Other
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LanguagesSpanish, English, French, Catalan/Valencian
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Scientific MembershipsIEEE EMBS
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Journal RefereesMedical Physics
Publications (104) View all
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Article: Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models.
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ABSTRACT: The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients.Journal of the American College of Cardiology 05/2012; 59(18):1629-41. · 14.16 Impact Factor -
Article: Surface mobility regulates skeletal stem cell differentiation.
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ABSTRACT: A family of polymer substrates which consists of a vinyl backbone chain with the side groups -COO(CH(2))(x)H, with x = 1, 2, 4, was prepared. Substrates with similar chemical groups but decreasing stiffness, characterized by their elastic modulus at 37 °C, as well as surface mobility, characterized by the glass transition temperature, were obtained. We have investigated whether these subtle variations in polymer chemistry lead to alterations in fibronectin (FN) adsorption and mesenchymal stem cell response. The same FN density was adsorbed on every substrate (∼450 ng cm(-2)) although the supramolecular organization of the protein at the material interface, as obtained with AFM, was different for x = 1 and the other two surfaces (x = 2, 4). Consequently, this allows one to investigate the effect of physical properties of the matrix on stem cell differentiation after ruling out any influence of protein activity. Cell adhesion was quantified by calculating the size distribution of focal adhesions. Mesenchymal stem cell differentiation to the osteoblastic lineage was determined by quantifying protein levels for osteocalcin, osteopontin and Runx2, in the absence of any additional osteogenic soluble factors in the culture media, but as a direct effect of material properties. The findings indicate the potential to modulate skeletal progenitor cell commitment to the osteoblastic lineage through surface mobility of the underlying material surface.Integrative Biology 03/2012; 4(5):531-9. · 4.51 Impact Factor -
Article: Effect of topological cues on material-driven fibronectin fibrillogenesis and cell differentiation.
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ABSTRACT: Fibronectin (FN) assembles into fibrillar networks by cells through an integrin-dependent mechanism. We have recently shown that simple FN adsorption onto poly(ethyl acrylate) surfaces (PEA), but not control polymer (poly(methyl acrylate), PMA), also triggered FN organization into a physiological fibrillar network. FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules. In the present study, we investigate the influence of topological cues on the material-driven FN assembly and the myogenic differentiation process. Aligned and random electrospun fibers were prepared. While FN fibrils assembled on the PEA fibers as they do on the smooth surface, the characteristic distribution of globular FN molecules observed on flat PMA transformed into non-connected FN fibrils on electrospun PMA, which significantly enhanced cell differentiation. The direct relationship between the fibrillar organization of FN at the material interface and the myogenic process was further assessed by preparing FN gradients on smooth PEA and PMA films. Isolated FN molecules observed at one edge of the substrate gradually interconnected with each other, eventually forming a fully developed network of FN fibrils on PEA. In contrast, FN adopted a globular-like conformation along the entire length of the PMA surface, and the FN gradient consisted only of increased density of adsorbed FN. Correspondingly, the percentage of differentiated cells increased monotonically along the FN gradient on PEA but not on PMA. This work demonstrates an interplay between material chemistry and topology in modulating material-driven FN fibrillogenesis and cell differentiation.Journal of Materials Science Materials in Medicine 12/2011; 23(1):195-204. · 2.32 Impact Factor -
Article: Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry.
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ABSTRACT: To evaluate dipyridamole cardiac magnetic resonance (MR) imaging in the prediction of major events (MEs) in patients with ischemic chest pain in a large multicenter registry. Institutional ethics committee approval and written informed consent were obtained. A total of 1722 patients who were undergoing cardiac MR imaging for chest pain were included. Wall motion abnormalities (WMAs) at rest, hyperemia perfusion defect (PD), late gadolinium enhancement (LGE), and inducible WMA were analyzed (abnormal if more than one abnormal segment was seen) with the 17-segment model. A cardiac MR categorization was created: category 1, no PD, LGE, or inducible WMA; category 2, PD without LGE and inducible WMA; category 3, LGE without inducible WMA; and category 4, inducible WMA. The association with ME was analyzed by using Cox proportional hazard regression multivariate models. During a median follow-up period of 308 days, 61 MEs (4%) occurred (36 cardiac deaths, 25 nonfatal myocardial infarctions). MEs were associated with a greater extent of WMA, PD, LGE, and inducible WMA (P ≤ .001 for all analyses). In multivariable analyses, PD (P = .002) and inducible WMA (P = .0001) were the only cardiac MR predictors. ME rate in categories 1, 2, 3, and 4 was 2% (14 of 901 patients), 3% (six of 219 patients), 4% (15 of 409 patients), and 14% (26 of 193 patients), respectively (category 4 vs category 1, adjusted P < .001). Cardiac MR-directed revascularization was performed in 242 patients (14%) and reduced the risk of ME in only category 4 (7% [six of 92 patients] vs 26% [26 of 101 patients], P = .0004). Dipyridamole cardiac MR imaging can be used to predict MEs in patients with ischemic chest pain. Patients with inducible WMA are at the highest risk for MEs and benefit the most from revascularization.Radiology 11/2011; 262(1):91-100. · 5.73 Impact Factor -
Article: "PINOT": time-resolved parallel magnetic resonance imaging with a reduced dynamic field of view.
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ABSTRACT: This article introduces a novel method named "Parallel Imaging and Noquist in Tandem" (PINOT) for accelerated image acquisition of cine cardiac magnetic resonance imaging. This method combines two prior information formalisms, the SPACE-RIP implementation of parallel imaging and the Noquist method for reduced-data image reconstruction with prior knowledge of static and dynamic regions in the field of view. The general theory is presented, and supported by results from experiments using time-resolved two-dimensional simulation data and retrospectively sub-sampled magnetic resonance imaging data with acceleration factors around 4. A signal-to-noise ratio analysis and a comparison study with TSENSE and k-t SENSE show that PINOT performs favorably in preserving edge detail, at a cost in signal-to-noise ratio and computational complexity.Magnetic Resonance in Medicine 04/2011; 65(4):1062-74. · 2.96 Impact Factor
