A nanoparticle ink allowing the high precision visualization of tissue engineered scaffolds by MRI

Hydrogels are widely used as cell scaffolds in several biomedical applications. Once implanted in vivo, cell scaffolds must often be visualized, and monitored overtime. However, cell scaffolds appear poorly contrasted in most biomedical imaging modalities such as magnetic resonance imaging (MRI). MRI is the imaging technique of choice for high-resolution visualization of low-density, water-rich tissues. Attempts to enhance hydrogel contrast in MRI are performed with “negative” contrast agents that produce several image artifacts impeding the delineation of the implant’s contours. In this study, a magnetic ink based on ultra-small iron oxide nanoparticles (USPIONs; <5 nm diameter cores) is developed and integrated into biocompatible alginate hydrogel used in cell scaffolding applications. Relaxometric properties of the magnetic hydrogel are measured, as well as biocompatibility and MR-visibility (T1-weighted mode; in vitro and in vivo). A 2-week MR follow-up study is performed in the mouse model, demonstrating no image artifacts, and the retention of “positive” contrast overtime, which allows very precise delineation of tissue grafts with MRI. Finally, a 3D-contouring procedure developed to facilitate graft delineation and geometrical conformity assessment is applied on an inverted template alginate pore network. This proof-of-concept establishes the possibility to reveal precisely engineered hydrogel structures using this USPIONs ink high-visibility approach

Finding the refraction law using the ant colony algorithm and the Fermat’s principle

info:eu-repo/semantics/publishe

Monte Carlo simulations of the magnetic behaviour of iron oxide nanoparticle ensembles : taking size dispersion, particle anisotropy, and dipolar interactions into account

In this work, the magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) submitted to an external magnetic field are studied using a Metropolis algorithm. The influence on the M(B) curves of the size distribution of the nanoparticles, of uniaxial anisotropy, and of dipolar interaction between the cores are examined, as well as the influence of drying the samples under a zero or non-zero magnetic field. It is shown that the anisotropy impacts the shape of the magnetization curves, which then deviate from a pure Langevin behaviour, whereas the dipolar interaction has no influence on the curves at 300 K for small particles (with a radius of $$3\,\hbox {nm}$$). The fitting of the magnetization curves of particles with magnetic anisotropy to a Langevin model (including a size distribution of the particles) can then lead to erroneous values of the distribution parameters. The simulation results are qualitatively compared to experimental results obtained for iron oxide nanoparticles (with a $$3.21\, \hbox {nm}$$ median radius)

Improvement of the Off-Resonance Saturation, an MRI sequence for positive contrast with SPM particles: Theoretical and experimental study

The SuperParaMagnetic particles (SPM particles) are used as contrast agents in MRI and produce negative contrast with conventional T2 or T2(∗)-weighted sequences. Unfortunately, the SPM particle detection on images acquired with such sequences is sometimes difficult because negative contrast can be created by artifacts such as air bubbles or calcification. To overcome this problem, new sequences as Off-Resonance Saturation (ORS) were developed to produce positive contrast with SPM particles. This work explores a new way to optimize the contrast generated by the ORS sequence by increasing the number of saturation pulses applied before the imaging sequence. This modified sequence is studied with numerical simulations and experiments on agarose gel phantoms. A theoretical model able to predict the contrast for different values of the sequence parameters is also developed. The results show that the contrast increases with the saturation pulses number with an optimal value of three saturation pulses in order to avoid artifacts and limit the Specific Absorption Rate (SAR) effect. The dependence of the contrast on the SPM particle concentration and sequence parameters is comparable to what was observed for the ORS sequence

Effect of magnetic field and iron content on NMR proton relaxation of liver, spleen and brain tissues

Iron accumulation is observed in liver and spleen during hemochromatosis and important neurodegenerative diseases involve iron overload in brain. Storage of iron is ensured by ferritin, which contains a magnetic core. It causes a darkening on T2-weighted MR images. This work aims at improving the understanding of the NMR relaxation of iron-loaded human tissues, which is necessary to develop protocols of iron content measurements by MRI. Relaxation times measurements on brain, liver and spleen samples were realized at different magnetic fields. Iron content was determined by atomic emission spectroscopy. For all samples, the longitudinal relaxation rate (1/T1) of tissue protons decreases with the magnetic field up to 1 T, independently of iron content, while their transverse relaxation rate (1/T2) strongly increases with the field, either linearly or quadratically, or a combination thereof. The extent of the inter-echo time dependence of 1/T2 also varies according to the sample. A combination of theoretical models is necessary to describe the relaxation of iron-containing tissues. This can be due to the presence, inside tissues, of ferritin clusters of different sizes and densities. When considering all samples, a correlation (r2 SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Bottom-up study of the MRI positive contrast created by the Off-Resonance Saturation sequence

Superparamagnetic iron oxide nanoparticles (SPM particles) are used in MRI to highlight regions such as tumors through negative contrast. Unfortunately, sources as air bubbles or tissues interfaces also lead to negative contrast, which complicates the image interpretation. New MRI sequences creating positive contrast in the particle surrounding, such as the Off-Resonance Saturation sequence (ORS), have thus been developed. However, a theoretical study of the ORS sequence is still lacking, which hampers the optimization of this sequence. For this reason, this work provides a self-consistent analytical expression able to predict the dependence of the contrast on the sequence parameters and the SPM particles properties. This expression was validated by numerical simulations and experiments on agarose gel phantoms on a 11.7 T scanner system. It provides a fundamental understanding of the mechanisms leading to positive contrast, which could allow the improvement of the sequence for future in vivo applications. The influence of the SPM particle relaxivities, the SPM particle concentration, the echo time and the saturation pulse parameters on the contrast were investigated. The best contrast was achieved with SPM particles possessing the smallest transverse relaxivity, an optimal particle concentration and for low echo times

Theoretical and experimental study of ON-Resonance Saturation, an MRI sequence for positive contrast with superparamagnetic nanoparticles

Superparamagnetic iron oxide nanoparticles (SPM particles) are widely used in MRI as negative contrast agents. Their detection is sometimes difficult because negative contrast can be caused by different artifacts. To overcome this problem, MRI protocols achieving positive contrast specific to SPM particles were developed such as the ON-Resonance Saturation (ONRS) sequence. The aim of the present work is to achieve a bottom-up study of the ONRS sequence by an understanding of the physical mechanisms leading to positive contrast. A complete theoretical modeling, a novel numerical simulation approach and experiments on agarose gel phantoms on a 11.7 T MRI system were carried out for this purpose. The influence of the particle properties and concentration - as well as the effect of the sequence parameters on the contrast - were investigated. It was observed that theory and experiments were in strong agreement. The tools developed in this work allowed to predict the parameters leading to the maximum contrast. For example, particles presenting a low transverse relaxivity can provide an interesting positive contrast after optimization of their concentration in the sample