Quantitative assessment of angiogenesis using ultrasound multiple scattering

摘要 血管生成被认为是癌症恶性的生物标志物。超声(US)成像，超分辨率 超声、微多普勒和声学血管造影术使血管网络成像成为可能，但信息 由这些图像提供的信息不是定量的。 我们提出了基于超声多次散射的血管生成实时定量评估方法。 根据原始超声数据进行分析。建议的USMS参数将使生物标志物的开发成为可能 癌症侵袭性。我们将验证我们的方法在癌症中的应用，但这种新的生物医学 成像技术将在癌症以外的领域找到应用(例如动脉粥样硬化)。 对于乳腺癌的诊断，X-射线乳房X光检查在某些人群中可能无效，目前存在MRI 在成本、可及性和一些禁忌症方面的一些挑战与使用Gd造影剂有关。 传统的美国是高度敏感的，但缺乏特异性。一个更具体的美国工具将提高我们的能力 区分不确定的非致命性疾病和致命性癌症，并对一种显著的 高危人群的百分比。 评估肿瘤血管生成的预后价值的研究发现， 微血管密度增加，预后恶化。在多次散射之间存在一种关系 血管充盈造影剂时的参数和血管密度。我们假设 测量UMS参数将使评估血管密度成为可能，从而提高 超声波用于癌症诊断。 为了验证这一假设，我们建议开发、优化和验证新的超声方法，利用 多重散射方法。这些方法将使微观的定量表征成为可能。 血管生成的体系结构，导致超声特异性的提高。 在这个项目中，我们将：i)开发和优化一种定量超声方法来评估微血管密度 和各向异性非侵入性。二)确立多重散射可用于以下目的的概念证明 在两项啮齿动物研究中表征血管生成和评估肿瘤的恶性程度。Ii)验证我们的新技术 在对人类患者的初步研究中，并将开发的方法的诊断能力与 目前可用的标准护理点超声波。 这项研究将极大地提高US血管生成成像的特异性，并使对比- 增强超声(CEUS)成为诊断癌症的可靠和广泛使用的临床工具，或 斑块破裂可能性的评估。最终，开发的方法将用于诊断和 它不仅可以用于癌症监测，还可以发现其他应用，如预测动脉粥样硬化斑块破裂。

ABSTRACT Angiogenesis is recognized as a biomarker of cancer malignancy. Ultrasonic (US) imaging, super-resolution ultrasound, micro Doppler and acoustic angiography enable the imaging of vessel networks, but the information provided by these images is not quantitative. We propose real-time quantitative assessment of angiogenesis based on Ultrasound Multiple Scattering (USMS) analysis from raw ultrasound data. The proposed USMS parameters will enable the development of biomarkers of cancer aggressiveness. We will validate our methods for cancer applications, but this novel biomedical imaging technology will find applications beyond cancer (to atherosclerosis for example). For breast cancer diagnosis, X-Ray mammography can be ineffective in some populations and MRI present some challenges of cost, accessibility, and some contra-indications related to the use of Gadolinium contrast. Conventional US is highly sensitive but lacks specificity. A more specific US tool would improve our ability to discriminate indeterminate non-lethal disease from lethal cancers, and make a clinical impact on a notable percentage of the at-risk population. Studies assessing the prognostic value of tumor angiogenesis have found a positive association between increasing microvessel densities and worsening prognosis. There is a relationship between multiple scattering parameters and vascular density when vessels are populated by contrast agents. We hypothesize that measuring USMS parameters will enable assessing vascular density and therefore increase the specificity of ultrasound for cancer diagnosis. To verify this hypothesis, we propose to develop, optimize and validate novel ultrasound methods utilizing multiple scattering approaches. These methods will enable the quantitative characterization of the micro- architecture of angiogenesis, leading to improvements in ultrasound specificity. In this project, we will: i) Develop and optimize a quantitative ultrasound method to assess microvascular density and anisotropy non-invasively. ii) Establish the proof of concept that multiple scattering can be used to characterize angiogenesis and assess tumor malignancy in two rodent studies. ii) Validate our new technology in a preliminary study on human patients, and compare the diagnostic power of the developed methods to the currently available standard point of care ultrasound. This research will dramatically increase the specificity of US imaging of angiogenesis, and enable Contrast- Enhanced Ultrasound (CEUS) to become a reliable and widely used clinical tool for the diagnosis of cancer, or the evaluation of likelihood of plaque rupture. Ultimately, the methods developed will be used for diagnosis and monitoring of cancer, and could find other applications such as the prediction of plaque rupture in atherosclerosis.