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（由适用提供）：卵巢癌是女性十种最常见的癌症类型之一，估计在美国，有71名妇女将在其一生中患上卵巢癌。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，为了改善患者的生存和成像技术，附加质量的早期和准确表征是临床当务之急，可以在实现这一目标中发挥关键作用。目前，附加质量是用标准血统超声（EV US）成像的，对比度增强了磁共振成像（MRI）或计算机断层扫描（CT），但功能性生物标志物可能是重要的预后参数，以改善此类质量的表征。我们的小组一直在开发一种新的对比度特异性的美国成像方式：亚谐波成像（SHI），因为相对于其他美国对比模式，组织的抑制作用很高。我们已经表明，SHI可以使用临床认可的对比剂的剂量检测与人类肿瘤血管生成相关的缓慢而小的血流。最近，我们创建了Shi动力学的参数图像（即，像素时间强度曲线； TICS），发现癌症相对于良性病变具有明显更高的灌注（P = 0.0014）。因此，该项目的基本目的是基于来自美国对比微泡的亚谐波信号来得出定性和定量的SHI生物标志物，该信号可用于改善附加质量的表征为良性或恶性。 SHI算法将在最先进的美国扫描仪（Epiq； Philips Healthcare，Bothell，WA）上实施，具有广泛的带宽，弯曲的阵列EV传感器，用于辅助质量的体内体内Shi（特定AIM 1）。将成像6个犬的卵巢以证明SHI描述宏观和微血管性的能力（后者是肿瘤血管生成的模型）。接下来，与中性激活测定法相比，将使用shi tics和结果估算卵巢中的灌注。作为概念验证，试点研究，我们将根据恶性指数的风险（RMI）招募大约45名妇女进行手术的女性。受试者将使用EV SHI进行研究，以识别和优化TIC参数作为SHI生物标志物，以评估ADNEXAL微血管，以试图诊断良性或恶性疾病。 TIC参数还将转换为SHI参数图像，并将其与标准EV我们以及MRI和RMI病变表征相比，将病理作为参考标准（特定目标2）。最后，将EV SHI对图像血管生成的能力与CD31染色的外科手术标本进行比较，CD31是血管生成的免疫组织化学预测指标（特定目标3）。这将是朝着将该方法转化为筛查高风险附属肿块患者的临床试验的长期目标的第一步。