Quantitative assessment of angiogenesis using ultrasound multiple scattering

使用超声多重散射定量评估血管生成

• 批准号: 10718807
• 负责人: Marie Muller
• 金额: $ 55.84万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718807
• 关键词: Acoustics; Angiography; Anisotropy; Architecture; Artificial Implants; Atherosclerosis; Benchmarking; Benign; Biopsy; Blood Vessels; Breast; Breast Magnetic Resonance Imaging; Cancer Model; Chronic; Clinical; Contrast Media; Data; Deposition; Detection; Diagnosis; Diffusion; Disease; Evaluation; Frequencies; Gadolinium; Genetically Engineered Mouse; Histology; Human; Image; Imaging Techniques; Imaging technology; Immunofluorescence Immunologic; Kidney Failure; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Mammary Ultrasonography; Mammography; Measurement; Measures; Methods; Microbubbles; Monitor; Morbidity - disease rate; Morphology; Neoplasms in Vascular Tissue; Network-based; Nutrient; Oxygen; Patients; Population; Populations at Risk; Primary carcinoma of the liver cells; Prognosis; Property; Rattus; Research; Resolution; Rodent; Roentgen Rays; Rupture; Safety; Screening procedure; Sensitivity and Specificity; Specificity; Structure; Techniques; Thinness; Time; Travel; Tumor Angiogenesis; Ultrasonic Transducer; Ultrasonic wave; Ultrasonics; Ultrasonography; Vascularization; Woman; X-Ray Computed Tomography; angiogenesis; biomarker development; biomedical imaging; breast cancer diagnosis; cancer biomarkers; cancer diagnosis; contrast enhanced; cost; density; diagnostic value; elastography; follow-up; human subject; improved; in vivo; malignant breast neoplasm; mechanical properties; mortality; neovasculature; new technology; novel; perfusion imaging; point of care; prognostic value; psychosocial; quantitative ultrasound; screening; tool; tumor; ultra high resolution; ultrasound; young woman

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.

摘要 血管生成被认为是恶性肿瘤的生物标志物。超声（US）成像，超分辨率 超声、微多普勒和声学血管造影术能够对血管网络进行成像，但信息 这些图像提供的信息不是定量的。 我们提出了基于超声多重散射（USMS）的血管生成实时定量评估 分析原始超声数据。拟议的USMS参数将使生物标志物的发展成为可能 癌症的侵略性。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 成像技术将发现癌症以外的应用（例如动脉粥样硬化）。 对于乳腺癌诊断，X射线乳房X线摄影在某些人群中可能无效，而MRI存在 与钆造影剂使用相关的一些成本、可及性挑战和一些禁忌症。 常规US高度敏感，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与致命性癌症，并对一个显着的临床影响， 占危险人口的百分比。 评估肿瘤血管生成预后价值的研究发现， 增加微血管密度和恶化预后。多重散射和 参数和血管密度。我们假设 测量USMS参数将能够评估血管密度，从而增加 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， 多重散射方法这些方法将使定量表征的微观， 血管生成的结构，导致超声特异性的改善。 在这个项目中，我们将：i）开发和优化定量超声方法来评估微血管密度 和非侵入性的各向异性。ii）建立多重散射可用于以下的概念证明： 在两项啮齿动物研究中表征血管生成并评估肿瘤恶性程度。（二）推广新技术 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 目前可用的标准床旁超声。 这项研究将大大提高血管生成的US成像的特异性，并使造影剂， 增强超声（CEUS）成为一种可靠和广泛使用的临床工具，用于诊断癌症，或 评估斑块破裂的可能性。最终，开发的方法将用于诊断和 监测癌症，并可能发现其他应用，如预测动脉粥样硬化斑块破裂。