Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction

Background: Intrauterine growth restriction (IUGR) induces fetal cardiac remodelling and dysfunction, which persists postnatally and may explain the link between low birth weight and increased cardiovascular mortality in adulthood. However, the cellular and molecular bases for these changes are still not well understood. We tested the hypothesis that IUGR is associated with structural and functional gene expression changes in the fetal sarcomere cytoarchitecture, which remain present in adulthood. Methods and results: IUGR was induced in New Zealand pregnant rabbits by selective ligation of the utero-placental vessels. Fetal echocardiography demonstrated more globular hearts and signs of cardiac dysfunction in IUGR. Second harmonic generation microscopy (SHGM) showed shorter sarcomere length and shorter A-band and thick-thin filament interaction lengths, that were already present in utero and persisted at 70 postnatal days (adulthood). Sarcomeric M-band (GO: 0031430) functional term was over-represented in IUGR fetal hearts. Conclusion: The results suggest that IUGR induces cardiac dysfunction and permanent changes on the sarcomere

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique

Automated cardiac sarcomere analysis from second harmonic generation images

Automatic quantification of cardiac muscle properties in tissue sections might provide important information related to different types of diseases. Second harmonic generation (SHG) imaging provides a stain-free microscopy approach to image cardiac fibers that, combined with our methodology of the automated measurement of the ultrastructure of muscle fibers, computes a reliable set of quantitative image features (sarcomere length, A-band length, thick–thin interaction length, and fiber orientation). We evaluated the performance of our methodology in computer-generated muscle fibers modeling some artifacts that are present during the image acquisition. Then, we also evaluated it by comparing it to manual measurements in SHG images from cardiac tissue of fetal and adult rabbits. The results showed a good performance of our methodology at high signal-to-noise ratio of 20 dB. We conclude that our automated measurements enable reliable characterization of cardiac fiber tissues to systematically study cardiac tissue in a wide range of conditions.The authors acknowledge the cvRemod project under the CENIT 20092012 program of the Industrial and Technological Development Center (CDTI). This study was partially supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (Ref. PI11/00051, PI11/01709, PI12/00801, and SAF2012-37196), Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa,” Spain; Obra Social ‘La Caixa,’ Spain; the Fundación Mutua Madrileña; Fundació Agrupació Mutua; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and the Seventh Framework Programme (FP7/2007-2013) under Grant No. 611823. P.G.C. was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, and A.G.T. was supported by IDIBAPS Predoctoral Programme

Automated cardiac sarcomere analysis from second harmonic generation images

Automatic quantification of cardiac muscle properties in tissue sections might provide important information related to different types of diseases. Second harmonic generation (SHG) imaging provides a stain-free microscopy approach to image cardiac fibers that, combined with our methodology of the automated measurement of the ultrastructure of muscle fibers, computes a reliable set of quantitative image features (sarcomere length, A-band length, thick–thin interaction length, and fiber orientation). We evaluated the performance of our methodology in computer-generated muscle fibers modeling some artifacts that are present during the image acquisition. Then, we also evaluated it by comparing it to manual measurements in SHG images from cardiac tissue of fetal and adult rabbits. The results showed a good performance of our methodology at high signal-to-noise ratio of 20 dB. We conclude that our automated measurements enable reliable characterization of cardiac fiber tissues to systematically study cardiac tissue in a wide range of conditions.The authors acknowledge the cvRemod project under the CENIT 20092012 program of the Industrial and Technological Development Center (CDTI). This study was partially supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (Ref. PI11/00051, PI11/01709, PI12/00801, and SAF2012-37196), Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa,” Spain; Obra Social ‘La Caixa,’ Spain; the Fundación Mutua Madrileña; Fundació Agrupació Mutua; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and the Seventh Framework Programme (FP7/2007-2013) under Grant No. 611823. P.G.C. was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, and A.G.T. was supported by IDIBAPS Predoctoral Programme

Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction

Background: Intrauterine growth restriction (IUGR) induces fetal cardiac remodelling and dysfunction, which persists postnatally and may explain the link between low birth weight and increased cardiovascular mortality in adulthood. However, the cellular and molecular bases for these changes are still not well understood. We tested the hypothesis that IUGR is associated with structural and functional gene expression changes in the fetal sarcomere cytoarchitecture, which remain present in adulthood./nMethods and Results: IUGR was induced in New Zealand pregnant rabbits by selective ligation of the utero-placental vessels. Fetal echocardiography demonstrated more globular hearts and signs of cardiac dysfunction in IUGR. Second harmonic generation microscopy (SHGM) showed shorter sarcomere length and shorter A-band and thick-thin filament interaction lengths, that were already present in utero and persisted at 70 postnatal days (adulthood). Sarcomeric M-band (GO: 0031430) functional term was over-represented in IUGR fetal hearts./nConclusion: The results suggest that IUGR induces cardiac dysfunction and permanent changes on the sarcomere.This study was supported by grants from Ministerio de Economia y Competitividad PN de I+D+I 2008-2011 (ref. SAF2009_08815, SAF2012-37196, and BIO2011-27069); Instituto de Salud Carlos III (ref. PI11/00051, PI11/01709, PI12/00801) cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa”; Centro para el Desarrollo Técnico Industrial (ref. cvREMOD 2009-2012) apoyado por el Ministerio de Economia y Competitividad y Fondo de inversión local para el empleo, Spain; The Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); Obra Social “La Caixa” (Spain); Fundació Mutua Madrileña (Spain); Fundació Agrupació Mutua (Spain); AGAUR 2009 SGR grant n° 1099; and Red Temática de Investigación Cooperativa en cancer (ref. RD06/0020/1019). I.T. was supported by a post-doctoral fellowship from Carlos III Institute of Health, Spain (CD08/00176) during the time these studies were performed. P.G.C. acknowledges grant support to the Programa de Ayudas Predoctorales de Formación en Investigación en Salud del Instituto Carlos III, Spain (FI12/00362). A.G.T. was supported by an IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) pre-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript