Imagerie par résonance magnétique

L'imagerie par résonance magnétique (IRM) est une technique d' permettant d'obtenir des vues en deux ou en trois dimensions de l'intérieur du corps de façon non invasive avec une résolution en contraste relativement élevée. L'IRM repose sur le principe de la résonance magnétique nucléaire (RMN) qui utilise les propriétés quantiques des noyaux atomiques pour la spectroscopie en analyse chimique. L'IRM nécessite un champ magnétique puissant et stable produit par un aimant supraconducteur qui crée une magnétisation des tissus par alignement des moments magnétiques de spin. Des champs magnétiques oscillants plus faibles, dits « radiofréquence », sont alors appliqués de façon à légèrement modifier cet alignement et produire un phénomène de précession qui donne lieu à un signal électromagnétique mesurable. La spécificité de l'IRM consiste à localiser précisément dans l'espace l'origine de ce signal RMN en appliquant des champs magnétiques non uniformes, des « gradients », qui vont induire

Stem cell-based cardiovascular tissue engineering

Thomas Krähenbühl

Cardiovascular diseases, including myocardial infarction, are the leading cause of death worldwide for both men and women. Current therapies are limited by the restricted intrinsic regeneration capacity of the heart and by the lack of organs for transplantation. Human embryonic stem (hES) cells have the capacity to differentiate into various cell types, including vascular cells for forming de novo blood vessels to potentially repair the infarcted heart after myocardial infarction. Our goal was to improve cardiac function after myocardial infarction through hES-based cardiovascular tissue engineering. Our findings summarized: Improved cardiac performance, attenuated left ventricular dilation and decreased infarct size in infarcted rats can be attained after co-injection of hES-derived vascular cells and Thymosin β4 (Tβ4) in matrix metalloproteinase (MMP)-responsive hydrogels. Enhanced vascular cell adhesion, survival and organization can be achieved when coencapsulating bioactive peptide Tβ4 in MMP-responsive matrix in vitro. Directed cardiac differentiation of pluripotent cells can be influenced by matrix elasticity, adhesion ligand concentration and MMP-sensitivity in vitro. We first systematically modulated a three-dimensional (3D) MMP-responsive hydrogel, mimicking key biochemical characteristics of natural collagenous matrices, the major constituent of cardiac extracellular matrices. We found that these synthetic poly(ethylene glycol) (PEG)-based hydrogels can direct differentiation of pluripotent cardioprogenitors, using P19 embryonal carcinoma (EC) cells as a model, along a cardiac lineage in vitro. In order to systematically probe 3D matrix effects on P19 EC differentiation, matrix elasticity, MMP-sensitivity and the concentration of a matrix-bound RGDSP peptide, which is relevant in early cardiac developments were modulated. Soft matrices (E = 320 ± 64 Pa), mimicking the elasticity of embryonic cardiac tissue, increased the fraction of cells expressing the early cardiac transcription factor Nkx2.5 around 2-fold compared to embryoid bodies (EB) in suspension. In contrast, stiffer matrices (E = 4040 ± 420 Pa) decreased the number of Nkx2.5-positive cells significantly. Further indicators of cardiac maturation were promoted by ligation of integrins relevant in early cardiac development (α5β1, αvβ3) by the RGDSP ligand in combination with the MMP-sensitivity of the matrix, with a 6-fold increased amount of myosin heavy chain (MHC)-positive cells as compared to EB in suspension. This precisely controlled 3D culture system thus may serve as a potential alternative to natural matrices for engineering cardiac tissue structures for cell culture and potentially therapeutic applications. Neovascularization of infarcted tissue is a promising alternative strategy to potentially restoring lost contractile performance by cardiac cells. Vascular cells and cytokines are known to contribute to the protection of cardiomyocytes from death after myocardial infarction, but also in endogenous recruitment of vascular cells and even cardiomyocytes. The in vitro potential of the synthetic MMP-responsive PEG-hydrogel as a bioactive co-encapsulation system for vascular cells and a small bioactive peptide, Tβ4, was then examined. Tβ4 was previously shown to enhance survival of vascular cells and cardiomyocytes in ischemic environments, stimulate neovascularization after cardiac injury by inducing endogenous endothelial cell migration to the ischemic site, as well as play a key role in down-regulating expression of inflammatory molecules. We show that the physical incorporation of Tβ4 in this bioactive matrix creates a 3D environment conducive for human umbilical vein endothelial cell (HUVEC) adhesion, survival, migration and organization. Gels with entrapped Tβ4 increased the survival of HUVEC compared to gels without Tβ4 (p < 0.05), and significantly up-regulated the endothelial genes vascular endothelial-cadherin and angiopoietin-2, whereas the von Willebrand factor was significantly down-regulated (all p < 0.05). Incorporation of Tβ4 significantly increased MMP-2 and MMP-9 secretion of encapsulated HUVEC (p < 0.05). The gel acts as a controlled Tβ4-release system, as MMP-2 and MMP-9 enzymes trigger the release. In addition, Tβ4 facilitated HUVEC attachment and induced vascular-like network formation upon the PEG-hydrogels. These MMP-responsive PEG-hydrogels may thus serve as controlled co-encapsulation system of vascular cells and bioactive factors for in situ regeneration of ischemic tissues. Finally, we employed these injectable MMP-responsive bioactive hydrogels with vasculo-typic adhesion molecule as a provisional in situ reservoir of vascular cells derived from hES cells and Tβ4 peptide, in infarcted hearts. Typically, after myocardial infarction, the performance-generating contractile cardiac tissue is partially replaced by non-contractile fibrotic tissue, driven by upregulated enzymes such as MMP. Here, magnetic resonance imaging (MRI) revealed enhanced contractile performance 3 days and 6 weeks after myocardial infarction (both p < 0.001), attenuated left ventricular dilation (p < 0.05) and decreased infarct size at 6 weeks (p < 0.05) as compared to infarcted rats with PBS injection. . We found the gel substituting the native degrading extracellular matrix in the infarcted myocardium and promoting structural organization of endothelial cells and cardiomyocytes, while the delivered hES-derived vascular cells formed de novo capillaries in the infarct zone.

EPFL2009

From volumetric graphical objects to surface registration

Eduardo Solanas Vilar

Relatively recent developments in medical imaging allow the anatomical and functional noninvasive study of internal organs of the body. One of the most complex and interesting organs in our body is the brain. Many efforts are being carried out to try to understand how it works, its internal connections, how different zones interact with each other, why, in some cases, a zone takes in charge a functionality of another damaged one, etc.; the questions are innumerable and the answers, if any, are sparse. Recently, magnetic resonance imaging (MRI) equipments have been developed to capture the functional activity of the brain. Unfortunately, functional images suffer from a lack of spatial resolution. Thus, the need of combining them with anatomical ones, which have a much higher quality. Nowadays these images provide precious information for diagnosis purposes and this is the reason for the need of imaging tools to extract and analyze the information which is present in those images, and which sometimes is not appreciable for the human eye. Acquired MRI images are presented as volumetric sets of data with which one can reconstruct a three dimensional volumetric model of the scanned organ. Nevertheless, sometimes physicians are just interested in the surface of the organ, for example in brain functional activation studies. In addition, many times it is important to be able to carry out group studies, or to locate a lesion with respect to a standard reference. To do such studies it is necessary to perform a transformation of the surfaces in order to put them into correspondence. Such technique is called registration. Unfortunately, volumetric registration does not give satisfactory results for surface registration purposes. The solution is to work directly with surfaces instead of processing the volumetric data. Unfortunately we do not have information about the surfaces, hence the need of computer graphics and computer vision techniques. The present work proposes a number of methods to help in the task of providing information from volumetric objects to surface registration. To achieve that some stages are necessary. The proposed stages are independent one from another so they can be used, or not, depending on the particular need. They can even be used for other purposes than those presented in the present work. The first two stages address the problem of image quality. This is a very important "preprocessing" step because posterior processing will depend on the image quality. Usually MR images are corrupted with different artifacts; among them a spatial-dependent bias field and a Riciandistributed noise. For the former a supervised correction is proposed, and for the later a directional spatial filter using a novel diffusivity function. After both stages the volumetric MRI data is ready to be classified. The purpose of the proposed classification process is to extract the white matter of the brain, given that sulci are better extracted from white matter than from the gray one. So far we have handled volumetric data, the next stage is concerned with the registration of the reconstructed white matter surface. This is achieved by means of a hierarchical representation of brain's sulci using level sets. The hierarchical representation and surface registration are carried out using the theory of partial differential equations (PDE) and level set methods. Validation studies are carried out independently in order to show the performance of the proposed approaches. Also a full scheme is proposed with the aim of presenting a complete approach from volumetric objects to surface registration.

EPFL2004

Using medical images acquired during routine clinical care for research purposes: a comprehensive medical informatics approach applied to the study of brain development from birth through 2 years of age as indexed by diffusion MRI

Vincent Alexis Roch

Biologic variability and dramatic changes of brain development in children aged 0 to 2 years make it challenging to accurately detect subtle abnormalities in single Magnetic Resonance Imaging (MRI) scans. Diffusion MRI (dMRI) indices such as Apparent Diffusion Coefficient (ADC) are reliable measures of water content in the brain and thus an excellent surrogate marker for brain development. Developing robust age-specific diffusion biomarkers for quantitative measurement of normative brain evolution would enhance our ability to detect subtle alterations due to tissue injuries or neuropathological disorders. Obtaining significant numbers of normative MRI scans for this age group means redirecting clinical data from hospital databases for research purposes. Therefore, this pilot project demonstrates the feasibility of identifying, retrieving and analyzing pediatric clinical dMRI data to investigate normal brain development from birth to 2 years. Research Patient Data Registry (RPDR) at Massachusetts General Hospital (MGH) was used to collect patient medical information and identify healthy children according to radiology reports. Corresponding MRI data were retrieved from MGH Picture Archiving and Communication System (PACS) using the prototype of Medical Imaging Informatics Bench to Bedside (mi2b2) software. A specific pipeline was created to handle the volume of studies and extract technical scan information used to identify comparable diffusion series; 193 studies were used for analysis. Two markers, whole brain average of ADC and Fractional Anisotropy (FA) values (WBAADC and WBAFA), were computed for each patient, their age-evolution across patients was investigated with different models. WBAADC and WBAFA seem to exhibit biexponential decay and increase respectively and might be gender-specific. These results have clinical implications for potentially determining the health status of an unknown individual, and research utility for continued development of these tools.

2011