterogeneity in patients with OA.
Knee cartilage was evaluated in 55 subjects who were categorized with radiography as healthy (n = 7) or as having mild OA (n = 20) or severe OA (n = 28). Cartilage regions were determined with manual segmentation of an MR image acquired with spoiled gradients and fat suppression. The segmentation was applied to a map of T2 relaxation time and was analyzed in four knee cartilage compartments (ie, the medial and lateral tibia and femur). Differences between cartilage compartment T2 values and subject groups were analyzed with analysis of covariance. Correlations of cartilage T2 values with clinically reported symptoms and cartilage thickness and volume were examined. Cartilage T2 values were converted to z scores per voxel on the basis of normal population values in the same cartilage compartment to better interpret cartilage heterogeneity and variation from normal.
Healthy subjects had mean T2 values of 32.1-35.0 msec, while patients with mild and severe OA had mean T2 values of 34.4-41.0 msec. All cartilage compartments except the lateral tibia showed significant (P <.05) increases in T2 relaxation time between healthy and diseased knees; however, no significant difference was found between patients with mild and severe OA. Correlation of T2 values with clinical symptoms and cartilage morphology was found predominantly in medial compartments.
Femoral and medial tibial cartilage T2 values increase with the severity of OA.
To assess the rate of cartilage loss, the change in bone marrow edema pattern and internal joint derangement at 1.5-T MRI in patients with knee osteoarthritis and to correlate these findings with the clinical Western Ontario and McMaster University Osteoarthitis (WOMAC) score.
Forty subjects (mean age 57.7+/-15 years; 16 females and 24 males) were recruited: 6 healthy volunteers (OA0), 17 patients with mild osteoarthritis (OA1) and 17 with severe osteoarthritis (OA2) based on the Kellgren-Lawrence scale. MR scans, radiographs and WOMAC scores were obtained at baseline, first follow-up (1.4+/-0.67 years; n=40) and second follow-up (2.4+/-0.4 years; n=26). Cartilage morphology, bone marrow edema (BME), meniscal and ligamentous pathology were assessed on MR images and quantified by two radiologists in consensus.
Full-thickness cartilage lesions were observed in 12/17 OA2 at baseline, in 13/17 at the first follow-up and in 7/10 at the second follow-up. Cartilage loss was found in eight patients at the first follow-up and five at the second follow-up. BME was observed in 23/40 patients at baseline, in 22/40 at the first follow-up and in 12/26 at the second follow-up. Changes in BME were visualized in 19/22 and 4/13 patients at the first and second follow-up, respectively. Changes in WOMAC scores over time did not correlate significantly with the amount of cartilage loss and the change in BME (P>0.05).
MRI is well suited to monitor the progression of OA in the longitudinal follow-up since it shows cartilage defects, BME and internal joint derangement, pathologies that are not visualized by radiographs. The lack of significant correlation between MRI findings and clinical findings is not unexpected, has been previously described and may in part be due to the fact that patients get more accustomed to their pain as the knee progressively degenerates.
Platelet-rich plasma (PRP) is a fraction of plasma that contains high levels of multiple growth factors. The purpose of this study was to examine the effects of PRP on cell proliferation and matrix synthesis by porcine chondrocytes cultured in alginate beads, conditions that promote the retention of the chondrocytic phenotype, in order to determine the plausibility of using this plasma-derived material for engineering cartilage.
PRP and platelet-poor plasma (PPP) were prepared from adult porcine blood. Adult porcine chondrocytes were cultured in the presence of 10% PRP, 10% PPP or 10% fetal bovine serum (FBS) for 3 days. Cell proliferation, proteoglycan (PG) and collagen synthesis were quantified, and the structure of newly synthesized PG and collagen was characterized.
Treatment with 10% PRP resulted in a small but significant increase in DNA content (+11%, vs FBS; P<0.01; vs PPP; P<0.001). PG and collagen syntheses by the PRP-treated chondrocytes were markedly higher than those by chondrocytes treated by FBS or PPP (PG; PRP: +115% vs FBS; +151% vs PPP, both P<0.0001, collagen; PRP: +163% vs FBS; +163% vs PPP, both P<0.0001). Biochemical analyses revealed that treatment with PRP growth factors did not markedly affect the types of PGs and collagens produced by porcine chondrocytes, suggesting that the cells remained phenotypically stable in the presence of PRP.
PRP isolated from autologous blood may be useful as a source of anabolic growth factors for stimulating chondrocytes to engineer cartilage tissue.
To prospectively compare cartilage T2 values after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) repair procedures.
The study had institutional review board approval by the ethics committee of the Medical University of Vienna; informed consent was obtained. Twenty patients who underwent MFX or MACT (10 in each group) were enrolled. For comparability, patients of each group were matched by mean age (MFX, 40.0 years +/- 15.4 [standard deviation]; MACT, 41.0 years +/- 8.9) and postoperative interval (MFX, 28.6 months +/- 5.2; MACT, 27.4 months +/- 13.1). Magnetic resonance (MR) imaging was performed with a 3-T MR imager, and T2 maps were calculated from a multiecho spin-echo measurement. Global, as well as zonal, quantitative T2 values were calculated within the cartilage repair area and within cartilage sites determined to be morphologically normal articular cartilage. Additionally, with consideration of the zonal organization, global regions of interest were subdivided into deep and superficial areas. Differences between cartilage sites and groups were calculated by using a three-way analysis of variance.
Quantitative T2 assessment of normal native hyaline cartilage showed similar results for all patients and a significant trend of increasing T2 values from deep to superficial zones (P < .05). In cartilage repair areas after MFX, global mean T2 was significantly reduced (P < .05), whereas after MACT, mean T2 was not reduced (P > or = .05). For zonal variation, repair tissue after MFX showed no significant trend between different depths (P > or = .05), in contrast to repair tissue after MACT, in which a significant increase from deep to superficial zones (P < .05) could be observed.
Quantitative T2 mapping seems to reflect differences in repair tissues formed after two surgical cartilage repair procedures. (c) RSNA, 2008.