Molecular, Functional, and Microstructural Imaging of Cervical Remodeling Biomarkers

宫颈重塑生物标志物的分子、功能和微观结构成像

• 批准号: 10895849
• 负责人: Mohammad Mehrmohammadi
• 金额: $ 29.86万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-29 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10895849
• 关键词: Acceleration; Acoustics; Address; Algorithms; Assessment tool; Biochemical; Biological Markers; Biomechanics; Blood Vessels; Cervical; Cervical Ripening; Cervix Incompetence; Cervix Uteri; Clinical; Clinical Research; Collagen; Complement; Correlation Studies; Detection; Diagnostic; Edema; Elasticity; Frequencies; Gestational Age; Health Care Costs; Histologic; Human; Image; Imaging Device; Incidence; Induced Labor; Inflammation; Lasers; Length; Manuals; Measurement; Measures; Modality; Modeling; Molecular; Monitor; Morphology; Motion; Movement; Multimodal Imaging; Mus; Neonatal Mortality; Outcome; Patients; Pharmaceutical Preparations; Physiologic pulse; Predictive Value; Pregnancy; Premature Birth; Procedures; Prostaglandins; Quantitative Evaluations; Radiation; Research; Risk; Safety; Shapes; Specificity; Spectrum Analysis; System; Techniques; Thick; Tissues; Ultrasonography; United States; Vagina; Viscosity; Visualization; Water; Woman; cervical remodeling; clinical application; clinical practice; clinical translation; diagnostic value; flexibility; imaging biomarker; imaging modality; improved; in vivo; instrument; mouse model; neonatal morbidity; neonate; non-invasive imaging; photoacoustic imaging; pregnant; premature; prototype; response; standard of care; structural imaging; success; translational study; ultrasound; viscoelasticity

Summary. Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity worldwide [1, 2], with an estimated incidence of 15 million neonates born preterm annually. Healthcare costs associated with prematurity are estimated to be >$26 billion annually in the United States [18]. The most common clinical indicator of risk for PTB is a short cervix, as determined by ultrasound (US) imaging identifies only 37.3% (low sensitivity) of women who will deliver <35 weeks of gestation, with a very limited positive predictive value of 17.8%. Cervical ripening during labor induction (more than 23% of pregnancies in United States) is accomplished by administration of drugs such as prostaglandin. Current standard of care relies on measuring cervical length and consistency by subjective/qualitative manual examination (a Bishop score), which has limited ability to determine the success of labor induction. Currently, there are no reliable, clinically translatable, and non-invasive imaging instruments capable of acquiring quantitative diagnostic information about the underlying mechanisms of cervical insufficiency and PTB. Similarly, there are no clinically applicable instruments for the objective and quantitative assessment of cervical ripening during labor induction. Therefore, there is an urgent need for an imaging instrument that enables quantitative visualization of pathophysiological changes of cervix at the molecular, microstructural, and functional levels. To address this unmet clinical need, we have been developing a combined multi-modal imaging instrument that merges Photoacoustic (PA), Viscoelasticity (VE), and conventional ultrasound (US) in a single transvaginal probe. In this instrument, PA imaging will provide quantitative measurements of molecular and microstructural mechanistic biomarkers of cervical remodeling (i.e. collagen network organization, water content, microvascular and oxygenation status); VE will assess the changes in tissue biomechanical biomarkers of cervical remodeling (i.e. degree of stiffness/softness and viscosity); and US for imaging cervical morphology (i.e. cervical length). Because TVUS is the standard of care imaging modality for monitoring cervical status during pregnancy and labor, the proposed multi-modal imaging instrument will add only 3-5 minutes to conventional TVUS examination and, therefore, will be readily acceptable in the routine clinical practice. The proposed instrument will have two immediate clinical applications: (a) improving the detection of patients at risk of PTB, particularly in a subset of women without an apparent short cervix; (b) objective and quantitative determination of cervical ripening status prior to induction of contractions, as a part of labor induction procedures. At the conclusion of this study, the diagnostic efficacy of the proposed technique to assess cervical ripening biomarkers will be quantitatively evaluated.

概括。 早产（PTB）是全球新生儿死亡率和发病率的主要原因[1，2]，估计 每年早产1500万新生儿的发病率。与早产相关的医疗保健费用是 在美国，每年估计每年为260亿美元[18]。最常见的临床指标 PTB是一个短宫颈，由超声（US）成像确定仅识别女性的37.3％（低灵敏度） 谁将提供<35周的妊娠期，积​​极的预测价值非常有限为17.8％。宫颈成熟 在劳动诱导期间（美国的怀孕的23％以上）是通过管理来完成的 前列腺素等药物。当前的护理标准依赖于测量宫颈长度和一致性 主观/定性手动检查（主教评分），该检查的能力有限 劳动归纳。目前，没有可靠的，临床上可以翻译和非侵入性成像仪器 能够获取有关宫颈基本机制的定量诊断信息 功能不全和PTB。同样，没有用于目标和定量的临床上适用的工具 评估劳动诱导过程中宫颈成熟。因此，迫切需要成像 能够定量可视化子宫颈病理生理变化的仪器 微观结构和功能水平。为了满足这种未满足的临床需求，我们一直在开发合并 合并光声（PA），粘弹性（VE）和常规的多模式成像仪器 单个经阴道探针中的超声（美国）。在此乐器中，PA成像将提供定量 宫颈重塑的分子和微结构机械生物标志物的测量（即胶原蛋白 网络组织，水含量，微血管和氧合状态）； VE将评估组织的变化 宫颈重塑的生物力学生物标志物（即刚度/柔软度和粘度的程度）；和我们 成像宫颈形态（即宫颈长度）。因为TVUS是护理成像模式的标准 监测怀孕和分娩期间的宫颈状态，拟议的多模式成像仪器将增加 传统的TVUS考试只有3-5分钟，因此在例程中很容易接受 临床实践。拟议的仪器将有两个立即的临床应用：（a）改进 检测有PTB风险的患者，特别是在没有明显短的宫颈的女性中； （b） 作为宫颈成熟状态的客观和定量确定在诱导收缩之前，作为一部分 劳动归纳程序。在这项研究的结束时，提出的技术对 评估宫颈成熟生物标志物将进行定量评估。

项目成果

A versatile multimodal optical modality based on Brillouin light scattering and photoacoustic effect.

基于布里渊光散射和光声效应的多功能多模态光学模态。

• DOI: 10.1101/2023.03.10.532144
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Shi,Chenjun;Yan,Yan;Mehrmohammadi,Mohammad;Zhang,Jitao
• 通讯作者: Zhang,Jitao

Methods for Monitoring Risk of Hypoxic Damage in Fetal and Neonatal Brains: A Review.

• DOI: 10.1159/000520987
• 发表时间: 2022
• 期刊: Fetal diagnosis and therapy
• 影响因子: 2.2
• 作者: Uzianbaeva L;Yan Y;Joshi T;Yin N;Hsu CD;Hernandez-Andrade E;Mehrmohammadi M
• 通讯作者: Mehrmohammadi M

Spectroscopic photoacoustic imaging of cervical tissue composition in excised human samples.

• DOI: 10.1371/journal.pone.0247385
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Yan Y;Basij M;Garg A;Varrey A;Alhousseini A;Hsu R;Hernandez-Andrade E;Romero R;Hassan SS;Mehrmohammadi M
• 通讯作者: Mehrmohammadi M

Collagenase treatment reduces the anisotropy of ultrasonic backscatter in rat myocardium by reducing collagen crosslinks.

• DOI: 10.14814/phy2.15849
• 发表时间: 2023-11
• 期刊: Physiological reports
• 影响因子: 2.5