Fatty Acid Composition of Proximal Femur Bone Marrow Adipose Tissue in Subjects With Systemic Lupus Erythematous Using 3 T Magnetic Resonance Spectroscopy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease with common musculoskeletal manifestations, notably reductions in bone quality. Bone marrow adipose tissue composition and quantity has been previously linked to bone quality and may play a role in SLE pathophysiology but has not been thoroughly studied. PURPOSE: To use magnetic resonance spectroscopy (MRS) to investigate bone marrow adipose tissue quantity and composition in proximal femur subregions of untreated SLE patients compared to controls and treated patients. STUDY TYPE: Prospective. SUBJECTS: A total of 64 female subjects: 28 SLE, 15 glucocorticoid (GC)-treated SLE and 21 matched controls. FIELD STRENGTH/SEQUENCE: Stimulated echo acquisition mode (STEAM) sequence at 3 T. ASSESSMENT: MRS was performed at multiple echo times in the femoral neck and trochanter regions and fatty acids (FA) composition was computed. STATISTICAL TESTS: Intergroup comparisons were carried out using ANOVA. A P value < 0.05 was considered statistically significant. RESULTS: SLE patients had significantly higher saturated FA compared to controls in both the femoral neck (+0.12) and trochanter (+0.11), significantly lower monounsaturated FA in the trochanter compared to controls (-0.05), and significantly lower polyunsaturated FA in the femoral neck compared to both controls (-0.07) and SLE patients on GC therapy (-0.05). DATA CONCLUSION: SLE patients have altered proximal femur marrow fat metabolism, which may reflect a manifestation of, or play a role in, the altered inflammatory response of these patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Artificial intelligence, osteoporosis and fragility fractures.

PURPOSE OF REVIEW: Artificial intelligence tools have found new applications in medical diagnosis. These tools have the potential to capture underlying trends and patterns, otherwise impossible with previous modeling capabilities. Machine learning and deep learning models have found a role in osteoporosis, both to model the risk of fragility fracture, and to help with the identification and segmentation of images. RECENT FINDINGS: Here we survey the latest research in the artificial intelligence application to the prediction of osteoporosis that has been published between January 2017 and March 2019. Around half of the articles that are covered here predict (by classification or regression) an indicator of osteoporosis, such as bone mass or fragility fractures; the other half of studies use tools for automatic segmentation of the images of patients with or at risk of osteoporosis. The data for these studies include diverse signal sources: acoustics, MRI, CT, and of course, X-rays. SUMMARY: New methods for automatic image segmentation, and prediction of fracture risk show promising clinical value. Though these recent developments have had a successful initial application to osteoporosis research, their development is still under improvement, such as accounting for positive/negative class bias. We urge care when reporting accuracy metrics, and when comparing such metrics between different studies.

Artificial Intelligence Applied to Osteoporosis: A Performance Comparison of Machine Learning Algorithms in Predicting Fragility Fractures From MRI Data.

BACKGROUND: A current challenge in osteoporosis is identifying patients at risk of bone fracture. PURPOSE: To identify the machine learning classifiers that predict best osteoporotic bone fractures and, from the data, to highlight the imaging features and the anatomical regions that contribute most to prediction performance. STUDY TYPE: Prospective (cross-sectional) case-control study. POPULATION: Thirty-two women with prior fragility bone fractures, of mean age = 61.6 and body mass index (BMI) = 22.7 kg/m2 , and 60 women without fractures, of mean age = 62.3 and BMI = 21.4 kg/m2 . Field Strength/ Sequence: 3D FLASH at 3T. ASSESSMENT: Quantitative MRI outcomes by software algorithms. Mechanical and topological microstructural parameters of the trabecular bone were calculated for five femoral regions, and added to the vector of features together with bone mineral density measurement, fracture risk assessment tool (FRAX) score, and personal characteristics such as age, weight, and height. We fitted 15 classifiers using 200 randomized cross-validation datasets. Statistical Tests: Data: Kolmogorov-Smirnov test for normality. Model Performance: sensitivity, specificity, precision, accuracy, F1-test, receiver operating characteristic curve (ROC). Two-sided t-test, with P < 0.05 for statistical significance. RESULTS: The top three performing classifiers are RUS-boosted trees (in particular, performing best with head data, F1 = 0.64 ± 0.03), the logistic regression and the linear discriminant (both best with trochanteric datasets, F1 = 0.65 ± 0.03 and F1 = 0.67 ± 0.03, respectively). A permutation of these classifiers comprised the best three performers for four out of five anatomical datasets. After averaging across all the anatomical datasets, the score for the best performer, the boosted trees, was F1 = 0.63 ± 0.03 for All-features dataset, F1 = 0.52 ± 0.05 for the no-MRI dataset, and F1 = 0.48 ± 0.06 for the no-FRAX dataset. Data Conclusion: Of many classifiers, the RUS-boosted trees, the logistic regression, and the linear discriminant are best for predicting osteoporotic fracture. Both MRI and FRAX independently add value in identifying osteoporotic fractures. The femoral head, greater trochanter, and inter-trochanter anatomical regions within the proximal femur yielded better F1-scores for the best three classifiers. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1029-1038.

3T chemical shift-encoded MRI: Detection of altered proximal femur marrow adipose tissue composition in glucocorticoid users and validation with magnetic resonance spectroscopy.

BACKGROUND: Osteoporosis (OP) results in weak bone and can ultimately lead to fracture. Drugs such as glucocorticoids can also induce OP (glucocorticoid-induced osteoporosis [GIO]). Bone marrow adipose tissue composition and quantity may play a role in OP pathophysiology, but has not been thoroughly studied in GIO compared to primary OP. PURPOSE/HYPOTHESIS: Chemical shift-encoded (CSE) MRI allows detection of subregional differences in bone marrow adipose tissue composition and quantity in the proximal femur of GIO compared to OP subjects and has high agreement with the reference standard of magnetic resonance spectroscopy (MRS). STUDY TYPE: Prospective. SUBJECTS: In all, 18 OP and 13 GIO subjects. FIELDS STRENGTH: 3T. SEQUENCE: Multiple gradient-echo, stimulated echo acquisition mode (STEAM). ASSESSMENT: Subjects underwent CSE-MRI in the proximal femurs, and for each parametric map regions of interest (ROIs) were assessed in the femoral head (fHEAD), femoral neck (fNECK), Ward's triangle (fTRIANGLE), and the greater trochanter (GTROCH). In addition, we compared CSE-MRI against the reference standard of MRS performed in the femoral neck and Ward's triangle. STATISTICAL TESTS: Differences between OP/GIO were investigated using the Mann-Whitney nonparametric test. Bland-Altman methodology was used to assess measurement agreement between CSE-MRI and MRS. RESULTS: GIO compared with OP subjects demonstrated: decreased monounsaturated fat fraction (MUFA) (-2.1%, P < 0.05) in fHEAD; decreased MUFA (-3.8%, P < 0.05), increased saturated fat fraction (SFA) (5.5%, P < 0.05), and decreased T2* (-3.8 msec, P < 0.05) in fNECK; decreased proton density fat fraction (PDFF) (-15.1%, P < 0.05), MUFA (-9.8%, P < 0.05), polyunsaturated fat fraction (PUFA) (-1.8%, P < 0.01), increased SFA (11.6%, P < 0.05), and decreased T2* (-5.4 msec, P < 0.05) in fTRIANGLE; and decreased T2* (-1.5 msec, P < 0.05) in GTROCH. There was high measurement agreement between MRI and MRS using the Bland-Altman test. DATA CONCLUSION: 3T CSE-MRI may allow reliable assessment of subregional bone marrow adipose tissue (bMAT) quantity and composition in the proximal femur in a clinically reasonable scan time. Glucocorticoids may alter the lipid profile of bMAT and potentially result in reduced bone quality. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:490-496.

3-T MR Imaging of Proximal Femur Microarchitecture in Subjects with and without Fragility Fracture and Nonosteoporotic Proximal Femur Bone Mineral Density.

Purpose To determine if 3-T magnetic resonance (MR) imaging of proximal femur microarchitecture can allow discrimination of subjects with and without fragility fracture who do not have osteoporotic proximal femur bone mineral density (BMD). Materials and Methods Sixty postmenopausal women (30 with and 30 without fragility fracture) who had BMD T scores of greater than -2.5 in the hip were recruited. All subjects underwent dual-energy x-ray absorptiometry to assess BMD and 3-T MR imaging of the same hip to assess bone microarchitecture. World Health Organization Fracture Risk Assessment Tool (FRAX) scores were also computed. We used the Mann-Whitney test, receiver operating characteristics analyses, and Spearman correlation estimates to assess differences between groups, discriminatory ability with parameters, and correlations among BMD, microarchitecture, and FRAX scores. Results Patients with versus without fracture showed a lower trabecular plate-to-rod ratio (median, 2.41 vs 4.53, respectively), lower trabecular plate width (0.556 mm vs 0.630 mm, respectively), and lower trabecular thickness (0.114 mm vs 0.126 mm) within the femoral neck, and higher trabecular rod disruption (43.5 vs 19.0, respectively), higher trabecular separation (0.378 mm vs 0.323 mm, respectively), and lower trabecular number (0.158 vs 0.192, respectively), lower trabecular connectivity (0.015 vs 0.027, respectively) and lower trabecular plate-to-rod ratio (6.38 vs 8.09, respectively) in the greater trochanter (P < .05 for all). Trabecular plate-to-rod ratio, plate width, and thickness within the femoral neck (areas under the curve [AUCs], 0.654-0.683) and trabecular rod disruption, number, connectivity, plate-to-rod ratio, and separation within the greater trochanter (AUCs, 0.662-0.694) allowed discrimination of patients with fracture from control subjects. Femoral neck, total hip, and spine BMD did not differ between and did not allow discrimination between groups. FRAX scores including and not including BMD allowed discrimination between groups (AUCs, 0.681-0.773). Two-factor models (one MR imaging microarchitectural parameter plus a FRAX score without BMD) allowed discrimination between groups (AUCs, 0.702-0.806). There were no linear correlations between BMD and microarchitectural parameters (Spearman ρ, -0.198 to 0.196). Conclusion 3-T MR imaging of proximal femur microarchitecture allows discrimination between subjects with and without fragility fracture who have BMD T scores of greater than -2.5 and may provide different information about bone quality than that provided by dual-energy x-ray absorptiometry. © RSNA, 2018.

Subchondral bone microarchitecture analysis in the proximal tibia at 7-T MRI.

Background Bone remodels in response to mechanical loads and osteoporosis results from impaired ability of bone to remodel. Bone microarchitecture analysis provides information on bone quality beyond bone mineral density (BMD). Purpose To compare subchondral bone microarchitecture parameters in the medial and lateral tibia plateau in individuals with and without fragility fractures. Material and Methods Twelve female patients (mean age = 58 ± 15 years; six with and six without previous fragility fractures) were examined with dual-energy X-ray absorptiometry (DXA) and 7-T magnetic resonance imaging (MRI) of the proximal tibia. A transverse high-resolution three-dimensional fast low-angle shot sequence was acquired (0.234 × 0.234 × 1 mm). Digital topological analysis (DTA) was applied to the medial and lateral subchondral bone of the proximal tibia. The following DTA-based bone microarchitecture parameters were assessed: apparent bone volume; trabecular thickness; profile-edge-density (trabecular bone erosion parameter); profile-interior-density (intact trabecular rods parameter); plate-to-rod ratio; and erosion index. We compared femoral neck T-scores and bone microarchitecture parameters between patients with and without fragility fracture. Results There was no statistical significant difference in femoral neck T-scores between individuals with and without fracture (-2.4 ± 0.9 vs. -1.8 ± 0.7, P = 0.282). Apparent bone volume in the medial compartment was lower in patients with previous fragility fracture (0.295 ± 0.022 vs. 0.317 ± 0.009; P = 0.016). Profile-edge-density, a trabecular bone erosion parameter, was higher in patients with previous fragility fracture in the medial (0.008 ± 0.003 vs. 0.005 ± 0.001) and lateral compartment (0.008 ± 0.002 vs. 0.005 ± 0.001); both P = 0.025. Other DTA parameters did not differ between groups. Conclusion 7-T MRI and DTA permit detection of subtle changes in subchondral bone quality when differences in BMD are not evident.

Cost-effectiveness of Virtual Bone Strength Testing in Osteoporosis Screening Programs for Postmenopausal Women in the United States.

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. © RSNA, 2017 Online supplemental material is available for this article.

Patient-specific Hip Fracture Strength Assessment with Microstructural MR Imaging-based Finite Element Modeling.

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. © RSNA, 2016 Online supplemental material is available for this article.

7T MRI of distal radius trabecular bone microarchitecture: How trabecular bone quality varies depending on distance from end-of-bone.

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 × 0.169 × 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.

MRI assessment of bone structure and microarchitecture.

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 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2017;46:323-337.

Novel association between bone mineral density scores and the prevalence of peripheral artery disease in both sexes.

The purpose of the current study was to investigate the association between bone mineral density (BMD) scores and the prevalence of peripheral artery disease (PAD) in a large cohort of subjects who underwent arterial Doppler assessments and calcaneal bone densitometry. The study was performed using data obtained from Life Line Screening Inc. Subjects were self-selected and paid for screening tests. The prevalence of PAD was significantly higher in men with osteopenia (4.5%) and osteoporosis (10.9%) compared to men with normal BMD (3.0%) ( p<0.001). Osteopenia (odds ratio (OR) 1.3) and osteoporosis (OR 2.3) were found to be independent risk factors for the presence of PAD in men. The prevalence of PAD was significantly higher in women with osteopenia (4.8%) and osteoporosis (11.8%) compared to women with normal BMD (3.3%) ( p<0.001). Osteopenia (OR 1.15) and osteoporosis (OR 1.8) were found to be independent risk factors for the presence of PAD in women. The current study reports a strong association of abnormal BMD analysis with the prevalence of PAD, which persists even when controlling for age and associated atherosclerotic risk factors. Although the mechanism by which these two disease processes is related is not completely elucidated, the presence of osteoporosis should make clinicians aware of the possibility of occult PAD or associated atherosclerotic disease in appropriate patients.

3 Tesla MRI detects deterioration in proximal femur microarchitecture and strength in long-term glucocorticoid users compared with controls.

BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is the most common secondary form of osteoporosis, and glucocorticoid users are at increased risk for fracture compared with nonusers. There is no established relationship between bone mineral density (BMD) and fracture risk in GIO. We used 3 Tesla (T) MRI to investigate how proximal femur microarchitecture is altered in subjects with GIO. METHODS: This study had institutional review board approval. We recruited 6 subjects with long-term (> 1 year) glucocorticoid use (median age = 52.5 (39.2-58.7) years) and 6 controls (median age = 65.5 [62-75.5] years). For the nondominant hip, all subjects underwent dual-energy x-ray absorptiometry (DXA) to assess BMD and 3T magnetic resonance imaging (MRI, 3D FLASH) to assess metrics of bone microarchitecture and strength. RESULTS: Compared with controls, glucocorticoid users demonstrated lower femoral neck trabecular number (-50.3%, 1.12 [0.84-1.54] mm(-1) versus 2.27 [1.88-2.73] mm(-1) , P = 0.02), plate-to-rod ratio (-20.1%, 1.48 [1.39-1.71] versus 1.86 [1.76-2.20], P = 0.03), and elastic modulus (-64.8% to -74.8%, 1.54 [1.22-3.19] GPa to 2.31 [1.87-4.44] GPa versus 6.15 [5.00-7.09] GPa to 6.59 [5.58-7.31] GPa, P < 0.05), and higher femoral neck trabecular separation (+192%, 0.705 [0.462-1.00] mm versus 0.241 [0.194-0.327] mm, P = 0.02). There were no differences in femoral neck trabecular thickness (-2.7%, 0.193 [0.184-0.217] mm versus 0.199 [0.179-0.210] mm, P = 0.94) or femoral neck BMD T-scores (+20.7%, -2.1 [-2.8 to -1.4] versus -2.6 [-3.3 to -2.5], P = 0.24) between groups. CONCLUSION: The 3T MRI can potentially detect detrimental changes in proximal femur microarchitecture and strength in long-term glucocorticoid users.

In vivo measurement reproducibility of femoral neck microarchitectural parameters derived from 3T MR images.

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 × 0.234 × 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.

7 Tesla MRI of bone microarchitecture discriminates between women without and with fragility fractures who do not differ by bone mineral density.

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 × 0.234 mm × 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).

Measurement reproducibility of magnetic resonance imaging-based finite element analysis of proximal femur microarchitecture for in vivo assessment of bone strength.

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.

Finite element analysis applied to 3-T MR imaging of proximal femur microarchitecture: lower bone strength in patients with fragility fractures compared with control subjects.

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 (R(2)) 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 (R(2) = 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.

Feasibility of three-dimensional MRI of proximal femur microarchitecture at 3 tesla using 26 receive elements without and with parallel imaging.

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.

MRI of the hip at 7T: feasibility of bone microarchitecture, high-resolution cartilage, and clinical imaging.

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 × 0.23 × 1-1.5 mm(3) ) for bone microarchitecture imaging; 2) T1-weighted 3D FLASH (water excitation) and volumetric interpolated breath-hold examination (VIBE) sequences (0.23 × 0.23 × 1.5 mm(3) ) 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 × 0.27 × 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.

In vivo estimation of bone stiffness at the distal femur and proximal tibia using ultra-high-field 7-Tesla magnetic resonance imaging and micro-finite element analysis.

The goal of this study was to demonstrate the feasibility of using 7-Tesla (7T) magnetic resonance imaging (MRI) and micro-finite element analysis (µFEA) 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 × 0.234 mm × 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 µFEA. 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 ≤ -0.54, P < 0.05), but not with cortical thickness (R < -0.11, P > 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 µFEA may be used as a method to provide insight into how structural properties of cortical or trabecular bone affect bone mechanical competence in vivo.