Faculty Bibliography

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.

PURPOSE: To use 7T magnetic resonance imaging (MRI) to determine how trabecular bone microarchitecture varies at the epiphysis, metaphysis, and diaphysis of the distal radius. MATERIALS AND METHODS: The distal radius of 24 females (mean age = 56 years, range = 24-78 years) was scanned on a 7T MRI using a 3D fast low-angle shot sequence (0.169 x 0.169 x 1 mm). Digital topological analysis was applied at the epiphysis, metaphysis, and diaphysis to compute: total trabecular bone volume; trabecular thickness, number, connectivity, and erosion index (a measure of network resorption). Differences and correlations were assessed using standard statistical methods. RESULTS: The metaphysis and epiphysis had 83-123% greater total bone volume and 14-16% greater trabecular number than the diaphysis (both P < 0.0001). The erosion index was significantly higher at the diaphysis than the metaphysis and epiphysis (both P < 0.01). The most elderly volunteers had lower trabecular number (<66 years mean 0.29 +/- 0.01; >/=66 years, 0.27 +/- 0.02, P < 0.05) and higher erosion index (<66 years mean 1.18 +/- 0.17; age >/=66 years, mean 1.42 +/- 0.46, P < 0.05) at the epiphysis; differences not detected by total trabecular bone volume. CONCLUSION: 7T MRI reveals trabecular bone microarchitecture varies depending on scan location at the end-of-bone, being of overall higher quality distally (epiphysis) than proximally (diaphysis). Age-related differences in trabecular microarchitecture can be detected by 7T MRI. The results highlight the potential sensitivity of 7T MRI to microarchitectural differences and the potential importance of standardizing scan location for future clinical studies of fracture risk or treatment response. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:872-878.

During the previous 2 decades, numerous surgical procedures have become available to treat osteochondral lesions of the talus. The objective of the present study was to use 7 Tesla (7T) magnetic resonance imaging (MRI) to quantify and compare T2 values (a marker of collagen architecture) of native tibiotalar cartilage and cartilage repair tissue in patients treated with a juvenile particulate allograft for osteochondral lesions of the talus. The institutional review board approved the present study, and all subjects provided written informed consent. We scanned the ankles of 7 cartilage repair patients using a 7T MRI scanner with a multi-echo spin-echo sequence to measure the cartilage T2 values. We assessed the cartilage T2 values in the talar repair tissue, adjacent native talar cartilage, and overlying tibial cartilage. We compared the differences between groups using the paired t test. The talar cartilage repair tissue demonstrated greater mean T2 relaxation times compared with the native adjacent talar cartilage (64.88 +/- 12.23 ms versus 49.56 +/- 7.82 ms; p = .043). The tibial cartilage regions overlying these talar cartilage regions demonstrated a trend toward greater T2 relaxation times (77.00 +/- 31.29 ms versus 59.52 +/- 7.89 ms; p = .067). 7T MRI can detect differences in T2 values in cartilage repair tissue compared with native cartilage and could be useful for monitoring the status of cartilage health after surgical intervention.