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  • Evaluating the Relationship between Dynamic Na[F-18]F-Uptake Parameters and MRI Knee Osteoarthritic Findings Watkins, L., MacKay, J., Haddock, B., Mazzoli, V., Uhlrich, S., Gold, G., Kogan, F. SOC NUCLEAR MEDICINE INC. 2020
  • Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population. NMR in biomedicine Watkins, L. E., Rubin, E. B., Mazzoli, V., Uhlrich, S. D., Desai, A. D., Black, M., Ho, G. K., Delp, S. L., Levenston, M. E., Beaupré, G. S., Gold, G. E., Kogan, F. 2020: e4310


    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.

    View details for DOI 10.1002/nbm.4310

    View details for PubMedID 32445515

  • Connecting the legs with a spring improves human running economy. The Journal of experimental biology Simpson, C. S., Welker, C. G., Uhlrich, S. D., Sketch, S. M., Jackson, R. W., Delp, S. L., Collins, S. H., Selinger, J. C., Hawkes, E. W. 2019


    Human running is inefficient. For every ten calories burned, less than one is needed to maintain a constant forward velocity-the remaining energy is, in a sense, wasted. The majority of this wasted energy is expended to support the bodyweight and redirect the center of mass during the stance phase of gait. An order of magnitude less energy is expended to brake and accelerate the swinging leg. Accordingly, most devices designed to increase running efficiency have targeted the costlier stance phase of gait. An alternative approach is seen in nature: spring-like tissues in some animals and humans are believed to assist leg swing. While it has been assumed that such a spring simply offloads the muscles that swing the legs, thus saving energy, this mechanism has not been experimentally investigated. Here we show that a spring, or 'exotendon', connecting the legs of a human reduces the energy required for running by 6.4±2.8%, and does so through a complex mechanism that produces savings beyond those associated with leg swing. The exotendon applies assistive forces to the swinging legs, increasing the energy optimal stride frequency. Runners then adopt this frequency, taking faster and shorter strides, and reduce the joint mechanical work to redirect their center of mass. Our study shows how a simple spring improves running economy through a complex interaction between the changing dynamics of the body and the adaptive strategies of the runner, highlighting the importance of considering each when designing systems that couple human and machine.

    View details for DOI 10.1242/jeb.202895

    View details for PubMedID 31395676

  • Assessment of acute bone loading in humans using [18F]NaF PET/MRI. European journal of nuclear medicine and molecular imaging Haddock, B., Fan, A. P., Uhlrich, S. D., Jorgensen, N. R., Suetta, C., Gold, G. E., Kogan, F. 2019


    PURPOSE: The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [18F]-sodium fluoride ([18F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading.METHODS: Twelve healthy subjects underwent two consecutive 50-min [18F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of KiNLR, K1, k2, k3, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUVmax were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone.RESULTS: Exercise induced a significant (p<<0.001) increase in [18F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K1 and blood volume) increased, whereas the NaF extraction fraction [k3/(k2+k3)] was reduced.CONCLUSIONS: Bone loading induces an acute response in bone physiology as quantified by [18F]NaF PET kinetics. Dynamic imaging after bone loading using [18F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.

    View details for DOI 10.1007/s00259-019-04424-2

    View details for PubMedID 31385012

  • Subject-specific toe-in or toe-out gait modifications reduce the larger knee adduction moment peak more than a non-personalized approach JOURNAL OF BIOMECHANICS Uhlrich, S. D., Slider, A., Beaupre, G. S., Shull, P. B., Delp, S. L. 2018; 66: 103–10


    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 ± 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 ± 17.1%, p = .013) or toed-out by 10° (11.0 ± 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.

    View details for PubMedID 29174534

    View details for PubMedCentralID PMC5859947