Multi-Modality Diffuse Fluorescence Imaging Applied to Preclinical Imaging in Mice

RÉSUMÉ Cette thèse vise à explorer l'information anatomique et fonctionnelle en développant de nouveaux systèmes d'imagerie de fluorescence macroscopiques à base de multi-modalité. L‘ajout de l‘imagerie anatomique à des modalités fonctionnelles telles que la fluorescence permet une meilleure visualisation et la récupération quantitative des images de fluorescence, ce qui en retour permet d'améliorer le suivi et l'évaluation des paramètres biologiques dans les tissus. Sur la base de cette motivation, la fluorescence a été combinée avec l‘imagerie ultrasonore (US) d'abord et ensuite l'imagerie par résonance magnétique (IRM). Dans les deux cas, les performances du système ont été caractérisées et la reconstruction a été évaluée par des simulations et des expérimentations sur des fantômes. Finalement, ils ont été utilisés pour des expériences d'imagerie moléculaire in vivo dans des modèles de cancer et d‘athérosclérose chez la souris. Les résultats ont été présentés dans trois articles, qui sont inclus dans cette thèse et décrits brièvement ci-dessous. Un premier article présente un système d'imagerie bimodalité combinant fluorescence à onde continue avec l‘imagerie à trois dimensions (3D) US. A l‘aide de stages X-Y motorisés, le système d'imagerie a été en mesure de recueillir l‘émission fluorescente et les échos acoustiques délimitant la surface 3D et la position des inclusions fluorescentes dans l'échantillon. Une validation sur fantômes, a montré que l'utilisation des priors anatomiques provenant des US améliorait la qualité de la reconstruction fluorescente. En outre, un étude pilote in-vivo en utilisant une souris Apo-E a évalué la faisabilité de cette approche d'imagerie double modalité pour de futures études pré-cliniques. Dans un deuxième effort, et sur la base du premier travail, nous avons amélioré le système d'imagerie par fluorescence-US au niveau des algorithmes, de la précision----------ABSTRACT This thesis aims to explore the anatomical and functional information by developing new macroscopic multi-modality fluorescence imaging schemes. Adding anatomical imaging to functional modalities such as fluorescence enables better visualization and recovery of fluorescence images, in turn, improving the monitoring and assessment of biological parameters in tissue. Based on this motivation, fluorescence was combined with ultrasound (US) imaging first and then magnetic resonance imaging (MRI). In both cases, the systems characterization and reconstruction performance were evaluated by simulations and phantom experiments. Eventually, they were applied to in vivo molecular imaging in models of cancer and atherosclerosis in mice. Results were presented in three peer-reviewed journals, which are included in this thesis and shortly described below. A first article presented a dual-modality imaging system combining continuous-wave transmission fluorescence imaging with three dimensional (3D) US imaging. Using motorized X-Y stages, the fluorescence-US imaging system was able to collect boundary fluorescent emission, and acoustic pulse-echoes delineating the 3D surface and position of fluorescent inclusions within the sample. A validation in phantoms showed that using the US anatomical priors, the fluorescent reconstruction quality was significantly improved. Furthermore, a pilot in-vivo study using an Apo-E mouse evaluated the feasibility of this dual-modality imaging approach for future animal studies. In a second endeavor, and based on the first work, we improved the fluorescence-US imaging system in terms of sampling precision and reconstruction algorithms. Specifically, now combining US imaging and profilometry, both the fluorescent target and 3D surface of sample could be obtained in order to achieve improved fluorescence reconstruction. Furthermore,

In Situ Mineralization of Magnetite Nanoparticles in Chitosan Hydrogel

Based on chelation effect between iron ions and amino groups of chitosan, in situ mineralization of magnetite nanoparticles in chitosan hydrogel under ambient conditions was proposed. The chelation effect between iron ions and amino groups in CS–Fe complex, which led to that chitosan hydrogel exerted a crucial control on the magnetite mineralization, was proved by X-ray photoelectron spectrum. The composition, morphology and size of the mineralized magnetite nanoparticles were characterized by X-ray diffraction, Raman spectroscopy, transmission electron microscopy and thermal gravity. The mineralized nanoparticles were nonstoichiometric magnetite with a unit formula of Fe2.85O4and coated by a thin layer of chitosan. The mineralized magnetite nanoparticles with mean diameter of 13 nm dispersed in chitosan hydrogel uniformly. Magnetization measurement indicated that superparamagnetism behavior was exhibited. These magnetite nanoparticles mineralized in chitosan hydrogel have potential applications in the field of biotechnology. Moreover, this method can also be used to synthesize other kinds of inorganic nanoparticles, such as ZnO, Fe2O3and hydroxyapatite

Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting antitumor nanovehicle in vitro

A synthetic method to prepare a core-shell-structured Fe(3)O(4)@SiO(2) as a safe nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron oxide is encapsulated inside nonporous silica as the core to provide magnetic targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell and renders new and improved functions because of the original biocompatible properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the nanovehicle was assayed by confocal laser scanning microscope using rhodamine B (RB) as a fluorescent marker in HeLa cells. The results show that the surface modification of the core-shell silica nanovehicle with OCMCS-FA enhances the internalization of nanovehicle to HeLa cells which over-express the folate receptor. The cell viability assay demonstrated that Fe(3)O(4)@SiO(2)-OCMCS-FA nanovehicle has low toxicity and can be used as an eligible candidate for drug delivery system. These unique advantages make the prepared core-shell nanovehicle promising for cancer-specific targeting and therapy

Regional variation in NAFLD prevalence and risk factors among people living with HIV in Europe: a meta-analysis

Background and Aim: Europe faces an elevated risk of nonalcoholic fatty liver disease (NAFLD) among people living with HIV (PLWH), contributing to the region’s highest global burden of NAFLD. However, the prevalence of NAFLD across various European countries and regions remains unclear. This study aims to investigate the prevalence and risk factors associated with NAFLD among PLWH across European countries. Methods: A systematic search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane Library. Data on the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, as well as the associated risk factors, were collected among PLWH in Europe. Results: Thirty-six studies from 13 European nations were included. The prevalence of NAFLD, NASH, and fibrosis were 42% (95%CI 37–48), 35% (95%CI 21–50) and 13% (95%CI 10–15), respectively. Male gender, BMI, waist circumference, Diabetes, hypertension, metabolic syndrome, dyslipidemia, triglycerides, HDL, LDL, ALT, AST, and years on antiretroviral therapy (ART) were found to be risk factors for NAFLD. High BMI and triglycerides were associated with NASH. Patients with high BMI and triglycerides are at increased risk of significant liver fibrosis. Conclusion: The high prevalence of NAFLD, NASH, and fibrosis among PLWH in Europe highlights the need for early screening, intervention, and increased research focus on adolescents living with HIV. Furthermore, the significant variations observed between countries and regions underscore the influence of related risk factors

Quantitative evaluation of gut microbiota composition in pancreatic cancer: a pooled study

Background: Prior research has demonstrated a positive association between the composition of gut microbiota and the incidence of pancreatic cancer. Nevertheless, a thorough quantitative and systematic evaluation of the distinct properties of gut microbiota in individuals diagnosed with pancreatic cancer has yet to be conducted. The objective of this study is to examine alterations in the diversity of intestinal microbiota in individuals diagnosed with pancreatic cancer. Methods: Search for relevant literature published before July 2023 in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library, without any language restrictions. Results: A total of 12 studies were included, including 535 patients with pancreatic cancer and 677 healthy controls. Analysis was conducted on 6 phyla, 16 genera, and 6 species. The study found significant and distinctive changes in the α-diversity of gut microbiota, as well as in the relative abundance of multiple gut bacterial groups at the phylum, genus, and species levels in pancreatic cancer patients. Conclusion: Overall, there are certain characteristic changes in the gut microbiota of pancreatic cancer patients. However, further research is warranted to elucidate the specific mechanism of action and the potential for treatment

Research on new energy vehicle charging prediction based on Monte Carlo algorithm and its impact on distribution network

With the vigorous promotion of new energy policies, the large-scale charging of new energy vehicles has put forward higher requirements for the safety and stability of the distribution network. Based on the daily driving habits and charging patterns of new energy vehicles, a Monte Carlo sampling algorithm was used to establish a charging load model for new energy vehicles. The model analyzed the driving range, charging load, and time related parameters of new energy vehicles. By analyzing the law of daily charging power of new energy vehicles, the overall trend of charging load of new energy vehicles is obtained. Combined with the daily electricity consumption law of the distribution network, the total load of the distribution network is obtained, and the degree of impact on the distribution network is analyzed. This provides direction for the scheduling of future electric vehicle charging behavior and the construction of related supporting facilities, and provides strong guidance for the optimization and upgrading of the distribution network

Atherosclerosis is associated with a decrease in cerebral microvascular blood flow and tissue oxygenation

Chronic atherosclerosis may cause cerebral hypoperfusion and inadequate brain oxygenation, contributing to the progression of cognitive decline. In this study, we exploited two-photon phosphorescence lifetime microscopy to measure the absolute partial pressure of oxygen (PO2) in cortical tissue in both young and old LDLR-/-, hApoB100+/+ mice, spontaneously developing atherosclerosis with age. Capillary red-blood-cell (RBC) speed, flux, hematocrit and capillary diameter were also measured by two-photon imaging of FITC-labelled blood plasma. Our results show positive correlations between RBC speed, flux, diameter and capillary-adjacent tissue PO2. When compared to the young mice, we observed lower tissue PO2, lower RBC speed and flux, and smaller capillary diameter in the old atherosclerotic mice. The old mice also exhibited a higher spatial heterogeneity of tissue PO2, and RBC speed and flux, suggesting a less efficient oxygen extraction

Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: a network meta-analysis

Objective: This study aimed to assess the efficacy of currently used anti-diabetic medications in the treatment of non-alcoholic fatty liver disease (NAFLD) without diabetes. DESIGN: The efficacy of various anti-diabetic medicines on non-alcoholic fatty liver disease in the absence of diabetes was evaluated by searching Pubmed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCT) only. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2), and the data were analyzed using Stata software (version 15.1). Results: All papers published between the time of the pooling and September 2022 were searched. There were a total of 18 randomized controlled studies with a total sample size of 1141 cases. The outcomes of interest included variations in alanine transaminase (ALT) and aspartate transaminase (AST). Rosiglitazone (SUCRA: 100%) and vildagliptin (SUCRA: 99.9%) were the best anti-diabetic medicines to improve ALT and AST, respectively, in patients with NAFLD without diabetes, according to the findings of this network meta-analysis. Conclusion: In accordance with the Network Ranking plot, Rosiglitazone was the best anti-diabetic medicine for improving ALT, and vildagliptin was the best for improving AST in patients with non-diabetic NAFLD