Faculty Bibliography

Osteoporosis is a disease of poor bone quality. Bone mineral density (BMD) has limited ability to discriminate between subjects without and with poor bone quality, and assessment of bone microarchitecture may have added value in this regard. Our goals were to use 7 T MRI to: (1) quantify and compare distal femur bone microarchitecture in women without and with poor bone quality (defined clinically by presence of fragility fractures); and (2) determine whether microarchitectural parameters could be used to discriminate between these two groups. This study had institutional review board approval, and we obtained written informed consent from all subjects. We used a 28-channel knee coil to image the distal femur of 31 subjects with fragility fractures and 25 controls without fracture on a 7 T MRI scanner using a 3-D fast low angle shot sequence (0.234 mm x 0.234 mm x 1 mm, parallel imaging factor = 2, acquisition time = 7 min 9 s). We applied digital topological analysis to quantify parameters of bone microarchitecture. All subjects also underwent standard clinical BMD assessment in the hip and spine. Compared to controls, fracture cases demonstrated lower bone volume fraction and markers of trabecular number, plate-like structure, and plate-to-rod ratio, and higher markers of trabecular isolation, rod disruption, and network resorption (p < 0.05 for all). There were no differences in hip or spine BMD T-scores between groups (p > 0.05). In receiver-operating-characteristics analyses, microarchitectural parameters could discriminate cases and controls (AUC = 0.66-0.73, p < 0.05). Hip and spine BMD T-scores could not discriminate cases and controls (AUC = 0.58-0.64, p >/= 0.08). We conclude that 7 T MRI can detect bone microarchitectural deterioration in women with fragility fractures who do not differ by BMD. Microarchitectural parameters might some day be used as an additional tool to detect patients with poor bone quality who cannot be detected by dual-energy X-ray absorptiometry (DXA).

Purpose To determine the feasibility of using finite element analysis applied to 3-T magnetic resonance (MR) images of proximal femur microarchitecture for detection of lower bone strength in subjects with fragility fractures compared with control subjects without fractures. Materials and Methods This prospective study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Postmenopausal women with (n = 22) and without (n = 22) fragility fractures were matched for age and body mass index. All subjects underwent standard dual-energy x-ray absorptiometry. Images of proximal femur microarchitecture were obtained by using a high-spatial-resolution three-dimensional fast low-angle shot sequence at 3 T. Finite element analysis was applied to compute elastic modulus as a measure of strength in the femoral head and neck, Ward triangle, greater trochanter, and intertrochanteric region. The Mann-Whitney test was used to compare bone mineral density T scores and elastic moduli between the groups. The relationship (R2) between elastic moduli and bone mineral density T scores was assessed. Results Patients with fractures showed lower elastic modulus than did control subjects in all proximal femur regions (femoral head, 8.51-8.73 GPa vs 9.32-9.67 GPa; P = .04; femoral neck, 3.11-3.72 GPa vs 4.39-4.82 GPa; P = .04; Ward triangle, 1.85-2.21 GPa vs 3.98-4.13 GPa; P = .04; intertrochanteric region, 1.62-2.18 GPa vs 3.86-4.47 GPa; P = .006-.007; greater trochanter, 0.65-1.21 GPa vs 1.96-2.62 GPa; P = .01-.02), but no differences in bone mineral density T scores. There were weak relationships between elastic moduli and bone mineral density T scores in patients with fractures (R2 = 0.25-0.31, P = .02-.04), but not in control subjects. Conclusion Finite element analysis applied to high-spatial-resolution 3-T MR images of proximal femur microarchitecture can allow detection of lower elastic modulus, a marker of bone strength, in subjects with fragility fractures compared with control subjects. MR assessment of proximal femur strength may provide information about bone quality that is not provided by dual-energy x-ray absorptiometry. (c) RSNA, 2014.

PURPOSE: High-resolution imaging of deeper anatomy such as the hip is challenging due to low signal-to-noise ratio (SNR), necessitating long scan times. Multi-element coils can increase SNR and reduce scan time through parallel imaging (PI). We assessed the feasibility of using a 26-element receive coil setup to perform 3 Tesla (T) MRI of proximal femur microarchitecture without and with PI. MATERIALS AND METHODS: This study had institutional review board approval. We scanned 13 subjects on a 3T scanner using 26 receive-elements and a three-dimensional fast low-angle shot (FLASH) sequence without and with PI (acceleration factors [AF] 2, 3, 4). We assessed SNR, depiction of individual trabeculae, PI performance (1/g-factor), and image quality with PI (1 = nonvisualization to 5 = excellent). RESULTS: SNR maps demonstrate higher SNR for the 26-element setup compared with a 12-element setup for hip MRI. Without PI, individual proximal femur trabeculae were well-depicted, including microarchitectural deterioration in osteoporotic subjects. With PI, 1/g values for the 26-element/12-element receive-setup were 0.71/0.45, 0.56/0.25, and 0.44/0.08 at AF2, AF3, and AF4, respectively. Image quality was: AF1, excellent (4.8 +/- 0.4); AF2, good (4.2 +/- 1.0); AF3, average (3.3 +/- 1.0); AF4, nonvisualization (1.4 +/- 0.9). CONCLUSION: A 26-element receive-setup permits 3T MRI of proximal femur microarchitecture with good image quality up to PI AF2. J. Magn. Reson. Imaging 2014;40:229-238. (c) 2013 Wiley Periodicals, Inc.

PURPOSE: To demonstrate the feasibility of performing bone microarchitecture, high-resolution cartilage, and clinical imaging of the hip at 7T. MATERIALS AND METHODS: This study had Institutional Review Board approval. Using an 8-channel coil constructed in-house, we imaged the hips of 15 subjects on a 7T magnetic resonance imaging (MRI) scanner. We applied: 1) a T1-weighted 3D fast low angle shot (3D FLASH) sequence (0.23 x 0.23 x 1-1.5 mm3 ) for bone microarchitecture imaging; 2) T1-weighted 3D FLASH (water excitation) and volumetric interpolated breath-hold examination (VIBE) sequences (0.23 x 0.23 x 1.5 mm3 ) with saturation or inversion recovery-based fat suppression for cartilage imaging; 3) 2D intermediate-weighted fast spin-echo (FSE) sequences without and with fat saturation (0.27 x 0.27 x 2 mm) for clinical imaging. RESULTS: Bone microarchitecture images allowed visualization of individual trabeculae within the proximal femur. Cartilage was well visualized and fat was well suppressed on FLASH and VIBE sequences. FSE sequences allowed visualization of cartilage, the labrum (including cartilage and labral pathology), joint capsule, and tendons. CONCLUSION: This is the first study to demonstrate the feasibility of performing a clinically comprehensive hip MRI protocol at 7T, including high-resolution imaging of bone microarchitecture and cartilage, as well as clinical imaging. J. Magn. Reson. Imaging 2013;. (c) 2013 Wiley Periodicals, Inc.

Atypical femoral fractures, deformities of the subtrochanteric region of the femur identified with plain anteroposterior or lateral lower extremity radiographs and characterized by a specific fracture pattern, are uncommon manifestations in osteoporotic patients. However, the high prevalence of these fractures in patients receiving long-term bisphosphonate therapy led to the many investigations of this association. The purpose of this article is to evaluate and address the link between this fracture type with long-term bisphosphonate therapy, outline the clinical scenario and better define treatment options for optimal care and recovery. In order to do this, a PubMed search was carried out for significant articles using the following keywords: 'alendronate', 'fracture', 'atypical' and 'femur'. 2013 Future Medicine Ltd

Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation. INTRODUCTION: The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls. METHODS: This study had institutional review board approval. We recruited nine female modern dancers (25.7 +/- 5.8 years, 1.63 +/- 0.06 m, 57.1 +/- 4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1 +/- 4.8 years, 1.6 +/- 0.04 m, 55.8 +/- 5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE = 31 ms/5.1 ms, 0.234 mm x 0.234 mm x 1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups. RESULTS: Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p < 0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p < 0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p > 0.07), but adjustment for cortical bone cross-sectional area did not (p < 0.03). CONCLUSIONS: Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation.

The clinical diagnosis of osteoporosis has evolved over the past 20 years to emphasize the relationship between compromised bone strength and fracture susceptibility. The goal of treatment of osteoporosis is fracture prevention. The aging of the American population will place additional burdens on our healthcare system among which will be the need to treat and prevent the estimated increase in fracture rates projected over the next 10 years. There is a significant number of currently available bone strengthening medications used in the treatment of osteoporosis, and this report highlights the effects of these drugs on bone mineral density values and on the relative rates of fragility fractures when these drugs are compared to placebo in clinical trials of subjects with osteoporosis. Identifying those individuals most in need of immediate treatment to prevent fractures remains a challenge despite the use of fracture risk assessment tools, which assess bone mineral density and clinical parameters in order to define an individual's risk of fracture over a finite period of time. Newer tools that may help better define bone strength (resistance to fracture) include high resolution MRI and finite element analysis of the MRI generated images, and this technology and our experience with it is briefly reviewed in this report. There are a number of new classes of drugs in development for the treatment of osteoporosis, and the clinician is likely to have additional antiresorptive and anabolic agents as treatment options for this condition over the next few years.

The goal of this study was to demonstrate the feasibility of using 7-Tesla (7T) magnetic resonance imaging (MRI) and micro-finite element analysis (microFEA) to evaluate mechanical and structural properties of whole, cortical, and trabecular bone at the distal femur and proximal tibia in vivo. 14 healthy subjects were recruited (age 40.7 +/- 15.7 years). The right knee was scanned on a 7T MRI scanner using a 28 channel-receive knee coil and a three-dimensional fast low-angle shot sequence (TR/TE 20 ms/5.02 ms, 0.234 mm x 0.234 mm x 1 mm, 80 axial images, 7 min 9 s). Bone was analyzed at the distal femoral metaphysis, femoral condyles, and tibial plateau. Whole, cortical, and trabecular bone stiffness was computed using microFEA. Bone volume fraction (BVF), bone areas, and cortical thickness were measured. Trabecular bone stiffness (933.7 +/- 433.3 MPa) was greater than cortical bone stiffness (216 +/- 152 MPa) at all three locations (P < 0.05). Across locations, there were no differences in bone stiffness (whole, cortical, or trabecular). Whole, cortical, and trabecular bone stiffness correlated with BVF (R >/= 0.69, P < 0.05) and inversely correlated with corresponding whole, cortical, and trabecular areas (R 0.05). Whole, cortical, and trabecular stiffness correlated with body mass index (R >/= 0.62, P < 0.05). In conclusion, at the distal femur and proximal tibia, trabecular bone contributes 66-74% of whole bone stiffness. 7T MRI and microFEA may be used as a method to provide insight into how structural properties of cortical or trabecular bone affect bone mechanical competence in vivo.