Faculty Bibliography

Purpose To investigate whether assessment of bone strength with quantitative computed tomography (CT) in combination with dual-energy x-ray absorptiometry (DXA) is cost-effective as a screening tool for osteoporosis in postmenopausal women. Materials and Methods A state-transition microsimulation model of osteoporosis for postmenopausal women aged 55 years or older was developed with a lifetime horizon and U.S. societal perspective. All model inputs were derived from published literature. Three strategies were compared: no screening, DXA with T score-dependent rescreening intervals, and a combination of DXA and quantitative CT with different intervals (3, 5, and 10 years) at different screening initiation ages (55-65 years). Oral bisphosphonate therapy was started if DXA hip T scores were less than or equal to -2.5, 10-year risk for hip fracture was greater than 3% (World Health Organization Fracture Risk Assessment Tool score, or FRAX), 10-year risk for major osteoporotic fracture was greater than 20% (FRAX), quantitative CT femur bone strength was less than 3000 N, or occurrence of first fracture (eg, hip, vertebral body, wrist). Outcome measures were incremental cost-effectiveness ratios (ICERs) in 2015 U.S. dollars per quality-adjusted life year (QALY) gained and number of fragility fractures. Probabilistic sensitivity analysis was also performed. Results The most cost-effective strategy was combined DXA and quantitative CT screening starting at age 55 with quantitative CT screening every 5 years (ICER, $2000 per QALY). With this strategy, 12.8% of postmenopausal women sustained hip fractures in their remaining life (no screening, 18.7%; DXA screening, 15.8%). The corresponding percentages of vertebral fractures for DXA and quantitative CT with a 5-year interval, was 7.5%; no screening, 11.1%; DXA screening, 9%; for wrist fractures, 14%, 17.8%, and 16.4%, respectively; for other fractures, 22.6%, 30.8%, and 27.3%, respectively. In probabilistic sensitivity analysis, DXA and quantitative CT at age 55 years with quantitative CT screening every 5 years was the best strategy in more than 90% of all 1000 simulations (for thresholds of $50 000 per QALY and $100 000 per QALY). Conclusion Combined assessment of bone strength and bone mineral density is a cost-effective strategy for osteoporosis screening in postmenopausal women and has the potential to prevent a substantial number of fragility fractures. (c) RSNA, 2017 Online supplemental material is available for this article.

The goal of this paper was to evaluate the possibility of bi-component T1rho and T2 relaxation mapping of human skeletal muscle at 3 T in clinically feasible scan times. T1rho- and T2-weighted images of calf muscle were acquired using a modified 3D-SPGR sequence on a standard 3 T clinical MRI scanner. The mono- and biexponential models were fitted pixel-wise to the series of T1rho and T2 weighted images. The biexponential decay of T1rho and T2 relaxations was detected in ~30% and ~40% of the pixels across all volunteers, respectively. Monoexponential and bi-exponential short and long T1rho relaxation times were estimated to be 26.9 ms, 4.6 ms (fraction 22%) and 33.2 ms (fraction: 78%), respectively. Similarly, the mono- and bi-exponential short and long T2 relaxation times were 24.7 ms, 4.2 ms (fraction 15%) and 30.4 ms (fraction 85%) respectively. The experiments had good repeatability with RMSCV < 15% and ICC > 60%. This approach could potentially be used in exercise intervention studies or in studies of inflammatory myopathies or muscle fibrosis, permitting greater sensitivity and specificity via measurement of different water compartments and their fractions.

The purpose of this study was to demonstrate the feasibility of biexponential T1rho relaxation mapping of human knee cartilage in vivo. A three-dimensional, customized, turbo-flash sequence was used to acquire T1rho -weighted images from healthy volunteers employing a standard 3-T MRI clinical scanner. A series of T1rho -weighted images was fitted using monoexponential and biexponential models with two- and four-parametric non-linear approaches, respectively. Non-parametric Kruskal-Wallis and Mann-Whitney U-statistical tests were used to evaluate the regional relaxation and gender differences, respectively, with a level of significance of P = 0.05. Biexponential relaxations were detected in the cartilage of all volunteers. The short and long relaxation components of T1rho were estimated to be 6.9 and 51.0 ms, respectively. Similarly, the fractions of short and long T1rho were 37.6% and 62.4%, respectively. The monoexponential relaxation of T1rho was 32.6 ms. The experiments showed good repeatability with a coefficient of variation (CV) of less than 20%. A biexponential relaxation model showed a better fit than a monoexponential model to the T1rho relaxation decay in knee cartilage. Biexponential T1rho components could potentially be used to increase the specificity to detect early osteoarthritis by the measurement of different water compartments and their fractions.

Osteoporosis is a disease of weak bone and increased fracture risk caused by low bone mass and microarchitectural deterioration of bone tissue. The standard-of-care test used to diagnose osteoporosis, dual-energy x-ray absorptiometry (DXA) estimation of areal bone mineral density (BMD), has limitations as a tool to identify patients at risk for fracture and as a tool to monitor therapy response. Magnetic resonance imaging (MRI) assessment of bone structure and microarchitecture has been proposed as another method to assess bone quality and fracture risk in vivo. MRI is advantageous because it is noninvasive, does not require ionizing radiation, and can evaluate both cortical and trabecular bone. In this review article, we summarize and discuss research progress on MRI of bone structure and microarchitecture over the last decade, focusing on in vivo translational studies. Single-center, in vivo studies have provided some evidence for the added value of MRI as a biomarker of fracture risk or treatment response. Larger, prospective, multicenter studies are needed in the future to validate the results of these initial translational studies. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2016.

INTRODUCTION: Difficulty determining anatomic rotation following intramedullary (IM) nailing of the femur continues to be problematic for surgeons. Clinical exam and fluoroscopic imaging of the hip and knee have been used to estimate femoral version, but are inaccurate. We hypothesize that 3D c-arm imaging can be used to accurately measure femoral version following IM nailing of femur fractures to prevent rotational malreduction. METHODS: A midshaft osteotomy was created in a femur Sawbone to simulate a transverse diaphyseal fracture. An intramedullary (IM) nail was inserted into the Sawbone femur without locking screws or cephalomedullary fixation. A goniometer was used to simulate four femoral version situations after IM nailing: 20 degrees retroversion, 0 degrees version, 15 degrees anteversion, and 30 degrees anteversion. In each simulated position, 3D c-arm imaging and, for comparison purposes, perfect lateral radiographs of the knee and hip were performed. The femoral version of each simulated 3D and fluoroscopic case was measured and the results were tabulated. RESULTS: The measured version from the 3D c-arm images was 22.25 degrees retroversion, 0.66 degrees anteversion, 19.53 degrees anteversion, and 25.15 degrees anteversion for the simulated cases of 20 degrees retroversion, 0 degrees version, 15 degrees anteversion, and 30 degrees anteversion, respectively. The lateral fluoroscopic views were measured to be 9.66 degrees retroversion, 12.12 degrees anteversion, 20.91 degrees anteversion, and 18.77 degrees anteversion for the simulated cases, respectively. CONCLUSION: This study demonstrates the utility of a novel intraoperative method to evaluate femur rotational malreduction following IM nailing. The use of 3D c-arm imaging to measure femoral version offers accuracy and reproducibility.

Objectives: Continuous gradient-echo (GRE) acquisition or "dynamic magnetic resonance imaging", allows for high-speed examination of pathologies based on joint motion. We sought to assess the efficacy of a radial GRE sequence with in the characterization of patellofemoral maltracking. Methods: Patients with suspected patellofemoral maltracking and asymptomatic volunteers were scanned using GRE (Siemens LiveView WIP; Malvern, PA, USA) at 3T in the axial plane at the patella level through a range of flexion-extension (0-30degree). The mean time to perform the dynamic component ranged from 3-7 mins. Lateral maltracking (amount patella moved laterally through knee ranging) was measured. Patella lateralization was categorized as normal (<= 2mm), mild (2-5mm), moderate (5-10mm), or severe (>10mm). Tibial tuberosity: trochlear groove (TT: TG) distance, trochlea depth, Insall-Salvati ratio, and patellofemoral cartilage quality (according to the modified Outerbridge grading system) were also assessed. Results: Eighteen symptomatic (6 men; 12 women, age range 14-51 years) and 10 asymptomatic subjects (6 men; 4 women, age range 25-68 years) were included. Two symptomatic patients underwent bilateral examinations. Lateralization in the symptomatic group was normal (n=10), mild (n=2), moderate (n=5) and severe (n=3). There was no abnormal maltracking in the volunteer group. Lateral tracking significantly correlated with TT: TG distance (F=38.0; p<.0001), trochlea depth (F=5.8; p=.023), Insall-Salvati ratio (F=4.642; p=.04) and Outerbridge Patella score (F=6.6; p=.016). Lateral tracking did not correlate with Outerbridge Trochlear score. Conclusion: Lateral tracking measured on GRE was found to significantly correlate with current measures of patellar instability including, TT: TG, trochlea depth, and the Insall-Salvati ratio. GRE is a rapid and easily performed addition to the standard protocol for kinematic patellofemoral motion and can add dynamic information on patellofemoral tracking. This may be help determine if an isolated MPFL or an MPFL reconstruction and tibial tubercle osteotomy is needed to treat patella instability

Purpose To describe a nonlinear finite element analysis method by using magnetic resonance (MR) images for the assessment of the mechanical competence of the hip and to demonstrate the reproducibility of the tool. Materials and Methods This prospective study received institutional review board approval and fully complied with HIPAA regulations for patient data. Written informed consent was obtained from all subjects. A nonlinear finite element analysis method was developed to estimate mechanical parameters that relate to hip fracture resistance by using MR images. Twenty-three women (mean age +/- standard deviation, 61.7 years +/- 13.8) were recruited from a single osteoporosis center. To thoroughly assess the reproducibility of the finite element method, three separate analyses were performed: a test-retest reproducibility analysis, where each of the first 13 subjects underwent MR imaging on three separate occasions to determine longitudinal variability, and an intra- and interoperator reproducibility analysis, where a single examination was performed in each of the next 10 subjects and four operators independently performed the analysis two times in each of the subjects. Reproducibility of parameters that reflect fracture resistance was assessed by using the intraclass correlation coefficient and the coefficient of variation. Results For test-retest reproducibility analysis and inter- and intraoperator analyses for proximal femur stiffness, yield strain, yield load, ultimate strain, ultimate load, resilience, and toughness in both stance and sideways-fall loading configurations each had an individual median coefficient of variation of less than 10%. Additionally, all measures had an intraclass correlation coefficient higher than 0.99. Conclusion This experiment demonstrates that the finite element analysis model can consistently and reliably provide fracture risk information on correctly segmented bone images. (c) RSNA, 2016 Online supplemental material is available for this article.

Osteoarthritis (OA) is characterized by cartilage destruction and chondrocytes have a central role in this process. With age and inflammation chondrocytes have reduced capacity to synthesize and maintain ATP, a molecule important for cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its metabolite, fall after treatment of mouse chondrocytes and rat tibia explants with IL-1beta, an inflammatory mediator thought to participate in OA pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5'nucleotidase (an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA and chondrocytes lacking A2AR develop an 'OA phenotype' with increased expression of Mmp13 and Col10a1. Adenosine replacement by intra-articular injection of liposomal suspensions containing adenosine prevents development of OA in rats. These results support the hypothesis that maintaining extracellular adenosine levels is an important homeostatic mechanism, loss of which contributes to the development of OA; targeting adenosine A2A receptors might treat or prevent OA.

RATIONALE AND OBJECTIVES: Severe progressive multifocal heterotopic ossification (HO) is a rare occurrence seen predominantly in patients who have fibrodysplasia ossificans progressiva (FOP) and is difficult to quantitate owing to patient-, disease-, logistical-, and radiation-related issues. The purpose of this study was to develop and validate a scoring system based on plain radiographs for quantitative assessment of HO lesions in patients with FOP. MATERIALS AND METHODS: Institutional review board approval was obtained from the University of Pennsylvania, and all data comply with Health Insurance Portability and Accountability Act regulations. The University of Pennsylvania Institutional Animal Care and Use Committee approved the use of mice in this study. First, we used a mouse model of FOP-like HO to validate a semiquantitative analog scale for estimating relative heterotopic bone volume. Second, we used this validated scale to estimate the relative amount of HO from a retrospective analysis of plain radiographs from 63 patients with classic FOP. Finally, the scale was applied to a retrospective analysis of computed tomographic images from three patients with FOP. RESULTS: In the FOP-mouse model, the observed rating on the analog scale is highly correlated to heterotopic bone volumes measured by microcomputed tomography (R2 = 0.89). The scoring system that was applied to radiographs of patients with FOP captured the clinical range of HO typically present at all axial and appendicular sites. Analysis of computed tomographic scans of patients with FOP found that observed radiograph ratings were highly correlated with HO volume (R2 = 0.80). CONCLUSIONS: The scoring system described here could enable practical, quantitative assessment of HO in clinical trials to evaluate new treatment modalities, especially for FOP. The development of the six-point analog scale described here provides and validates a much-needed, reproducible, and quantifiable method for describing and assessing HO in patients with FOP. This scale has the potential to be a key descriptor that can inform patients with FOP and clinicians about disease progression and response of HO lesions to interventions and treatments.