Produit de contraste | EPFL Graph Search

En , un produit (ou agent) de contraste est une substance qui augmente artificiellement le contraste permettant de visualiser une structure anatomique (par exemple, un organe) ou pathologique (par exemple, une tumeur) naturellement peu ou pas contrastée, et que l'on aurait donc du mal à distinguer des tissus voisins. Le principe de fonctionnement du produit de contraste dépend de la technique d'imagerie utilisée : en radiographie, on exploite la capacité du produit à absorber les rayons X ; en , les composés utilisés sont choisis en fonction de leurs propriétés magnétiques ; en échographie, on utilisera des substances dont l'écho aux ultrasons est caractéristique, en optique les composés émettent à une longueur d'onde donnée que l'on va détecter. Un produit de contraste peut être administré par voie entérale, anale, vaginale, urinaire ou parentérale (notamment par injection intraveineuse ou intra-articulaire). Imagerie par rayons X Pour l'imagerie par rayons X (radiog

Second harmonic scattering of water in a biological context

Tereza Schönfeldová

Water is one of the most abundant molecules in the universe. It forms a hydrogen bond network with unique structure and dynamics. Hydrogen bonding is highly relevant to many biological processes including membrane formation, protein folding, adsorption, and lubrication. However, the underlying molecular interactions within water and between water and membranes are difficult to study and hence not fully understood. In this thesis, we utilize second harmonic scattering (SHS) to investigate inhomogeneities in bulk water, probe structural changes in lipid bilayer membranes, and detect and characterize protein-membrane interactions. Firstly, we explore the structure of bulk water in comparison to a common model liquid, carbon tetrachloride. Combining SHS measurements and molecular dynamics simulations, we report on the nanoscale inhomogeneities in bulk water that occur on femtosecond timescales. We attribute the rise in the coherent second harmonic (SH) intensity to charge density fluctuations with enhanced nanoscale polarizabilities around transient voids. Even though the transient voids also exist in carbon tetrachloride, they do not show polarizability fluctuations and the SH response of carbon tetrachloride thus corresponds to that of a model isotropic liquid. Then, we study the structure of water around large unilamellar vesicles (LUVs), which serve as a model for cell membranes. We focus on the role of water during the lipid melting phase transition. Using SHS, differential scanning calorimetry, and temperature-dependent zeta-potential measurements, we investigate the structural changes of hydration shells around the vesicle membrane. We use lipids with phosphoserine, phosphocholine, and phosphate headgroups and observe different hydration behavior upon the lipid melting transition depending on the membrane composition. Next, we characterize the interface of membranes composed of lipids containing phosphocholine and phosphate headgroups in solutions with different CaCl2 concentrations. We observe that the SH intensity is decreasing with the addition of CaCl2, which we attribute to the formation of a condensed layer of Na+ counterions on the inner leaflet of the LUVs. Additionally, we extract the vesicle surface potential and second-order surface susceptibility from SHS data for membranes with different content of lipids with phosphate headgroups, and observe composition dependent behaviour which suggests structural membrane reorganization. We continue by exploring protein-membrane interactions using water as a contrast agent. We study a pore-forming toxin, perfringolysin O (PFO), known for selective insertion into cholesterol-rich membranes. Combining SHS measurements and cryo-electron microscopy, we compare the interaction between PFO and LUV membranes with a high and low cholesterol content. By obtaining a sub-picomolar insertion constant of PFO, we show that SHS can be used to determine protein-membrane binding constants in concentration ranges not accessible by conventional methods.Finally, we investigate the interaction of protein aerolysin and its mutants with lipid membranes. We observe changes in surface charge in the cap region of membrane-bound aerolysin at different pH of the surrounding solution. By combining SHS with single-channel measurements, we obtain the membrane binding constant of wild-type aerolysin and its mutants, and we dissect their pore-forming mechanism.

EPFL2022

Dinuclear gadolinium (III) chelates

Jéröme Costa

In 2003, the Nobel Assembly at the Karolinska Institute has awarded the Nobel Prize in Medicine or Physiology to Paul Lauterbur and Peter Mansfield for their seminal discoveries concerning the development of Magnetic Resonance Imaging (MRI), a non-invasive diagnosis technique notably used in medicine to visualize the human internal organs and to distinguish between healthy and pathological cells. For this purpose, contrast agents are valuable tools that enhance this distinction which is resulting from the difference in the water content of the different tissues. These drugs are used nowadays in more than 30% of the 60 millions MRI examinations performed each year. And both numbers are still growing fast. Most of the contrast agents contain a paramagnetic ion (GdIII) that accelerates the relaxation of the water protons by providing them a new relaxation pathway. Relaxivity is a way of quantifying the contrast agent efficiency and is governed by four key parameters: hydration number of the lanthanide ion, water exchange rate, electronic relaxation rate and rotational correlation time of the system. A judicious simultaneous optimization of these parameters is predicted to result in a 20-fold increase in relaxivity compared to the currently used contrast agents. In this work, with the aim of increasing the relaxivity and better understanding the involved mechanisms, the synthesis and physico-chemical characterization of new dinuclear GdIII complexes, based on thoroughly studied monomeric equivalents, were performed. We particularly stressed the outmost importance of introducing rigidity together with the increased size of the system, for a flexible assembly will hinder the relaxivity gain brought by the higher molecular weight. This rigidity is induced by using an aromatic linker between the chelating subunits or by means of the self-assembling properties of terpyridine units around FeII or RuII. We investigated the thermodynamic stability, which in crucial for toxicological reason, the spectrophotometric properties, and the rotational and water exchange dynamics of these complexes. As a result, a remarkable increase in relaxivity is obtained for all the studied compounds with respect to the clinically used actual contrast agents. Finally, insights into a promising novel class of MRI contrast agents acting simultaneously as luminescence probes are provided.

EPFL2005