Faculty Bibliography

PURPOSE: To evaluate the within-day and between-day measurement reproducibility of in vivo 3D MRI assessment of trabecular bone microarchitecture of the proximal femur. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPPA)-compliant, Institutional Review Board (IRB)-approved study was conducted on 11 healthy subjects (mean age = 57.4 +/- 14.1 years) with written informed consent. All subjects underwent a 3T MRI hip scan in vivo (0.234 x 0.234 x 1.5 mm) at three timepoints: baseline, second scan same day (intrascan), and third scan 1 week later (interscan). We applied digital topological analysis and volumetric topological analysis to compute the following microarchitectural parameters within the femoral neck: total bone volume, bone volume fraction, markers of trabecular number (skeleton density), connectivity (junctions), plate-like structure (surfaces), plate width, and trabecular thickness. Reproducibility was assessed using root-mean-square coefficient of variation (RMS-CV) and intraclass correlation coefficient (ICC). RESULTS: The within-day RMS-CVs ranged from 2.3% to 7.8%, and the between-day RMS-CVs ranged from 4.0% to 7.3% across all parameters. The within-day ICCs ranged from 0.931 to 0.989, and the between-day ICCs ranged from 0.934 to 0.971 across all parameters. CONCLUSION: These results demonstrate high reproducibility for trabecular bone microarchitecture measures derived from 3T MR images of the proximal femur. The measurement reproducibility is within a range suitable for clinical cross-sectional and longitudinal studies in osteoporosis. J. Magn. Reson. Imaging 2015;42:1339-1345.

INTRODUCTION: Osteoporosis is a disease of weak bone. Our goal was to determine the measurement reproducibility of magnetic resonance assessment of proximal femur strength. METHODS: This study had institutional review board approval, and written informed consent was obtained from all subjects. We obtained images of proximal femur microarchitecture by scanning 12 subjects three times within 1 week at 3T using a high-resolution 3-D FLASH sequence. We applied finite element analysis to compute proximal femur stiffness and femoral neck elastic modulus. RESULTS: Within-day and between-day root-mean-square coefficients of variation and intraclass correlation coefficients ranged from 3.5 to 6.6 % and 0.96 to 0.98, respectively. CONCLUSION: The measurement reproducibility of magnetic resonance assessment of proximal femur strength is suitable for clinical studies of disease progression or treatment response related to osteoporosis bone-strengthening interventions.

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: 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 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: 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.

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.

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 past year has been a dynamic one for clinicians and researchers with an interest in osteoporosis. This update will focus on the issue of the relationship between bisphosphonate treatment and atypical femoral fractures, highlight the advances in imaging techniques that are increasingly being studied as adjuncts to bone density testing, and explore re- cent evidence that suggests that osteoporosis medications may be linked to an increase in life expectancy. Since the first case reports describing unusual femur fractures in long term users of bisphosphonates began to appear, there has been great interest in identifying why and whether this class of drug can cause these atypical fractures. There have been a significant number of large studies that seem to suggest that these fractures do occur with an increased frequency among subjects who have used bisphosphonates over an extended period of time, but that these events are relatively rare. The occurrence of these fractures have helped to fashion new treatment regimens with periods of "drug holidays" often recommended to people with lower short-term and intermediate-term fracture risk. It is important to remind the reader that bisphosphonates prevent many typical hip and vertebral compression fractures, particularly in the higher risk elderly patient and that a rational balance be struck so that those in need of continued osteoporosis treatment receive it. Advances in imaging, such as high resolution MRI and peripheral micro CT scanners, are allowing investigators to non-invasively assess bone microarchitecture and bone stiffness of individuals as a means of trying to more accurately define those subjects who might be at increased risk of fracture and who might benefit from bone strengthening medication. Finally, this update will briefly review the emerging data that suggests that anti-resorptive medication may extend life expectancy beyond that which can be expected solely by reducing the incidence of future fractures.