Subharmonic Contrast Ultrasound for Improved Characterization of Adnexal Masses

次谐波造影超声可改善附件肿块的表征

• 批准号: 9133321
• 负责人: Flemming Forsberg
• 金额: $ 16.97万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133321
• 关键词: Adnexal Mass; Algorithms; Benign; Biological Assay; Biological Markers; Blood flow; Breast; C10; Cancerous; Canis familiaris; Clinical; Clinical Management; Clinical Trials; Contrast Media; Data; Definity; Development; Diagnosis; Disease; Enrollment; Evaluation; Goals; Health; Healthcare; Human; Image; Imaging Techniques; Kinetics; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Medical Imaging; Methods; Microbubbles; Modeling; Neutrons; Operative Surgical Procedures; Ovarian; Ovary; PECAM1 gene; Pathology; Patients; Perfusion; Pilot Projects; Play; Process; Reference Standards; Risk; Role; Schedule; Signal Transduction; Specimen; Staining method; Stains; Techniques; Technology; Testing; Time; Tissues; Transducers; Translating; Tumor Angiogenesis; Ultrasonography; United States; Unnecessary Surgery; Woman; X-Ray Computed Tomography; advanced disease; angiogenesis; base; cancer imaging; cancer type; contrast enhanced; dosage; high risk; imaging biomarker; imaging modality; immunohistochemical markers; improved; improved outcome; in vivo; indexing; innovation; minimally invasive; mortality; novel; prognostic; screening; tool

 DESCRIPTION (provided by applicant): Ovarian cancer is one of the ten most common types of cancer in women and an estimated 1 in 71 women in the United States will develop ovarian cancer in their lifetime. Regrettably, almost 75 % of women are diagnosed with advanced disease, which greatly increases mortality. Hence, earlier and accurate characterization of adnexal masses is a clinical imperative in order to improve patient's survival and imaging techniques can play a critical role in fulfilling this goal. Currently adnexal masses are imaged with standard endovaginal ultrasound (EV US), with contrast enhanced magnetic resonance imaging (MRI) or computed tomography (CT), but functional biomarkers may be important prognostic parameters to improve on the characterization of such masses. Our group has been developing a new contrast-specific US imaging modality: subharmonic imaging (SHI), because of the excellent suppression of tissue echoes relative to other US contrast modes. We have shown that SHI can detect the slow, small volume blood flow associated with tumor angiogenesis in humans using clinically approved dosages of US contrast agents. Recently, we created parametric images of SHI kinetics (i.e., pixel by pixel time intensity curves; TICs) and found cancers to have significantly higher perfusion relative to benign lesions (p = 0.0014). Hence, the fundamental aim of this project is to derive qualitative and quantitative SHI biomarkers, based on subharmonic signals from US contrast microbubbles, which can be used to improve the characterization of adnexal masses as benign or malignant. The SHI algorithm will be implemented on a state-of-the-art US scanner (EPIQ; Philips Healthcare, Bothell, WA) with a broad bandwidth, curved array EV transducer for in vivo SHI of adnexal masses (Specific Aim 1). The ovaries of 6 canines will be imaged to demonstrate the ability of SHI to depict macro- and micro-vascularity (the latter as a model for tumor angiogenesis). Next, perfusion in the ovaries will be estimated using SHI TICs and results compared to a neutron activation assay. As a proof-of-concept, pilot study, we will enroll approximately 45 women with adnexal masses scheduled for surgery based on the risk of malignancy index (RMI). Subjects will be studied with EV SHI to identify and optimize TIC parameters as SHI biomarkers to evaluate adnexal microvascularity in an attempt to diagnose benign or malignant disease. The TIC parameters will also be converted into SHI parametric images and compared to the standard EV US as well as MRI and RMI lesion characterization with pathology as the reference standard (Specific Aim 2). Finally, the ability of EV SHI to image angiogenesis will be compared to surgical specimens stained for CD31, an immunohistochemical predictor of angiogenesis (Specific Aim 3). This will be a first step towards the long-term goal of translating this method into a clinical trial for screening of high-risk patients with adnexal masses.

 描述(申请人提供)：卵巢癌是女性最常见的十种癌症之一，据估计，美国每71名女性中就有一人会在一生中患上卵巢癌。令人遗憾的是，近75%的妇女被诊断出患有晚期疾病，这大大增加了死亡率。因此，为了提高患者的存活率，对附件肿块进行早期准确的定性是临床上的当务之急，而影像技术在实现这一目标中起着至关重要的作用。目前附件肿块的成像是通过标准的经阴道超声(EV US)、增强磁共振成像(MRI)或计算机断层扫描(CT)，但功能生物标志物可能是改善此类肿块特征的重要预后参数。我们小组一直在开发一种新的对比度特定的超声成像方式：亚谐波成像(SHI)，因为相对于其他超声对比剂模式，它对组织回波的抑制效果很好。我们已经证明，使用临床批准的剂量的US造影剂，SHI可以检测到与人类肿瘤血管生成相关的缓慢、小容量的血流。最近，我们创建了SHI动力学的参数图像(即逐个像素的时间强度曲线；TICS)，发现相对于良性病变，癌症的血流灌注明显更高(p=0.0014)。因此，本项目的基本目标是根据超声造影剂微泡的亚谐信号，提取定性和定量的SHI生物标志物，用于改善附件肿块的良、恶性特征。SHI算法将在最先进的US扫描仪(EPIQ；Philps Healthcare，Bothell，WA)上实施，该扫描仪具有宽带、曲面阵列EV换能器，可用于附件肿块的活体SHI(特定目标1)。我们将对6只犬的卵巢进行成像，以显示SHI显示大血管和微血管的能力(后者可作为肿瘤血管生成的模型)。下一步，将使用SHI TICS和与中子激活试验相比较的结果来估计卵巢的灌注量。作为一项概念验证、先导性研究，我们将根据恶性风险指数(RMI)招募约45名有附件肿块的女性患者进行手术。受试者将进行EV SHI研究，以确定和优化TIC参数作为SHI生物标志物，以评估附件微血管，试图诊断良恶性疾病。TIC参数还将被转换为SHI参数图像，并与标准EV US以及以病理为参考标准的MRI和RMI病变特征进行比较(特定目标2)。最后，EV SHI成像血管生成的能力将与CD31染色的手术标本进行比较，CD31是血管生成的免疫组织化学预测指标(特定目标3)。这将是朝着将这种方法转化为筛查附件肿块高危患者的临床试验的长期目标迈出的第一步。