Browsing by Author "Xavier, Aline"

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    Assessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy
    (2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.
    Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
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    Characterization of Direct Localization Algorithms for Ultrasound Super-Resolution Imaging in a Multibubble Environment: A Numerical and Experimental Study
    (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2022) Xavier, Aline; Alarcon, Hector; Espindola, David
    Localization plays a significant role in the production of ultrasound localization microscopy images. For instance, detecting more microbubbles reduces the time of acquisition, while localizing them more accurately improves the resolution of the images. Previous approaches to compare the multiple localization algorithms rely on numerical simulation of a single steady microbubble, with or without modeling its nonlinear response. In real-life situations, vessels have a nonconstant velocity profile, which creates relative movement, producing dynamically overlapped microbubbles even at low concentrations. These complexities deteriorate the behavior of the localization algorithms. To incorporate these effects on the characterization of the localization methods, we designed a virtual medium containing four microtubes of different inner diameters, where single-pixel microbubbles were allowed to flow within each microtube with a parabolic velocity profile. A finite difference method was used to simulate the propagation of ultrasound waves to obtain B-mode images that fed four direct microbubbles localization algorithms (i.e., weighted centroid, 2D-spline interpolation, parabolic fitting, and onset detection). The performance of these methods was quantified using the number of microbubbles detected, the microbubbles distribution, the full width at half maximum, the maximum velocity, and the computational time as metrics. Our simulation results suggest that 2D-spline and paraboloid fitting were the best methods, detecting 100% of the microbubbles with an error in their distribution of 249 and 244 microbubbles, respectively. Both methods with a computational time cost of 18% and 7% lower than weighted centroid, respectively. We also present an experimental comparison of these localization methods, finding results similar to the numerical ones.
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    Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS−/− mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
    (2023) Lavin, Begoña; Eykyn, Thomas; Phinikaridou, Alkystis; Xavier, Aline; Kumar, Shravan; Buqué, Xabier; Aspichueta, Patricia; Sing-Long C., Carlos A.; Arrese, Marco; Botnar, René Michael; Andía Kohnenkampf, Marcelo Edgardo
    Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS−/− mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS−/− mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3−/− mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS−/− murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.
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    Exact classification of nmr spectra from nmr signals
    (Institute of Electrical and Electronics Engineers Inc., 2024) Lehmann, Pedro Izquierdo; Xavier, Aline; Andia Kohnenkampf, Marcelo Edgardo; Sing Long Collao, Carlos Alberto
    Nuclear magnetic resonance (NMR) spectroscopy is routinely used to study the properties of matter. Therefore, different materials can be classified according to their NMR spectra. However, the NMR spectra cannot be observed directly, and only the NMR signal, which is a sum of complex exponentials, is directly observable in practice. A popular approach to recover the spectrum is to perform harmonic retrieval, i.e., to reconstruct exactly the spectrum from the NMR signal. However, even when this approach fails, the spectrum might still be classified accurately. In this work, we model the spectrum as an atomic measure to study the performance of classifying the spectrum from the NMR signal, and to determine how it degrades in the presence of additive noise and changes in field intensity. Although we focus on NMR signals, our results are broadly applicable to sum-of-exponential signals. We show numerical results illustrating our claims.
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    Sex differences in the relationship between body composition and MASLD progression in a murine model of metabolic syndrome
    (Elsevier Inc., 2025) Manjarrés Madrid, Laura; Xavier, Aline; Gonzalez Jara, Leticia Andrea; Garrido Ahumada, Camila Florencia; Zacconi Flavia, Cristina Milagro; Rivera K.; Parra L.; Phinikaridou A.; Besa Correa, Cecilia; Andía Kohnenkampf, Marcelo Edgardo
    Metabolic dysfunction-associated steatotic liver disease (MASLD) progression exhibits significant sex differences, with males generally developing more severe disease. This study used an endothelial nitric oxide synthase knockout (eNOS KO) murine model to investigate sex-specific MASLD progression under a Western diet intervention. Magnetic resonance imaging (MRI) assessed body composition and liver and skeletal muscle fat fraction, revealing greater visceral fat, liver volume, and liver-to-muscle fat ratios in males. Dimensionality reduction and clustering analyses identified distinct sex-specific MASLD phenotypes and progression patterns. Histological evaluations confirmed greater liver damage in males, evidenced by higher MAFLD Activity Scores. These findings highlight the critical role of sex as a biological variable in MASLD pathology and emphasize the influence of body composition and fat distribution on disease progression. The study underscores the utility of advanced imaging and analytical techniques for refining non-invasive diagnostics and guiding sex-specific interventions, paving the way for personalized MASLD management strategies.