Regional maps of rib cortical bone thickness and cross-sectional geometry

Here we present detailed regional bone thickness and cross-sectional measurements from full adult ribs using high resolution CT scans processed with a cortical bone mapping technique. Sixth ribs from 33 subjects ranging from 24 to 99 years of age were used to produce average cortical bone thickness maps and to provide average ± 1SD corridors for expected cross-section properties (cross-sectional areas and inertial moments) as a function of rib length. Results obtained from CT data were validated at specific rib locations using direct measurements from cut sections. Individual thickness measurements from CT had an accuracy (mean error) and precision (SD error) of -0.013 ± 0.167 mm (R2 coefficient of determination of 0.84). CT-based measurement errors for rib cross-sectional geometry were -0.1 ± 13.1% (cortical bone cross-sectional area) and 4.7 ± 1.8% (total cross-sectional area). Rib cortical bone thickness maps show the expected regional variation across a typical rib’s surface. The local mid-rib maxima in cortical thickness along the pleural rib aspect ranged from range 0.9 to 2.6 mm across the study population with an average map maximum of 1.4 mm. Along the cutaneous aspect, rib cortical bone thickness ranged from 0.7 to 1.9 mm with an average map thickness of 0.9 mm. Average cross-sectional properties show a steady reduction in total cortical bone area from 10% along the rib’s length through to the sternal end, whereas overall cross-sectional area remains relatively constant along the majority of the rib’s length before rising steeply towards the sternal end. On average, male ribs contained more cortical bone within a given cross-section than was seen for female ribs. Importantly, however, this difference was driven by male ribs having larger overall cross-sectional areas, rather than by sex differences in the bone thickness observed at specific local cortex sites. The cortical bone thickness results here can be used directly to improve the accuracy of current human body and rib models. Furthermore, the measurement corridors obtained from adult subjects across a wide age range can be used to validate future measurements from more widely available image sources such as clinical CT where gold standard reference measures (e.g. such as direct measurements obtained from cut sections) are otherwise unobtainable.Cortical Bone Mapping (CBM) of whole-rib CT scans was performed and maps of average adult cortical bone thickness and rib cross-sectional geometry were produced. Results were validated against cross-sectional rib histology images, whereby bone thickness accuracy was measured at under 0.02 mm and precision was measured at under 0.17 mm. Subsequent errors in bone cross-sectional area were under 5%. Results can drive advancements in the fidelity of current human body computational models.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152009/1/joa13045.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152009/2/joa13045_am.pd

Independent measurement of femoral cortical thickness and cortical bone density using clinical CT.

The local structure of the proximal femoral cortex is of interest since both fracture risk, and the effects of various interventions aimed at reducing that risk, are associated with cortical properties focused in particular regions rather than dispersed over the whole bone. Much of the femoral cortex is less than 3mm thick, appearing so blurred in clinical CT that its actual density is not apparent in the data, and neither thresholding nor full-width half-maximum techniques are capable of determining its width. Our previous work on cortical bone mapping showed how to produce more accurate estimates of cortical thickness by assuming a fixed value of the cortical density for each hip. However, although cortical density varies much less over the proximal femur than thickness, what little variation there is leads to errors in thickness measurement. In this paper, we develop the cortical bone mapping technique by exploiting local estimates of imaging blur to correct the global density estimate, thus providing a local density estimate as well as more accurate estimates of thickness. We also consider measurement of cortical mass surface density and the density of trabecular bone immediately adjacent to the cortex. Performance is assessed with ex vivo clinical QCT scans of proximal femurs, with true values derived from high resolution HRpQCT scans of the same bones. We demonstrate superior estimation of thickness than is possible with alternative techniques (accuracy 0.12 ± 0.39 mm for cortices in the range 1-3mm), and that local cortical density estimation is feasible for densities >800 mg/cm(3).This is the accepted manuscript of an article published in Medical Image Analysis (GM Treece, AH Gee, Medical Image Analysis 2015, 20(1), 249–264

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites

High-Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal Women-A 3-Month Intervention Study.

Bone adapts to loading in several ways, including redistributing bone mass and altered geometry and microarchitecture. Because of previous methodological limitations, it is not known how the bone material strength is affected by mechanical loading in humans. The aim of this study was to investigate the effect of a 3-month unilateral high-impact exercise program on bone material properties and microarchitecture in healthy postmenopausal women. A total of 20 healthy and inactive postmenopausal women (aged 55.6 ± 2.3 years [mean ± SD]) were included and asked to perform an exercise program of daily one-legged jumps (with incremental number, from 3×10 to 4×20 jumps/d) during 3 months. All participants were asked to register their performed jumps in a structured daily diary. The participants chose one leg as the intervention leg and the other leg was used as control. The operators were blinded to the participant's choice of leg for intervention. The predefined primary outcome was change in bone material strength index (BMSi), measured at the mid tibia with a handheld reference probe indentation instrument (OsteoProbe). Bone microstructure, geometry, and density were measured with high-resolution peripheral quantitative computed tomography (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal). Differences were analyzed by related samples Wilcoxon signed rank test. The overall compliance to the jumping program was 93.6%. Relative to the control leg, BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no differences were found for any of the XtremeCT-derived bone parameters. In conclusion, a unilateral high-impact loading program increased BMSi in postmenopausal women rapidly without affecting bone microstructure, geometry, or density, indicating that intense mechanical loading has the ability to rapidly improve bone material properties before changes in bone mass or structure. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus

In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression. INTRODUCTION: T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat. METHODS: Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (n = 6/group). RESULTS: ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %, p < 0.01), but this difference disappeared as their glucose control deteriorated and by week 14, ZDF rats had lower sclerostin levels than control rats (-44 %, p < 0.0001). Bone sclerostin mRNA (qPCR) and protein (immunohistochemistry) were similar in ZDF, and lean rats at 14 weeks and genotype did not affect the number of empty osteocytic lacunae in cortical and trabecular bone. CONCLUSION: T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone

Structural Optimisation: Biomechanics of the Femur

A preliminary iterative 3D meso-scale structural model of the femur was developed, in which bar and shell elements were used to represent trabecular and cortical bone respectively. The cross-sectional areas of the bar elements and the thickness values of the shell elements were adjusted over successive iterations of the model based on a target strain stimulus, resulting in an optimised construct. The predicted trabecular architecture, and cortical thickness distribution showed good agreement with clinical observations, based on the application of a single leg stance load case during gait. The benefit of using a meso-scale structural approach in comparison to micro or macro-scale continuum approaches to predictive bone modelling was achievement of the symbiotic goals of computational efficiency and structural description of the femur.Comment: Accepted by Engineering and Computational Mechanics (Proceedings of the ICE

Variability of Child Rib Bone Hounsfield Units using in vivo Computed Tomography

The variability assessment of the rib bone mechanical properties during the growth process is still missing. These properties could not be obtained in vivo on children. Relationships have been obtained between Hounsfield Units from computed tomography (CT) and mechanical properties (e.g. for the cortical bone on adults). As a first step for investigation of the mechanical properties of child ribs, the aim of this study was to determine the Hounsfield Units variation of child ribs from CT‐scan data, by rib level, along the rib and within the rib sections. Twenty‐seven right ribs of levels 4, 6 and 9 were processed from 11 thoracic CT scans of children without bone lesions aged between 1 and 10 years. A first set of 10 equidistributed cross‐sections normal to the rib midline were extracted. Sixteen equally distributed elements defined 4 areas into the cortical band: internal, external, caudal and cranial. Within the rib sections, Hounsfield Units were found significantly higher in internal and external areas than in caudal and cranial. In a further step using calibrated CT scans, it would be possible to derive the mechanical properties of in vivo child ribs using bone density correlation with Hounsfield Units

T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound.

BackgroundCurrent clinical protocols for MR-guided focused ultrasound (MRgFUS) treatment of osseous lesions, including painful bone metastases and osteoid osteomas, rely on measurement of the temperature change in adjacent muscle to estimate the temperature of the bone. The goal of this study was to determine if T2-based thermometry could be used to monitor the temperature change in bone marrow during focused ultrasound ablation of bone lesions.MethodsWe investigated the dependence of T2 on temperature in ex vivo bovine yellow bone marrow at 3T and studied the influence of acquisition parameters on the T2 measurements. We examined if T2 changes in red bone marrow caused by the ablation of ex vivo trabecular bone were reversible and measured the patterns of heating and tissue damage. The technique was validated during the ablation of intact ex vivo bone samples and an in vivo animal model.ResultsResults of the calibration experiment showed a linear relationship (7 ms/°C) between T2 change and temperature and could be used to quantify the temperature during heating of up to 60 °C. During trabecular bone ablation, we observed a linear relationship (5.7 ms per °C) between T2 and temperature during the heating stage of the experiment. After cool down, there was residual T2 elevation (~35 ms) in the ablated area suggesting irreversible tissue changes. In ex vivo and in vivo cortical bone ablation experiments, we observed an increase in T2 values in the marrow adjacent to the intersection of the cortical bone and the beam path. The in vivo experiment showed excellent correspondence between the area of T2 elevation in marrow during the ablation and the resulting non-enhancing area in the post-contrast images.ConclusionsIn this study, we have demonstrated that T2-based thermometry can be used in vivo to measure the heating in the marrow during bone ablation. The ability to monitor the temperature within the bone marrow allowed more complete visualization of the heat distribution into the bone, which is important for local lesion control

Optical properties of tissue measured using terahertz pulsed imaging.

The first demonstrations of terahertz imaging in biomedicine were made several years ago, but few data are available on the optical properties of human tissue at terahertz frequencies. A catalogue of these properties has been established to estimate variability and determine the practicality of proposed medical applications in terms of penetration depth, image contrast and reflection at boundaries. A pulsed terahertz imaging system with a useful bandwidth 0.5-2.5 THz was used. Local ethical committee approval was obtained. Transmission measurements were made through tissue slices of thickness 0.08 to 1 mm, including tooth enamel and dentine, cortical bone, skin, adipose tissue and striated muscle. The mean and standard deviation for refractive index and linear attenuation coefficient, both broadband and as a function of frequency, were calculated. The measurements were used in simple models of the transmission, reflection and propagation of terahertz radiation in potential medical applications. Refractive indices ranged from 1.5 ± 0.5 for adipose tissue to 3.06 ± 0.09 for tooth enamel. Significant differences (P<0.05) were found between the broadband refractive indices of a number of tissues. Terahertz radiation is strongly absorbed in tissue so reflection imaging, which has lower penetration requirements than transmission, shows promise for dental or dermatological applications