Longitudinal Alterations of Cerebral Blood Flow in High-Contact Sports.

OBJECTIVE: Repetitive head trauma is common in high-contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes. METHODS: We prospectively studied 63 American football (high-contact cohort) and 34 volleyball (low-contact controls) male collegiate athletes, tracking CBF using 3D pseudocontinuous arterial spin labeling magnetic resonance imaging for up to 4 years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co-registering to T1-weighted images. A linear mixed effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position-based head impact risk and baseline Standardized Concussion Assessment Tool score. Additionally, we evaluated early (1-5 days) and delayed (3-6 months) post-concussion rCBF changes (in-study concussion). RESULTS: Supratentorial gray matter rCBF declined in football compared with volleyball (sport-time interaction p = 0.012), with a strong effect in the parietal lobe (p = 0.002). Football players with higher position-based impact-risk had lower occipital rCBF over time (interaction p = 0.005), whereas players with lower baseline Standardized Concussion Assessment Tool score (worse performance) had relatively decreased rCBF in the cingulate-insula over time (interaction effect p = 0.007). Both cohorts showed a left-right rCBF asymmetry that decreased over time. Football players with an in-study concussion showed an early increase in occipital lobe rCBF (p = 0.0166). INTERPRETATION: These results suggest head impacts may result in an early increase in rCBF, but cumulatively a long-term decrease in rCBF. ANN NEUROL 2023;94:457-469.

Nanostructure surveys of macroscopic specimens by small-angle scattering tensor tomography.

The mechanical properties of many materials are based on the macroscopic arrangement and orientation of their nanostructure. This nanostructure can be ordered over a range of length scales. In biology, the principle of hierarchical ordering is often used to maximize functionality, such as strength and robustness of the material, while minimizing weight and energy cost. Methods for nanoscale imaging provide direct visual access to the ultrastructure (nanoscale structure that is too small to be imaged using light microscopy), but the field of view is limited and does not easily allow a full correlative study of changes in the ultrastructure over a macroscopic sample. Other methods of probing ultrastructure ordering, such as small-angle scattering of X-rays or neutrons, can be applied to macroscopic samples; however, these scattering methods remain constrained to two-dimensional specimens or to isotropically oriented ultrastructures. These constraints limit the use of these methods for studying nanostructures with more complex orientation patterns, which are abundant in nature and materials science. Here, we introduce an imaging method that combines small-angle scattering with tensor tomography to probe nanoscale structures in three-dimensional macroscopic samples in a non-destructive way. We demonstrate the method by measuring the main orientation and the degree of orientation of nanoscale mineralized collagen fibrils in a human trabecula bone sample with a spatial resolution of 25 micrometres. Symmetries within the sample, such as the cylindrical symmetry commonly observed for mineralized collagen fibrils in bone, allow for tractable sampling requirements and numerical efficiency. Small-angle scattering tensor tomography is applicable to both biological and materials science specimens, and may be useful for understanding and characterizing smart or bio-inspired materials. Moreover, because the method is non-destructive, it is appropriate for in situ measurements and allows, for example, the role of ultrastructure in the mechanical response of a biological tissue or manufactured material to be studied.

Retrieving neuronal orientations using 3D scanning SAXS and comparison with diffusion MRI.

While diffusion MRI (dMRI) is currently the method of choice to non-invasively probe tissue microstructure and study structural connectivity in the brain, its spatial resolution is limited and its results need structural validation. Current ex vivo methods employed to provide 3D fiber orientations have limitations, including tissue-distorting sample preparation, small field of view or inability to quantify 3D fiber orientation distributions. 3D fiber orientation in tissue sections can be obtained from 3D scanning small-angle X-ray scattering (3D sSAXS) by analyzing the anisotropy of scattering signals. Here we adapt the 3D sSAXS method for use in brain tissue, exploiting the high sensitivity of the SAXS signal to the ordered molecular structure of myelin. We extend the characterization of anisotropy from vectors to tensors, employ the Funk-Radon-Transform for converting scattering information to real space fiber orientations, and demonstrate the feasibility of the method in thin sections of mouse brain with minimal sample preparation. We obtain a second rank tensor representing the fiber orientation distribution function (fODF) for every voxel, thereby generating fODF maps. Finally, we illustrate the potential of 3D sSAXS by comparing the result with diffusion MRI fiber orientations in the same mouse brain. We show a remarkably good correspondence, considering the orthogonality of the two methods, i.e. the different physical processes underlying the two signals. 3D sSAXS can serve as validation method for microstructural MRI, and can provide novel microstructural insights for the nervous system, given the method's orthogonality to dMRI, high sensitivity to myelin sheath's orientation and abundance, and the possibility to extract myelin-specific signal and to perform micrometer-resolution scanning.

Validation study of small-angle X-ray scattering tensor tomography.

Small-angle scattering tensor tomography (SASTT) is a recently developed technique able to tomographically reconstruct the 3D reciprocal space from voxels within a bulk volume. SASTT extends the concept of X-ray computed tomography, which typically reconstructs scalar values, by reconstructing a tensor per voxel, which represents the local nanostructure 3D organization. In this study, the nanostructure orientation in a human trabecular-bone sample obtained by SASTT was validated by sectioning the sample and using 3D scanning small-angle X-ray scattering (3D sSAXS) to measure and analyze the orientation from single voxels within each thin section. Besides the presence of cutting artefacts from the slicing process, the nanostructure orientations obtained with the two independent methods were in good agreement, as quantified with the absolute value of the dot product calculated between the nanostructure main orientations obtained in each voxel. The average dot product per voxel over the full sample containing over 10 000 voxels was 0.84, and in six slices, in which fewer cutting artefacts were observed, the dot product increased to 0.91. In addition, SAXS tensor tomography not only yields orientation information but can also reconstruct the full 3D reciprocal-space map. It is shown that the measured anisotropic scattering for individual voxels was reproduced from the SASTT reconstruction in each voxel of the 3D sample. The scattering curves along different 3D directions are validated with data from single voxels, demonstrating SASTT's potential for a separate analysis of nanostructure orientation and structural information from the angle-dependent intensity distribution.

Uncovering microstructural architecture from histology.

Microstructural tissue organization underlies the complex connectivity of the brain and controls properties of connective, muscle, and epithelial tissue. However, discerning microstructural architecture with high resolution for large fields of view remains prohibitive. We address this challenge with computational scattered light imaging (ComSLI), which exploits the anisotropic light scattering of aligned structures. Using a rotating lightsource and a high-resolution camera, ComSLI determines fiber architecture with micrometer resolution from histological sections across preparation and staining protocols. We show complex fiber architecture in brain and non-brain sections, including histological paraffin-embedded sections with various stains, and demonstrate its applicability on animal and human tissue, including disease cases with altered microstructure. ComSLI opens new avenues for investigating fiber architecture in new and archived sections across organisms, tissues, and diseases.

Scientific Committee guidance on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments.

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases, which may be present in different epidemiological study designs. It then describes key epidemiological concepts relevant for evidence appraisal. This includes brief explanations for measures of association, exposure assessment, statistical inference, systematic error and effect modification. The guidance then describes the concept of external validity and the principles of appraising epidemiological studies. The customisation of the study appraisal process is explained including tailoring of tools for assessing the risk of bias (RoB). Several examples of appraising experimental and observational studies using a RoB tool are annexed to the document to illustrate the application of the approach. The latter part of this guidance focuses on different steps of evidence integration, first within and then across different streams of evidence. With respect to risk characterisation, the guidance considers how evidence from human epidemiological studies can be used in dose-response modelling with several different options being presented. Finally, the guidance addresses the application of uncertainty factors in risk characterisation when using evidence from human epidemiological studies.

Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI.

Disentangling human brain connectivity requires an accurate description of nerve fiber trajectories, unveiled via detailed mapping of axonal orientations. However, this is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer axonal connectivity because it is sensitive to axonal alignment, but it has limited spatial resolution and specificity. Scattered light imaging (SLI) and small-angle X-ray scattering (SAXS) reveal axonal orientations with microscopic resolution and high specificity, respectively. Here, we apply both scattering techniques on the same samples and cross-validate them, laying the groundwork for ground-truth axonal orientation imaging and validating dMRI. We evaluate brain regions that include unidirectional and crossing fibers in human and vervet monkey brain sections. SLI and SAXS quantitatively agree regarding in-plane fiber orientations including crossings, while dMRI agrees in the majority of voxels with small discrepancies. We further use SAXS and dMRI to confirm theoretical predictions regarding SLI determination of through-plane fiber orientations. Scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, facilitating detailed investigations of complex fiber architecture in the animal and human brain.

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering.

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods. STATEMENT OF SIGNIFICANCE: To study how the nerve fibers in our brain are interconnected, scientists need to visualize their trajectories, which often cross one another. Here, we show the unique capacity of small-angle X-ray scattering (SAXS) to study these fiber crossings without use of labeling, taking advantage of SAXS's specificity to myelin - the insulating sheath that is wrapped around nerve fibers. We use SAXS to detect double and triple crossing fibers and unveil intricate crossings in mouse, pig, vervet monkey, and human brains. This non-destructive method can uncover complex fiber trajectories and validate other less specific imaging methods (e.g., MRI or microscopy), towards accurate mapping of neuronal connectivity in the animal and human brain.

Microstructural Alterations in Tract Development in College Football and Volleyball Players: A Longitudinal Diffusion MRI Study.

BACKGROUND AND OBJECTIVES: Repeated impacts in high-contact sports such as American football can affect the brain's microstructure, which can be studied using diffusion MRI. Most imaging studies are cross-sectional, do not include low-contact players as controls, or lack advanced tract-specific microstructural metrics. We aimed to investigate longitudinal changes in high-contact collegiate athletes compared with low-contact controls using advanced diffusion MRI and automated fiber quantification. METHODS: We examined brain microstructure in high-contact (football) and low-contact (volleyball) collegiate athletes with up to 4 years of follow-up. Inclusion criteria included university and team enrollment. Exclusion criteria included history of neurosurgery, severe brain injury, and major neurologic or substance abuse disorder. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of subconcussive and concussive impacts, and associations between diffusion changes with clinical, behavioral, and sports-related measures. RESULTS: Forty-nine football and 24 volleyball players (271 total scans) were included. Football players had significantly divergent trajectories in multiple microstructural metrics and tracts. Longitudinal increases in fractional anisotropy and axonal water fraction, and decreases in radial/mean diffusivity and orientation dispersion index, were present in volleyball but absent in football players (all findings |T-statistic|> 3.5, p value <0.0001). This pattern was present in the callosum forceps minor, superior longitudinal fasciculus, thalamic radiation, and cingulum hippocampus. Longitudinal differences were more prominent and observed in more tracts in concussed football players (n = 24, |T|> 3.6, p < 0.0001). An analysis of immediate postconcussion scans (n = 12) demonstrated a transient localized increase in axial diffusivity and mean/radial kurtosis in the uncinate and cingulum hippocampus (|T| > 3.7, p < 0.0001). Finally, within football players, those with high position-based impact risk demonstrated increased intracellular volume fraction longitudinally (T = 3.6, p < 0.0001). DISCUSSION: The observed longitudinal changes seen in football, and especially concussed athletes, could reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, nondecreasing axonal dispersion. This prospective longitudinal study demonstrates divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and repeated subconcussive impact-related alteration of white matter development in football athletes.

SAXS imaging reveals optimized osseointegration properties of bioengineered oriented 3D-PLGA/aCaP scaffolds in a critical size bone defect model.

Healing large bone defects remains challenging in orthopedic surgery and is often associated with poor outcomes and complications. A major issue with bioengineered constructs is achieving a continuous interface between host bone and graft to enhance biological processes and mechanical stability. In this study, we have developed a new bioengineering strategy to produce oriented biocompatible 3D PLGA/aCaP nanocomposites with enhanced osseointegration. Decellularized scaffolds -containing only extracellular matrix- or scaffolds seeded with adipose-derived mesenchymal stromal cells were tested in a mouse model for critical size bone defects. In parallel to micro-CT analysis, SAXS tensor tomography and 2D scanning SAXS were employed to determine the 3D arrangement and nanostructure within the critical-sized bone. Both newly developed scaffold types, seeded with cells or decellularized, showed high osseointegration, higher bone quality, increased alignment of collagen fibers and optimal alignment and size of hydroxyapatite minerals.

Guidance on protocol development for EFSA generic scientific assessments.

EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the 'Draft framework for protocol development for EFSA's scientific assessments' published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub-questions is proposed: the 'APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross-cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub-questions, including uncertainty analysis. Five possible approaches to answering individual (sub-)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi-formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and - not covered in this guidance - generating empirical evidence ex novo. The guidance is complemented by a standalone 'template' for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.

Iron and Alzheimer's Disease: From Pathology to Imaging.

Alzheimer's disease (AD) is a debilitating brain disorder that afflicts millions worldwide with no effective treatment. Currently, AD progression has primarily been characterized by abnormal accumulations of ß-amyloid within plaques and phosphorylated tau within neurofibrillary tangles, giving rise to neurodegeneration due to synaptic and neuronal loss. While ß-amyloid and tau deposition are required for clinical diagnosis of AD, presence of such abnormalities does not tell the complete story, and the actual mechanisms behind neurodegeneration in AD progression are still not well understood. Support for abnormal iron accumulation playing a role in AD pathogenesis includes its presence in the early stages of the disease, its interactions with ß-amyloid and tau, and the important role it plays in AD related inflammation. In this review, we present the existing evidence of pathological iron accumulation in the human AD brain, as well as discuss the imaging tools and peripheral measures available to characterize iron accumulation and dysregulation in AD, which may help in developing iron-based biomarkers or therapeutic targets for the disease.

The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts.

Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks.

The workshop titled "Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks" was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders' trust for implementation of NAM evidence and AOPs into chemical risk assessment.

Minimum Information Required to Annotate Food Safety Risk Assessment Models (MIRARAM).

In the last decades, mathematical models and model-based simulations became important elements not only in the area of risk assessment concerning microbiological and chemical hazards but also in modelling biological phenomena in general. Unfortunately, many of the developed models are published in non-standardized ways, which hinders efficient exchange, re-use and continuous improvement of models within the risk assessment domain. The establishment of guidelines for model annotation is an important pre-condition to overcome these obstacles. Additionally, implementation of annotation guidelines can improve transparency, quality control and even aid the clarification of intellectual property rights. Here, we address the question of "What is the minimum set of metadata that should be provided for a model in the risk assessment domain?". The proposed guideline focuses on food safety risk assessment models and is called "Minimum Information Required to Annotate food safety Risk Assessment Models (MIRARAM)". MIRARAM supports the model creator during the model documentation step and could also be used as a checklist by scientific journal editors or database curators. Software developers could take up MIRARAM and develop easy-to-use software tools or new features in existing programs that can help model creators to provide proposed model annotations in harmonized file formats. Based on experiences from similar guidelines in related scientific disciplines (like systems biology), it is expected that MIRARAM could contribute to the promotion of application and re-use of models as well as to implementing more standardized quality control in the food safety modelling domain.

Toward a Comprehensive Delineation of White Matter Tract-Related Deformation.

Finite element (FE) models of the human head are valuable instruments to explore the mechanobiological pathway from external loading, localized brain response, and resultant injury risks. The injury predictability of these models depends on the use of effective criteria as injury predictors. The FE-derived normal deformation along white matter (WM) fiber tracts (i.e., tract-oriented strain) recently has been suggested as an appropriate predictor for axonal injury. However, the tract-oriented strain only represents a partial depiction of the WM fiber tract deformation. A comprehensive delineation of tract-related deformation may improve the injury predictability of the FE head model by delivering new tract-related criteria as injury predictors. Thus, the present study performed a theoretical strain analysis to comprehensively characterize the WM fiber tract deformation by relating the strain tensor of the WM element to its embedded fiber tract. Three new tract-related strains with exact analytical solutions were proposed, measuring the normal deformation perpendicular to the fiber tracts (i.e., tract-perpendicular strain), and shear deformation along and perpendicular to the fiber tracts (i.e., axial-shear strain and lateral-shear strain, respectively). The injury predictability of these three newly proposed strain peaks along with the previously used tract-oriented strain peak and maximum principal strain (MPS) were evaluated by simulating 151 impacts with known outcome (concussion or non-concussion). The results preliminarily showed that four tract-related strain peaks exhibited superior performance than MPS in discriminating concussion and non-concussion cases. This study presents a comprehensive quantification of WM tract-related deformation and advocates the use of orientation-dependent strains as criteria for injury prediction, which may ultimately contribute to an advanced mechanobiological understanding and enhanced computational predictability of brain injury.

Neuroradiologic Evaluation of MRI in High-Contact Sports.

Background and Purpose: Athletes participating in high-contact sports experience repeated head trauma. Anatomical findings, such as a cavum septum pellucidum, prominent CSF spaces, and hippocampal volume reductions, have been observed in cases of mild traumatic brain injury. The extent to which these neuroanatomical findings are associated with high-contact sports is unknown. The purpose of this study was to determine whether there are subtle neuroanatomic differences between athletes participating in high-contact sports compared to low-contact athletic controls. Materials and Methods: We performed longitudinal structural brain MRI scans in 63 football (high-contact) and 34 volleyball (low-contact control) male collegiate athletes with up to 4 years of follow-up, evaluating a total of 315 MRI scans. Board-certified neuroradiologists performed semi-quantitative visual analysis of neuroanatomic findings, including: cavum septum pellucidum type and size, extent of perivascular spaces, prominence of CSF spaces, white matter hyperintensities, arterial spin labeling perfusion asymmetries, fractional anisotropy holes, and hippocampal size. Results: At baseline, cavum septum pellucidum length was greater in football compared to volleyball controls (p = 0.02). All other comparisons were statistically equivalent after multiple comparison correction. Within football at baseline, the following trends that did not survive multiple comparison correction were observed: more years of prior football exposure exhibited a trend toward more perivascular spaces (p = 0.03 uncorrected), and lower baseline Standardized Concussion Assessment Tool scores toward more perivascular spaces (p = 0.02 uncorrected) and a smaller right hippocampal size (p = 0.02 uncorrected). Conclusion: Head impacts in high-contact sport (football) athletes may be associated with increased cavum septum pellucidum length compared to low-contact sport (volleyball) athletic controls. Other investigated neuroradiology metrics were generally equivalent between sports.

Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue.

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin's nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method's sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

Clinicopathological evaluation of downer dairy cows with fatty liver.

This study evaluated the relationship between severity of fatty liver and macromineral status in downer dairy cows and determined the usefulness of selected biochemical analytes for assessing prognosis. Blood and liver biopsy specimens were obtained from 36 Holstein downer cows shortly after the cows became recumbent and before they were treated. Liver tissue was examined histologically and serum activity of liver-derived enzymes and concentration of total lipids, triglycerides, bile acids, glucose, beta-hydroxybutyrate, acetoacetic acid, total bilirubin, non-esterified fatty acids (NEFA), cholesterol and macrominerals (Ca, Mg, K, Na, P) were determined. Fatty liver infiltration was severe in 44% of the cows and moderate in 44%. Serum activities of ornithine carbamoyltransferase and glutamate dehydrogenase, and NEFA/cholesterol ratio were good indicators of fatty liver. Cows with severe fatty liver had the lowest mean K values. The prognosis is guarded for downer cows with moderate and severe fatty liver and when total bilirubin concentration is high.

Comparison of absorbable and nonabsorbable sutures for intradermal skin closure in cats.

Paired skin incisions were made in 6 cats and closed intradermally with the copolymer of glycolide, ɛ-caprolacton, and trimethylene-carbonate, or polypropylene suture. The macroscopic and histologic appearance of the incisions was compared. Polypropylene suture compared favorably to glycolide, ɛ-caprolacton, and trimethylene-carbonate suture for closure of skin incisions in cats.