Faculty Bibliography

Background/Purpose : Osteoporosis and bone fractures are a frequent cause of morbidity in systemic lupus erythematosus (SLE), and are felt to be related both to disease activity and glucocorticoid (GC) exposure. Dual energy X-ray absorptiometry (DEXA) is the standard tool to assess bone density, but it does not measure bone quality or strength and is not a robust predictor of fractures in SLE. Clinical 3T MRI scans have been shown to assess information about bone not captured by DEXA. This study aims to evaluate factors associated with bone structure measured by DEXA and MRI in an SLE cohort. Methods : DEXAs were performed on 31 women with SLE and 3T MRI of the non-dominant hip were performed on 29 of these cases. Results were associated with multiple demographic, clinical and laboratory measures. MRI parameters measured included trabecular plate width (PW), trabecular plate to rod ratio (PRR), plate volume fraction (PVF), rod volume fraction (RVF), trabecular bone thickness (Tb.Th), trabecular spacing (Tb.Sp) and trabecular network area (TNA). DEXA BMD was measured, and osteoporosis (OP) was defined as hip, spine or femoral neck Z score < -2.0 in premenopausal women, and T score < -2.5 in others, and low bone density (LBD) as Z score < -2.0 in premenopausal women and T score < -1.0 in others. Results : By DEXA, 8/31 (25.8%) had OP and 12 (38.7%) had LBD. History of lymphopenia (75.0% vs. 31.8%, p=0.049) and lower concurrent HCQ dose (340 vs. 400 mg, p=0.006) associated with DEXA OP, while older age (48.3 vs. 36.3 y, p=0.024) associated with LBD. Higher ESR was inversely correlated with favorable bone structure (PW r(22) = -.49, p=0.025, PRR rs = -.51, p=0.018, PVF rs = -.51, p=0.018, RVF rs = .51, p=0.018, Tb.Th rs = -.58, p=0.005, Tb.Sp rs = .44, p=0.046, TNA rs = -.50, p=0.022). Higher CRP was likewise inversely correlated with favorable bone structure (PW r(20) = -.61, p=0.004, PRR rs = -.57, p=0.009, PVF rs = -.57, p=0.009, RVF rs =.57, p=0.009, Tb.Th rs = -.56, p=.011, Tb.Sp rs =.67, p=0.001, TNA rs = -.64, p=0.002). A history of lupus nephritis was associated with unfavorable bone structure (PW 705.3 vs. 833.3 mum, p=0.048, PRR 6.6 vs. 8.1, p=0.024, PVF 0.83 vs. 0.89, p=0.024, RVF 0.17 vs. 0.11, p=0.024, Tb.Th 178.1 vs. 193.4 mm, p=0.012, Tb.Sp 358.6 vs. 296.5 mm, p=0.056, TNA 0.41 vs. 0.54 (1/mm), p=0.009). ESR, CRP and history of lupus nephritis were not significantly associated with DEXA hip BMD, OP or LBD. MRI parameters for favorable bone structure were inversely correlated with DEXA hip BMD (PW r(28) = -.47, p=0.011, Tb.Th rs = -.53, p=0.003) and BMI (PW r(28) = -.54, p=0.003, TbTh rs = -.72, p< 0.001, TNA rs = -.44, p=0.017). Conclusion : Higher ESR and CRP and a history of lupus nephritis associated with MRI parameters of unfavorable bone structure, but did not associate with DEXA abnormalities in SLE patients. MRI may be a more sensitive tool than DEXA to measure inflammatory effects on bone and potentially cumulative dose of steroid exposure. There were inverse correlations of MRI parameters with traditional osteoporosis risk factors and BMD measures on DEXA, and it is possible that each tool evaluates different aspects of bone health. Further evaluation of MRI screening for fracture risk in SLE and GC exposed individuals is warranted to better quantify risk and guide treatment

BACKGROUND:tissues may provide a more comprehensive evaluation of OA. PURPOSE/OBJECTIVE:tissues on a clinical 3 T scanner. STUDY TYPE/METHODS:Prospective. POPULATION/METHODS:Phantom, two bovine whole knee joint and Achilles tendon specimens, 10 healthy volunteers with no known inflammation, trauma or pain in the knee or ankle. FIELD STRENGTH/SEQUENCE/UNASSIGNED: ASSESSMENT/RESULTS:relaxation components were assessed in the patellar tendon (PT), anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and Achilles tendon (AT). STATISTICAL TESTS/UNASSIGNED:Kruskal-Wallis with post-hoc Dunn's test for multiple pairwise comparisons. RESULTS:relaxation of (median [IQR]) 15.9 [14.5] msec, 23.6 [9.4] msec, 17.4 [7.4] msec, and 5.8 [10.2] msec in the PT, ACL, PCL, and AT, respectively. The bicomponent analysis showed the short and long components (with their relative fractions) of 0.65 [1.0] msec (46.9 [15.3]%) and 37.3 [18.4] msec (53.1 [15.3]%) for PT, 1.7 [2.1] msec (42.5 [12.5]%) and 43.7 [17.8] msec (57.5 [12.5]%) for ACL, and 1.2 [1.9] msec (42.6 [14.0]%) and 27.7 [14.7] msec (57.3 [14.0]%) for PCL and 0.4 [0.02] msec (58.8 [13.3]%/) and 31.3 [10.8] msec (41.2 [13.3]%) for AT. Statistically significant (P ≤ 0.05) differences were observed in the mono- and biexponential relaxation between several regions. DATA CONCLUSION/UNASSIGNED: LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019.

BACKGROUND:in the knee menisci can potentially be used as noninvasive biomarkers in detecting early-stage osteoarthritis (OA). PURPOSE/OBJECTIVE:relaxation mapping of human knee menisci. STUDY TYPE/METHODS:Prospective. POPULATION/METHODS:Eight healthy volunteers with no known inflammation, trauma, or pain in the knee and three symptomatic subjects with early knee OA. FIELD STRENGTH/SEQUENCE/UNASSIGNED:-weighted images on a 3 T MRI scanner. ASSESSMENT/RESULTS:relaxation values were assessed in 11 meniscal regions of interest (ROIs) using monoexponential and biexponential models. STATISTICAL TESTS/UNASSIGNED:Nonparametric rank-sum tests, Kruskal-Wallis test, and coefficient of variation. RESULTS:-long, respectively. DATA CONCLUSION/UNASSIGNED:was increased in medial, lateral, and body menisci of early OA while the biexponential numbers were decreased in early OA patients. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019.

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/UNASSIGNED: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/METHODS:Prospective. SUBJECTS/METHODS:In all, 18 OP and 13 GIO subjects. FIELDS STRENGTH/UNASSIGNED:3T. SEQUENCE/UNASSIGNED:Multiple gradient-echo, stimulated echo acquisition mode (STEAM). ASSESSMENT/RESULTS: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/UNASSIGNED: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: DATA CONCLUSION/UNASSIGNED: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/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PURPOSE OF REVIEW/OBJECTIVE: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/RESULTS:Here we survey the latest research in the artificial intelligence application to the prediction of osteoporosis that is 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/CONCLUSIONS: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.

BACKGROUND:A current challenge in osteoporosis is identifying patients at risk of bone fracture. PURPOSE/OBJECTIVE: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/METHODS:Prospective (cross-sectional) case-control study. POPULATION/METHODS:. Field Strength/ Sequence: 3D FLASH at 3T. ASSESSMENT/RESULTS: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/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Currently, clinical determination of pathologic fracture risk in the hip is conducted using measures of defect size and shape in the stance loading condition. However, these measures often do not consider how changing lesion locations or how various loading conditions impact bone strength. The goal of this study was to determine the impact of defect location on bone strength parameters in both the sideways fall and stance-loading conditions. We recruited 20 female subjects aged 48-77 years for this study and performed MRI of the proximal femur. Using these images, we simulated 10-mm pathologic defects in greater trochanter, superior, middle, and inferior femoral head, superior, middle, and inferior femoral neck, and lateral, middle, and medial proximal diaphysis to determine the effect of defect location on change in bone strength by performing finite element analysis. We compared the effect of each osteolytic lesion on bone stiffness, strength, resilience, and toughness. For the sideways fall loading, defects in the inferior femoral head (12.21%) and in the greater trochanter (6.43%) resulted in the greatest overall reduction in bone strength. For the stance loading, defects in the mid femoral head (-7.91%) and superior femoral head (-7.82%) resulted in the greatest overall reduction in bone strength. Changes in stiffness, yield force, ultimate force, resilience, and toughness were not found to be significantly correlated between the sideways fall and stance-loading for the majority of defect locations, suggesting that calculations based on the stance-loading condition are not predictive of the change in bone strength experienced in the sideways fall condition. While stiffness was significantly related to yield force (R²â€¯> 0.82), overall force (R²â€¯> 0.59), and resilience (R²â€¯> 0.55), in both, the stance-loading and sideways fall conditions for most defect locations, stiffness was not significantly related to toughness. Therefore, structure-dependent measure such as stiffness may not fully explain the post-yield measures, which depend on material failure properties. The data showed that MRI-based models have the sensitivity to determine the effect of pathologic lesions on bone strength.

BACKGROUND:Osteoporotic hip fractures heavily cost the health care system. Clinicians and patients can benefit from improved tools to assess bone health. Herein, we aim to develop a three-dimensional magnetic resonance imaging (MRI) method to assess cortical bone thickness and assess the ability of the method to detect regional changes in the proximal femur. METHODS:Eighty-nine patients underwent hip magnetic resonance imaging. FireVoxel and 3DSlicer were used to generate three-dimensional proximal femur models. ParaView was used to define five regions: head, neck, greater trochanter, intertrochanteric region, and subtrochanteric region. Custom software was used to calculate the cortical bone thickness and generate a color map of the proximal femur. Mean cortical thickness values for each region were calculated. Statistical t-tests were performed to evaluate differences in cortical thickness based on proximal femur region. Measurement reliability was evaluated using coefficient of variation, intraclass correlation coefficients, and overlap metrics. RESULTS:Three-dimensional regional cortical thickness maps for all subjects were generated. The subtrochanteric region was found to have the thickest cortical bone and the femoral head had the thinnest cortical bone. There were statistically significant differences between regions (p < 0.01) for all possible comparisons. CONCLUSIONS:Cortical bone is an important contributor to bone strength, and its thinning results in increased hip fracture risk. We describe the development and measurement reproducibility of an MRI tool permitting assessment of proximal femur cortical thickness. This study represents an important step toward longitudinal clinical trials interested in monitoring the effectiveness of drug therapy on proximal femur cortical thickness.