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DOE OSTI2020

Scalable method for micro-CT analysis enables large scale quantitative characterization of brain lesions and implants

Anatomic evaluation is an important aspect of many studies in neuroscience; however, it often lacks information about the three-dimensional structure of the brain. Micro-CT imaging provides an excellent, nondestructive, method for the evaluation of brain structure, but current applications to neurophysiological or lesion studies require removal of the skull as well as hazardous chemicals, dehydration, or embedding, limiting their scalability and utility. Here we present a protocol using eosin in combination with bone decalcification to enhance contrast in the tissue and then employ monochromatic and propagation phase-contrast micro-CT imaging to enable the imaging of brain structure with the preservation of the surrounding skull. Instead of relying on descriptive, time-consuming, or subjective methods, we develop simple quantitative analyses to map the locations of recording electrodes and to characterize the presence and extent of hippocampal brain lesions.

3-D reconstruction↗

DOE OSTI2023

Mechanical behavior analysis using small-size graphite disc compression testing with digital image correlation methods

The ASTM International Standard Test Method for Tensile Stress-Strain of Carbon and Graphite (ASTM C749) requires dog-bone shaped specimens. Unfortunately, specimen sizes required in ASTM C749 are much too large for irradiation within a test reactor and are incompatible with irradiation capsule volumes, molten salt degradation facilities, or oxidation apparatus. The ASTM International Standard Test Method for Tensile Strength Estimate by Disc Compression of Manufactured Graphite (ASTM D8289) was developed as an alternative that provides a means for testing tensile properties using smaller specimens when geometric constraints are present. However, the important stress–strain relation throughout the test loading history that could be recorded using ASTM C749 is lost by using ASTM D8289 because of the difficulties involved with using traditional strain gauges or extensometers on such a small specimen. In this work, a digital image correlation (DIC) method, which uses a full-field noncontact surface displacement measurement technique, was applied along with the ASTM D8289 splitting tensile test on eight small samples of graphite grade Mersen 2114 to track their deformation during compressive loading. Initial results showed that the DIC technique can measure the surface displacement/strain on these small (Ø6 × 3 mm) graphite specimens with high accuracy and good repeatability, indicating that the DIC technique, combined with the small-disc splitting tensile test in ASTM D8289, can capture the strain evolution in the test. In conclusion, further comparison of measured strains with analytical and numerical simulation results provides additional understanding of the mechanical behaviour of this nuclear graphite material in complex stress states.

36 MATERIALS SCIENCE↗

NASA NTRS2014

Expanding the Description of Spaceflight Effects beyond Bone Mineral Density [BMD]: Trabecular Bone Score [TBS] in ISS Astronauts

Dual-energy x-ray absorptiometry [DXA] is the widely-applied bone densitometry method used to diagnose osteoporosis in a terrestrial population known to be at risk for age-related bone loss. This medical test, which measures areal bone mineral density [aBMD] of clinically-relevant skeletal sites (e.g., hip and spine), helps the clinician to identify which persons, among postmenopausal women and men older than 50 years, are at high risk for low trauma or fragility fractures and might require an intervention. The most recognized osteoporotic fragility fracture is the vertebral compression fracture which can lead to kyphosis or hunched backs typically seen in the elderly. DXA measurement of BMD however is recognized to be insufficient as a sole index for assessing fracture risk. DXA's limitation may be related to its inability to monitor changes in structural parameters, such as trabecular vs. cortical bone volumes, bone geometry or trabecular microarchitecture. Hence, in order to understand risks to human health and performance due to space exposure, NASA needs to expand its measurements of bone to include other contributors to skeletal integrity. To this aim, the Bone and Mineral Lab conducted a pilot study for a novel measurement of bone microarchitecture that can be obtained by retrospective analysis of DXA scans. Trabecular Bone Score (TBS) assesses changes to trabecular microarchitecture by measuring the grey color "texture" information extracted from DXA images of the lumbar spine. An analysis of TBS in 51 ISS astronauts was conducted to assess if TBS could detect 1) an effect of spaceflight and 2) a response to countermeasures independent of DXA BMD. In addition, changes in trunk body lean tissue mass and in trunk body fat tissue mass were also evaluated to explore an association between body composition, as impacted by ARED exercise, and bone microarchitecture. The pilot analysis of 51 astronaut scans of the lumbar spine suggests that, following an ISS mission, DXA BMD and TBS are detecting different effects of ARED exercise and of ARED + Bisphosphonate on the lumbar spine of astronauts. There is emerging evidence associating reduced TBS with terrestrial metabolic bone disorders where a TBS <1.200 is associated with "degraded" while > 1.350 is associated with "normal." However, it is not possible to conclude how the spaceflight-induced changes in TBS increase risk for vertebral fractures in the astronaut or if changes in body composition of the trunk region could be an indirect method of assessing exercise effect on bone microarchitecture. More importantly, this pilot analysis demonstrates a new, minimal risk approach for monitoring changes to vertebral bone microarchitecture. This method could help assess the combined skeletal effects of spaceflight with the effects of aging in the astronaut after return to Earth.

Sibonga, J. D.↗

DOE OSTI2020

Compositions for therapeutics, targeted PET imaging and methods of their use

Described herein is a chelator for radiolabels (e.g., 89Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator for 89Zr is the ligand, 3,4,3-(LI-1,2-HOPO) (“HOPO”), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG. 1, the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g., 89Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG. 4 and FIG. 5. Such a bifunctional ligand can eliminate (e.g., 89Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.

Lewis, Jason S.↗

NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Spinal Cord Injury↗

NASA NTRS2025

Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

Risk Surveillance↗

NASA NTRS1996

Structural relations between collagen and mineral in bone as determined by high voltage electron microscopic tomography

Aspects of the ultrastructural interaction between collagen and mineral crystals in embryonic chick bone have been examined by the novel technique of high voltage electron microscopic tomography to obtain three-dimensional information concerning extracellular calcification in this tissue. Newly mineralizing osteoid along periosteal surfaces of mid-diaphyseal regions from normal chick tibiae was embedded, cut into 0.25 microns thick sections, and documented at 1.0 MV in the Albany AEI-EM7 high voltage electron microscope. The areas of the tissue studied contained electron dense mineral crystals associated with collagen fibrils, some marked by crystals disposed along their cylindrically shaped lengths. Tomographic reconstructions of one site with two mineralizing fibrils were computed from a 5 degrees tilt series of micrographs over a +/- 60 degrees range. Reconstructions showed that the mineral crystals were platelets of irregular shape. Their sizes were variable, measured here up to 80 x 30 x 8 nm in length, width, and thickness, respectively. The longest crystal dimension, corresponding to the c-axis crystallographically, was generally parallel to the collagen fibril long axis. Individual crystals were oriented parallel to one another in each fibril examined. They were also parallel in the neighboring but apparently spatially separate fibrils. Crystals were periodically (approximately 67 nm repeat distance) arranged along the fibrils and their location appeared to correspond to collagen hole and overlap zones defined by geometrical imaging techniques. The crystals appeared to be continuously distributed along a fibril, their size and number increasing in a tapered fashion from a relatively narrow tip containing smaller and infrequent crystals to wider regions having more densely packed and larger crystals. Defined for the first time by direct visual 3D imaging, these data describe the size, shape, location, orientation, and development of early crystals in normal bone collagen. The results suggest that platelet-shaped crystals are arranged in channels or grooves which are formed by collagen hole zones in register and that crystal sizes may exceed the dimensions of hole zones. Such data agree with those from mineral-matrix interaction in normally calcifying avian tendon obtained by similar high voltage tomographic means, but in addition they indicate a possible gradual and continuous deposition of crystals in collagen of bone unlike tendon and imply that individual collagen fibrils in local regions of osteoid are organized such that they all may be aligned in a coherent manner.

NASA Discipline Number 40-40↗

NASA NTRS1987

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Schneider, Victor S.↗

NASA NTRS2016

A Flexible Method for Producing F.E.M. Analysis of Bone Using Open-Source Software

This project, performed in support of the NASA GRC Space Academy summer program, sought to develop an open-source workflow methodology that segmented medical image data, created a 3D model from the segmented data, and prepared the model for finite-element analysis. In an initial step, a technological survey evaluated the performance of various existing open-source software that claim to perform these tasks. However, the survey concluded that no single software exhibited the wide array of functionality required for the potential NASA application in the area of bone, muscle and bio fluidic studies. As a result, development of a series of Python scripts provided the bridging mechanism to address the shortcomings of the available open source tools. The implementation of the VTK library provided the most quick and effective means of segmenting regions of interest from the medical images; it allowed for the export of a 3D model by using the marching cubes algorithm to build a surface mesh. To facilitate the development of the model domain from this extracted information required a surface mesh to be processed in the open-source software packages Blender and Gmsh. The Preview program of the FEBio suite proved to be sufficient for volume filling the model with an unstructured mesh and preparing boundaries specifications for finite element analysis. To fully allow FEM modeling, an in house developed Python script allowed assignment of material properties on an element by element basis by performing a weighted interpolation of voxel intensity of the parent medical image correlated to published information of image intensity to material properties, such as ash density. A graphical user interface combined the Python scripts and other software into a user friendly interface. The work using Python scripts provides a potential alternative to expensive commercial software and inadequate, limited open-source freeware programs for the creation of 3D computational models. More work will be needed to validate this approach in creating finite-element models.

gravitational physiology↗

DOE OSTI2025

Stochastic parametric skeletal dosimetry model for humans: Pediatric and adult computational skeleton phantoms for internal bone marrow dosimetry

Currently, computational phantoms that simulate skeletal tissues are used in active red bone marrow (AM) internal dosimetry. Up-to-date reference computational phantoms recommended by the ICRP are based on the analysis of CT-images of cadavers. Such phantoms have significant disadvantages. One disadvantage is that the assessment of uncertainty due to the population variability of skeleton dimensions and microstructure results from the limited availability of autopsy material. Another disadvantage is the simplified modelling of cortical layer and bone microarchitecture. A method of stochastic parametric skeletal dosimetry modelling of the bone structures – SPSD modelling – has been developed as an alternative to the ICRP reference phantoms. In the framework of this approach, skeletal phantom parameters are evaluated based on extensively reviewed results of published measurements of real bones. The SPSD approach allows for the assessment of both population-average values and their variability. SPSD-phantoms of the skeleton are modelled in voxel representation. They consist of smaller phantoms of the bone sites – segments – described by simple geometric shapes with uniform microarchitecture parameters. Such segmentation makes it possible to account for non-homogeneous skeletal microarchitecture and to model the bone structure with the required voxel resolution to elaborate suitable skeletal phantoms. The current study presents the parameters of the SPSD skeletal phantoms for the following age-groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old (male and female), and adult (male and female). This skeletal phantom can be used for dosimetry as an alternative to available reference phantoms for bone-seeking radionuclides. The above-mentioned age- and sex-specific skeletal phantoms are comprised of 289 unique segments. The characteristics of the SPSD phantoms do not contradict published data and are in good agreement with the measurement results of real bones.

Science & Technology - Other Topics↗

DOE OSTI2025

Light output and neutron detection efficiency of boron-based neutron scintillator screens for neutron imaging

Recent research has explored the development of boron-based neutron scintillator screens, which potentially offer improved spatial resolution and neutron capture efficiency compared to traditional lithium-based screens. This work builds upon previous efforts to improve boron-based neutron scintillators by assessing a newer generation of boron-based scintillator screens fabricated using different compositions and fabrication approaches compared to previous generations of screens. Some of the test screens exhibit higher light output than previous efforts and higher neutron capture efficiency than lithium-based screens. This paper describes the current state of screen development, measurement results for the most recent generation of screens, and future activities.

46 - INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AN↗

DOE OSTI2025

Sulfur Species in Zinc-Rich Condylar Zones of a Rat Temporomandibular Joint

We performed synchrotron-based micro-X-ray absorption near-edge spectroscopy (µ-XANES) coupled with micro-X-ray fluorescence (µ-XRF) for the identification of elements that included biometal zinc (Zn) and nonmetal sulfur (S) (and its species) in the condylar zones of a rat temporomandibular joint (TMJ). Zone-specific spatial localization of biometal Zn and nonmetal S from a materials viewpoint when correlated with hypoxia inducible factor-1α (HIF-1α) (a surrogate for tissue oxygenation) can provide insights into Zn-specific redox pathways at the vulnerable subchondral interface. Histologic localization of Zn, HIF-1α, and sulfur-rich proteoglycans (PGs) were mapped using an optical microscope. The µ-XRF maps coupled with site-specific micro-X-ray diffraction (µ-XRD) patterns were used to underline Zn-incorporated biological apatite in the subchondral bone and the bone of a rat TMJ condyle. Results demonstrated an association between Zn, PG, and HIF-1α histologic maps with µ-XRF, µ-XANES, and µ-XRD data and provided insights into plausible biological S species in Zn-enriched zones of a rat TMJ condyle. Spatially localized Zn and S underscore their roles in cell and tissue functions in a zone-specific manner. Elemental Zn with organic and inorganic S species at the cartilage-bone interface and the biomineral phase of Zn-enriched biological apatite from subchondral bone to condylar bone were ascertained using µ-XRF-XANES and µ-XRF-XRD. The coupled µ-XRF-XANES in situ complemented with µ-XRF-XRD in situ and immunohistochemistry provided valuable biological insights into zone-specific biological pathways in rat TMJ condyles. Based on these data, we present a workflow to reliably map and correlate S species within Zn-enriched regions of cartilage, bone, and their interface. We suggest the use of this correlative and complementary microspectroscopic spatial information for zone-specific localization of biometal Zn and nonmetal S to gain insights into plausible microanatomy-specific oxidative stress in the TMJ.

apatites↗

NASA NTRS2017

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

vascular↗

NASA NTRS1981

Experiment K305: Quantitative analysis of selected bone parameters. Supplement 3A: Trabecular spacing and orientation in the long bones

Values of mean trabecular spacing computed from optical diffraction patterns of 1:1 X-ray micrographs of tibial metaphysis and those obtained by standard image digitization techniques show excellent agreement. Upper limits on values of mean trabecular orientation deduced from diffraction patterns and the images are also in excellent agreement. Values of the ratio of mean trabecular spatial density in a region of 300 micrometers distal to the downwardly directed convexity in the cartilage growth plate to the value adjacent to the plate determined for flight animals sacrificed at recovery were significantly smaller than values for vivarium control animals. No significant differences were found in proximal regions. No significant differences in mean trabecular orientation were detected. Decreased values of trabecular spatial density and of both obsteoblastic activity and trabecular cross-sectional area noted in collateral researches suggest decreased modeling activity under weightlessness.

Judy, M. M.↗

NASA NTRS2004

NASA Tech Briefs, November 2004

Topics include: Multifunction Imaging and Spectroscopic Instrument; Position-Finding Instrument Built Around a Magnetometer; Improved Measurement of Dispersion in an Optical Fiber; Probe for Sampling of Interstitial Fluid From Bone; Neuropsychological Testing of Astronauts; Method of Calibration for a Large Cathetometer System; Four-Channel PC/104 MIL-STD-1553 Circuit Board; Improved Method of Locating Defects in Wiring Insulation; Strobe Traffic Lights Warn of Approaching Emergency Vehicles; Improved Timing Scheme for Spaceborne Precipitation Radar; Concept for Multiple-Access Free-Space Laser Communications; Variable Shadow Screens for Imaging Optical Devices; Verifying Diagnostic Software; Initial Processing of Infrared Spectral Data; Activity-Centric Approach to Distributed Programming; Controlling Distributed Planning; New Material for Surface-Enhanced Raman Spectroscopy; Treated Carbon Nanofibers for Storing Energy in Aqueous KOH; Advanced Infant Car Seat Would Increase Highway Safety; Development of Biomorphic Flyers; Second-Generation Six-Limbed Experimental Robot; Miniature Linear Actuator for Small Spacecraft; Process for Making Single-Domain Magnetite Crystals; A New Process for Fabricating Random Silicon Nanotips; Resin-Transfer-Molding of a Tool Face; Improved Phase-Mask Fabrication of Fiber Bragg Gratings; Tool for Insertion of a Fiber-Optic Terminus in a Connector; Nanofluidic Size-Exclusion Chromatograph; Lightweight, Low-CTE Tubes Made From Biaxially Oriented LCPs; Using Redundancy To Reduce Errors in Magnetometer Readings; Compact Instrument for Measuring Profile of a Light Beam; Multilayer Dielectric Transmissive Optical Phase Modulator; Second-Generation Multi-Angle Imaging Spectroradiometer; Real-Time Adaptive Color Segmentation by Neural Networks; Research and Development in Optical Communications; Tests of Multibeam Scintillation Mitigation on Laser Uplinks; and Spaceborne Infrared Atmospheric Sounder.

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NASA NTRS2018

Design and Development of Modules to Support Live Microscopic Imaging on Ground-Based Microgravity Simulators

In space, astronauts are exposed to environmental stressors that often result in physiological changes. One prominent stressor in spaceflight is microgravity, and research has shown that long term microgravity exposure causes muscle atrophy, bone loss, cardiovascular concerns, and vision impairment. It is critical to understand how altered gravity affects physiology on the cellular, molecular, and gene level in order to accurately assess health risks and to develop effective countermeasures. Ground-based microgravity simulators such as random positioning machines (RPMs) are used to produce some of the biological effects of altered gravity on different cell types and organisms. Real-time imaging during simulations are of particular interest as we can study how basic cell functions such as cell division, cell migration, and proliferation progress under microgravity conditions. However, design limitations of present microgravity simulators such as susceptibility to parasitic vibration and displacement of the sample from the center of rotation challenge the accuracy of experiment results and live images. We have developed a cell culture sample holder module suitable for live microscopic imaging on an RPM. CAD modeling and 3D printing technology were used to implement modifications to the sample holder and to install a digital microscope to perform live bright-field and fluorescent imaging. Vibration damping materials were also investigated to allow for stable imaging while the microgravity simulator was within a cell culture incubator. Novel methods and hardware modifications for improving live cell imaging on ground-based microgravity simulators were proposed and discussed.

3D printing↗

NASA NTRS2003

Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy

BACKGROUND: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy. METHODS: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography. FINDINGS: Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left-ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05). INTERPRETATION: These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is re-established.

NASA Discipline Cardiopulmonary↗

NASA NTRS2007

NASA Tech Briefs, December 2007

Topics include: Ka-Band TWT High-Efficiency Power Combiner for High-Rate Data Transmission; Reusable, Extensible High-Level Data-Distribution Concept; Processing Satellite Imagery To Detect Waste Tire Piles; Monitoring by Use of Clusters of Sensor-Data Vectors; Circuit and Method for Communication Over DC Power Line; Switched Band-Pass Filters for Adaptive Transceivers; Noncoherent DTTLs for Symbol Synchronization; High-Voltage Power Supply With Fast Rise and Fall Times; Waveguide Calibrator for Multi-Element Probe Calibration; Four-Way Ka-Band Power Combiner; Loss-of-Control-Inhibitor Systems for Aircraft; Improved Underwater Excitation-Emission Matrix Fluorometer; Metrology Camera System Using Two-Color Interferometry; Design and Fabrication of High-Efficiency CMOS/CCD Imagers; Foam Core Shielding for Spacecraft CHEM-Based Self-Deploying Planetary Storage Tanks Sequestration of Single-Walled Carbon Nanotubes in a Polymer PPC750 Performance Monitor Application-Program-Installer Builder Using Visual Odometry to Estimate Position and Attitude Design and Data Management System Simple, Script-Based Science Processing Archive Automated Rocket Propulsion Test Management Online Remote Sensing Interface Fusing Image Data for Calculating Position of an Object Implementation of a Point Algorithm for Real-Time Convex Optimization Handling Input and Output for COAMPS Modeling and Grid Generation of Iced Airfoils Automated Identification of Nucleotide Sequences Balloon Design Software Rocket Science 101 Interactive Educational Program Creep Forming of Carbon-Reinforced Ceramic-Matrix Composites Dog-Bone Horns for Piezoelectric Ultrasonic/Sonic Actuators Benchtop Detection of Proteins Recombinant Collagenlike Proteins Remote Sensing of Parasitic Nematodes in Plants Direct Coupling From WGM Resonator Disks to Photodetectors Using Digital Radiography To Image Liquid Nitrogen in Voids Multiple-Parameter, Low-False-Alarm Fire-Detection Systems Mosaic-Detector-Based Fluorescence Spectral Imager Plasmoid Thruster for High Specific-Impulse Propulsion Analysis Method for Quantifying Vehicle Design Goals Improved Tracking of Targets by Cameras on a Mars Rover Sample Caching Subsystem Multistage Passive Cooler for Spaceborne Instruments GVIPS Models and Software Stowable Energy-Absorbing Rocker-Bogie Suspensions

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