Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population.

Chemical exchange saturation transfer of glycosaminoglycans, gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 T and higher. However, its utility at 3 T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3 T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison with T2 and T1ρ measures. We hypothesize that gagCEST asymmetry at 3 T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including 10 healthy subjects and 32 subjects with medial OA, were included in the study. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects, and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3 T to assess the repeatability of the volumetric gagCEST sequence at 3 T. For healthy and OA subjects, gagCEST asymmetry and T2 and T1ρ relaxation times were calculated for the femoral articular cartilage to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single-slice acquisitions (p = 0.015). The average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T2 and T1ρ relaxation times were elevated in OA subjects (p < 0.001 for both) compared with healthy controls and both were moderately correlated with total KOOS scores (rho = -0.181 and rho = -0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 min and high gagCEST asymmetry at 3 T, did not vary significantly between healthy subjects and those with mild-moderate OA. This further supports a limited utility for gagCEST imaging at 3 T for assessment of early changes in cartilage composition in OA.

A viscoelastic constitutive model can accurately represent entire creep indentation tests of human patella cartilage.

Cartilage material properties provide important insights into joint health, and cartilage material models are used in whole-joint finite element models. Although the biphasic model representing experimental creep indentation tests is commonly used to characterize cartilage, cartilage short-term response to loading is generally not characterized using the biphasic model. The purpose of this study was to determine the short-term and equilibrium material properties of human patella cartilage using a viscoelastic model representation of creep indentation tests. We performed 24 experimental creep indentation tests from 14 human patellar specimens ranging in age from 20 to 90 years (median age 61 years). We used a finite element model to reproduce the experimental tests and determined cartilage material properties from viscoelastic and biphasic representations of cartilage. The viscoelastic model consistently provided excellent representation of the short-term and equilibrium creep displacements. We determined initial elastic modulus, equilibrium elastic modulus, and equilibrium Poisson's ratio using the viscoelastic model. The viscoelastic model can represent the short-term and equilibrium response of cartilage and may easily be implemented in whole-joint finite element models.

Comparison of MRI and ¹8F-NaF PET/CT in patients with patellofemoral pain.

PURPOSE: To determine whether bone metabolic activity corresponds to bone and cartilage damage in patients with patellofemoral pain. MATERIALS AND METHODS: We acquired magnetic resonance imaging (MRI) and (18) F-NaF positron emission tomography (PET) / computed tomography (CT) scans of the knees of 22 subjects. We compared locations of increased tracer uptake on the (18) F-NaF PET images to bone marrow edema and cartilage damage visualized on MRI. RESULTS: We found that increased bone activity on (18) F-NaF PET does not always correspond to structural damage in the bone or cartilage as seen on MRI. CONCLUSION: Our results suggest that (18) F-NaF PET/CT may provide additional information in patellofemoral pain patients compared to MRI.

Corrigendum: Long-Term Cognitive Impairments and Pathological Alterations in a Mouse Model of Repetitive Mild Traumatic Brain Injury.

[This corrects the article DOI: 10.3389/fneur.2014.00012.].

Changes in foot progression angle during gait reduce the knee adduction moment and do not increase hip moments in individuals with knee osteoarthritis.

People with knee osteoarthritis who adopt a modified foot progression angle (FPA) during gait often benefit from a reduction in the knee adduction moment. It is unknown, however, whether changes in the FPA increase hip moments, a surrogate measure of hip loading, which will increase the mechanical demand on the joint. This study examined how altering the FPA affects hip moments. Individuals with knee osteoarthritis walked on an instrumented treadmill with their baseline gait, 10° toe-in gait, and 10° toe-out gait. A musculoskeletal modeling package was used to compute joint moments from the experimental data. Fifty participants were selected from a larger study who reduced their peak knee adduction moment with a modified FPA. In this group, participants reduced the first peak of the knee adduction moment by 7.6% with 10° toe-in gait and reduced the second peak by 11.0% with 10° toe-out gait. Modifying the FPA reduced the early-stance hip abduction moment, at the time of peak hip contact force, by 4.3% ± 1.3% for 10° toe-in gait (p = 0.005, d = 0.49) and by 4.6% ± 1.1% for 10° toe-out gait (p < 0.001, d = 0.59) without increasing the flexion and internal rotation moments (p > 0.15). Additionally, 74% of individuals reduced their total hip moment at time of peak hip contact force with a modified FPA. In summary, when adopting a FPA modification that reduced the knee adduction moment, participants, on average, did not increase surrogate measures of hip loading.

Personalization improves the biomechanical efficacy of foot progression angle modifications in individuals with medial knee osteoarthritis.

Modifying the foot progression angle during walking can reduce the knee adduction moment, a surrogate measure of medial knee loading. However, not all individuals reduce their knee adduction moment with the same modification. This study evaluates whether a personalized approach to prescribing foot progression angle modifications increases the proportion of individuals with medial knee osteoarthritis who reduce their knee adduction moment, compared to a non-personalized approach. Individuals with medial knee osteoarthritis (N=107) walked with biofeedback instructing them to toe-in and toe-out by 5° and 10° relative to their self-selected angle. We selected individuals' personalized foot progression angle as the modification that maximally reduced their larger knee adduction moment peak. Additionally, we used lasso regression to identify which secondary kinematic changes made a 10° toe-in gait modification more effective at reducing the first knee adduction moment peak. Seventy percent of individuals reduced their larger knee adduction moment peak by at least 5% with a personalized foot progression angle modification, which was more than (p≤0.002) the 23-57% of individuals who reduced it with a uniformly assigned 5° or 10° toe-in or toe-out modification. When toeing-in, greater reductions in the first knee adduction moment peak were related to an increased frontal-plane tibia angle (knee more medial than ankle), a more valgus knee abduction angle, reduced contralateral pelvic drop, and a more medialized center of pressure in the foot reference frame. In summary, personalization increases the proportion of individuals with medial knee osteoarthritis who may benefit from a foot progression angle modification.

Maintaining femoral bone density in adults: how many steps per day are enough?

UNLABELLED: The amount and intensity of walking to maintain a healthy skeleton is unknown. This study examined the relationship between habitual walking activity and femoral bone mineral density (BMD) in healthy individuals using a quantitative theory for bone maintenance. Our results suggest a gender, weight, and speed sensitivity of walking interventions. INTRODUCTION: Walking has been extensively promoted for the prevention of osteoporosis. The amount and intensity of walking to maintain a healthy skeleton is unknown and evidence to support a specific target of steps per day is lacking. The goal of our study was to examine the relationship between habitual walking activity and femoral bone mineral density (BMD) in healthy individuals using a quantitative theory for bone maintenance. METHODS: Habitual walking activity and total femur BMD were measured in 105 individuals (49-64 years). An index of cumulative loading (bone density index, BDI) was examined as a predictor of BMD. The BDI-BMD relationship was used to predict the steps per day to maintain healthy BMD values for a range of body weights (BW) and walking speeds. RESULTS: For females but not for males, BDI was correlated with BMD (r (2) = 0.19, p < 0.001). The total required steps per day to maintain a T-score of -1.0 for a female with the average BW of the study cohort, walking at 1.00 m/s is 4,892 steps/day. Substantially more steps (18,568 steps/day) are required for a female with a BW 20% lighter than the average for our female cohort. For these lighter females, only at a walking speed greater than 1.32 m/s was 10,000 steps/day sufficient to maintain a T-score of -1.0. CONCLUSIONS: Our results suggest a gender, weight, and speed sensitivity of walking interventions for osteoporosis. In persons of low BW, the necessary steps per day to maintain BMD can be substantially greater than the often-quoted 10,000 steps.

Tibiofemoral forces during FES rowing in individuals with spinal cord injury.

The purpose of this study is to determine the tibiofemoral forces during functional electrical stimulation (FES) rowing in individuals with spinal cord injury (SCI). We analysed the motion of five participants with SCI during FES rowing, with simultaneous measurements of (i) three-dimensional marker trajectories, (ii) foot reaction forces (FRFs), (iii) ergometer handle forces, and (iv) timestamps for electrical stimulation of the quadriceps and hamstrings muscles. We created full-body musculoskeletal models in OpenSim to determine subject-specific tibiofemoral forces during FES rowing. The peak magnitudes of tibiofemoral forces averaged over five participants with SCI were 2.43 ± 0.39 BW and 2.25 ± 0.71 BW for the left and right legs, respectively. The peak magnitudes of FRFs were 0.19 ± 0.04 BW in each leg. The peak magnitude of handle forces was 0.47 ± 0.19 BW. Peak tibiofemoral force was associated with peak FRF (magnitudes, R2 = 0.56, p = 0.013) and peak handle force (magnitudes, R2 = 0.54, p = 0.016). The ratios of peak magnitude of tibiofemoral force to peak magnitude of FRF were 12.9 ± 1.9 (left) and 11.6 ± 2.4 (right), and to peak magnitude of handle force were 5.7 ± 2.3 (left) and 4.9 ± 0.9 (right). This work lays the foundation for developing a direct exercise intensity metric for bone mechanical stimulus at the knee during rehabilitation exercises. Clinical Significance: Knowledge of tibiofemoral forces from exercises such as FES rowing may provide clinicians the ability to personalize rehabilitation protocols to ensure that an SCI patient is receiving the minimum dose of mechanical stimulus necessary to maintain bone health.

pyKNEEr: An image analysis workflow for open and reproducible research on femoral knee cartilage.

Transparent research in musculoskeletal imaging is fundamental to reliably investigate diseases such as knee osteoarthritis (OA), a chronic disease impairing femoral knee cartilage. To study cartilage degeneration, researchers have developed algorithms to segment femoral knee cartilage from magnetic resonance (MR) images and to measure cartilage morphology and relaxometry. The majority of these algorithms are not publicly available or require advanced programming skills to be compiled and run. However, to accelerate discoveries and findings, it is crucial to have open and reproducible workflows. We present pyKNEEr, a framework for open and reproducible research on femoral knee cartilage from MR images. pyKNEEr is written in python, uses Jupyter notebook as a user interface, and is available on GitHub with a GNU GPLv3 license. It is composed of three modules: 1) image preprocessing to standardize spatial and intensity characteristics; 2) femoral knee cartilage segmentation for intersubject, multimodal, and longitudinal acquisitions; and 3) analysis of cartilage morphology and relaxometry. Each module contains one or more Jupyter notebooks with narrative, code, visualizations, and dependencies to reproduce computational environments. pyKNEEr facilitates transparent image-based research of femoral knee cartilage because of its ease of installation and use, and its versatility for publication and sharing among researchers. Finally, due to its modular structure, pyKNEEr favors code extension and algorithm comparison. We tested our reproducible workflows with experiments that also constitute an example of transparent research with pyKNEEr, and we compared pyKNEEr performances to existing algorithms in literature review visualizations. We provide links to executed notebooks and executable environments for immediate reproducibility of our findings.

Bone changes in the lower limbs from participation in an FES rowing exercise program implemented within two years after traumatic spinal cord injury.

Objective: To determine the effect of a functional electrical stimulation (FES) rowing program on bone mineral density (BMD) when implemented within two years after SCI.Design: Prospective.Setting: Health Care Facility.Participants: Convenience sample; four adults with recent (<2 years) traumatic, motor complete SCI (C7-T12 AIS A-B).Intervention: A 90-session FES rowing exercise program; participants attended 30-minute FES training sessions approximately three times each week for the duration of their participation.Outcome Measures: BMD in the distal femur and tibia were measured using peripheral Quantitative Computed Tomography (pQCT) at enrollment (T0) and after 30 (T1), 60 (T2), and 90 (T3) sessions. Bone stimulus was calculated for each rower at each time point using the average number of weekly loading cycles, peak foot reaction force, and bone mineral content from the previous time point. A regression analysis was used to determine the relationship between calculated bone stimulus and change in femoral trabecular BMD between time points.Results: Trabecular BMD in the femur and tibia decreased for all participants in T0-1, but the rate of loss slowed or reversed between T1-2, with little-to-no bone loss for most participants during T2-3. The calculated bone stimulus was significantly correlated with change in femoral trabecular BMD (P = 0.016; R2 = 0.458).Conclusion: Consistent participation in an FES rowing program provides sufficient forces and loading cycles to reduce or reverse expected bone loss at the distal femur and tibia, at least temporarily, in some individuals within two years after SCI.Trial Registration: NCT02008149.

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces.

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p = 0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.

Gender differences exist in the hip joint moments of healthy older walkers.

Gender differences in the incidence of symptomatic hip osteoarthritis (OA), changes in hip cartilage volume and hip joint space and rates hip arthroplasty of older people are reported in the literature. As the rate of progression of OA is in part mechanically modulated it is possible that this gender bias may be related to inherent differences (if they exist) in walking mechanics between older males and females. The purpose of this study was to examine potential mechanisms for gender differences in hip joint mechanics during walking by testing the hypotheses that females would exhibit higher hip flexion, adduction and internal rotation moments but not significantly greater normalized ground reaction forces (GRFs). Forty-two healthy subjects (21 male, 21 female), ages 50-79yr were recruited for gait analysis. In support of the hypotheses, greater external hip adduction and internal rotation along with hip extension moments were found for females compared to males after normalizing for body size for all self-selected walking speeds. Differences in walking style (kinematics) were the main determinants in the joint kinetic differences as no differences in the normalized GRFs were found. As external joint moments are surrogate measures of the joint contact forces, the results of this study suggest the hip joint stress for the female population is higher compared to male population. This is in favor of a hypothesis that the increased joint contact stress in a female population could contribute to a greater joint degeneration at the hip in females as compared with males.

A new software tool (VA-BATTS) to calculate bending, axial, torsional and transverse shear stresses within bone cross sections having inhomogeneous material properties.

INTRODUCTION: This study introduces, validates and demonstrates a new automated software tool (VA-BATTS) to calculate bone stresses within a bone cross section subjected to bending, axial, torsional and transverse shear far-field loading conditions, using quantitative computed tomography (QCT) data. METHODS: A QCT image is imported and processed to generate a 2D finite element (FE) mesh of the bone with inhomogeneous (CT-based) transversely isotropic material properties. Bending and axial stresses are determined using inhomogeneous beam theory; torsional and transverse shear stresses are calculated using a new 2D FE formulation. RESULTS: Validation studies show excellent agreement between results obtained using VA-BATTS and results obtained using analytical 2D models and inhomogeneous 3D FE models. DISCUSSION: Out-of-plane bone stresses can be accurately calculated using a 2D analysis. Material inhomogeneity can have a marked effect on predicted stresses. In three-point bending experiments, transverse shear may present important contributions to the failure potential. The software is available at https://simtk.org/home/va-batts.

Subject-specific toe-in or toe-out gait modifications reduce the larger knee adduction moment peak more than a non-personalized approach.

The knee adduction moment (KAM) is a surrogate measure for medial compartment knee loading and is related to the progression of knee osteoarthritis. Toe-in and toe-out gait modifications typically reduce the first and second KAM peaks, respectively. We investigated whether assigning a subject-specific foot progression angle (FPA) modification reduces the peak KAM by more than assigning the same modification to everyone. To explore the effects of motor learning on muscle coordination and kinetics, we also evaluated the peak knee flexion moment and quadriceps-hamstring co-contraction during normal walking, when subjects first learned their subject-specific FPA, and following 20 min of training. Using vibrotactile feedback, we trained 20 healthy adults to toe-in and toe-out by 5° and 10° relative to their natural FPA, then identified the subject-specific FPA as the angle where each subject maximally reduced their larger KAM peak. When walking at their subject-specific FPA, 18 subjects significantly reduced their larger KAM peak; 8 by toeing-in and 10 by toeing-out. On average, subjects reduced their larger KAM peak by 18.6 ±â€¯16.2% when walking at their subject-specific FPA, which was more than the reductions achieved when all subjects toed-in by 10° (10.0 ±â€¯17.1%, p = .013) or toed-out by 10° (11.0 ±â€¯18.3%, p = .002). Quadriceps-hamstring co-contraction and the peak knee flexion moment increased when subjects first learned their subject-specific FPA, but only co-contraction returned to baseline levels following training. These findings demonstrate that subject-specific gait modifications reduce the peak KAM more than uniformly assigned modifications and have the potential to slow the progression of medial compartment knee osteoarthritis.

Effectiveness of conservative treatment for patellofemoral pain syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence regarding the effectiveness of conservative treatment in reducing patellofemoral pain. DATA SOURCES: CENTRAL, MEDLINE, CINAHL, and PEDro databases. STUDY SELECTION: Adults with patellofemoral pain, randomized controlled trials only, any conservative treatment compared with placebo, sham, other conservative treatment, or no treatment. Two independent reviewers. DATA EXTRACTION: Data were extracted from the full-text of the articles, based on Cochrane Collaboration recommendations. The outcome of interest was the difference between groups regarding change in pain severity. DATA SYNTHESIS: The majority of studies were underpowered. More than 80% of the 37 trials did not show a clinically significant benefit. Clinically significant effects of different sizes were found for 7 trials (6 studies out of 7 had short follow-ups). These effects were found for: (i) pulsed electromagnetic fields combined with home exercise -33.0 (95% CI -45.2 to -20.8); (ii) hip muscle strengthening -65.0 (95% CI -87.7 to -48.3) and -32.0 (-37.0 to -27.0); (iii) weight-bearing exercise -40.0 (95% CI -49.4 to -30.6); (iv) neuromuscular facilitation combined with aerobic exercise and stretching -60.1 (95% CI -66.9 to -54.5); (v) postural stabilization -24.4 (95% CI -33.5 to -15.3); and (vi) patellar bracing -31.6 (95% CI -35.2 to -28.0). CONCLUSION: There is no evidence that a single treat-ment modality works for all patients with patellofemoral pain. There is limited evidence that some treatment modalities may be beneficial for some subgroups of patients with patellofemoral pain.

Pixel-Based DXA-Derived Structural Properties Strongly Correlate with pQCT Measures at the One-Third Distal Femur Site.

While bone mineral density has been traditionally used to quantify fracture risk for individuals with spinal cord injuries, recent studies are including engineering measurements such as section modulus and cross sectional moment of inertia. These are almost exclusively calculated by peripheral QCT scanners which, unlike DXA scanners, are rarely found in clinical settings. Using fifty-four fresh frozen femora, we developed and validated a pixel-by-pixel method to calculate engineering properties at the distal femur using a Hologic QDR-1000 W DXA scanner and compared them against similar parameters measured using a Stratec XCT-3000 peripheral QCT scanner. We found excellent agreement between standard DXA and pixel-by-pixel measured BMD (r 2 = 0.996). Cross-sectional moment of inertia about the anteroposterior axis measured using DXA and pQCT correlated very strongly (r 2 = 0.99). Cross-sectional moment of inertia about the anteroposterior axis measured using DXA also correlated strongly with pQCT measured bone strength index (r 2 = 0.99). These correlations indicate that DXA scans can measure equivalent pQCT parameters, and some existing DXA scans can be reprocessed with pixel-by-pixel techniques. Ultimately, these engineering parameters may help better quantify fracture-risk in fracture-prone populations such as those with spinal cord injuries.