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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2004

Noninvasive Investigation of Bone Adaptation in Humans Cumulative Daily Mechanical Loading

Our Research Objective is to measure the spatial distribution of bone mass throughout the entire internal volume of a bone such as the human calcaneus or heel bone. Currently, x-ray computed tomography (CT) is the only practical three-dimensional imaging technology capable of measuring bone density within small contiguous volumetric regions of a bone. spectrum of energies in the x-ray beam producing the image. We have developed a computational method of correcting these errors, provided the x-ray spectrum is known or measured (Yan et al., 2000). Monitoring serial changes in volumetric bone density with age, disuse, exercise or A CT image contains measurement errors in bone density caused by the broad drug therapy also requires accurate image registration.

Whalen, Robert T.↗
DOE OSTI2022

Primary radiation damage in bone evolves via collagen destruction by photoelectrons and secondary emission self-absorption

X-rays are invaluable for imaging and sterilization of bones, yet the resulting ionization and primary radiation damage mechanisms are poorly understood. Here we monitor in-situ collagen backbone degradation in dry bones using second-harmonic-generation and X-ray diffraction. Collagen breaks down by cascades of photon-electron excitations, enhanced by the presence of mineral nanoparticles. We observe protein disintegration with increasing exposure, detected as residual strain relaxation in pre-stressed apatite nanocrystals. Damage rapidly grows from the onset of irradiation, suggesting that there is no minimal ‘safe’ dose that bone collagen can sustain. Ionization of calcium and phosphorous in the nanocrystals yields fluorescence and high energy electrons giving rise to structural damage that spreads beyond regions directly illuminated by the incident radiation. Our findings highlight photoelectrons as major agents of damage to bone collagen with implications to all situations where bones are irradiated by hard X-rays and in particular for small-beam mineralized collagen fiber investigations.

36 MATERIALS SCIENCE↗
NASA NTRS1996

Trabecular Bone Mechanical Properties and Fractal Dimension

Countermeasures for reducing bone loss and muscle atrophy due to extended exposure to the microgravity environment of space are continuing to be developed and improved. An important component of this effort is finite element modeling of the lower extremity and spinal column. These models will permit analysis and evaluation specific to each individual and thereby provide more efficient and effective exercise protocols. Inflight countermeasures and post-flight rehabilitation can then be customized and targeted on a case-by-case basis. Recent Summer Faculty Fellowship participants have focused upon finite element mesh generation, muscle force estimation, and fractal calculations of trabecular bone microstructure. Methods have been developed for generating the three-dimensional geometry of the femur from serial section magnetic resonance images (MRI). The use of MRI as an imaging modality avoids excessive exposure to radiation associated with X-ray based methods. These images can also detect trabecular bone microstructure and architecture. The goal of the current research is to determine the degree to which the fractal dimension of trabecular architecture can be used to predict the mechanical properties of trabecular bone tissue. The elastic modulus and the ultimate strength (or strain) can then be estimated from non-invasive, non-radiating imaging and incorporated into the finite element models to more accurately represent the bone tissue of each individual of interest. Trabecular bone specimens from the proximal tibia are being studied in this first phase of the work. Detailed protocols and procedures have been developed for carrying test specimens through all of the steps of a multi-faceted test program. The test program begins with MRI and X-ray imaging of the whole bones before excising a smaller workpiece from the proximal tibia region. High resolution MRI scans are then made and the piece further cut into slabs (roughly 1 cm thick). The slabs are X-rayed again and also scanned using dual-energy X-ray absorptiometry (DEXA). Cube specimens are then cut from the slabs and tested mechanically in compression. Correlations between mechanical properties and fractal dimension will then be examined to assess and quantify the predictive capability of the fractal calculations.

Hogan, Harry A.↗
NASA NTRS1997

Biochemical markers in the assessment of bone disease

As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.

Review↗
NASA NTRS2009

A Biomechanical Approach to Assessing Hip Fracture Risk

Bone loss in microgravity is well documented, but it is difficult to quantify how declines in bone mineral density (BMD) contribute to an astronaut's overall risk of fracture upon return. This study uses a biomechanical approach to assessing hip fracture risk, or Factor of Risk (Phi), which is defined as the ratio of applied load to bone strength. All long-duration NASA astronauts from Expeditions 1-18 were included in this study (n=25), while crewmembers who flew twice (n=2) were treated as separate subjects. Bone strength was estimated based on an empirical relationship between areal BMD at the hip, as measured by DXA, and failure load, as determined by mechanical testing of cadaver femora. Fall load during a sideways fall was calculated from a previously developed biomechanical model, which takes into account body weight, height, gender, and soft tissue thickness overlying the lateral aspect of the hip that serves to attenuate the impact force. While no statistical analyses have been performed yet, preliminary results show that males in this population have a higher FOR than females, with a post- flight Phi of 0.87 and 0.36, respectively. FOR increases 5.1% from preflight to postflight, while only one subject crossed the fracture "threshold" of Phi = 1, for a total of 2 subjects with a postflight Phi > 1. These results suggest that men may be at greater risk for hip fracture due largely in part to their relatively thin soft tissue padding as compared to women, since soft tissue thickness has the highest correlation (R(exp 2)= .53) with FOR of all subject-specific parameters. Future work will investigate changes in FOR during recovery to see if baseline risk levels are restored upon return to 1-g activity. While dual x-ray absorptiometry (DXA) is the most commonly used clinical measure of bone health, it fails to provide compartment-specific information that is useful in assessing changes to bone quality as a result of microgravity exposure. Peripheral quantitative computed tomography (pQCT) accomplishes this by imaging transverse "slices" of the long bones. This project was a re-analysis of a 90 day bed rest study to determine if changes to cortical and trabecular compartments could be detected in the distal tibia with statistical significance using a new pQCT image analysis method. Nearly all changes in bone mineral density (BMD) and cross sectional area (CSA) measures were seen with statistical significance, with the exception of a change in cortical BMD. Total bone CSA increased by 1.1 % (p =0.01), cortical CSA decreased by - 5.6% (p<0.001) and trabecular CSA increased by 1.76% (p=0.007); the combination of which suggests bone resorption occurred at the endocortical surface in response to mechanical unloading by bed rest. Furthermore, total BMD and trabecular BMD decreased (-3.8%, p=0.001 and -2.8%, p =0.007, respectively), while decreases in cortical BMD failed to reach significance (-1.2%, p=0.07). Given that compartment-specific changes are seen with significance and are likely to influence bone strength, it is recommended that pQCT remain a standard measure used in bed rest because it provides a unique measure by which to better evaluate the efficacy of countermeasures to microgravity-induced bone loss.

Ellman, Rachel↗
NASA NTRS1992

Method for improved prediction of bone fracture risk using bone mineral density in structural analysis

A non-invasive in-vivo method of analyzing a bone for fracture risk includes obtaining data from the bone such as by computed tomography or projection imaging which data represents a measure of bone material characteristics such as bone mineral density. The distribution of the bone material characteristics is used to generate a finite element method (FEM) mesh from which load capability of the bone can be determined. In determining load capability, the bone is mathematically compressed, and stress, strain force, force/area versus bone material characteristics are determined.

Cann, Christopher E.↗
DOE OSTI2022

Using ultrasonic attenuation in cortical bone to infer distributions on pore size

Here, in this work we infer the underlying distribution on pore radius in human cortical bone samples using ultrasonic attenuation data. We first discuss how to formulate polydisperse attenuation models using a probabilistic approach and the Waterman Truell model for scattering attenuation. We then compare the Independent Scattering Approximation and the higher-order Waterman Truell models’ forward predictions for total attenuation in polydisperse samples. Following this, we formulate an inverse problem under the Prohorov Metric Framework coupled with variational regularization to stabilize this inverse problem. We then use experimental attenuation data taken from human cadaver samples and solve inverse problems resulting in nonparametric estimates of the probability density function on pore radius. We compare these estimates to the “true” microstructure of the bone samples determined via microCT imaging. We find that our methodology allows us to reliably estimate the underlying microstructure of the bone from attenuation data.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2024

Spatial control of perilacunar canalicular remodeling during lactation

Abstract Osteocytes locally remodel their surrounding tissue through perilacunar canalicular remodeling (PLR). During lactation, osteocytes remove minerals to satisfy the metabolic demand, resulting in increased lacunar volume, quantifiable with synchrotron X-ray radiation micro-tomography (SRµCT). Although the effects of lactation on PLR are well-studied, it remains unclear whether PLR occurs uniformly throughout the bone and what mechanisms prevent PLR from undermining bone quality. We used SRµCT imaging to conduct an in-depth spatial analysis of the impact of lactation and osteocyte-intrinsic MMP13 deletion on PLR in murine bone. We found larger lacunae undergoing PLR are located near canals in the mid-cortex or endosteum. We show lactation-induced hypomineralization occurs 14 µm away from lacunar edges, past a hypermineralized barrier. Our findings reveal that osteocyte-intrinsic MMP13 is crucial for lactation-induced PLR near lacunae in the mid-cortex but not for whole-bone resorption. This research highlights the spatial control of PLR on mineral distribution during lactation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2014

Facial Soft Tissue Measurement in Microgravity-induces Fluid Shifts

Fluid shifts are a well‐known phenomenon in microgravity, and one result is facial edema. Objective measurement of tissue thickness in a standardized location could provide a correlate with the severity of the fluid shift. Previous studies of forehead tissue thickness (TTf) suggest that when exposed to environments that cause fluid shifts, including hypergravity, head‐down tilt, and high‐altitude/lowpressure, TTf changes in a consistent and measurable fashion. However, the technique in past studies is not well described or standardized. The International Space Station (ISS) houses an ultrasound (US) system capable of accurate sub‐millimeter measurements of TTf. We undertook to measure TTf during long‐duration space flight using a new accurate, repeatable and transferable technique. Methods: In‐flight and post‐flight B‐mode ultrasound images of a single astronaut's facial soft tissues were obtained using a Vivid‐q US system with a 12L‐RS high‐frequency linear array probe (General Electric, USA). Strictly mid‐sagittal images were obtained involving the lower frontal bone, the nasofrontal angle, and the osseo‐cartilaginous junction below. Single images were chosen for comparison that contained identical views of the bony landmarks and identical acoustical interface between the probe and skin. Using Gingko CADx DICOM viewing software, soft tissue thickness was measured at a right angle to the most prominent point of the inferior frontal bone to the epidermis. Four independent thickness measurements were made. Conclusions: Forehead tissue thickness measurement by ultrasound in microgravity is feasible, and our data suggest a decrease in tissue thickness upon return from microgravity environment, which is likely related to the cessation of fluid shifts. Further study is warranted to standardize the technique with regard to the individual variability of the local anatomy in this area.

Marshburn, Thomas↗
NASA NTRS1981

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Young, D. R.↗
DOE OSTI2022

Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation

ABSTRACT Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case–control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic controls (n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1990

Regional distribution of mineral and matrix in the femurs of rats flown on Cosmos 1887 biosatellite

The location and nature of the defect in mineralization known to occur in growing animals after spaceflight are studied. The distribution of bone mineral density in situ is mapped, and these images are correlated with the chemical composition of the diaphyseal bone. Concentrations of mineral and osteocalcin are found to be low in the distal half of the diaphysis and concentrations of collagen to be low with evidence of increased synthesis in the proximal half of the diaphysis of the flight bones. X-ray microtomography indicates a longitudinal gradient of decreasing mineralization toward the distal diaphysis. Analysis of embedded sections by backscattered electrons reveals patterns of mineral distribution in the proximal, central, and distal regions of the diaphysis and also shows a net reduction in mineral levels toward the distal shaft. Increases in mineral density to higher fractions in controls are less in the flight bones at all three levels.

Mechanic, Gerald L.↗
NASA NTRS1999

Plantar soft tissue thickness during ground contact in walking

A technique is introduced for the measurement of plantar soft tissue thickness during barefoot walking. Subjects stepped into an adjustable Plexiglas frame which ensured that the required bony landmarks were appropriately positioned relative to a linear ultrasound probe connected to a conventional 7.5 MHz ultrasound scanner. Clear images of the metatarsal condyles or other foot bones were obtained throughout ground contact. Subsequent analysis of the video taped images using a motion analysis system allowed the tissue displacement to be calculated as a function of time. The tissue underneath the second metatarsal head was shown to undergo an average maximum compression of 45.7% during the late stages of ground contact during first step gait in a group of five normal subjects with a mean unloaded tissue thickness of 15.2 mm. The technique has a number of applications, including use in the validation of deformation predicted by finite element models of the soft tissue of the foot, and the study of alterations in the cushioning properties of the heel by devices which constrain the displacement of the heel pad.

Non-NASA Center↗
NASA NTRS1996

Serial Scanning and Registration of High Resolution Quantitative Computed Tomography Volume Scans for the Determination of Local Bone Density Changes

Progress in development of the methods required to study bone remodeling as a function of time is reported. The following topics are presented: 'A New Methodology for Registration Accuracy Evaluation', 'Registration of Serial Skeletal Images for Accurately Measuring Changes in Bone Density', and 'Precise and Accurate Gold Standard for Multimodality and Serial Registration Method Evaluations.'

Whalen, Robert T.↗
NASA NTRS2014

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long-Duration Astronauts

Bone loss due to long‐duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight‐induced changes in bone mineral density (BMD) and structure result in increased fracture incidence. NASA astronauts currently fly 5 to 6‐month missions on the International Space Station (ISS) and at least one 12‐month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT) and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone micro‐architecture from lumbar spine (LS). DXA scans are routinely performed pre‐ and postflight on all ISS astronauts to follow BMD changes associated with spaceflight. Trabecular Bone Score (TBS) is a relatively new method that measures grey‐scale‐level texture information extracted from LS DXA images and correlates with 3D parameters of bone micro‐architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: Lumbar Spine (L1‐4) DXA scans from 51 astronauts (mean age, 47 +/- 4 yrs) were divided into 3 groups based on the exercise regimens performed onboard the ISS. "Pre‐ARED" (exercise using a load‐limited resistive exercise device, <300 lb), "ARED" (exercise with a high‐load resistive exercise device, up to 600 lb) and "Bisphos+ARED" group (ARED exercise and a 70‐mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre‐ and post‐flight scans. LSC for the LS in our laboratory is 0.025 g/sq. cm. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. Data were analyzed using a paired, 2‐tailed Student's t‐test for the difference between pre‐ and postflight means. Percent change and % change per month are noted. Interpretation: Our data suggest that: TBS and DXA both detected significant decrements in the LS in these pre‐ ARED astronauts, not unexpected given the insufficient loads provided by this early exercise device. TBS did not detect significant changes in the ARED or Bisphos+ARED groups while DXA did detect significant changes in the ARED astronauts. These findings suggest that DXA and TBS are detecting independent effects of bone loss interventions tested in ISS astronauts in space, which may be due to distinct effects of interventions on mineral content of separate cortical vs. trabecular bone. Conclusion: TBS, in conjunction with DXA BMD, may provide additional insight into the nature of changes (or lack thereof) in the microstructure of trabecular bone and the areal BMD of vertebral bodies.

Smith, Scott A.↗
DOE OSTI2022

Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment

Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2014

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means.

Sibonga, Jean D.↗
NASA NTRS1995

Non-invasive assessment of otolith formation during development of the Japanese red-bellied newt, Cynops pyrrhogaster

Pre-mated adult female newts and embryos have been flown on the International Microgravity Laboratory-2 (IML-2) Space Shuttle flight in 1994 (Wiederhold et al., 1992b). With the specimens available from this flight, the calcification of otoliths, ulna, radius and backbone of the flown larvae and adult newts were analyzed. The experiments presented here studied the development of the otoliths on the ground. Otoliths of living newts, from embryo to adult, were observed in situ with the application of a new X-ray and bio-imaging analyzer system. For the establishment of this method, newts at different developmental stages were used. An imaging plate temporarily stores the X-ray energy pattern at the bio-imaging analyzer. A latent image on the imaging plate was transformed into a digital time series signal with an image reader. Acquired digital information was computed with the image processor. The processed information was recorded on film with an image recorder, in order to visualize it on an enlargement computed radiograph. To analyze development of the otoliths, photo-stimulated luminescence level was detected by an image analyzer, using transmitted X-ray photons. A single clump of otoconia could first be seen at stage 33. Stage-36 embryos first have distinguishable otoliths, with the utricle in front and saccule behind. Our results show that this X-ray method detects the otoliths equally as well as sectioning. In the newt, the mandibular/maxillary bone formed before the spine. It is suspected that for the newt embryo, living in water, feeding becomes necessary prior to support of the body.

NASA Discipline Neuroscience↗