Lili Shi, Allan K N Alencar, Kenneth F Swan, Dylan J Lawrence, Gabriella Pridjian, Carolyn L Bayer
{"title":"靶向超声增强成像定量子痫前期大鼠胎盘分子变化。","authors":"Lili Shi, Allan K N Alencar, Kenneth F Swan, Dylan J Lawrence, Gabriella Pridjian, Carolyn L Bayer","doi":"10.1007/s11307-025-01988-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents.</p><p><strong>Methods: </strong>A targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target α<sub>ν</sub>β<sub>3</sub> integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n = 6) and RUPP (n = 6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant ( <math><msub><mi>K</mi> <mi>b</mi></msub> </math> ) of the placenta.</p><p><strong>Results: </strong>The RUPP group showed a significant reduction in the value of <math><msub><mi>K</mi> <mi>b</mi></msub> </math> compared to the NP group (p < 0.05). A histogram of the placental <math><msub><mi>K</mi> <mi>b</mi></msub> </math> was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio.</p><p><strong>Conclusions: </strong>The BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"274-284"},"PeriodicalIF":3.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062038/pdf/","citationCount":"0","resultStr":"{\"title\":\"Quantifying Molecular Changes in the Preeclamptic Rat Placenta with Targeted Contrast-Enhanced Ultrasound Imaging.\",\"authors\":\"Lili Shi, Allan K N Alencar, Kenneth F Swan, Dylan J Lawrence, Gabriella Pridjian, Carolyn L Bayer\",\"doi\":\"10.1007/s11307-025-01988-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents.</p><p><strong>Methods: </strong>A targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target α<sub>ν</sub>β<sub>3</sub> integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n = 6) and RUPP (n = 6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant ( <math><msub><mi>K</mi> <mi>b</mi></msub> </math> ) of the placenta.</p><p><strong>Results: </strong>The RUPP group showed a significant reduction in the value of <math><msub><mi>K</mi> <mi>b</mi></msub> </math> compared to the NP group (p < 0.05). A histogram of the placental <math><msub><mi>K</mi> <mi>b</mi></msub> </math> was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio.</p><p><strong>Conclusions: </strong>The BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.</p>\",\"PeriodicalId\":18760,\"journal\":{\"name\":\"Molecular Imaging and Biology\",\"volume\":\" \",\"pages\":\"274-284\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062038/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11307-025-01988-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging and Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11307-025-01988-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Quantifying Molecular Changes in the Preeclamptic Rat Placenta with Targeted Contrast-Enhanced Ultrasound Imaging.
Purpose: Abnormal placental remodeling is linked to various pregnancy-related diseases, including preeclampsia (PE). This study applies a bicompartmental (BCM) model to quantify molecular expression changes in the placenta, indicative of abnormal placental remodeling, and evaluates the effectiveness of targeted contrast-enhanced ultrasound (T-CEUS) in detecting the abnormal placental vasculature. The BCM model provides high temporal resolution and differentiation of anatomical artery structures within the placenta by analyzing the distribution of contrast agents.
Methods: A targeted contrast agent (TCA) composed of gas-filled microbubbles (MB), with a surface-conjugated peptide to target ανβ3 integrin, a biomarker for angiogenesis, was used for quantifying placental vascular development. CEUS images were acquired from timed pregnant Sprague Dawley rats with experimentally-induced reduced uterine perfusion pressure (RUPP) placental insufficiency. On gestational day (GD) 18 of a 21-day gestation, CEUS images were acquired from both Normal pregnant (NP; n = 6) and RUPP (n = 6) dams after injection of the TCA. The BCM model was used to estimate the binding dynamics of the TCA, providing a parametric map of the binding constant ( ) of the placenta.
Results: The RUPP group showed a significant reduction in the value of compared to the NP group (p < 0.05). A histogram of the placental was compared to alternative analyses (differential target enhancement, dTE and late enhancement, LE) to demonstrate that it can differentiate between anatomical artery structures with a higher contrast-to-background ratio.
Conclusions: The BCM method differentiates molecular changes associated with the abnormal placental development associated with PE. It also reveals more intricate internal anatomical structures of the placenta in comparison to dTE and LE, suggesting that the BCM could enhance early detection and monitoring of PE.
期刊介绍：
Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures.
Some areas that are covered are:
Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes.
The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets.
Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display.
Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging.
Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics.
Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations.
Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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