Early anterior cruciate ligament reconstruction does not affect 5 year change in knee cartilage thickness: secondary analysis of a randomized clinical trial.

OBJECTIVE: To compare 5-year change in femorotibial cartilage thickness in 121 young, active adults with an acute anterior cruciate ligament (ACL) tear randomized to a strategy of structured rehabilitation plus early ACL reconstruction (ACLR) or structured rehabilitation plus optional delayed ACLR. DESIGN: 62 patients were randomized to early ACLR, 59 to optional delayed ACLR. Magnetic resonance imaging (MRI) was acquired within 4 weeks of injury, at two- and 5-years follow-up. Main outcome was 5-year change in overall femorotibial cartilage thickness. Secondary outcomes included the location-independent cartilage ChangeScore, summarizing thinning and thickening in 16 femorotibial subregions. An exploratory as-treated comparison was performed additionally. RESULTS: Baseline and at least one follow-up MRI were available for 117 patients. Over 5 years, a comparable increase in overall femorotibial cartilage thickness was observed for patients randomized to early ACLR (n = 59) and patients randomized to optional delayed ACLR (n = 58, adjusted mean difference: -5 µm, 95% CI: [-118, 108]µm). However, the location-independent cartilage ChangeScore was greater in those treated with early ACLR than in patients treated with optional delayed ACLR (adjusted mean difference: 403 µm [119, 687]µm). As-treated analysis showed no between-group differences for the main outcome, while the location-independent cartilage ChangeScore was greater for patients treated with early (adjusted mean difference: 632 µm [268, 996]µm) or delayed ACLR (adjusted mean difference: 449 µm [108, 791]µm) than for patients treated with rehabilitation alone. CONCLUSIONS: In young active adults with acute ACL-injury, choice of treatment strategy for the injured ACL did not modify the magnitude of 5-year change in overall femorotibial cartilage thickness. TRIAL REGISTRATION: ISRCTN84752559.

Differences in subchondral bone size after one year in osteoarthritic and healthy knees.

OBJECTIVE: Increase of subchondral bone area (tAB) in OA has been reported, but it remains unclear if this is specific to OA. We investigated differences in knee tAB after one year in healthy subjects and in those with radiographic OA (rOA). METHOD: MR images of 899 right knees from the OA Initiative were acquired at baseline and one year follow-up (year-1). Medial and lateral tibial cartilage (MT and LT) and weight-bearing femoral cartilage (cMF and cLF) were segmented and tAB computed. Subjects were stratified into: healthy controls, pre-rOA (K&L grades 0 and 1, with OA risk factors), established rOA (K&L grades 2-4), and independently with regards to joint space narrowing (without, with medial, lateral and bilateral JSN). Primary analysis tested if tAB was different between baseline and year-1 in rOA. Exploratory analyses investigated whether: (1) tAB changes differed between healthy controls and those with rOA; (2) tAB differences were greater in higher K&L grades; and (3) tAB was different between baseline and year-1 in JSN. Significance was set at P < 0.0125. RESULTS: Differences in tAB were found in rOA in MT, cMF and cLF (ranging from +0.2% to +0.4%; P < 0.001), but not in healthy controls or pre-rOA. Rates of change did not differ between groups. Within the JSN groups differences of 0.2-0.4% were found in the femur (P < 0.05). CONCLUSION: We find that knee tABs differ in rOA between baseline and year-1, but the change was not greater than in healthy knees, and is restricted to the femur in JSN.

Five-year followup of knee joint cartilage thickness changes after acute rupture of the anterior cruciate ligament.

OBJECTIVE: Anterior cruciate ligament (ACL) rupture involves an increased risk of osteoarthritis. The purpose of this study was to explore changes in cartilage thickness over 5 years after ACL rupture. METHODS: A total of 121 young active adults (ages 18-35 years; 26% women) from the Knee ACL, Nonsurgical versus Surgical Treatment (KANON) study, who had acute traumatic rupture of the ACL were studied. Sagittal magnetic resonance images were acquired within 4 weeks of ACL rupture (baseline) and at the 2-year and 5-year followup assessments. Medial and lateral femorotibial cartilage was segmented (with blinding to acquisition order), and the mean cartilage thickness was computed across 16 femorotibial subregions. Total femorotibial cartilage thickness change was the primary analytic focus. Maximal subregional mean cartilage thickness loss (ordered value 1 [OV1]) and gain (ordered value 16 [OV16]), independent of its specific location in individual knees, were the secondary analytic focus. RESULTS: Overall femorotibial cartilage thickness increased by 31 µm/year over 5 years (95% confidence interval 18, 44). The increase was similar in men and women and was significantly greater in those younger, as compared with those older, than the median age (25.3 years). The rate of total cartilage thickness change did not differ significantly between the first 2 years and the later 3 years. However, the maximal annualized subregional cartilage loss (OV1) and gain (OV16) were both significantly greater (P < 0.001 and P < 0.05, respectively) during the earlier interval than during the later interval (-115 versus -54 µm [OV1] and 116 versus 69 µm [OV16]). CONCLUSION: Cartilage thickening was observed over 5 years following ACL injury, particularly in the medial femorotibial compartment and in younger subjects. Major perturbations in cartilage homeostasis were seen over the first 2 years after ACL rupture, with simultaneous subregional thinning and thickening occurring within the same cartilage plate or compartment.

Longitudinal analysis of MR spin-spin relaxation times (T2) in medial femorotibial cartilage of adolescent vs mature athletes: dependence of deep and superficial zone properties on sex and age.

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.

Relative distribution of quadriceps head anatomical cross-sectional areas and volumes--sensitivity to pain and to training intervention.

INTRODUCTION: Quadriceps heads are important in biomechanical stabilization and in the pathogenesis osteoarthritis of the knee. This is the first study to explore the relative distribution of quadriceps head anatomical cross-sectional areas (ACSA) and volumes, and their response to pain and to training intervention. METHODS: The relative proportions of quadriceps heads were determined in 48 Osteoarthritis Initiative participants with unilateral pain (65% women; age 45-78 years). Quadriceps head volumes were also measured in 35 untrained women (45-55 years) before and after 12-week training intervention. Cross-sectional areas of the vastus medialis (VM), inter-medius (VIM), and lateralis (VL), and of the rectus femoris (RF) were determined from axial T1-weighted MR images. RESULTS: The proportion of the VM on the total quadriceps ACSA increased from proximal to distal. The difference in quadriceps ACSA of painful (vs. pain-free) limbs was -5.4% for the VM (p<0.001), -6.8% for the VL (p<0.01), -2.8% for the VIM (p=0.06), and +3.4% for the RF (p=0.67) but the VM/VL ratio was not significantly altered. The muscle volume increase during training intervention was +4.2% (p<0.05) for VM, +1.3% for VL, +2.0% for VIM (p<0.05) and +1.6% for RF. CONCLUSION: The proportion of quadriceps head relative to total muscle ACSA and volume depends on the anatomical level studied. The results suggest that there may be a differential response of the quadriceps heads to pain-induced atrophy and to training-related hypertrophy. Studies in larger samples are needed to ascertain whether the observed differences in response to pain and training are statistically and clinically significant.

Lateral and medial joint space narrowing predict subsequent cartilage loss in the narrowed, but not in the non-narrowed femorotibial compartment--data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the predictive value of unicompartimental joint space narrowing (JSN) for MRI-based cartilage thickness loss in the narrowed and the non-narrowed femorotibial compartment. METHODS: 922 knees from 922 Osteoarthritis Initiative (OAI) participants (62.2 ± 9.0 years, 61% females) with radiographic OA (158 without JSN [noJSN], 175 with lateral JSN [latJSN], 589 with medial JSN [medJSN]) were analyzed using 3 T MRI. One-year cartilage thickness change was determined in the lateral (LFTC) and medial femorotibial compartment (MFTC), and in femorotibial subregions. The probability of subsequent cartilage loss was calculated using predefined thresholds. The predictive value of JSN for the probability and magnitude of cartilage loss was compared between latJSN, medJSN and noJSN knees using Fisher's exact and Mann-Whitney-U tests. RESULTS: The probability of cartilage loss was greater in the narrowed compartment of latJSN/medJSN knees (34.9%/32.4%) than in noJSN knees (13.3%/12.7%, P ≤ 6.4 × 10(-6)) and so was the magnitude of cartilage thickness change (P ≤ 8.2 × 10(-6)). No significant differences were observed between the narrowed compartments of latJSN vs. medJSN knees (probability: P = 0.58, magnitude: P = 0.19) or between the non-narrowed compartment of latJSN/medJSN vs. noJSN knees (probability: P ≥ 0.35, magnitude: P = ≥0.23). These results were confirmed by the location-independent ordered value (OV) analyses of femorotibial subregions. CONCLUSION: The predictive value of latJSN for lateral compartment cartilage loss was comparable to that of medJSN for medial compartment cartilage loss, whereas cartilage loss in the non-narrowed compartment was similar to that in noJSN knees. These findings provide important clues to predicting progression of knee OA, and in tailoring inclusion criteria for clinical trials.

How do short-term rates of femorotibial cartilage change compare to long-term changes? Four year follow-up data from the osteoarthritis initiative.

OBJECTIVE: To compare unbiased estimates of short- vs long-term cartilage loss in osteoarthritic knees. METHOD: 441 knees [216 Kellgren Lawrence (KL) grade 2, 225 KL grade 3] from participants of the Osteoarthritis Initiative were studied over a 4-year period. Femorotibial cartilage thickness was determined using 3 T double echo steady state magnetic resonance imaging, the readers being blinded to time points. Because common measurement time points bias correlations, short-term change (year-1 to year-2: Y1 â†’ Y2) was compared with long-term change (baseline to year-4: BL â†’ Y4), and initial (BL â†’ Y1) with subsequent (Y2 â†’ Y4) observation periods. RESULTS: The mean femorotibial cartilage thickness change (standardized response mean) was -1.2%/-0.8% (-0.42/-0.28) over 1 (BL â†’ Y1/Y1 â†’ Y2), -2.1%/-2.5% (-0.56/-0.55) over 2 (BL â†’ Y2/Y2 â†’ Y4), -3.3% (-0.63) over 3 (Y1 â†’ Y4), and -4.5% (-0.78) over 4 years. Spearman correlations were 0.33 for Y1 â†’ Y2 vs BL â†’ Y4, and 0.17 for BL â†’ Y1 vs Y2 â†’ Y4 change. Percent agreement between knees showing progression during Y1 â†’ Y2 vs BL â†’ Y4 was 59%, and 64% for BL â†’ Y1 vs Y2 â†’ Y4. The area under the receiver operating characteristic curve was 0.66 for using Y1 â†’ Y2 to predict BL â†’ Y4, and 0.59 for using BL â†’ Y1 to predict Y2 â†’ Y4 change. CONCLUSION: Weak to moderate correlations and agreement were observed between individual short- vs long-term cartilage loss, and between initial and subsequent observation periods. Hence, longer observation periods are recommended to achieve robust results on cartilage loss in individual knees. At cohort and subcohort level (e.g., KLG3 vs KLG2 knees), the mean cartilage loss increased almost linearly with the length of the observation period and was constant throughout the study.

Side differences of thigh muscle cross-sectional areas and maximal isometric muscle force in bilateral knees with the same radiographic disease stage, but unilateral frequent pain - data from the osteoarthritis initiative.

OBJECTIVE: To determine whether anatomical thigh muscle cross-sectional areas (MCSAs) and strength differ between osteoarthritis (OA) knees with frequent pain compared with contra-lateral knees without pain, and to examine the correlation between MCSAs and strength in painful vs painless knees. METHODS: Forty-eight subjects (31 women; 17 men; age 45-78 years) were drawn from 4,796 Osteoarthritis Initiative (OAI) participants, in whom both knees displayed the same radiographic stage (KLG2 or 3), one with frequent pain (most days of the month within the past 12 months) and the contra-lateral one without pain. Axial MR images were used to determine MCSAs of extensors, flexors and adductors at 35% femoral length (distal to proximal) and in two adjacent 5 mm images. Maximal isometric extensor and flexor forces were used as provided from the OAI database. RESULTS: Painful knees showed 5.2% lower extensor MCSAs (P=0.00003; paired t-test), and 7.8% lower maximal extensor muscle forces (P=0.003) than contra-lateral painless knees. There were no significant differences in flexor forces, or flexor and adductor MCSAs (P>0.39). Correlations between force and MCSAs were similar in painful and painless OA knees (0.44

Nocturnal changes in knee cartilage thickness in young healthy adults.

Magnetic resonance imaging (MRI) allows one to analyze cartilage physiology in vivo. Cartilage deforms during loading, but little is known about its recovery after deformation. Here we study 'nocturnal' changes in knee cartilage thickness and whether postexercise deformation differs between morning and evening. Axial magnetic resonance (MR) images were acquired in the right knees of 17 healthy volunteers (age 23.5 ± 3.0 years) after a normal day, and then after 30 deep knee bends. Coronal images were additionally acquired in 8 of these volunteers after a normal day and then after 2 min of static loading of the leg with 150% body weight. The volunteers then remained unloaded overnight and the same protocol was repeated in the morning. A significant increase (p < 0.01) in cartilage thickness was observed between evening (preexercise) and morning (preexercise): +2.4% in the patella, +8.4% in the medial tibia and +6.2% in the lateral tibia. Deformation in the morning (-6.8/ -4.6/-5.1%) was generally greater than that in the evening (-5.4/-3.2/-3.7%), but this difference did not reach statistical significance. No significant difference in the nocturnal thickness increase (or postexercise deformation) was observed between men and women. We conclude that knee cartilage (thickness) recovers overnight by approximately 2-8%, independent of sex. Given the lack of 'predeformation' after nocturnal periods of unloading, morning postexercise deformation of the cartilage may have a greater magnitude than evening postexercise deformation.

Morphometric differences between the medial and lateral meniscus in healthy men - a three-dimensional analysis using magnetic resonance imaging.

The objective of this work was to characterize tibial plateau coverage and morphometric differences of the medial (MM) and lateral meniscus (LM) in a male reference cohort using three-dimensional imaging. Coronal multiplanar reconstructions of a sagittal double-echo steady state with water excitation magnetic resonance sequence (slice thickness: 1.5 mm, and in-plane resolution: 0.37 × 0.70 mm) were analyzed in 47 male participants without symptoms, signs or risk factors of knee osteoarthritis of the reference cohort of the Osteoarthritis Initiative. The medial and lateral tibial (LT) plateau cartilage area and the tibial, femoral and external surfaces of the MM and LM were manually segmented throughout the entire knee. This process was assisted by parallel inspection of a coronal intermediately weighted turbo spin echo sequence. Measures of tibial coverage, meniscus size, and meniscus position were computed three-dimensionally for the total menisci, the body, and the anterior and the posterior horn. The LM was found to cover a significantly greater (p < 0.001) proportion of the LT plateau (59 ± 6.8%) than the MM of the medial plateau (50 ± 5.5%). Whereas the volume of both menisci was similar (2.444 vs. 2.438 ml; p = 0.92), the LM displayed larger tibial and femoral surface areas (p < 0.05) and a smaller maximal (7.2 ± 1.0 vs. 7.7 ± 1.1 mm; p < 0.01) and mean thickness (2.7 ± 0.3 vs. 2.8 ± 0.3 mm; p < 0.001) than the medial one. Also, the LM displayed less (physiological) extrusion than the medial one. These data may guide strategies for meniscal tissue engineering and transplantation aiming to restore normal joint conditions.

Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging.

In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI-based grading of the tibial cartilage was also compared with a 'macroscopic' grading based on direct visual inspection of dissected joints. The test-retest precision for MRI-based measurement was ≤6.4%. MRI-based measurements correlated well with volumes of surgically resected cartilage (r = 0.97, pair-wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non-operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP-treated group than in the non-treated group.

MRI-based extended ordered values more efficiently differentiate cartilage loss in knees with and without joint space narrowing than region-specific approaches using MRI or radiography--data from the OA initiative.

OBJECTIVE: The sensitivity to change of quantitative analysis of cartilage in knee osteoarthritis using magnetic resonance imaging (MRI) is compromised by the spatial heterogeneity of cartilage loss. We explore whether extended (medial-lateral) "ordered values" (OVs) are superior to conventional approaches of analyzing subregional cartilage thickness loss and to radiography, in differentiating rates of progression in knees with and without joint space narrowing (JSN). METHODS: 607 Osteoarthritis Initiative (OAI) participants (308 without and 299 with baseline JSN at baseline) were studied over 12 months. Subregional femorotibial cartilage loss was determined in all knees, and changes in minimum joint space width (mJSW) in a subset of 290 knees. Subregional thickness changes in medial and lateral tibial and femoral cartilages were sorted in ascending order (OV1-16). A Wilcoxon rank-sum test was used to compare rates of change in knees with and without JSN. RESULTS: JSN-knees displayed greater cartilage loss than those without JSN, with minimal P-values of 0.008 for femorotibial subregions, 3.3×10(-4) for medial OV1, and 5.4×10(-7) for extended (medial and lateral) OV1. mJSW measurements (n=290) did not discriminate between longitudinal rates of change in JSN vs no-JSN knees (P=0.386), whereas medial OV1 (P=5.1×10(-4)) and extended OV1 did (P=2.1×10(-5)). CONCLUSION: Extended OVs showed higher sensitivity to detecting differences in longitudinal rates of cartilage loss in knees with and without baseline JSN than anatomical (sub)regions and radiography. The OV technique also circumvents challenges of selecting particular regions "a priori" in clinical trials and may thus provide a powerful tool in studying risk factors or treatment efficacy in osteoarthritis.

Comparison of 1-year vs 2-year change in regional cartilage thickness in osteoarthritis results from 346 participants from the Osteoarthritis Initiative.

OBJECTIVE: To compare femorotibial cartilage thickness changes over a 2- vs a 1-year observation period in knees with radiographic knee osteoarthritis (OA). METHODS: One knee of 346 Osteoarthritis Initiative (OAI) participants was studied at three time points [baseline (BL), year-1 (Y1), year-2 (Y2) follow-up]: 239 using coronal fast low angle shot (FLASH) and 107 using sagittal double echo at steady state (DESS) MR imaging. Changes in cartilage thickness were assessed in femorotibial cartilage plates and subregions, after manual segmentation with blinding to time-point. RESULTS: The standardized response mean (SRM) of total joint cartilage thickness over 2 years was modestly higher than over 1 year (FLASH: -0.44 vs -0.32/-0.28 [first/second year]; DESS: -0.42 vs -0.39/-0.18). For the subregion showing the largest change per knee (OV1), the 2-year SRM was similar or lower (FLASH: -1.20 vs -1.22/-1.61; DESS: -1.38 vs -1.64/-1.51) than the 1-year SRM. The changes in total joint cartilage thickness were not significantly different in the first and second year (FLASH: -0.8% vs -0.7%; DESS: -1.3% vs -0.8%) and were negatively correlated. Analysis of smallest detectable changes (SDCs) revealed that only few participants displayed significant progression in both consecutive periods. The location of the subregion contributing to OV1 in each knee was highly inconsistent between the first and second year observation period. CONCLUSIONS: The SRM of region-based cartilage thickness change in OA is modestly larger following a 2-year vs a 1-year observation period, while it is relatively similar when an OV-approach is chosen. Structural progression displays strong temporal and spatial heterogeneity at an individual knee level that should be considered when planning clinical trials.

Reference values and Z-scores for subregional femorotibial cartilage thickness--results from a large population-based sample (Framingham) and comparison with the non-exposed Osteoarthritis Initiative reference cohort.

OBJECTIVE: To establish sex-specific (subregional) reference values of cartilage thickness and potential maximal Z-scores in the femorotibial joint. METHODS: The mean cartilage thickness (ThCtAB.Me) in femorotibial compartments, plates and subregions was determined on coronal magnetic resonance imaging (MRI) from a population-based sample (Framingham) and from a healthy reference sample of the Osteoarthritis Initiative (OAI). RESULTS: 686 Framingham participants (309 men, 377 women, age 62 ± 8 years) had no radiographic femorotibial osteoarthritis (OA) ("normals") and 376 (156 men, 220 women) additionally had no MRI features of cartilage lesions ("supernormals"). The Framingham "normals" had thinner cartilage in the medial (3.59 mm) than in the lateral femorotibial compartment (3.86 mm). Medially, the femur displayed thicker cartilage (1.86 mm) than the tibia (1.73 mm), and laterally the tibia thicker cartilage (2.09 mm) than the femur (1.77 mm). The thickest cartilage was observed in central, and the thinnest in external femorotibial subregions. Potential maximal Z-scores ranged from 5.6 to 9.8 throughout the subregions; men displayed thicker cartilage but similar potential maximal Z-scores as women. Mean values and potential maximal Z-scores in Framingham "supernormals" and non-exposed OAI reference participants (112 participants without symptoms or risk factors of knee OA) were similar to Framingham "normals". CONCLUSIONS: We provide reference values and potential maximal Z-scores of cartilage thickness in middle aged to elderly non-diseased populations without radiographic OA. Results were similar for "supernormal" participants without MRI features of cartilage lesions, and in a cohort without OA symptoms or risk factors. A cartilage thickness loss of around 27% is required for attaining a Z-score of -2.

Femorotibial cartilage morphology: reproducibility of different metrics and femoral regions, and sensitivity to change in disease.

This study was designed to characterize the reproducibility and sensitivity to change of magnetic resonance imaging-based cartilage morphology metrics and femoral regions of interest (ROIs), in order to provide preferable outcome measures in longitudinal studies of cartilage morphology. Test-retest acquisitions were obtained at 3 tesla (T) in 33 subjects with and without radiographic signs of osteoarthritis (OA) (reproducibility study) as well as baseline and 2-year follow-up acquisitions in 28 subjects with radiographic signs of advanced OA (sensitivity study). Cartilage was segmented in the tibia and two distinct anatomical femoral ROIs, a 'long' ROI extending 60% from the trochlear notch to the posterior end of the condyles, and a 'short' ROI extending to the intercondylar bone bridge. Coefficients of variation (reproducibility study) and standardized response means (SRMs, sensitivity study) were obtained for different morphology metrics and anatomical regions. The subchondral bone area of the long ROI was 20% greater and less variable than that of the short ROI; cartilage morphology metrics were generally more reproducible in the long ROI. Normalized cartilage volume (VCtAB) and mean cartilage thickness (over the entire subchondral bone area; ThCtAB.Me) tended to be more reproducible and more sensitive to change (SRM up to -0.62) than cartilage volume (SRM up to -0.44), cartilage thickness over the cartilaginous area (ThCcAB; SRM up to -0.48) or maximum cartilage thickness (ThCtAB; SRM up to -0.35). The long femoral cartilage ROI provided more reproducible measurements than the short one. VCtAB and ThCtAB.Me may be preferable metrics in longitudinal studies of articular cartilage adaptation or OA.

Correlation between single-slice muscle anatomical cross-sectional area and muscle volume in thigh extensors, flexors and adductors of perimenopausal women.

Quantitative data on muscle volume (MV) are important for estimating maximal muscle power. The objective of this study was to determine the correlation between anatomical cross-sectional areas (ACSAs) and the MV in thigh muscles (extensors, flexors, adductors, and sartorius) in perimenopausal women, and to identify at which proximal-to-distal level a single-slice ACSA measurement with magnetic resonance imaging (MRI) displays the highest correlation in each of these. Axial MRIs of the thigh were acquired in 41 perimenopausal women aged 50.8 +/- 3.2 years. Segmentation of the extensors, flexors, adductors, and the sartorius was performed between the femoral neck (0%) and the distal end of the intermediate vastus (100%). MVs were determined by numerical integration, and the ACSA was calculated from three-dimensional reconstructions at 10% intervals from proximal to distal. The extensors contributed 50%, the flexors 19%, the adductors 28%, and the sartorius 3% of the total thigh MV. Maximal correlations between ACSA and MV were observed at the 20-40% proximal-to-distal level in the extensors (R (2) = 0.73), at 30% in the adductors (R (2) = 0.82), and at 70% in the flexors (R (2) = 0.72) and sartorius (R (2) = 0.85), respectively. ACSA at 50% displayed the highest overall correlations (R (2) >or= 0.69) with MV for all muscle groups. Single-slice ACSAs from MRI displayed high correlations with MVs. Although the (proximal to distal) measurement locations with the highest correlation varied between the muscle groups, a single slice at the 50% location achieved the best compromise in terms of correlation between ACSA and MV across extensors, flexors, adductors and the sartorius.

Presence, location, type and size of denuded areas of subchondral bone in the knee as a function of radiographic stage of OA - data from the OA initiative.

OBJECTIVE: To assess the presence, location, type and size of denuded areas of subchondral bone (dAB) in the femorotibial joint, measured quantitatively with 3T MRI, in a large subset of OAI participants. METHODS: One knee of 633 subjects (250 men, 383 women, aged 61.7+/-9.6 y) were studied, spanning all radiographic osteoarthritis (OA) stages. dABs were determined quantitatively using segmentations of coronal FLASHwe images, representing areas where the subchondral bone was not covered by cartilage. Post hoc visual examination of segmented images determined whether dABs represented full thickness cartilage loss or internal osteophyte. RESULTS: 7% Of the knees were Kellgren & Lawrence (KL) grade 0, 6% grade 1, 41% grade 2, 41% grade 3, and 5% grade 4. 39% Of the participants (48% of the men and 33% of the women) displayed dABs; 61% of the dABs represented internal osteophytes. 1/47 Participants with KL grade 0 displayed 'any' dAB whereas 29/32 of the KL grade 4 knees were affected. Even as early as KL grade 1, 29% of the participants showed dABs. There were significant relationships of dAB with increasing KL grades (P<0.001) and with ipsi-compartimental JSN (P< or =0.001). Internal osteophytes were more frequent laterally (mainly posterior tibia and internal femur) whereas full thickness cartilage loss was more frequent medially (mainly external tibia and femur). CONCLUSIONS: dABs occur already at earliest stages of radiographic OA (KL grades 1 and 2) and become more common (and larger) with increasing disease severity. Almost all KL grade 4 knees exhibited dABs, with cartilage loss being more frequent than internal osteophytes.

Effects of exercise intervention on knee morphology in middle-aged women: a longitudinal analysis using magnetic resonance imaging.

INTRODUCTION: Epidemiological studies show a positive relationship between physical activity and cartilage volume, suggesting that exercise may protect against osteoarthritis. Cross-sectional experimental studies, however, have failed to show significant differences in knee cartilage morphology between athletes and nonathletic controls. The aim of the study was to test the hypothesis that knee cartilage morphology, specifically regional cartilage thickness and global subchondral bone area, is modified in sedentary, untrained adult women who increased their physical fitness during a 3-month supervised exercise intervention. MATERIALS AND METHODS: Thirty-eight untrained women, aged 45-55 years, were randomly assigned to: endurance training (n = 18), strength training (n = 15) and autogenic training (control group, n = 5). Patellar and femorotibial knee cartilage morphology was determined before and after the 3-month supervised training intervention, using magnetic resonance imaging and state-of-the-art image analysis. RESULTS: Whereas the endurance training group showed a significant increase in cardiorespiratory fitness and the strength training group a significant increase in the maximal voluntary isometric contraction force of the leg, this study did not show significant differences in knee cartilage thickness and volume, subchondral bone area or regional cartilage thickness between baseline and follow-up acquisitions within any intervention group. DISCUSSION: This randomized longitudinal study provides no evidence that a 3-month exercise intervention in untrained middle-aged women can significantly alter knee joint morphology. Longitudinal evidence supporting that a training program, successful in increasing physical fitness, can also induce functional adaptation of articular tissues and may protect against knee osteoarthritis, remains to be presented.

Sensitivity to change of cartilage morphometry using coronal FLASH, sagittal DESS, and coronal MPR DESS protocols--comparative data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: The Osteoarthritis Initiative (OAI) is targeted at identifying sensitive biomarkers and risk factors of symptomatic knee osteoarthritis (OA) onset and progression. Quantitative cartilage imaging in the OAI relies on validated fast low angle shot (FLASH) sequences that suffer from relatively long acquisition times, and on a near-isotropic double echo steady-state (DESS) sequence. We therefore directly compared the sensitivity to cartilage thickness changes and the correlation of these protocols longitudinally. METHODS: Baseline (BL) and 12 month follow-up data of 80 knees were acquired using 1.5 mm coronal FLASH and 0.7 mm sagittal DESS (sagDESS) sequences. In these and in 1.5 mm coronal multi-planar reconstructions (MPR) of the DESS the medial femorotibial cartilage was segmented with blinding to acquisition order. In the weight-bearing femoral condyle, a 60% (distance between the trochlear notch and the posterior femur) and a 75% region of interest (ROI) were studied. RESULTS: The standardized response mean (SRM = mean change/standard deviation of change) in central medial femorotibial (cMFTC) cartilage thickness was -0.34 for coronal FLASH, -0.37 for coronal MPR DESS, -0.36 for sagDESS with the 60% ROI, and -0.38 for the 75% ROI. Using every second 0.7 mm sagittal slice (DESS) yielded similar SRMs in cMFTC for the 60% and 75% ROI from odd (-0.35/-0.36) and even slice numbers (-0.36/-0.39), respectively. BL cartilage thickness displayed high correlations (r > or = 0.94) between the three protocols; the correlations of longitudinal changes were > or = 0.79 (Pearson) and > or = 0.45 (Spearman). CONCLUSIONS: Cartilage morphometry with FLASH and DESS displays similar longitudinal sensitivity to change. Analysis of every second slice of the 0.7 mm DESS provides adequate sensitivity to change.

Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees.

OBJECTIVE: To explore whether longitudinal change in cartilage thickness in femorotibial subregions of knees with radiographic osteoarthritis (ROA) differs from that in healthy knees. METHODS: 3T coronal magnetic resonance (MR) images were acquired in 152 women at seven clinical centers at baseline (BL) and 24 months. Knees from 75 women with signs of ROA in either anterior-posterior or Lyon schuss radiographs were compared with those from 77 asymptomatic healthy controls without ROA to identify knees showing greater change in cartilage thickness than expected based on observations in healthy knees. The femorotibial cartilage thickness was determined in BL and follow-up MR images across five tibial and three femoral subregions in the medial/lateral compartment, respectively. RESULTS: A substantial portion of knees with ROA were classified as having longitudinal cartilage thinning (28%) or thickening (20%) in at least one medial femorotibial subregion based on comparisons to longitudinal changes observed in healthy knees; only 5% showed both subregional thinning and thickening across (different) medial subregions at the same time. Whereas the estimated proportion of Kellgren Lawrence grade (KLG) 3 knees (n=28) with significant medial cartilage thinning (46%) was substantially greater than that with cartilage thickening (18%), the estimated percentages of KLG2 knees (n=30) with significant medial thinning (20%) and thickening (23%) were similar. CONCLUSION: This exploratory study indicates that OA may not be a one-way-road of cartilage loss. Subregional analysis suggests that, compared with healthy knees, cartilage changes in ROA may occur in both directions. Medial femorotibial cartilage thickening was observed as frequently as cartilage thinning in KLG2 knees.