Placental Pathology: Digital Assessment and Validation

胎盘病理学：数字评估和验证

• 批准号: 7749593
• 负责人: Carolyn M Salafia
• 金额: $ 12.58万
• 依托单位: PLACENTAL ANALYTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7749593
• 关键词: Academic Medical Centers; Acute; Age; Algorithms; Amniotic Fluid; Antibiotics; Arts; Attention; Biological Assay; Birth; Caring; Cerebral Palsy; Cerebrum; Characteristics; Childhood; Childhood Asthma; Clinical; Clinical assessments; Color; Commit; Complex; Computer software; Consensus; Data; Data Set; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; Etiology; Exposure to; Goals; Gold; Hematoxylin and Eosin Staining Method; Histologic; Histology; Hormones; Hospitals; Human Resources; Image; Image Analysis; Individual; Infant; Infant Care; Infection; Inflammation; Inflammatory; Inflammatory Response; Institution; Karyorrhexis; Laboratories; Laboratory Research; Liquid substance; Lung; Marketing; Maternity Hospitals; Measurement; Measures; Membrane; Methodology; Methods; Metric; Molecular; Morbidity - disease rate; Mothers; Nature; Neonatal; Newborn Infant; Nuclear; Outcome; Pathologist; Pathology; Patients; Perinatal; Perinatal Exposure; Phase; Physicians; Placenta; Pregnancy Outcome; Premature Birth; Preparation; Proteomics; Recurrence; Reproducibility; Research; Residencies; Resources; Risk; Risk Factors; Sampling; Sensitivity and Specificity; Services; Severities; Slide; Specificity; Staining method; Stains; System; Testing; Time; Tissues; Training; Triage; Umbilical Cord Blood; Umbilical cord structure; Validation; Variant; Vasculitis; base; chorionic plate; clinical practice; cost; cytokine; density; digital; fetal; hospital laboratories; image processing; imaging Segmentation; instrument; interest; intraamniotic infection; intraventricular hemorrhage; maternal serum; mortality; neonatal sepsis; neutrophil; novel; pathogen; public health relevance; research clinical testing; tool; white matter damage

DESCRIPTION (provided by applicant): Intraamniotic infection is a major risk factor for preterm birth (the greatest single agent of perinatal morbidity and mortality) as well as a contributor to the development of cerebral palsy and other significant childhood diseases. As such, its diagnosis needs to be both reliable (reproducible in the same patient, and across patients and institutions) and valid (consistently predictive of important clinical features of infection, including severity, duration and risk of sequelae such as neonatal sepsis). Unfortunately, current diagnostic pathology "gold standards" are neither reliable nor have they been validated against measures other than "group consensus", a poor substitute for biologically valid endpoints such as amniotic fluid or cord blood proteomics. Only a handful of US pathologists possess expertise in this diagnosis, with most of these physicians located in academic medical centers, limiting both the absolute numbers of infants who can be provided services as well as where such care can be provided. The vast majority of US maternity hospitals therefore effectively lack access to the expert personnel needed to provide such care, resulting in a system in which only a small proportion of newborns can be accurately and reliably assessed for exposure to intraamniotic infections. In this Phase 1 proposal, we will, first, make our algorithms robust to the variability in hematoxylin and eosin staining that would be expected in slides prepared from diverse hospital laboratories. Next, in order to validate these measures, we will take advantage of 2 large data sets in which placentas have already been collected, sampled, sectioned and stained, and slides have been scored (using current standard methods) and digitized, and a team of expert pathologists who have been involved with the data sets and are committed to the project. Using these resources, we will determine the reliability of our product, image analysis software that is a toolbox of algorithm-based image segmentation tools that can replace the current "best practice" (semi-quantitation of neutrophil infiltrates) in routine hematoxylin and eosin (H&E) stained slides. Validation against both expert pathologists and biologically germane endpoints (amniotic fluid or cord blood proteomics related to infection/inflammation associated molecules) will prepare this diagnostic tool for market introduction to provide state of the art diagnostic care for infants beyond the reach of the small cadre of "expert" placental pathologists. In effect, this tool will open the potential for reliable, reproducible and valid diagnoses to be performed at any hospital in the world that can produce a hematoxylin and eosin stained slide. PUBLIC HEALTH RELEVANCE: The fetal inflammatory response, defined as elevated levels of inflammatory cytokines in cord blood and by vasculitis in the umbilical and chorionic vessels of the placenta, predicts recurrence risk for preterm birth (optimizing next pregnancy outcomes), and risks of intraventricular hemorrhage, cerebral white matter damage, cerebral palsy, childhood asthma and lung damage more generally. The current histologic tools used to measure inflammation are limited to a semiquantative estimation of neutrophil number with limited reproducibility even among "experts". Placental Analytics has developed a set of image processing algorithms for digitized histology slides that promises reliable quantification of the current "gold standard" for histologic assessment of intraamniotic infection (i.e., neutrophil number), as well as quantification of neutrophil karyorrhexis that may correlate with age/duration of infection more precisely than any current histologic method.

描述（由申请人提供）：羊水内感染是早产（最大的围产期发病率和死亡率的最大单一药物）的主要危险因素，也是导致脑瘫和其他重大儿童疾病发展的贡献者。因此，其诊断必须是可靠的（在同一患者中以及在患者和机构中可重复），并且有效（始终可以预测感染的重要临床特征，包括严重程度，持续时间和后遗症的风险，例如新生儿败血症）。不幸的是，当前的诊断病理学“黄金标准”既不可靠，也不是针对“组共识”以外的其他措施进行验证，这是对生物有效终点（例如羊水或脐带血蛋白质组学）的不良替代品。在这种诊断中，只有少数美国病理学家拥有专业知识，其中大多数医生都位于学术医疗中心，这限制了可以提供服务的绝对数量以及可以提供此类护理的地方。因此，我们中的绝大多数产科医院实际上缺乏提供提供此类护理所需的专家人员的机会，从而导致了一个系统，在这种系统中，只有一小部分新生儿才能准确，可靠地评估以暴露于哺乳性内部感染中。在此第1阶段提案中，我们将首先使我们的算法对苏木精和曙红染色的可变性有牢固的态度，这些变异性可以预期在不同医院实验室制备的幻灯片中。接下来，为了验证这些措施，我们将利用2个大数据集，其中胎盘已经被收集，采样，切片和染色，并且对幻灯片进行了评分（使用当前的标准方法）和数字化，以及与数据集有关并致力于项目的专家病理学家团队。使用这些资源，我们将确定产品的可靠性，图像分析软件，该软件是基于算法的图像分割工具的工具箱，可以替代常规苏木精和曙红（H＆E）染色的当前“最佳实践”（中性粒细胞浸润的半定量）。针对专家病理学家和生物学上的端点（与感染/炎症相关分子有关的羊水或脐带血蛋白质组学）的验证将为市场介绍提供此诊断工具，以为“专家”胎盘病理学家的少量干燥范围为婴儿提供最先进的诊断护理。实际上，该工具将在世界上任何可以产生苏木精和曙红染色滑梯的医院进行可靠，可重现和有效诊断的潜力。 PUBLIC HEALTH RELEVANCE: The fetal inflammatory response, defined as elevated levels of inflammatory cytokines in cord blood and by vasculitis in the umbilical and chorionic vessels of the placenta, predicts recurrence risk for preterm birth (optimizing next pregnancy outcomes), and risks of intraventricular hemorrhage, cerebral white matter damage, cerebral palsy, childhood asthma and lung damage more generally.用于测量炎症的当前组织学工具仅限于中性粒细胞数的半定量估计，即使在“专家”中，可重复性有限。胎盘分析已经开发了一组图像处理算法，用于数字化的组织学滑梯，有望对当前的“金标准”进行可靠的量化，用于对膜内感染的组织学评估（即中性粒细胞数），以及中性粒细胞核核酸的量化与任何精确性的抗性方法相比。