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

The relationship of whole human vertebral body creep to geometric, microstructural and material properties

INTRODUCTION: Creep, the time-dependent deformation of a structure under prolonged load, is understood to play an important role in deformity of vertebrae due to progressive accumulation of residual strain [1]. Permanent deformation resulting from creep may develop at physiological load levels and contribute to ultimate failure of the bone tissue [2,3]. To date, creep properties have not been described in isolated human vertebral bodies. We aim to establish relationships between measures of creep of whole human cadaveric vertebrae and geometric, microstructural and hard tissue properties. METHODS: Thoracic 12 vertebrae were harvested under local IRB approval from 23 donors (13M/10F, 41-97y). Specimens were scanned using microcomputed tomography (μCT), dual x-ray absorptiometry (DXA), and high resolution computed tomography (CT). Standard quantities representing geometric, microstructural and material type properties of the bone tissue were calculated from the three modalities. Within each variable type, parameters causing high multicollinearity (as determined by a variance inflation factor\u3e5) were eliminated. The final set of parameters consisted of 3 geometric (CTderived bone volume [Vol], anterior-posterior projected area [Area.AP], and average cortical thickness [Ct.Th]), 4 microstructural (μCT bone volume fraction [BV/TV], trabecular thickness [Tb.Th], degree of anisotropy [DA], and connectivity density [Conn.Dn]), and 2 material variables (average [GV.Av] and standard deviation [GV.SD] of μCT gray value-based tissue mineral density). Bone mineral density (BMD) was also calculated from DXA in AP (BMD.AP) and LM (BMD.LM) directions and from CT in cancellous (cBMD), shell (shBMD), and integral (iBMD) volumes. Specimens were then loaded to 1000N and held for 2 hours, load was removed, and recovery was recorded for another 2 hours [1]. Creep deformation (Dcr, ptB-ptA Fig.1), creep recovery (Rcr, ptC-ptD Fig.1), residual displacement (Dres, ptD Fig.1), and residual from creep alone (Dres-cr, Dcr-Rcr) were calculated. In order to correct for the dependence of creep parameters on elastic displacement, displacements were normalized using elastic deformation (ptA Fig.1) (i.e., Dcr-norm, Rcr-norm, Dres-norm, Dres-cr-norm). A function of the form “Dcr = a(1-EXP(-(t/τcr)n))+Ct” (τcr: time constant; n: stretch exponent; C: creep rate) was fit to the creep portion of the data (pts A to B, Fig.1). Multiple regression models were constructed using a stepwise procedure to examine relationships between measures of creep and geometric, microstructural, and material parameters (JMP 10, SAS Institute). If a BMD variable was found to be significantly correlated to a creep variable, the BMD variable was introduced first and forced to stay in the model. Significance in multiple regression models was considered as p\u3c0.05. RESULTS: Creep, recovery and creep rate were associated with BMD but residual displacement measures were not (Table 1). Normalization of creep variables by vertebral stiffness eliminated BMD variables from the models. GV.SD positively contributed to models of Dres, Dres-norm, Dres-cr, and Dres-cr-norm. Conn.Dn positively contributed to models of Dcr (Fig. 2) and Dres-cr and negatively contributed to models of C. DISCUSSION: Creep deformations generally demonstrated inverse relationships with measures of bone density and vertebral size, indicating, not surprisingly, that bones that are larger and denser deform and recover less in the creep process [4]. However, BMD variables were not significant in models of displacement normalized by stiffness, indicating that the ability of BMDs to predict creep behavior may be limited by the strength of the relationship between creep and elastic behavior. The variability of GVs (GV.SD), but not their average, was consistently present in all significant deformation models, even those normalized by stiffness. This result agrees with previously reported associations of mineral density variability with creep deformations for whole rat vertebral bodies [5]. The arrangement of de sities within the bone phase, independent from microstructural organization and average bone mass, may thus be a factor in creep of vertebral bone. A correlation between mineral density variability and creep rate, but not deformations, was noted in human vertebral cancellous cores [6] suggesting that excised tissue may not fully reflect the creep behavior of the whole vertebra. Further work is needed to understand the relative contribution of mineralization distributions in the cancellous, shell and endplate components of a vertebra to its creep and how this contribution is affected by disease. After taking into account BMD and tissue mineral heterogeneity, Conn.Dn was positively correlated with Dcr and Dres-cr, suggesting that, all things being equal, creep response improves with decreased connectivity. This finding seems counterintuitive but not entirely unfounded, as previous studies have demonstrated negative correlations between stiffness and Conn.Dn [7,8]. The negative correlation found between creep rate and Conn.Dn suggests that this effect is due to a faster response to load in vertebrae with higher connectivity and that creep displacement will eventually get higher for vertebrae with less connectivity. However, the duration for this to be observed may be longer than a day-night cycle, i.e., too long to be beneficial [2]. When the dependence of creep on elastic displacement is separated by normalization, Conn.Dn was no longer present in the models, suggesting that the association of Conn.Dn with Dcr and Dres is not independent from its association with stiffness. The presented models help in understanding the relationships between the time dependent deformation of vertebral bone and geometric, microstructural and material properties; however, a portion of the variability is not explained by the current set of parameters. Although image-based predictors of vertebral creep are potentially useful, further work is needed to identify additional tissue properties that can fully describe the creep behavior of a human vertebra. (Figure Presented)

The relationship of whole human vertebral body creep to geometric, microstructural, and material properties

Creep, the time dependent deformation of a structure under load, is an important viscoelastic property of bone and may play a role in the development of permanent deformity of the vertebrae in vivo leading to clinically observable spinal fractures. To date, creep properties and their relationship to geometric, microstructural, and material properties have not been described in isolated human vertebral bodies. In this study, a range of image-based measures of vertebral bone geometry, bone mass, microarchitecture and mineralization were examined in multiple regression models in an effort to understand their contribution to creep behavior. Several variables, such as measures of mineralization heterogeneity, average bone density, and connectivity density persistently appeared as significant effects in multiple regression models (adjusted r2: 0.17-0.56). Although further work is needed to identify additional tissue properties to fully describe the portion of variability not explained by these models, these data are expected to help understand mechanisms underlying creep and improve prediction of vertebral deformities that eventually progress to a clinically observable fracture

Whole human vertebral body creep is associated with DTS-derived texture parameters.

INTRODUCTION: Despite the potential importance of creep in development of vertebral fractures, little information is available in regards to clinically measurable predictors of creep properties in human vertebral bone. Digital tomosynthesis (DTS) combines relatively high in-plane resolution (150-300 μm) with about 1/5th the radiation dose as compared to computed tomography [1]. In this study, we examined DTS for its ability to provide image texture based predictors of creep properties in whole cadaveric vertebral bodies. METHODS: Under local IRB approval, thoracic 12 vertebrae were dissected and cleaned of soft tissue from 23 donors (13M/10F, 41-97y). Specimens were scanned using digital tomosynthesis (DTS), dual x-ray absorptiometry (DXA), and high resolution computed tomography (CT). Bone mineral density (BMD) was calculated from DXA in AP (BMD.AP) and LM (BMD.LM) directions and from CT in cancellous (cBMD), shell (shBMD) and integral (iBMD) volumes. DTS scans were performed in AP (producing a stack of coronal plane image) and LM (producing a stack of sagittal plane images) views while aligned axially (0°), transversely (90°) or obliquely (23°) to the super-inferior axis of the vertebrae. A cuboidal volume of interest from each image stack was analyzed using fractal (fractal dimension [FD], lacunarity [λ], slope lacunarity [Sλ]), mean intercept length (MIL) and line fraction deviation (LFD) methods as previously described [2]. For MIL and LFD parameters, Average (.Av), standard deviation (.SD), degree of anisotropy (.DA, ratio of maximum to minimum MIL or LFD), and maximum (.Max) were recorded within each slice, from which stack average and standard deviation were calculated (Fig 1). Within each scanning configuration, parameters causing high multicollinearity (as determined by a variance inflation factor\u3e5) were eliminated. Specimens were then loaded to 1000N and held for 2 hours, load was removed, and recovery was recorded for another 2 hours. Creep deformation (Dcr, ptB-ptA Fig.2), creep recovery (Rcr, ptC-ptD Fig.2), residual displacement (Dres, ptD Fig.2), and residual from creep (Dres-cr, Dcr-Rcr) were calculated. In order to account for the dependence of creep displacement parameters on vertebral stiffness, displacements were normalized using the initial elastic deformation (ptA Fig.2) (i.e., Dcr-norm, Rcr-norm, Dres-norm, Dres-cr-norm). A function of the form “Dcr = a(1-EXP(-(t/τcr)n))+Ct” was fit to the creep portion of the data (pts A to B, Fig.2) to calculate time constant (τcr), stretch exponent (n) and creep rate (C) variables. Multiple regression models were constructed using a stepwise procedure to examine relationships between measures of creep and DTS texture parameters (JMP 10, SAS Institute). If a BMD variable was found to be significantly correlated to a creep variable, the BMD variable was introduced first and forced to stay in the model. Significance in multiple regression models was considered as p\u3c0.05. RESULTS: Dcr was significantly correlated with BMD.LM, and Rcr with BMD.AP; these BMDs were forced as first terms in their associated models. The most explanatory set of variables for Dcr (R2adj=0.33) were BMD.LM (-, p\u3c0.04) and Av(LFD.Max) (+, p\u3c0.04) measured from oblique LM scanning configuration, while Rcr (R2adj=0.17) was only associated with BMD.AP (-, p\u3c0.05). When normalized by stiffness to eliminate the contribution of elastic displacement, models for both Dcr-norm (R2adj=0.68; See Fig. 3) and Rcr-norm (R2adj=0.51) contained Av(λ) (p\u3c0.0001,0.0003 respectively) and Av(MIL.DA) (p\u3c0.0006,0.02 respectively), both from Axial AP scans. Both Dres (R2adj=0.47) and Dres-cr (R2adj=0.39) showed negative correlations with Av(FD) (p\u3c0.0009,0.003 respectively) and SD(FD) (p\u3c0.04,0.02 respectively) (Dres: Axial AP, Dres-cr: Transverse LM). The most explanatory models for Dres-norm (R2adj=0.49) and Dres-cr-norm (R2adj=0.65) demonstrated positive correlations with SD(MIL.Max) (p\u3c0.0005,0.00003 respectively) and negative correlations with SD(LFD.Max) (p\u3c0.02,0.02 respectively) in Trans erse LM scans. R2adj increased when displacements were normalized for stiffness (from 0.17-0.47 to 0.49-0.65). Creep rate was significantly correlated with all measured BMDs, with iBMD being the most significant, and the most explanatory model for creep rate (R2adj=0.61) included both iBMD (-, p\u3c0.0001) and Av(LFD.DA) (+, p\u3c0.003) (Axial AP scans). When alternative models from axial AP scans only were assessed for Dres-norm and Dres-cr-norm, it was noted that Dres-cr-norm could also be modeled with Av(λ) and Av(MIL.DA) (R2adj=0.57, p\u3c0.0002,0.02) and Dres-norm with Av(λ) alone (R2adj=0.26, p\u3c0.02). The most explanatory axial-AP model for C (R2adj=0.48) included a MIL.DA (+, p\u3c0.05) term together with iBMD (-,p\u3c0.002). DISCUSSION: We demonstrated that DTS-derived variables of cancellous bone texture are associated with creep properties of human vertebrae, independently from BMD variables. More strikingly, normalizing for stiffness eliminates BMD variables from models of Dcr and Rcr and only DTS variables remain, suggesting that DTS texture is related to vertebral creep independently from the elastic properties of the vertebra whereas BMD is not. Standard clinical DTS scanning configuration involves AP views and an axial scan direction. When models from the AP axial scans alone were considered, a unified set of variables (Av(MIL.DA) and Av(λ)) associated with all measured creep displacements could be identified. Lacunarity is a fractal measure related to the variability of the size of gaps in a porous texture [4], while MIL.DA represents anisotropy of trabecular structure. Both lacunarity [5] and anisotropy [6] are understood to significantly change with age and osteoporosis. The relationships of these measures of image texture with creep may help provide, independent from bone mass, important clinical indicators of the progression toward eventual vertebral deformity. (Figure Presented)

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 R(2): 0.14-0.68) than those with bone density parameters forced in the models (adjusted R(2): 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

Osteoporotik insan ve hayvan kemiklerinde malzeme özelliklerinin mekanik ve ultrasonik yöntemlerle araştırılması

TÜBİTAK MİSAG31.03.1995Bu çalışma iki ana bölümden oluşmuştur. Birinci bölümün amacı, heparin, kalsitonin ve tamoksifenin osteoporoz başlangıcı ve gelişimindeki etkisini biyomekanik yöntemlerle araştırmak ve böylece bu ilaçların klinik kullanımına yardımcı olmaktır. Çalışmanın kontrollü deneysel bu kısmı için 32 dişi beyaz Yeni Zelanda tavşanı kullanılmıştır. Femur, humerus ve tibia kemiklerine bütün olarak üç-noktalı eğilme testleri uygulanırken aynı örneklerin proksimal uçlarına basınç testleri uygulanmıştır. Tavşan kemikleri sabit et kalınlığına sahip kalın duvarlı eliptik tüpler olarak varsayılarak ilaç uygulanmış grupların kemiklerinin rijiditeleri ile kontrol gurubundakilerinkiler karşılaştırılmıştır. Sonuçlar, heparinin ortak görüşe uygun Dolarak önceden iddia edildiği gibi osteoporoz yarattığı, tamoksifenin bu etkiyi geri çevirmekte etkili olduğunu göstermiş, kalsitonin ise yorum yapılacak bir sonuca götürmemiştir. Çalışmanın ikinci bölümünde, osteoporozlu insan femur başlarının ultrasonik özellikleri araştırılmıştır. Yedi osteoporozlu insan örneği kullanılarak çevresel, radyal ve aksiyel yönlerdeki ultrasonik hızlar ve elastik modüller deneysel olarak saptanmıştır. Üç değişik frekans kullanılarak üç yöndeki ultrasonik sönümleme, Genişbantlı Ultrasonik Sönümleme İndisi cinsinden saptanmaya çalışılmıştır. Sonuçlar aynı örneklerin Singh indisleriyle karşılaştırılmış ve yöntemlerin verimi tartışılmıştır. Ultrasonik yöntemlerin yararlı olduğu sonucuna varılmıştır. Fakat kesin ve hassas ölçümler hastanın yaşı ve cinsiyeti, osteoporoz derecesi, hazırlanan örneğin kemik içerisindeki yönü ve konumu gözönünde bulundurarak yapılan muntazam örneklemeyi gerektirmektedir

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 (F(max)) 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 (D(f)), collapse (D(c)) and recovery (D(r)) contain information distinct from strength and stiffness. Bone size (V) was present, independently, in multiple regression models of K, F(y), W(y), F(max), D(f), W(t), W(fc) and D(r) (p \u3c 0.05 to p \u3c 0.0001), areal BMD in models of D(y), W(y), F(max), W(f), F(c), W(t), W(yf) and W(ct) (p \u3c 0.04 to p \u3c 0.0001), Sh.Th in models of D(f), F(c) and ε(r) (p \u3c 0.02 to p \u3c 0.002), EP.Th.S in models of F(c) and W(ct) (p \u3c 0.004 to p \u3c 0.0006), EP.Th.I in the model of W(ct) (p \u3c 0.02), FD in models of F(y), D(y) and F(max) (p \u3c 0.03 to p \u3c 0.004), Tb.Sp in models of K and D(y) (p \u3c 0.002 to p \u3c 0.0004), Conn.Dn in the model of D(f) (p \u3c 0.0009), and SMI in the model of W(t) (p \u3c 0.02). R(2)(adj) varied from 0.12 (D(r)) to 0.80 (W(t)) 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