Faculty Bibliography

Osteoporosis is associated with increased risk of fractures, which is clinically defined by low bone mineral density. Increasing evidence suggests that trabecular bone (TB) micro-architecture is an important determinant of bone strength and fracture risk. We present an improved volumetric topological analysis algorithm based on fuzzy skeletonization, results of its application on in vivo MR imaging, and compare its performance with digital topological analysis. The new VTA method eliminates data loss in the binarization step and yields accurate and robust measures of local plate-width for individual trabeculae, which allows classification of TB structures on the continuum between perfect plates and rods. The repeat-scan reproducibility of the method was evaluated on in vivo MRI of distal femur and distal radius, and high intra-class correlation coefficients between 0.93 and 0.97 were observed. The method's ability to detect treatment effects on TB micro-architecture was examined in a 2 years testosterone study on hypogonadal men. It was observed from experimental results that average plate-width and plate-to-rod ratio significantly improved after 6 months and the improvement was found to continue at 12 and 24 months. The bone density of plate-like trabeculae was found to increase by 6.5% (p = 0.06), 7.2% (p = 0.07) and 16.2% (p = 0.003) at 6, 12, 24 months, respectively. While the density of rod-like trabeculae did not change significantly, even at 24 months. A comparative study showed that VTA has enhanced ability to detect treatment effects in TB micro-architecture as compared to conventional method of digital topological analysis for plate/rod characterization in terms of both percent change and effect-size.

Automating the process of femoroacetabular cartilage identification from magnetic resonance imaging (MRI) images has important implications to guiding clinical care by providing a temporal metric that allows for optimizing the timing for joint preservation surgery. In this paper, we evaluate a new automated cartilage segmentation method using a time trial, segmented volume comparison, overlap metrics, and Euclidean distance mapping. We report interrater overlap metrics using the true fast imaging with steady-state precession MRI sequence of 0.874, 0.546, and 0.704 for the total overlap, union overlap, and mean overlap, respectively. This method was 3.28x faster than manual segmentation. This technique provides clinicians with volumetric cartilage information that is useful for optimizing the timing for joint preservation procedures.

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. J. MAGN. RESON. IMAGING 2015;42:1489-1496.

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.

In vivo MRI has revolutionized the diagnosis and treatment of musculoskeletal disorders over the past 3 decades. Traditionally performed at 1.5 T, MRI at higher field strengths offers several advantages over lower field strengths including increased signal-to-noise ratio, higher spatial resolution, improved spectral resolution for spectroscopy, improved sensitivity for X-nucleus imaging, and decreased image acquisition times. However, the physics of imaging at higher field strengths also presents technical challenges. These include B0 and B1+ field inhomogeneity, design and construction of dedicated radiofrequency (RF) coils for use at high field, increased chemical shift and susceptibility artifacts, increased RF energy deposition (specific absorption rate), increased metal artifacts, and changes in relaxation times compared with the lower field scanners. These challenges were overcome in optimizing high-field (HF) (3 T) MRI over a decade ago. HF MRI systems have since gained universal acceptance for clinical musculoskeletal imaging and have also been widely utilized for the study of musculoskeletal anatomy and physiology. Recently there has been an increasing interest in exploring musculoskeletal applications of ultrahigh field (UHF) (7 T) systems. However, technical challenges similar to those encountered when moving from 1.5 T to 3 T have to be overcome to optimize 7 T musculoskeletal imaging. In this narrative review, we discuss the many potential opportunities and technical challenges presented by the HF and UHF MRI systems. We highlight recent developments in in vivo imaging of musculoskeletal tissues that benefit most from HF imaging including cartilage, skeletal muscle, and bone.

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.

Purpose: Elevated bone marrow fat content and elevated intramuscular fat content increase the risk for osteoporotic fracture, but it is unknown if such changes are associated with detrimental changes in bone microarchitecture and bone mass. Our goal was to determine the association between femoral neck bone marrow fat fraction and gluteal muscle fat fraction with: 1) femoral neck bone microarchitecture and 2) femoral neck bone mineral density (BMD). Materials and Methods: This study was HIPAA compliant and institutional review board approved. Written informed consent was obtained. Hips of forty-two consecutive patients referred from the osteoporosis clinic at our institution (mean-age 60.2 +/- 7.5 years) underwent dual-energy X-ray absorptiometry (DXA), high-spatial resolution three-dimensional 3 T MRI with volumetric topological analysis (VTA-MRI), and fat quantification with IDEAL-MRI. Femoral neck BMD T-scores (DXA) and trabecular bone microarchitecture parameters (VTA-MRI) were calculated. Proton density fat fractions (IDEAL-MRI) of the femoral neck bone marrow (FFmarrow) and the gluteus maximus muscle (FFmuscle) were measured by two independent readers. Interreader agreement was calculated using intraclass correlation coefficients (ICC). FFmarrow and FFmuscle were correlated with BMD, bone microarchitecture parameters, age, and body-massindex (BMI). Results: FFmarrow (mean from both readers 70.2 +/- 6.5 %) and FFmuscle (11.3 +/- 3.8 %) measurements showed excellent interreader agreement (ICC = 0.955/0.995; both p < 0.0005). No statistically significant correlation between FFmarrow and BMD was found (r = -0.257, p = 0.155). Age- and BMI-adjusted FFmarrow inversely correlated with trabecular plate-to-rod ratio (r = -0.335; p = 0.049) and trabecular plate-width (r = -0.345; p = 0.042), but not with bone volume fraction (r = 0.155; p = 0.374). FFmarrow correlated with age (r = 0.383; p = 0.021), but not with BMI (r = 0.132; p = 0.445). FFmuscle showed no correlation with BMD or bone microarchitecture. FFmuscle was independently correlated with BMI (r = 0.557; <0.0005) and age (r = 0.438; p = 0.008). Conclusion: Bone marrow fat content inversely correlated with trabecular plate-to-rod ratio and plate-width, but not BMD, suggesting that the increased fracture risk in the setting of elevated bone marrow fat content may in part be mediated via microarchitectural deterioration, rather than via reduced BMD. Gluteal muscle fat content did not correlate with changes in femoral neck microarchitecture or BMD, suggesting that intramuscular fat content may increase fracture risk independent of detrimental changes in bone microarchitecture and BMD. Overall, highresolution 3 T MRI of bone microarchitecture combined with IDEAL-based fat quantification can help provide insight into the relationship between adipose bone marrow, lean muscle mass, and possible mechanisms of osteoporotic fracture risk in vivo

PURPOSE: To determine how subchondral bone microarchitecture is altered in patients with mild knee osteoarthritis. MATERIALS AND METHODS: This study had Institutional Review Board approval. We recruited 24 subjects with mild radiographic knee osteoarthritis and 16 healthy controls. The distal femur was scanned at 7T using a high-resolution 3D FLASH sequence. We applied digital topological analysis to assess bone volume fraction, markers of trabecular number (skeleton density), trabecular network osteoclastic resorption (erosion index), plate-like structure (surface), rod-like structure (curve), and plate-to-rod ratio (surface-curve ratio). We used two-tailed t-tests to compare differences between osteoarthritis subjects and controls. RESULTS: 7T magnetic resonance imaging (MRI) detected deterioration in subchondral bone microarchitecture in both medial and lateral femoral condyles in osteoarthritis subjects as compared with controls. This was manifested by lower bone volume fraction (-1.03% to -5.43%, P < 0.04), higher erosion index (+8.49 to +22.76%, P < 0.04), lower surface number (-2.31% to -9.63%, P < 0.007), higher curve number (+6.85% to +16.93%, P < 0.03), and lower plate-to-rod ratio (-7.92% to -21.71%, P < 0.05). CONCLUSION: The results provide further support for the concept that poor subchondral bone quality is associated with osteoarthritis and may serve as a potential therapeutic target for osteoarthritis interventions.J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.

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 explore the feasibility of T1rho mapping of menisci at 3T in discriminating between patients with acute anterior cruciate ligament (ACL) injury and healthy controls. MATERIALS AND METHODS: Thirty-three subjects were included in the study and subdivided into two subgroups: 16 healthy controls (4 females, 12 males; mean age = 34.4 +/- 10.2 years, age range 24-63 years), 17 patients with ACL injury (3 females, 14 males; mean age = 29.8 +/- 10.8 years, age range 18-61 years). T1rho images from all subjects were acquired on a 3T MR scanner using a spin-lock-based 3D GRE sequence and computed for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in the sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were also acquired for cartilage assessment using Whole-Organ MR Imaging Score (WORMS) grading. Mixed model two-way analysis of variance (ANOVA) was performed to determine whether there were any significant differences among subregional, compartmental, and whole structure T1rho values of meniscus between healthy controls and ACL-injured patients. RESULTS: Lateral posterior (29 +/- 8 msec) and medial central (25 +/- 7 msec) meniscus subregions in healthy controls had significantly lower T1rho values (P < 0.05) than the corresponding meniscus subregions in ACL-injured patients. Significantly lower meniscus T1rho values (P < 0.05) were also identified in lateral compartment in healthy controls (26 +/- 6 msec) than that of ACL-injured patients (33 +/- 4 msec). Subjects' total WORMS between healthy controls and ACL-injured patients had significant differences (P < 0.05). CONCLUSIONS: These preliminary results indicate that T1rho mapping is possibly feasible in detecting meniscus degeneration and may be useful in distinguishing ACL-injured patients. J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.