Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent

Background. The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods. The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs) (iron(II);iron(III);octadecacyanide) doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3) were calculated from the SPECT scans for each dedicated volume of interest (VOI) of liver, kidneys, salivary glands, heart, lungs, and brain. Results. PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion. We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications

Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data

BACKGROUND: Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. METHODS: To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. RESULTS: Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. CONCLUSIONS: A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas

Multimodáls (RTG CT/SPECT/PET/MRI) in vivo képalkotás eredményeinek radiomikai kiértékelése állatkísérletes modellekben

Multimodal in vivo (X-ray CT/SPECT/PET/MRI) fusion hybrid imaging provides quantitative, comparable, sensitive, longitudinal and robust data, revealing important anatomical and functional information, respectively. Radiomics data handling and evaluation is an approach to increase further the biological value of information obtained by in vivo imaging. These data can be either morphologic, results of biochemical reactions, as well as positions of moving organ’s time-related information. The purpose of radiomics is to increase reliability, precision, accuracy or robustness of data, or decrease sample number, respectively. The main goal of this study, was to examine and present a spectrum of radiomics-based imaging in animal experiments, with the opportunity to adapt it to individual clinical imaging or monitoring of environmental systems, respectively. In developed countries the diseases of locomotor- and the respiratory- system are among the major public health problems. The latter is exacerbated by air pollution. Apart from that, environmental pollution is continuously growing and it exerts harmful effects on mankind in multifarious ways. According to the estimations in 2004 in the US leading to approximately 1.5 million fractures, which required bone grafting in ca. 500.000 cases. According to the WHO in 2012 around 7 million people died as a result of air pollution, including 3.1 million premature deaths caused by indoor and urban outdoor air pollution. In 2016 the air pollution is estimated to reduce the average global life expectancy with 1 year. According to the EPA sulfur dioxide and ground-level ozone precursors (nitrogen oxides and volatile organic compounds) derived mainly from fuel combustion are among the most frequent health hazards. Mineral oil and heavy metals are waste products mostly of municipal, industrial and commercial sectors and they represent 60% of soil pollution. Among them Cd has the ability to accumulate with biomagnification process, the excretion of Cd is very slow but its deleterious effects are severe and multifarious. Therefore possible contamination with Cd requires to be minimized. Our research group has established in vivo animal models utilizing radiomicsbased evaluation to elucidate details of bone formation (bone graft healing) and airpollution related lung diseases. Also a novel in vivo imaging approach to detect the effect of soil pollutant Cd in earthworm (Eisenia hortensis and Lumbricus terrestris) was developed. Utilizing X-ray CT and MDP SPECT with radiomics-based evaluation enabled the statistically significant discerning of poly (methyl methacrylate)-based bone cement graft (PMMA) and albumin coated, sterilized, antigen-extracted freezedried human bone grafts (HLBC). With X-ray CT reconstructed attenuation corresponding specific voxel's fractal dimension distribution profile, abstracted their quantity with histograms, separated to Gaussian-curves with calculated descriptive parameters, the discerning from each other of a sulfur dioxide gas exposed, of an airdiluted fresh mainstream cigarette smoke mixed with ozone-air gas mixture treated, and also of a control group was enabled. Using in vivo earthworms, after proper immobilization, the early effect of Cd pollution was revealed with FDG PET/MRI modalities. Multiple testing with the same animal, combined with radiomics-based evaluation methods increased cost-effectivity and decreased the necessary sample number of animals, in coherence with the European Union (EU) directive 2010/63/EU on the protection of animals. The health hazards and diseases investigated in the present work are prime examples of high individual and societal costs both in quality of life and in financial sense. The combination of screening, imaging and radiomics-based monitoring offers and effective opportunity to diagnose early and treat properly the lung or bone diseases and also to minimize the exposure of environmental pollutions. Moreover the bone formation evaluation method as well as the attenuation value correlated FD distribution pattern analysis of the chest X-ray CT may be even adapted into clinical practice to monitor surgical, pharmaceutical, and physical therapies. The developed earthworm test system may enhance the required strict environmental monitoring. This can even underpin decisions to decrease Cd concentration with the extensive and costly soil replacement intervention, if it is necessary. The thesis also leads the way to further more widespread studies both in clinical prevention and environmental protection enhanced by radiomics evaluation methods of image data

Novel radiomics evaluation of bone formation utilizing multimodal (SPECT/X-ray CT) in vivo imaging.

Although an extensive research is being undertaken, the ideal bone graft and evaluation method of the bone formation draw still a warranted attention. The purpose of this study was to develop a novel multimodal radiomics evaluation method, utilizing X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) with Tc-99m-Methyl diphosphonate (Tc-99m-MDP) tracer. These modalities are intended to provide quantitative data concerning the mineral bone density (after evaluation it is referred to as opacity) and the osteoblast activity, at the same time. The properties of bone formation process within poly (methyl methacrylate)-based bone cement graft (PMMA) was compared to that of albumin coated, sterilized, antigen-extracted freeze-dried human bone grafts (HLBC), in caudal vertebrae (C5) of rats. The animals were scanned at 3 and 8 weeks after surgery. In both groups, the mean opacity increased, while the mean Tc-99m-MDP activity decreased. The later parameter was significant (n = 4, p = 0.002) only in HLBC group. The linear regression analysis of PMMA-treated group variables (mean opacity increase; mean Tc-99m-MDP activity decrease), revealed a negative correlation with the medium strength (r = 0.395, p = 0.605). Whereas, it showed strong positive correlation when HLBC group variables were analyzed (r = 0.772, p = 0.012). These results indicate that using HLBC grafts is advantageous in terms of the osteoblast activity and bone vascularization over PMMA cement. Using this regression analysis method, we were able to distinguish characteristics that otherwise could not be distinguished by a regular data analysis. Hence, we propose utilizing this novel method in preclinical tests, and in clinical monitoring of bone healing, in order to improve diagnosis of bone-related diseases

Additional file 1: of Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data

Lists of the numerical features of the Gaussian curves for every mouse. (DOC 36 kb