| 1. |
- Casanova, Elisa A., et al.
(författare)
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SAXS imaging reveals optimized osseointegration properties of bioengineered oriented 3D-PLGA/aCaP scaffolds in a critical size bone defect model
- 2023
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 294
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Gao, Zirui, et al.
(författare)
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High-speed tensor tomography: iterative reconstruction tensor tomography (IRTT) algorithm
- 2019
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Ingår i: Acta Crystallographica Section A: Foundations and Advances. - 2053-2733. ; 75, s. 223-238
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Tidskriftsartikel (refereegranskat)abstract
- The recent advent of tensor tomography techniques has enabled tomographic investigations of the 3D nanostructure organization of biological and material science samples. These techniques extended the concept of conventional X-ray tomography by reconstructing not only a scalar value such as the attenuation coefficient per voxel, but also a set of parameters that capture the local anisotropy of nanostructures within every voxel of the sample. Tensor tomography data sets are intrinsically large as each pixel of a conventional X-ray projection is substituted by a scattering pattern, and projections have to be recorded at different sample angular orientations with several tilts of the rotation axis with respect to the X-ray propagation direction. Currently available reconstruction approaches for such large data sets are computationally expensive. Here, a novel, fast reconstruction algorithm, named iterative reconstruction tensor tomography (IRTT), is presented to simplify and accelerate tensor tomography reconstructions. IRTT is based on a second-rank tensor model to describe the anisotropy of the nanostructure in every voxel and on an iterative error backpropagation reconstruction algorithm to achieve high convergence speed. The feasibility and accuracy of IRTT are demonstrated by reconstructing the nanostructure anisotropy of three samples: a carbon fiber knot, a human bone trabecula specimen and a fixed mouse brain. Results and reconstruction speed were compared with those obtained by the small-angle scattering tensor tomography (SASTT) reconstruction method introduced by Liebi et al. [Nature (2015), 527, 349–352]. The principal orientation of the nanostructure within each voxel revealed a high level of agreement between the two methods. Yet, for identical data sets and computer hardware used, IRTT was shown to be more than an order of magnitude faster. IRTT was found to yield robust results, it does not require prior knowledge of the sample for initializing parameters, and can be used in cases where simple anisotropy metrics are sufficient, i.e. the tensor approximation adequately captures the level of anisotropy and the dominant orientation within a voxel. In addition, by greatly accelerating the reconstruction, IRTT is particularly suitable for handling large tomographic data sets of samples with internal structure or as a real-time analysis tool during the experiment for online feedback during data acquisition. Alternatively, the IRTT results might be used as an initial guess for models capturing a higher complexity of structural anisotropy such as spherical harmonics based SASTT in Liebi et al. (2015), improving both overall convergence speed and robustness of the reconstruction.
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| 3. |
- Georgiadis, Marios, et al.
(författare)
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Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Georgiadis, Panagiotis, et al.
(författare)
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DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia
- 2019
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 126, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.METHODS: We conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.RESULTS: We identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.CONCLUSIONS: This study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.
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| 5. |
- Guizar-Sicairos, Manuel, et al.
(författare)
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Validation study of small-angle X-ray scattering tensor tomography
- 2020
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Ingår i: Journal of Synchrotron Radiation. - 1600-5775 .- 0909-0495. ; 27, s. 779-787
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Liebi, Marianne, 1984, et al.
(författare)
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Small-angle X-ray scattering tensor tomography: Model of the three-dimensional reciprocal-space map, reconstruction algorithm and angular sampling requirements
- 2018
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Ingår i: Acta Crystallographica Section A: Foundations and Advances. - 2053-2733. ; 74:1, s. 12-24
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Tidskriftsartikel (refereegranskat)abstract
- Small-angle X-ray scattering tensor tomography, which allows reconstruction of the local three-dimensional reciprocal-space map within a three-dimensional sample as introduced by Liebi et al. [Nature (2015), 527, 349-352], is described in more detail with regard to the mathematical framework and the optimization algorithm. For the case of trabecular bone samples from vertebrae it is shown that the model of the three-dimensional reciprocal-space map using spherical harmonics can adequately describe the measured data. The method enables the determination of nanostructure orientation and degree of orientation as demonstrated previously in a single momentum transfer q range. This article presents a reconstruction of the complete reciprocal-space map for the case of bone over extended ranges of q. In addition, it is shown that uniform angular sampling and advanced regularization strategies help to reduce the amount of data required.The mathematical framework and reconstruction algorithm for small-angle scattering tensor tomography are introduced in detail, as well as strategies which help to reduce the amount of data and therewith the measurement time required. Experimental validation is provided for the application to trabecular bone.
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| 7. |
- Zhou, Zhou, 1990-, et al.
(författare)
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The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts
- 2022
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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