82 research outputs found

    Lifetime of magnetic excitations in supported ferromagnetic and antiferromagnetic spin-1/2 Heisenberg chains

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    The lifetime of magnetic excitations in finite 1D-supported Heisenberg chains of magnetic atoms is studied theoretically for a model system formed of S = 1/2 spins. Both ferromagnetic and antiferromagnetic cases are considered as well as open chains and rings of atoms. Different chain lengths are considered allowing extrapolation to infinite chains. All the excited magnetic states in the finite chains and rings are studied, not only the spin-wave mode. The magnetic excitations decay by electron-hole pair creation in the substrate. As the main result, for all the systems considered, the decay rate appears to vary approximately proportionally to the excitation energy of the state, with a proportionality constant independent of the strength of the Heisenberg exchange term. In certain finite systems, a stable state is evidenced at low energy, associated with a special spin coupling structure. © 2012 American Physical Society.Peer Reviewe

    Absorption reconstruction improves biodistribution assessment of fluorescent nanoprobes using hybrid Fluorescence-mediated tomography

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    Aim: Fluorescence-mediated tomography (FMT) holds potential for accelerating diagnostic and theranostic drug development. However, for proper quantitative fluorescence reconstruction, knowledge on optical scattering and absorption, which are highly heterogeneous in different (mouse) tissues, is required. We here describe methods to assess these parameters using co-registered micro Computed Tomography (µCT) data and nonlinear whole-animal absorption reconstruction, and evaluate their importance for assessment of the biodistribution and target site accumulation of fluorophore-labeled drug delivery systems.\ud \ud Methods: Besides phantoms with varying degrees of absorption, mice bearing A431 tumors were imaged 15 min and 48 h after i.v. injection of a fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) using µCT-FMT. The outer shape of mice and a scattering map were derived using automated segmentation of the µCT data. Furthermore, a 3D absorption map was reconstructed from the trans-illumination data. We determined the absorption of five interactively segmented regions (heart, liver, kidney, muscle, tumor). Since blood is the main near-infrared absorber in vivo, the absorption was also estimated from the relative blood volume (rBV), determined by contrast-enhanced µCT. We compared the reconstructed absorption with the rBV-based values and analyzed the effect of using the absorption map on the fluorescence reconstruction.\ud \ud Results: Phantom experiments demonstrated that absorption reconstruction is possible and necessary for quantitative fluorescence reconstruction. In vivo, the reconstructed absorption showed high values in strongly blood-perfused organs such as the heart, liver and kidney. The absorption values correlated strongly with the rBV-based absorption values, confirming the accuracy of the absorption reconstruction. Usage of homogenous absorption instead of the reconstructed absorption map resulted in reduced values in the heart, liver and kidney, by factors of 3.5, 2.1 and 1.4, respectively. For muscle and subcutaneous tumors, which have a much lower rBV and absorption, absorption reconstruction was less important.\ud \ud Conclusion: Quantitative whole-animal absorption reconstruction is possible and can be validated in vivo using the rBV. Usage of an absorption map is important when quantitatively assessing the biodistribution of fluorescently labeled drugs and drug delivery systems, to avoid a systematic underestimation of fluorescence in strongly absorbing organs, such as the heart, liver and kidney

    A multimodal imaging workflow for monitoring CAR T cell therapy against solid tumor from whole-body to single-cell level

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    CAR T cell research in solid tumors often lacks spatiotemporal information and therefore, there is a need for a molecular tomography to facilitate high-throughput preclinical monitoring of CAR T cells. Furthermore, a gap exists between macro- and microlevel imaging data to better assess intratumor infiltration of therapeutic cells. We addressed this challenge by combining 3D µComputer tomography bioluminescence tomography (µCT/BLT), light-sheet fluorescence microscopy (LSFM) and cyclic immunofluorescence (IF) staining. Methods: NSG mice with subcutaneous AsPC1 xenograft tumors were treated with EGFR CAR T cell (± IL-2) or control BDCA-2 CAR T cell (± IL-2) (n = 7 each). Therapeutic T cells were genetically modified to co-express the CAR of interest and the luciferase CBR2opt. IL-2 was administered s.c. under the xenograft tumor on days 1, 3, 5 and 7 post-therapy-initiation at a dose of 25,000 IU/mouse. CAR T cell distribution was measured in 2D BLI and 3D µCT/BLT every 3-4 days. On day 6, 4 tumors were excised for cyclic IF where tumor sections were stained with a panel of 25 antibodies. On day 6 and 13, 8 tumors were excised from rhodamine lectin-preinjected mice, permeabilized, stained for CD3 and imaged by LSFM. Results: 3D µCT/BLT revealed that CAR T cells pharmacokinetics is affected by antigen recognition, where CAR T cell tumor accumulation based on target-dependent infiltration was significantly increased in comparison to target-independent infiltration, and spleen accumulation was delayed. LSFM supported these findings and revealed higher T cell accumulation in target-positive groups at day 6, which also infiltrated the tumor deeper. Interestingly, LSFM showed that most CAR T cells accumulate at the tumor periphery and around vessels. Surprisingly, LSFM and cyclic IF revealed that local IL-2 application resulted in early-phase increased proliferation, but long-term overstimulation of CAR T cells, which halted the early added therapeutic effect. Conclusion: Overall, we demonstrated that 3D µCT/BLT is a valuable non-isotope-based technology for whole-body cell therapy monitoring and investigating CAR T cell pharmacokinetics. We also presented combining LSFM and MICS for ex vivo 3D- and 2D-microscopy tissue analysis to assess intratumoral therapeutic cell distribution and status

    Microbial load of rinsed and unrinsed body cavities of roe deer (Capreolus capreolus) on the killing day and after cold storage: A preliminary investigation

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    Ensuring good game meat hygiene is a challenge in the hunting supply chain. Game carcasses can be soiled with intestinal contents or other substances from the environment due to hunting and handling practices. This soiling can increase the microbial load (ML) of the carcass and the resulting game meat. The aim of this study was to investigate whether rinsing of soiled and unsoiled body cavities with drinking water can reduce the ML of carcasses. Carcasses of 23 roe deer (Capreolus capreolus) were processed, either rinsed (n = 12) or unrinsed (n = 11), and examined for ML. Swab and muscle samples were taken from the carcasses at killing day and after 3 days of cold storage. The levels of ML were comparable for the rinsed and unrinsed roe deer carcasses with an increase of Pseudomonas spp. during cold storage. Initial ML seems to be independent of visible soiling. Other factors affecting the initial ML should be determined in future studies

    Community survey results show that standardisation of preclinical imaging techniques remains a challenge

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    PURPOSE: To support acquisition of accurate, reproducible and high-quality preclinical imaging data, various standardisation resources have been developed over the years. However, it is unclear the impact of those efforts in current preclinical imaging practices. To better understand the status quo in the field of preclinical imaging standardisation, the STANDARD group of the European Society of Molecular Imaging (ESMI) put together a community survey and a forum for discussion at the European Molecular Imaging Meeting (EMIM) 2022. This paper reports on the results from the STANDARD survey and the forum discussions that took place at EMIM2022. PROCEDURES: The survey was delivered to the community by the ESMI office and was promoted through the Society channels, email lists and webpages. The survey contained seven sections organised as generic questions and imaging modality-specific questions. The generic questions focused on issues regarding data acquisition, data processing, data storage, publishing and community awareness of international guidelines for animal research. Specific questions on practices in optical imaging, PET, CT, SPECT, MRI and ultrasound were further included. RESULTS: Data from the STANDARD survey showed that 47% of survey participants do not have or do not know if they have QC/QA guidelines at their institutes. Additionally, a large variability exists in the ways data are acquired, processed and reported regarding general aspects as well as modality-specific aspects. Moreover, there is limited awareness of the existence of international guidelines on preclinical (imaging) research practices. CONCLUSIONS: Standardisation of preclinical imaging techniques remains a challenge and hinders the transformative potential of preclinical imaging to augment biomedical research pipelines by serving as an easy vehicle for translation of research findings to the clinic. Data collected in this project show that there is a need to promote and disseminate already available tools to standardise preclinical imaging practices

    Impact of the vegetation on the lignin pyrolytic signature of soil humic acids from Mediterranean soils

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    Humic acids (HAs) from 16 soils in Continental Mediterranean areas under potential vegetation consisting of sclerophyllic, mesophyllic or conifer forests in Madrid (Spain) were studied by Curie-Point pyrolysis. Statistical analyses based on the absolute and the relative abundances of the whole compound assemblages released by pyrolysis suggested that a considerable portion of the variance (inertia) associated with the vegetation was accounted for the lignin-derived compounds. In the studied samples, a set of 12 index-methoxyphenols was considered to have a discriminating potential comparable to that of the classical index phenols released from sedimentary organic matter by wet CuO alkaline oxidation. The ecological features most accurately reflected by the methoxyphenolic patterns consisted of: (i) the expected lack of syringol derivatives in HAs formed in soils under Gymnosperm plants, (ii) the diagnostic patterns of guaiacols in the HAs from soils under different species of Angiosperms (Quercus spp., Fraxinus, Castanea, grasses); (iii) the responsivity of the methoxyphenols to the extent of some types of soil perturbations: the highest environmental impact on the HA structure was found in soil after severe burning, not in the soil affected by medium-intensity fire.This research has been supported by the Spanish CICyT under grants AMB99- 0907 and AMB99-0226-02.Peer Reviewe

    Visualization of vascular remodelling after RMHV-ligation - From molecule to morphology

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