Stiffness and Strain Properties Derived From Digital Tomosynthesis-Based Digital Volume Correlation Predict Vertebral Strength Independently From Bone Mineral Density.

Vertebral fractures are the most common osteoporotic fractures, but their prediction using standard bone mineral density (BMD) measurements from dual energy X-ray absorptiometry (DXA) is limited in accuracy. Stiffness, displacement, and strain distribution properties derived from digital tomosynthesis-based digital volume correlation (DTS-DVC) have been suggested as clinically measurable metrics of vertebral bone quality. However, the extent to which these properties correlate to vertebral strength is unknown. To establish this relationship, two independent experiments, one examining isolated T11 and the other examining L3 vertebrae within the L2-L4 segments from cadaveric donors were utilized. Following DXA and DTS imaging, the specimens were uniaxially compressed to fracture. BMD, bone mineral content (BMC), and bone area were recorded for the anteroposterior and lateromedial views from DXA, stiffness, endplate to endplate displacement and distribution statistics of intravertebral strains were calculated from DTS-DVC and vertebral strength was measured from mechanical tests. Regression models were used to examine the relationships of strength with the other variables. Correlations of BMD with vertebral strength varied between experimental groups (R2adj = 0.19-0.78). DTS-DVC derived properties contributed to vertebral strength independently from BMD measures (increasing R2adj to 0.64-0.95). DTS-DVC derived stiffness was the best single predictor (R2adj = 0.66, p < 0.0001) and added the most to BMD in models of vertebral strength for pooled T11 and L3 specimens (R2adj = 0.95, p < 0.0001). These findings provide biomechanical relevance to DTS-DVC calculated properties of vertebral bone and encourage further efforts in the development of the DTS-DVC approach as a clinical tool.

Assessment of Intravertebral Mechanical Strains and Cancellous Bone Texture Under Load Using a Clinically Available Digital Tomosynthesis Modality.

Vertebral fractures are the most common osteoporotic fractures, but clinical means for assessment of vertebral bone integrity are limited in accuracy, as they typically use surrogate measures that are indirectly related to mechanics. The objective of this study was to examine the extent to which intravertebral strain distributions and changes in cancellous bone texture generated by a load of physiological magnitude can be characterized using a clinically available imaging modality. We hypothesized that digital tomosynthesis-based digital volume correlation (DTS-DVC) and image texture-based metrics of cancellous bone microstructure can detect development of mechanical strains under load. Isolated cadaveric T11 vertebrae and L2-L4 vertebral segments were DTS imaged in a nonloaded state and under physiological load levels. Axial strain, maximum principal strain, maximum compressive and tensile principal strains, and von Mises equivalent strain were calculated using the DVC technique. The change in textural parameters (line fraction deviation, anisotropy, and fractal parameters) under load was calculated within the cancellous centrum. The effect of load on measured strains and texture variables was tested using mixed model analysis of variance, and relationships of strain and texture variables with donor age, bone density parameters, and bone size were examined using regression models. Magnitudes and heterogeneity of intravertebral strain measures correlated with applied loading and were significantly different from background noise. Image texture parameters were found to change with applied loading, but these changes were not observed in the second experiment testing L2-L4 segments. DTS-DVC-derived strains correlated with age more strongly than did bone mineral density (BMD) for T11.

Digital Tomosynthesis and Fractal Analysis Predict Prevalent Vertebral Fractures in Patients With Multiple Myeloma: A Preliminary In Vivo Study.

OBJECTIVE. The objective of this study was to investigate the association of fractal-derived bone microstructural parameters with vertebral fracture status using in vivo digital tomosynthesis images of the spine. MATERIALS AND METHODS. Digital tomosynthesis images of the thoracic and lumbar spine from T1 to L5 were acquired from 36 patients with newly diagnosed multiple myeloma or monoclonal gammopathy of uncertain significance (age range, 39-85 years old). Scans were performed with patients in the supine position with reconstructed planes formed in the coronal direction. Bone mineral density (BMD) was recorded for 10 patients who had recently undergone dual x-ray absorptiometry. Vertebral fracture and lytic lesion status was determined by a radiologist from digital radiographs. Radiologist interpretation was reviewed to identify levels with a minimum number of fractures or lesions. For fractal analysis, the largest possible cuboid volume of interest within the cancellous bone was cropped from T7 and T11 images. Mean and SD of fractal variables between slices of fractal dimension (FD, a measure of self-similarity in the texture), mean lacunarity (λ, a measure of heterogeneity) and the slope of lacunarity versus box size relationship (Sλ, a measure of sensitivity of heterogeneity to size scale) were calculated using a box-counting method. A generalized estimating equation (GEE) platform was used to examine fractal variables as predictors of fracture status. RESULTS. Fracture status was not significantly associated with sex, race, age, stage of myeloma, presence of lesion in the spine, or BMD. In light of these results, no correction was made for these variables in further analyses of fractal variables. No interaction was found between vertebral level and any of the fractal variables (p = 0.12-0.77). Therefore, vertebral level was not considered further as an independent variable. Logistic regression analysis within GEE indicated that probability of fracture decreased with increasing mean FD (p = 0.02). In contrast, probability of fracture increased with increasing mean λ (p = 0.03). Although not to a statistically significant degree, probability of fracture increased with increasing mean Sλ (p = 0.08), SD of FD (p = 0.07), SD of λ (p = 0.07), and SD of Sλ (p = 0.06). CONCLUSION. We found FD and lacunarity calculated within the cancellous centrum of T7 and T11 vertebrae to be significantly associated with the presence of a vertebral fracture in this cohort. The decreased probability of fracture with increasing fractal dimension and increased probability of fracture with increasing lacunarity are consistent with the idea that cancellous bone with a better organized trabecular architecture is mechanically more competent. To our knowledge, this is the first in vivo evidence that fractal analysis of vertebral bone from tomosynthesis images may be useful in assessing vertebral fracture risk in patients with multiple myeloma.

Dynamic measurements of cervical neural foramina during neck movements in asymptomatic young volunteers.

PURPOSE: Neural foraminal dimensions are considered important in nerve root compression and development of cervical radiculopathy, but baseline data regarding their range during normal motion are not available. An in vivo study of cervical foraminal motion was conducted to characterize normal 3D dynamic foraminal dimensions during physiological neck motion and compare between different tasks and intervertebral segments. METHODS: Biplane X-ray imaging and computed tomography-based markerless tracking were used to measure foraminal height (FH) and width (FW) from five asymptomatic subjects during neck axial rotation and extension. FH and FW were quantified as the minimum (SI.Min and AP.Min), range (SI.Range and AP.Range), and median (SI.Med and AP.Med) of superoinferior (SI) and anteroposterior (AP) dimensions for each trial and as the coefficient of variation of these variables from three trials (SI.Med.CV and AP.Med.CV, SI.Range.CV and AP.Range.CV) at C3-4 through C6-7 levels for each subject. Differences were analyzed using mixed model ANOVA. RESULTS: AP.Range and AP.Med.CV were greater (P < 0.0001) while AP.Min and AP.Range.CV were smaller (P < 0.0006 and P < 0.0005) during neck extension than rotation. SI.Range and SI.Med.CV were greater for extension than rotation at C5-6 (P < 0.002 and P < 0.03), whereas SI.Med.CV was greater for rotation than extension at C3-4 (P < 0.03). AP.Range (P < 0.02), AP.Med.CV (P < 0.05), SI.Range (P < 0.0004), and SI.Med.CV (P < 0.02) were different between cervical levels, the latter two being during extension only. CONCLUSIONS: Patterns of FH and FW during normal motion are different between tasks and cervical levels. These findings are expected to provide a basis for future studies of spinal degeneration and surgical efficacy.

Mechanical loading causes detectable changes in morphometric measures of trabecular structure in human cancellous bone.

The relationships between mechanical loads and bone microstructure are of interest to those who seek to predict bone mechanical properties from microstructure or to predict how organization of bone microstructure is driven by mechanical loads. While strains and displacements in the material are inherently responsible for mechanically caused changes in the appearance of the microstructure, it is the morphometric measures of microstructural organization that are often available for assessment of bone quality. Therefore, an understanding of how strain history is reflected in morphometric measures of bone microstructure has practical implications in that it may provide clinically measurable indices of mechanical history in bone and improve interpretation of bone mechanical properties from microstructural information. The objective of the current study was to examine changes in morphometric measures of cancellous bone microstructure in response to varying levels of continuum level strains. The experimental approach included stereologic analysis of microcomputed tomography (µCT) images of human cancellous bone samples obtained at sequentially increasing levels of strain in a custom-made loading apparatus mounted in a µCT scanner. We found that the degree of anisotropy (DA) decreased from baseline to failure and from failure to postfailure. DA partially recovered from postfailure levels upon unloading; however, the final DA was less than at failure and less than at baseline. We also found that average trabecular thickness (Tb.Th.Av) increased with displacements at postfailure and did not recover when unloaded. Average trabecular number decreased when the specimens were unloaded. In addition, the heterogeneity of Tb.Th as measured by intra-specimen standard deviation (Tb.Th.SD) increased and that of trabecular number (Tb.N.SD) decreased with displacements at postfailure. Furthermore, the intraspecimen coefficient of variation of trabecular number decreased at postfailure displacements but did not recover upon unloading. Finally, the coefficient of variation of trabecular separation at unload was less than that at baseline. These measures can be developed into image-based indices to estimate strain history, damage, and residual mechanical properties where direct analysis of stresses and strains, such as through finite element modeling, may not be feasible. It remains to be determined how wide a time interval can be used to estimate strain history before remodeling becomes an overriding effect on the trabecular architecture.

Digital wrist tomosynthesis (DWT)-based finite element analysis of ultra-distal radius differentiates patients with and without a history of osteoporotic fracture.

Despite effective therapies for those at risk of osteoporotic fracture, low adherence to screening guidelines and limited accuracy of bone mineral density (BMD) in predicting fracture risk preclude identification of those at risk. Because of high adherence to routine mammography, bone health screening at the time of mammography using a digital breast tomosynthesis (DBT) scanner has been suggested as a potential solution. BMD and bone microstructure can be measured from the wrist using a DBT scanner. However, the extent to which biomechanical variables can be derived from digital wrist tomosynthesis (DWT) has not been explored. Accordingly, we measured stiffness from a DWT based finite element (DWT-FE) model of the ultra-distal (UD) radius and ulna, and correlate these to reference microcomputed tomography image based FE (µCT-FE) from five cadaveric forearms. Further, this method is implemented to determine in vivo reproducibility of FE derived stiffness of UD radius and demonstrate the in vivo utility of DWT-FE in bone quality assessment by comparing two groups of postmenopausal women with and without a history of an osteoporotic fracture (Fx; n = 15, NFx; n = 51). Stiffness obtained from DWT and µCT had a strong correlation (R2 = 0.87, p < 0.001). In vivo repeatability error was <5 %. The NFx and Fx groups were not significantly different in DXA derived minimum T-scores (p > 0.3), but stiffness of the UD radius was lower for the Fx group (p < 0.007). Logistic regression models of fracture status with stiffness of the nondominant arm as the predictor were significant (p < 0.01). In conclusion this study demonstrates the feasibility of fracture risk assessment in mammography settings using DWT imaging and FE modeling in vivo. Using this approach, bone and breast screening can be performed in a single visit, with the potential to improve both the prevalence of bone health screening and the accuracy of fracture risk assessment.

The relationship of whole human vertebral body creep to bone density and texture via clinically available imaging modalities.

Creep deformation of human vertebrae accumulates under physiological levels of load and is understood to contribute to the progression toward clinically observable vertebral fracture. However, little information is available in terms of clinically measurable predictors of creep behavior in human vertebrae. In this study, creep tests were performed on 22 human cadaveric T12 vertebrae (13 male, 9 female; age 41-90). Areal and volumetric bone density parameters were measured from the same specimens using dual x-ray absorptiometry and high resolution computed tomography. Image textural analyses (which probe the organization of image intensities within the cancellous bone in low resolution clinical imaging) were performed using digital tomosynthesis (DTS) images. Multiple regression models were constructed to examine the relationship between creep properties and bone density and DTS image textural parameters. For the standard clinical imaging configuration, models including DTS derived image textural parameters alone were generally more explanatory (adjusted R2: 0.14-0.68) than those with bone density parameters forced in the models (adjusted R2: 0.17-0.61). Metrics of textural heterogeneity and anisotropy presented as the most explanatory imaging markers for creep deformation and recovery from creep. These metrics of image texture may help provide, independent from bone mass, important clinically measurable indicators of the time dependent deformation of human vertebrae.

Uniaxial compressive properties of human lumbar 1 vertebrae loaded beyond compaction and their relationship to cortical and cancellous microstructure, size and density properties.

Lumbar 1 vertebrae are among those most commonly fracture due to osteoporosis. The strength of human vertebrae and its structural, microstructural and material determinants have been the subject of numerous studies. However, a comprehensive evaluation of properties beyond maximum load to fracture has not been available for the L1 vertebrae. The objective of this study was to document these properties in association with each other and with the geometric, density and cancellous and cortical structure properties for human L1 vertebrae. Bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), connectivity density (Conn.Dn), degree of anisotropy (DA), structure model index (SMI) and fractal dimension (FD) of the cancellous microstructure, tissue mineral density (TMD), and thickness of the cortical shell (Sh.Th) and superior and inferior endplates thicknesses (EP.Th.S and EP.Th.I) were measured using microcomputed tomography for 27 cadaveric L1 vertebrae. Volumetric cancellous, shell and integral bone mineral densities (vBMD, shBMD and iBMD) as well as vertebral volume (V), height and width were measured using high resolution CT. Areal whole vertebral body and regional BMDs were measured using dual energy x-ray absorptiometry (DXA) in coronal and lateral views. Specimens were then uniaxially compressed to 15% of their height to obtain vertebral stiffness (K) and strength (Fmax) as well as displacement (D), force (F) and energy (W) properties at characteristic points of the load-displacement curve including yield (y), fracture (f), compaction (c), final displacement (t) and residual after unload (r). Correlation and principal component analyses suggested displacements to failure (Df), collapse (Dc) and recovery (Dr) contain information distinct from strength and stiffness. Bone size (V) was present, independently, in multiple regression models of K, Fy, Wy, Fmax, Df, Wt, Wfc and Dr (p < 0.05 to p < 0.0001), areal BMD in models of Dy, Wy, Fmax, Wf, Fc, Wt, Wyf and Wct (p < 0.04 to p < 0.0001), Sh.Th in models of Df, Fc and εr (p < 0.02 to p < 0.002), EP.Th.S in models of Fc and Wct (p < 0.004 to p < 0.0006), EP.Th.I in the model of Wct (p < 0.02), FD in models of Fy, Dy and Fmax (p < 0.03 to p < 0.004), Tb.Sp in models of K and Dy (p < 0.002 to p < 0.0004), Conn.Dn in the model of Df (p < 0.0009), and SMI in the model of Wt (p < 0.02). R2adj varied from 0.12 (Dr) to 0.80 (Wt) for the multiple regression models for all significant variables. In conclusion, there is distinct information in forces and displacements associated with characteristic events occurring during uniaxial compression and recovery, specifically in displacements associated with compaction and recovery. Though there are common factors such as bone mass for some, distinct cancellous and cortical features likely contribute to these events in L1. The descriptive data reported here are expected to provide reference values for comparative and model building efforts, and the relationships found are expected to provide insight into mechanical functions of an L1 vertebra.

Measuring the thickness of vertebral endplate and shell using digital tomosynthesis.

The vertebral endplate and cortical shell play an important structural role and contribute to the overall strength of the vertebral body, are at highest risk of initial failure, and are involved in degenerative disease of the spine. The ability to accurately measure the thickness of these structures is therefore important, even if difficult due to relatively low resolution clinical imaging. We posit that digital tomosynthesis (DTS) may be a suitable imaging modality for measurement of endplate and cortical shell thickness owing to the ability to reconstruct multiplanar images with good spatial resolution at low radiation dose. In this study, for 25 cadaveric L1 vertebrae, average and standard deviation of endplate and cortical shell thickness were measured using images from DTS and microcomputed tomography (µCT). For endplate thickness measurements, significant correlations between DTS and µCT were found for all variables when comparing thicknesses measured in both the overall endplate volume (R2 = 0.25-0.54) and when measurements were limited to a central range of coronal or sagittal slices (R2 = 0.24-0.62). When compared to reference values from the overall shell volume, DTS thickness measurements were generally nonsignificant. However, when measurement of cortical shell thickness was limited to a range of central slices, DTS outcomes were significantly correlated with reference values for both sagittal and coronal central regions (R2 = 0.21-0.49). DTS may therefore offer a means for measurement of endplate thickness and, within a limited sagittal or coronal measurement volume, for measurement of cortical shell thickness.

Intervertebral kinematics during neck motion 6.5 years after fusion and artificial disc replacement.

BACKGROUND: Arthroplasty with artificial disc replacement for surgical treatment of cervical spine degeneration was introduced with the notion that motion-preserving approaches would prevent development of adjacent segment disease. Though clinical outcomes favor arthroplasty over the commonly used anterior cervical discectomy with fusion approach, clinical studies confirming the biomechanical basis of these results are lacking. The aim of this study was to compare intervertebral kinematics between arthroplasty and fusion patients 6.5 years post-surgery during physiological motion of the neck. METHODS: Using a biplane dynamic X-ray system, computed tomography imaging and model based tracking algorithms, three dimensional intervertebral kinematics were measured during neck axial rotation and extension in 14 patients treated for cervical radiculopathy with fusion (n = 8) or arthroplasty (n = 6). The measurements were performed at 2-year (baseline) and 6.5 year post-surgical time points, with the main interest being in the interaction between surgery types and time points. 3 translations and 3 rotations were investigated for the index (C5C6), and upper- (C4C5) and lower adjacent levels (C6C7). FINDINGS: Surgery-time interaction was significant for axial rotation (P < 0.04) and flexion-extension rotation (P < 0.005) in C4C5 during neck axial rotation, left-right translation (P < 0.04) in C5C6 and anterior-posterior translation in C6C7 (P < 0.04) during neck extension. In contrast with the expectations, axial rotation and flexion-extension decreased in C4C5 during neck rotation and anterior-posterior translation decreased in C6C7 during neck extension for fusion. INTERPRETATION: The findings do not support the notion that adjacent segment motion increases after fusion.

Bone health assessment via digital wrist tomosynthesis in the mammography setting.

Bone fractures attributable to osteoporosis are a significant problem. Though preventative treatment options are available for individuals who are at risk of a fracture, a substantial number of these individuals are not identified due to lack of adherence to bone screening recommendations. The issue is further complicated as standard diagnosis of osteoporosis is based on bone mineral density (BMD) derived from dual energy x-ray absorptiometry (DXA), which, while helpful in identifying many at risk, is limited in fully predicting risk of fracture. It is reasonable to expect that bone screening would become more prevalent and efficacious if offered in coordination with digital breast tomosynthesis (DBT) exams, provided that osteoporosis can be assessed using a DBT modality. Therefore, the objective of the current study was to explore the feasibility of using digital tomosynthesis imaging in a mammography setting. To this end, we measured density, cortical thickness and microstructural properties of the wrist bone, correlated these to reference measurements from microcomputed tomography and DXA, demonstrated the application in vivo in a small group of participants, and determined the repeatability of the measurements. We found that measurements from digital wrist tomosynthesis (DWT) imaging with a DBT scanner were highly repeatable ex vivo (error = 0.05%-9.62%) and in vivo (error = 0.06%-10.2%). In ex vivo trials, DWT derived BMDs were strongly correlated with reference measurements (R = 0.841-0.980), as were cortical thickness measured at lateral and medial cortices (R = 0.991 and R = 0.959, respectively) and the majority of microstructural measures (R = 0.736-0.991). The measurements were quick and tolerated by human patients with no discomfort, and appeared to be different between young and old participants in a preliminary comparison. In conclusion, DWT is feasible in a mammography setting, and informative on bone mass, cortical thickness, and microstructural qualities that are known to deteriorate in osteoporosis. To our knowledge, this study represents the first application of DBT for imaging bone. Future clinical studies are needed to further establish the efficacy for diagnosing osteoporosis and predicting risk of fragility fracture using DWT.

Vertebral stiffness measured via tomosynthesis-based digital volume correlation is strongly correlated with reference values from micro-CT-based DVC.

Digital tomosynthesis (DTS) is a clinically available modality that allows imaging of a patient's spine in supine and standing positions. The purpose of this study was to establish the extent to which vertebral displacement and stiffness derived from DTS-based digital volume correlation (DTS-DVC) are correlated with those from a reference method, i.e., microcomputed tomography-based DVC (µCT-DVC). T11 vertebral bodies from 11 cadaveric donors were DTS imaged twice in a nonloaded state and once under a fixed load level approximating upper body weight. The same vertebrae were µCT imaged in nonloaded and loaded states (40 µm voxel size). Vertebral displacements were calculated at each voxel using DVC with pairs of nonloaded and loaded images, from which endplate-to-endplate axial displacement (DDVC) and vertebral stiffness (SDVC) were calculated. Both DDVC and SDVC demonstrated strong positive correlations between DTS-DVC and µCT-DVC, with correlations being stronger when vertebral displacement was calculated using the median (R2=0.80; p<0.0002 and R2=0.93; p<0.0001, respectively) rather than average displacement (R2=0.63; p<0.004 and R2=0.69; p<0.002, respectively). In conclusion, the demonstrated relationship of DTS-DVC with the µCT standard supports further development of a biomechanics-based clinical assessment of vertebral bone quality using the DTS-DVC technique.

Correlation of neural foraminal motion after surgical treatment of cervical radiculopathy with long-term patient reported outcomes.

BACKGROUND: Post-surgical changes in adjacent segment motion are considered a factor in further development of degeneration and cervical radiculopathy. The objective was to examine the extent of correlations between physiological motion of cervical foramina and long-term patient reported outcomes (PRO). METHODS: Biplane X-ray imaging and CT-based markerless tracking were used to measure 3D static and dynamic dimensions during neck axial rotation and extension from 18 patients treated for C5-6 radiculopathy with fusion or arthroplasty. Minimum foraminal height (FH.Min) and width (FW.Min), and their range (FH.Range and FW.Range) achieved during a motion task were calculated for adjacent levels (C4-5 and C6-7) at 2.0±0.6 years post-surgery. The modified Japanese Orthopedic Association score (mJOAS), the Neck Disability Index (NDI) including the visual analogue scale (VAS) for neck and arm pain, and the EuroQol EQ-5D score were recorded at 6.5±1.1 years post-surgery. The relationships between 6.5-year outcomes and 2-year foraminal motion were examined using regression. RESULTS: Worsening patient-reported outcomes were generally associated with lower values of FW.Min (P<0.05 to P<0.008), the associations being stronger for neck extension (r2 up to 0.43). Dynamic foraminal measurements from the C6-7 level more significantly and consistently correlated with mJOAS, EQ-5D and NDI Arm Pain VAS (r2=0.27 to 0.43; P<0.03 to P<0.008), whereas those from the C4-5 level correlated with NDI Neck Pain VAS (r2=0.33; P<0.02). CONCLUSIONS: Dynamic 3D foraminal dimensions at 2-year post-surgery, notably FW.Min measured in neck extension at adjacent levels, were associated with PRO at 6.5 years post-surgery. These relationships provide insight into the motion related factors in development of pain and loss of function, and may help develop markers or objective outcome measures.

Dynamic foraminal dimensions during neck motion 6.5 years after fusion and artificial disc replacement.

OBJECTIVE: To compare changes in foraminal motion at two time points post-surgery between artificial disc replacement (ADR) and anterior cervical discectomy and fusion (ACDF). METHODS: Eight ACDF and 6 ADR patients (all single-level C5-6) were tested at 2 years (T1) and 6.5 years (T2) post-surgery. The minimum foraminal height (FH.Min) and width (FW.Min) achieved during neck axial rotation and extension, and the range of these dimensions during motion (FH.Rn and FW.Rn, respectively) were measured using a biplane dynamic x-ray system, CT imaging and model-based tracking while patients performed neck axial rotation and extension tasks. Two-way mixed ANOVA was employed for analysis. RESULTS: In neck extension, significant interactions were found between year post-surgery and type of surgery for FW.Rn at C5-6 (p<0.006) and C6-7 (p<0.005), and for FH.Rn at C6-7 (p<0.01). Post-hoc analysis indicated decreases over time in FW.Rn for ACDF (p<0.01) and increases in FH.Rn for ADR (p<0.03) at the C6-7 adjacent level. At index level, FW.Rn was comparable between ACDF and ADR at T1, but was smaller for ACDF than for ADR at T2 (p<0.002). In axial rotation, differences were found between T1 and T2 but did not depend on type of surgery (p>0.7). CONCLUSIONS: Changes were observed in the range of foraminal geometry at adjacent levels from 2 years to 6.5 years post-surgery that were different between ACDF and ADR for neck extension. These changes are contrary to the notion that motion at adjacent levels continue to increase following ACDF as compared to ADR over the long term.

Analysis of crystals leading to joint arthropathies by Raman spectroscopy: comparison with compensated polarized imaging.

The current study assessed the feasibility of the application of Raman spectroscopy toward the diagnosis of gout and pseudogout. First, the lowest concentrations of monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD) crystals detectable by Raman spectroscopy were investigated by mixing known amounts of synthetic crystals with synovial fluid in the concentration range of 1 to 100 microg/mL. Second, a digestion protocol was developed for clinical samples to improve crystal extraction. The ensuing centrifugation of the digest congregated crystals at a well-defined point and allowed for point-and-shoot Raman analysis without having to conduct an extensive search for individual crystals. Finally, synovial fluid samples obtained from patients (n = 35) were cross-analyzed by polarized light microscopy (PLM) and the Raman method to compare and contrast the diagnoses of the two methods. It was found that Raman spectroscopy can detect MSUM and CPPD crystals with good sensitivity and specificity at concentrations as low as 5 microg/mL and 2.5 microg/mL, respectively, using the current method. This detection limit of Raman analysis is lower than that reported for PLM. Raman and PLM diagnoses of clinical samples agreed in 32 out of 35 samples in the entire sample pool. However, the rate of disagreement between PLM-based and Raman-based diagnoses was noteworthy within the subset of diseased samples (3 out of 10), indicating that PLM has limitations and that the confirmation by a secondary method is essential for a reliable outcome. The proposed protocol of sample preparation and Raman analysis ascribes baseline feasibility to the diagnosis of gout and pseudogout by Raman spectroscopy, thus justifying further studies using a larger clinical sample set for obtaining sensitivity and specificity.

Increased microstructural variability is associated with decreased structural strength but with increased measures of structural ductility in human vertebrae.

The lack of accuracy in the prediction of vertebral fracture risk from average density measurements, all external factors being equal, may not just be because bone mineral density (BMD) is less than a perfect surrogate for bone strength but also because strength alone may not be sufficient to fully characterize the structural failure of a vertebra. Apart from bone quantity, the regional variation of cancellous architecture would have a role in governing the mechanical properties of vertebrae. In this study, we estimated various microstructural parameters of the vertebral cancellous centrum based on stereological analysis. An earlier study indicated that within-vertebra variability, measured as the coefficient of variation (COV) of bone volume fraction (BV/TV) or as COV of finite element-estimated apparent modulus (E(FE)) correlated well with vertebral strength. Therefore, as an extension to our earlier study, we investigated (i) whether the relationships of vertebral strength found with COV of BV/TV and COV of E(FE) could be extended to the COV of other microstructural parameters and microcomputed tomography-estimated BMD and (ii) whether COV of microstructural parameters were associated with structural ductility measures. COV-based measures were more strongly associated with vertebral strength and ductility measures than average microstructural measures. Moreover, our results support a hypothesis that decreased microstructural variability, while associated with increased strength, may result in decreased structural toughness and ductility. The current findings suggest that variability-based measures could provide an improvement, as a supplement to clinical BMD, in screening for fracture risk through an improved prediction of bone strength and ductility. Further understanding of the biological mechanisms underlying microstructural variability may help develop new treatment strategies for improved structural ductility.

Analytical approach to recovering bone porosity from effective complex shear modulus.

This work deals with the study of the analytical relations between porosity of cancellous bone and its mechanical properties. The Stieltjes representation of the effective shear complex modulus of cancellous bone is exploited to recover porosity. The microstructural information is contained in the spectral measure in this analytical representation. The spectral function can be recovered from the effective measurements over a range of frequencies. The problem of reconstruction of the spectral measure is very ill-posed. Regularized algorithm is derived to ensure stability of the results. The proposed method does not use any specific assumptions about the microgeometry of bone. The approach does not rely on correlation analysis, it uses analytical relationships. For validation purposes, complex shear modulus over a range of frequencies was calculated by the finite element method using micro-computed tomography (micro-CT) images of human cancellous bone. The calculated values were used in numerical algorithm to recover bone porosity. At the microlevel, bone was modeled as a heterogeneous medium composed of trabeculae tissue and bone marrow treated as transversely isotropic elastic and isotropic viscoelastic materials, respectively. Recovered porosity values are in excellent agreement with true porosity found from the corresponding micro-CT images.

Cancellous bone properties and matrix content of TGF-beta2 and IGF-I in human tibia: a pilot study.

Transforming and insulin-like growth factors are important in regulating bone mass. Thus, one would anticipate correlations between matrix concentrations of growth factors and functional properties of bone. We therefore investigated the relationships of (1) TGF-beta2 and (2) IGF-I matrix concentrations with the trabecular microstructure, stress distribution, and mechanical properties of tibial cancellous bone from six male human cadavers. Trabecular stress amplification (VMExp/sigma(app)) and variability (VMCOV) were calculated using microcomputed tomography (muCT)-based finite element simulations. Bone volume fraction (BV/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), connectivity (Eu.N), and anisotropy (DA) were measured using 3-D morphometry. Bone stiffness and strength were measured by mechanical testing. Matrix concentrations of TGF-beta2 and IGF-I were measured by ELISA. We found higher matrix concentrations of TGF-beta2 were associated with higher Tb.Sp and VMExp/sigma(app) for pooled data and within subjects. Similarly, a higher matrix concentration of IGF-I was associated with lower stiffness, strength, BV/TV and Tb.Th and with higher BS/BV, Tb.Sp, VMExp/sigma(app) and VMCOV for pooled data and within subjects. IGF-I and Tb.N were negatively associated within subjects. It appears variations of the stress distribution in cancellous bone correlate with the variation of the concentrations of TGF-beta2 and IGF-I in bone matrix: increased local matrix concentrations of growth factors are associated with poor biomechanical and architectural properties of tibial cancellous bone.

Digital tomosynthesis based digital volume correlation: A clinically viable noninvasive method for direct measurement of intravertebral displacements using images of the human spine under physiological load.

PURPOSE: We have developed a clinically viable method for measurement of direct, patient-specific intravertebral displacements using a novel digital tomosynthesis based digital volume correlation technique. These displacements may be used to calculate vertebral stiffness under loads induced by a patient's body weight; this is particularly significant because, among biomechanical variables, stiffness is the strongest correlate of bone strength. In this proof of concept study, we assessed the feasibility of the method through a preliminary evaluation of the accuracy and precision of the method, identification of a range of physiological load levels for which displacements are measurable, assessment of the relationship of measured displacements with microcomputed tomography based standards, and demonstration of the in vivo application of the technique. METHODS: Five cadaveric T11 vertebrae were allocated to three groups in order to study (a) the optimization of digital volume correlation algorithm input parameters, (b) accuracy and precision of the method and the ability to measure displacements at a range of physiological load levels, and (c) the correlation between displacements measured using tomosynthesis based digital volume correlation vs. high resolution microcomputed tomography based digital volume correlation and large scale finite element models. Tomosynthesis images of one patient (Female, 60 yr old) were used to calculate displacement maps, and in turn stiffness, using images acquired in both standing and standing-with-weight (8 kg) configurations. RESULTS: We found that displacements were accurate (2.28 µm total error) and measurable at physiological load levels (above 267 N) with a linear response to applied load. Calculated stiffness among three tested vertebral bodies was within an acceptable range relative to reported values for vertebral stiffness (5651-13260 N/mm). Displacements were in good qualitative and quantitative agreement with both microcomputed tomography based finite element (r2  = 0.762, P < 0.001) and digital volume correlation (r2  = 0.799, P < 0.001) solutions. For one patient tested twice, once standing and once holding weights, results demonstrated excellent qualitative reproducibility of displacement distributions with superior endplate displacements increasing by 22% with added weight. CONCLUSIONS: The results of this work collectively suggest the feasibility of the method for in vivo measurement of intravertebral displacements and stiffness in humans. These findings suggest that digital volume correlation using digital tomosynthesis imaging may be useful in understanding the mechanical response of bone to disease and may further enhance our ability to assess fracture risk and treatment efficacy for the spine.

Trabecular shear stress amplification and variability in human vertebral cancellous bone: relationship with age, gender, spine level and trabecular architecture.

Trabecular shear stress magnitude and variability have been implicated in damage formation and reduced bone strength associated with bone loss for human vertebral bone. This study addresses the issue of whether these parameters change with age, gender or anatomical location, and if so whether this is independent of bone mass. Additionally, 3D-stereology-based architectural parameters were examined in order to establish the relationship between stress distribution parameters and trabecular architecture. Eighty cancellous bone specimens were cored from the anterior region of thoracic 12 and donor-matched lumbar 1 vertebrae from a randomly selected population of 40 cadavers. The specimens were scanned at 21-microm voxel size using microcomputed tomography (microCT) and reconstructed at 50microm. Bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone surface-to-volume ratio (BS/BV), degree of anisotropy (MIL1/MIL3), and connectivity density (-#Euler/Vol) were calculated directly from micro-CT images. Large-scale finite element models were constructed and superoinferior compressive loading was simulated. Apparent cancellous modulus (EFEM) was calculated. The average trabecular von Mises stress generated per uniaxial apparent stress (sigma (-)VM / sigmaapp) and coefficient of variation of trabecular von Mises stresses (COV) were calculated as measures of the magnitude and variability of shear stresses in the trabeculae. Mixed-models and regression were used for analysis. sigma(-)VM / sigmaapp and COV were not different between genders and vertebrae. Both sigma(-)VM / sigmaapp and COV increased with age accompanied by a decrease in BV/TV. Strong relationship of sigma(-)VM / sigmaapp with BV/TV was found whereas COV was strongly related to EFEM/(BV/TV). The results from T12 and L1 were not different and highly correlated with each other. The relationship of sigma(-)VM / sigmaapp with COV was observed to be different between males and females. This difference could not be explained by architectural parameters considered in this study. Our results support the relevance of trabecular shear stress amplification and variability in age-related vertebral bone fragility. The relationships found are expected to help understand the micro-mechanisms by which cancellous bone mass and mechanical properties are modulated through a collection of local stress parameters.