Innovations in laboratory-based dynamic micro-CT to accelerate in situ research.

In the past few years, dynamic computed tomography (CT) approaches or uninterrupted acquisitions of deforming materials have rapidly emerged as an essential technique to understand material evolution, facilitating in situ investigations ranging from mechanical deformation to fluid flow in porous materials and beyond. Developments at synchrotron facilities have led this effort, pointing to the future of the technique. In the laboratory, recent developments at TESCAN XRE have made it possible to image, reconstruct and inspect dynamic processes in the laboratory with a temporal resolution below 10 s, meaning that an entire acquisition from 0 to 360° is completed within 10 s. The aim of this study is to explore the challenges and innovations that have led to the ability to perform high speed, dynamic acquisitions. A unique horizontally rotating gantry based micro-CT system was developed to facilitate complex in situ experiments. In doing so, the sample stays fixed while source and detector are uninterruptedly rotating around a vertical axis. In this work, the dynamic CT method with this rotating gantry based system will be described by two application examples: (1) deformation and collapse of a delicate beer foam and (2) in situ baking process of pastry. For the pastry baking process, an oven was needed to reach baking temperature. In a conventional micro-CT system, where the sample rotates, it is not so obvious to rotate an oven with sensor and heating cables. On the other hand, the delicate foam of a collapsing beer head is able to rotate, but because of the tangential convection during fast rotation (<10 s), it could influence the bubble detachment and liquid drainage and thus also the foam degradation. To investigate both processes, a horizontally rotating gantry based micro-CT is required. For both examples it was possible to quantify the key parameters such as pore size and distribution to better understand the rise and fall of porous foams. These examples will highlight the recent progress in adapting micro-CT workflows to accommodate uninterrupted imaging of dynamic events and point to opportunities for future continued development. LAY DESCRIPTION: Micro-CT allows the nondestructive visualisation of internal structures and is being used routinely in the field of Material Science, Geoscience, Life Science and more. Because of its nondestructive aspect, micro-CT is optimal to take repetitive scans of the same sample over time. The combination of taking different scans over time is so called time-resolved CT. By doing so, crucial insights can be obtained on how materials form, deform and perform over time or under certain external conditions. TESCAN XRE have made it possible to image, reconstruct and inspect dynamic processes in the laboratory with a temporal resolution below 10 s. The dynamic CT method will be described through the lens of two application examples: (1) deformation and collapse of a delicate beer foam and (2) in situ baking process of pastry. These examples will highlight the recent progress in adapting micro-CT workflows to accommodate imaging of dynamic events and point to opportunities for future continued development.

Microstructural evolution during sintering of copper particles studied by laboratory diffraction contrast tomography (LabDCT).

Pressureless sintering of loose or compacted granular bodies at elevated temperature occurs by a combination of particle rearrangement, rotation, local deformation and diffusion, and grain growth. Understanding of how each of these processes contributes to the densification of a powder body is still immature. Here we report a fundamental study coupling the crystallographic imaging capability of laboratory diffraction contrast tomography (LabDCT) with conventional computed tomography (CT) in a time-lapse study. We are able to follow and differentiate these processes non-destructively and in three-dimensions during the sintering of a simple copper powder sample at 1050 °C. LabDCT quantifies particle rotation (to <0.05° accuracy) and grain growth while absorption CT simultaneously records the diffusion and deformation-related morphological changes of the sintering particles. We find that the rate of particle rotation is lowest for the more highly coordinated particles and decreases during sintering. Consequently, rotations are greater for surface breaking particles than for more highly coordinated interior ones. Both rolling (cooperative) and sliding particle rotations are observed. By tracking individual grains the grain growth/shrinkage kinetics during sintering are quantified grain by grain for the first time. Rapid, abnormal grain growth is observed for one grain while others either grow or are consumed more gradually.

Non-destructive mapping of grain orientations in 3D by laboratory X-ray microscopy.

The ability to characterise crystallographic microstructure, non-destructively and in three-dimensions, is a powerful tool for understanding many aspects related to damage and deformation mechanisms in polycrystalline materials. To this end, the technique of X-ray diffraction contrast tomography (DCT) using monochromatic synchrotron and polychromatic laboratory X-ray sources has been shown to be capable of mapping crystal grains and their orientations non-destructively in 3D. Here we describe a novel laboratory-based X-ray DCT modality (LabDCT), enabling the wider accessibility of the DCT technique for routine use and in-depth studies of, for example, temporal changes in crystallographic grain structure non-destructively over time through '4D' in situ time-lapse studies. The capability of the technique is demonstrated by studying a titanium alloy (Ti-ß21S) sample. In the current implementation the smallest grains that can be reliably detected are around 40 µm. The individual grain locations and orientations are reconstructed using the LabDCT method and the results are validated against independent measurements from phase contrast tomography and electron backscatter diffraction respectively. Application of the technique promises to provide important insights related to the roles of recrystallization and grain growth on materials properties as well as supporting 3D polycrystalline modelling of materials performance.

Experimental Characterization of the Anatomical Structures of the Lumbar Spine Under Dynamic Sagittal Bending.

Underbody blast (UBB) events transmit high-rate vertical loads through the seated occupant’s lumbar spine and have a high probability of inducing severe injury. While previous studies have characterized the lumbar spine under quasi-static loading, additional work should focus on the complex kinetic and kinematic response under high loading rates. To discern the biomechanical influence of the lumbar spine’s anatomical structures during dynamic loading, the axial force, flexion-extension moments and range of motion for lumbar motion segments (n=18) were measured during different states of progressive dissection. Pre-compression was applied using a static mass while dynamic bending was applied using an offset drop mass. Dynamic loading resulted in peak axial loads of 4,224±133 N, while maximum peak extension and flexion moments were 19.6±12.5 and -44.8±8.6 Nm in the pre-dissected state, respectively. Upon dissection, transection of the interspinous ligament, ligamentum flavum and facet capsules resulted in significantly larger flexion angles, while the removal of the posterior elements increased the total peak angular displacement in extension from 3.3±1.5 to 5.0±1.7 degrees (p=0.002). This study provides insight on the contribution of individual anatomical components on overall lumbar response under high-rate loading, as well as validation data for numerical models.

Automated Measurement Technique for the Determination of Regional Skull and Scalp Constituent Thickness.

The human skull is a multi-layered composite system critical in protecting the brain during head impact. Head impact studies investigating skull injury thresholds have suggested that the skull and scalp thickness affect the risk of fracture. Therefore, accurately determining the dimensions of skull-scalp constituents is a necessary step in attributing the contribution to response, failure mechanisms and in developing high fidelity human models. However, prior methods to collect these data include physical measurements of biopsies and manual segmentation in X-ray images. These methods are invasive and impractical for clinical applications, or insufficient to characterize the regional variance in the skull-scalp constituents for a full mechanical strength characterization. The newly developed methods in this study describe an automated, regional, and objective-based measurement technique to characterize the average thickness and variance in skull and scalp constituents using quantitative computed tomography (QCT). The developed approach was successfully employed on 7 specimens at 5 anatomically defined locations. Results report the thicknesses for each layer, with the layer of greatest variation being the trabecular bone (diploë) having a standard deviation of 35.6% of its mean thickness. These results will be used to define skull morphology for modeling relative impact injury risk that will be experimentally validated.

Material Parameter Determination of an L4-L5 Motion Segment Finite Element Model Under High Loading Rates.

Underbody blast (UBB) events impart vertical loads through a victim’s lumbar spine, resulting in fracture, paralysis, and disc rupture. Validated biofidelic lumbar models allow characterization of injury mechanisms and development of personal protective equipment. Previous studies have focused on lumbar mechanics under quasi-static loading. However, it is unclear how the role and response of individual spinal components of the lumbar spine change under dynamic loading. The present study leverages high-rate impacts of progressively dissected two-vertebra lumbar motion segments and Split-Hopkinson pressure bar tissue characterization to identify and validate material properties of a high-fidelity lumbar spine finite element model for UBB. The annulus fibrosus was modeled as a fiber-reinforced Mooney-Rivlin material, while ligaments were represented by nonlinear spring elements. Optimization and evaluation of material parameters was achieved by minimizing the root-mean-square (RMS) of compressive displacement and sagittal rotation for selected experimental conditions. Applying dynamic based material models and parameters resulted in a 0.42% difference between predicted and experiment axial compression during impact loading. This dynamically optimized lumbar model is suited for cross validation against whole-lumbar loading scenarios, and prediction of injury during UBB and other dynamic events.

[Testing of vaccines. The challenge of testing complex combination vaccines]. / Prüfung von Impfstoffen. Die Herausforderung der Prüfung komplexer Kombinationsimpfstoffe.

Vaccines are biologicals. This group of medicinal products is produced with a predefined variability based on the biological starting materials used. Vaccines are subject to official control authority batch release performed by the Paul-Ehrlich-Institut (PEI). To release batches to the market, experimental testing has to be conducted by an official medicines control laboratory as the PEI. It is the aim of this independent testing to demonstrate the conformity of quality criteria with conditions set in the marketing authorization for each lot produced. The testing is performed on the basis of vaccine specific batch release guideline and due to the difficult and time consuming testing procedures often run in parallel with manufacturers testing. If test results comply with the predefined criteria, the lot in question is released. This article describes the challenge of official control authority batch release testing of two complex combination vaccines.

Response of thoracolumbar vertebral bodies to high rate compressive loading - biomed 2013.

Underbody blast (UBB) events created by improvised explosive devices are threats to warfighter survivability. High intensity blast waves emitted from these devices transfer large forces through vehicle structures to occupants, often resulting in injuries including debilitating spinal fractures. The vertical loading vector through the spine generates significant compressive forces at high strain rates. To better understand injury mechanisms and ultimately better protect vehicle occupants against UBB attacks, high-fidelity computational models are being developed to predict the human response to dynamic loading characteristic of these events. This effort details the results from a series of 23 high-rate compression tests on vertebral body specimen. A high-rate servo-hydraulic test system applied a range of compressive loading rates (.01 mm/s to 1238 mm/s) to vertebral bodies in the thoracolumbar region (T7-L5). The force-deflection curves generated indicate rate dependent sensitivity of vertebral stiffness, ultimate load and ultimate deflection. Specimen subjected to high-rate dynamic loading to failure experienced critical structural damage at 5.5% ± 2.1% deflection. Compared to quasi-static loading, vertebral bodies had greater stiffness, greater force to failure, and lower ultimate failure deflection at high rates. Post-failure, an average loss in height of 15% was observed, along with a mean reduction in strength of 48%. The resulting data from these tests will allow for enhanced biofidelity of computational models by characterizing the vertebral stiffness response and ultimate deflection at rates representative of UBB events.

Effect of skull flexural properties on brain response during dynamic head loading - biomed 2013.

The skull-brain complex is typically modeled as an integrated structure, similar to a fluid-filled shell. Under dynamic loads, the interaction of the skull and the underlying brain, cerebrospinal fluid, and other tissue produces the pressure and strain histories that are the basis for many theories meant to describe the genesis of traumatic brain injury. In addition, local bone strains are of interest for predicting skull fracture in blunt trauma. However, the role of skull flexure in the intracranial pressure response to blunt trauma is complex. Since the relative time scales for pressure and flexural wave transmission across the skull are not easily separated, it is difficult to separate out the relative roles of the mechanical components in this system. This study uses a finite element model of the head, which is validated for pressure transmission to the brain, to assess the influence of skull table flexural stiffness on pressure in the brain and on strain within the skull. In a Human Head Finite Element Model, the skull component was modified by attaching shell elements to the inner and outer surfaces of the existing solid elements that modeled the skull. The shell elements were given the properties of bone, and the existing solid elements were decreased so that the overall stiffness along the surface of the skull was unchanged, but the skull table bending stiffness increased by a factor of 2.4. Blunt impact loads were applied to the frontal bone centrally, using LS-Dyna. The intracranial pressure predictions and the strain predictions in the skull were compared for models with and without surface shell elements, showing that the pressures in the mid-anterior and mid-posterior of the brain were very similar, but the strains in the skull under the loads and adjacent to the loads were decreased 15% with stiffer flexural properties. Pressure equilibration to nearly hydrostatic distributions occurred, indicating that the important frequency components for typical impact loading are lower than frequencies based on pressure wave propagation across the skull. This indicates that skull flexure has a local effect on intracranial pressures but that the integrated effect of a dome-like structure under load is a significant part of load transfer in the skull in blunt trauma.

Development of a miniaturized position sensing system for measuring brain motion during impact - biomed 2013.

Since 2000, the Department of Defense has documented more than 253,000 cases of Traumatic Brain Injury (TBI). A significant portion of these injuries were attributed to explosive events, yet ninety-eight percent were non-penetrating. Understanding the response of the brain to blast events is critical, yet the mechanisms of brain injury from explosive trauma are poorly understood. This knowledge gap has led to an increased research focus on devices capable of investigating human brain response to non-penetrating, blast-induced loading. Furthermore, traumatic brain injury is a major issue for the civilian population as well with over 1.7 million cases of TBI per year in the US, primarily from falls and motor vehicle accidents. Current head surrogates and instrumentation are incapable of directly measuring critical parameters associated with TBI, such as brain motion, during dynamic loading. To this end, a novel sensor system for measuring brain motion inside of a human head surrogate was conceptualized and developed. The positioning system is comprised of a set of three fixed “generator” coils and a plurality of mobile, miniaturized “receiver” coil triads. Each generator coil transmits a sinusoidal electromagnetic signal at a unique frequency, and groups of three orthogonally arranged “receiver” coils detect these signals. Because of the oscillatory nature of these signals, the magnetic flux through the coil is always changing, allowing the application of Faraday’s Law of Induction and the point dipole model of an electric field to model the strength and direction of the field vector at any given point. Thus, the strength of the signal measured by a particular receiver coil depends on its position and orientation relative to the fixed position of the generators. These predictable changes are used to determine the six degrees of freedom (6-DOF) motion of the receiver. To calibrate and validate the system, a receiver coil was moved about in a controlled manner, and its actual position recorded by optical methods. Comparing the known position to the computed position at each time instance, a set of calibration constants were developed for each receiver triad. These constants were then utilized to convert receiver signal data into actual receiver position and orientation. Comparing this test case and several others like it, mean error was determined to be almost always less than 1.0 mm, and less than 0.5 mm >85% of the time. Additionally, high rate validation was conducted to confirm operation of the system in the impact domain. A coil was accelerated to approximately 15 m/sec along a fixed axis by ballistic impact and tracked by high speed video. The computed position was within 1 mm of the actual position 93% of the time and within 0.5 mm 83% of the time. The successful development and calibration of this sensing system now enables the direct measurements of brain displacement due to mechanical insults applied to a human head surrogate.

Human head-neck computational model for assessing blast injury.

A human head finite element model (HHFEM) was developed to study the effects of a blast to the head. To study both the kinetic and kinematic effects of a blast wave, the HHFEM was attached to a finite element model of a Hybrid III ATD neck. A physical human head surrogate model (HSHM) was developed from solid model files of the HHFEM, which was then attached to a physical Hybrid III ATD neck and exposed to shock tube overpressures. This allowed direct comparison between the HSHM and HHFEM. To develop the temporal and spatial pressures on the HHFEM that would simulate loading to the HSHM, a computational fluid dynamics (CFD) model of the HHFEM in front of a shock tube was generated. CFD simulations were made using loads equivalent to those seen in experimental studies of the HSHM for shock tube driver pressures of 517, 690 and 862 kPa. Using the selected brain material properties, the peak intracranial pressures, temporal and spatial histories of relative brain-skull displacements and the peak relative brain-skull displacements in the brain of the HHFEM compared favorably with results from the HSHM. The HSHM sensors measured the rotations of local areas of the brain as well as displacements, and the rotations of the sensors in the sagittal plane of the HSHM were, in general, correctly predicted from the HHFEM. Peak intracranial pressures were between 70 and 120 kPa, while the peak relative brain-skull displacements were between 0.5 and 3.0mm.

MR imaging findings in the reticular formation in siblings with MPV17-related mitochondrial depletion syndrome.

Hepatocerebral MPV17-MDS is quite rare (<30 confirmed cases), with limited findings described on MR imaging. We report 2 siblings having abnormalities within the reticular formation of the lower brain stem and within the reticulospinal tracts at the cervicocranial junction on T2WI. The presence of these MR imaging findings (relative to previous reports) raises the possibility that they represent subtle but characteristic findings corresponding to clinically observed abnormalities of tone encountered with this recently described disorder.

Verification and implementation of a modified split Hopkinson pressure bar technique for characterizing biological tissue and soft biosimulant materials under dynamic shear loading.

Modeling human body response to dynamic loading events and developing biofidelic human surrogate systems require accurate material properties over a range of loading rates for various human organ tissues. This work describes a technique for measuring the shear properties of soft biomaterials at high rates of strain (100-1000 s(-1)) using a modified split Hopkinson pressure bar (SHPB). Establishing a uniform state of stress in the sample is a fundamental requirement for this type of high-rate testing. Input pulse shaping was utilized to tailor and control the ramping of the incident loading pulse such that a uniform stress state could be maintained within the specimen from the start of the test. Direct experimental verification of the stress uniformity in the sample was obtained via comparison of the force measured by piezoelectric quartz force gages on both the input and the output sides of the shear specimen. The technique was demonstrated for shear loading of silicone gel biosimulant materials and porcine brain tissue. Finite element simulations were utilized to further investigate the effect of pulse shaping on the loading rate and rise time. Simulations also provided a means for visualization of the degree of shear stress and strain uniformity in the specimen during an experiment. The presented technique can be applied to verify stress uniformity and ensure high quality data when measuring the dynamic shear modulus of soft biological simulants and tissue.

Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI.

Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC-1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b-SPIOs) for improved macrophage detection in plaques. CD11b-SPIOs and non-targeted SPIOs (control-SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO-induced MRI signal extinction, intracellular iron-content was significantly higher in monoytes/macrophages incubated with CD11b-SPIO than with control-SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b-SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE(-/-)-knockout mice on a Western-type diet were imaged before and 48 h after contrast agent injection of either CD11b-SPIOs or control-SPIOs, using a 9.4 T animal MRI system. The SPIO-induced change in the MRI signal was quantified, as well as the macrophage-content by anti-CD68 immunhistochemistry and the iron-content by Prussian-blue staining. However, SPIO-induced signal extinction in in vivo-MRI was similar in CD11b-SPIO and control-SPIO-injected animals, with a non-significant trend towards an improved uptake of CD11b-SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI-data indicated an increased uptake of targeted CD11b-SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non-targeted SPIOs. Therefore, CD11b-targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE(-/-)-knockout-model. However, the impressive correlation between MRI and histology data encourages further development of inflammation- and plaque-specific contrast agents for vulnerable plaque imaging.

Computational and experimental models of the human torso for non-penetrating ballistic impact.

Both computational finite element and experimental models of the human torso have been developed for ballistic impact testing. The human torso finite element model (HTFEM), including the thoracic skeletal structure and organs, was created in the finite element code LS-DYNA. The skeletal structure was assumed to be linear-elastic while all internal organs were modeled as viscoelastic. A physical human surrogate torso model (HSTM) was developed using biosimulant materials and the same anthropometry as the HTFEM. The HSTM response to impact was recorded with piezoresistive pressure sensors molded into the heart, liver and stomach and an accelerometer attached to the sternum. For experimentation, the HSTM was outfitted with National Institute of Justice (NIJ) Level I, IIa, II and IIIa soft armor vests. Twenty-six ballistic tests targeting the HSTM heart and liver were conducted with 22 caliber ammunition at a velocity of 329 m/s and 9 mm ammunition at velocities of 332, 358 and 430 m/s. The HSTM pressure response repeatability was found to vary by less than 10% for similar impact conditions. A comparison of the HSTM and HTFEM response showed similar pressure profiles and less than 35% peak pressure difference for organs near the ballistic impact point. Furthermore, the peak sternum accelerations of the HSTM and HTFEM varied by less than 10% for impacts over the sternum. These models provide comparative tools for determining the thoracic response to ballistic impact and could be used to evaluate soft body armor design and efficacy, determine thoracic injury mechanisms and assist with injury prevention.

Mechanical properties of soft human tissues under dynamic loading.

The dynamic response of soft human tissues in hydrostatic compression and simple shear is studied using the Kolsky bar technique. We have made modifications to the technique that allow loading of a soft tissue specimen in hydrostatic compression or simple shear. The dynamic response of human tissues (from stomach, heart, liver, and lung of cadavers) is obtained, and analyzed to provide measures of dynamic bulk modulus and shear response for each tissue type. The dynamic bulk response of these tissues is easily described by a linear fit for the bulk modulus in this pressure range, whereas the dynamic shearing response of these tissues is strongly non-linear, showing a near exponential growth of the shear stress.

A conceptual model for leadership development.

Collaboration among schools of public health and national, state, and local health agencies has resulted in creation of comprehensive public health workforce education and training initiatives that offer integrated, sequential, and accessible professional development programs, including a nation-wide network of public health leadership institutes. A conceptual model for leadership development is presented. It contains seven elements considered critical for design of leadership programs in public health: capacity/competence needs; program target; area served; program content; training level; learning approach; and implementation methods. This model can be used to design leadership as well as public health workforce education and training programs.

Competency development in public health leadership.

The professional development of public health leaders requires competency-based instruction to increase their ability to address complex and changing demands for critical services. This article reviews the development of the Leadership Competency Framework by the National Public Health Leadership Development Network and discusses its significance. After reviewing pertinent literature and existing practice-based competency frameworks, network members developed the framework through sequential use of workgroup assignments and nominal group process. The framework is being used by network members to develop and refine program competency lists and content; to compare programs; to develop needs assessments, baseline measures, and performance standards; and to evaluate educational outcomes. It is a working document, to be continually refined and evaluated to ensure its continued relevance to performance in practice. Understanding both the applications and the limits of competency frameworks is important in individual, program, and organizational assessment. Benefits of using defined competencies in designing leadership programs include the integrated and sustained development of leadership capacity and the use of technology for increased access and quality control.

Complete intrusion of a maxillary right primary central incisor.

This clinical article presents a rare presentation of complete intrusion of a maxillary right primary central incisor. Routine examination of a 29-month old female patient revealed an intrusion injury where the primary central incisor was displaced through the floor of the nasal cavity. The traumatic impaction was erroneously diagnosed as an avulsion injury by the attending emergency room physician and later discovered by the dental team during routine care. The injury was documented with radiographs. The intruded incisor was removed through the right naris utilizing general anesthesia to manage behavior and surgical access. This article emphasizes the importance of radiographs and demonstrates the need to involve the dental professional in initial assessment of dental trauma.