Micro-tumor detection by quantifying tumor-induced vascular abnormalities (PQ-13)

通过量化肿瘤引起的血管异常来检测微肿瘤 (PQ-13)

• 批准号: 8699388
• 负责人: Paul A Dayton
• 金额: $ 19.66万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699388
• 关键词: 3-Dimensional; Acoustics; Algorithms; Angiography; Biological Markers; Biopsy; Blood Vessels; Breast; Breast Cancer Early Detection; Caliber; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Contrast Media; Core Biopsy; Data; Detection; Development; Diagnosis; Diagnostic Imaging; Discriminant Analysis; Disease; Early Diagnosis; Equation; Evaluation; Excision; Fibrosis; Gadolinium; Genetic Engineering; Genetically Engineered Mouse; Goals; Gold; Grant; Gray unit of radiation dose; Growth; Guidelines; Human; Image; Imaging Techniques; Imaging technology; Impairment; Ionizing radiation; Kidney; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Gland Parenchyma; Mammography; Metric; Microscopy; Modeling; Morphology; Mus; Noise; North Carolina; Onset of illness; Operative Surgical Procedures; Optics; Output; Parents; Pathology; Pathology Report; Patient Care; Patients; Pilot Projects; Population; Predictive Value; Probability; Process; Radiology Specialty; Reader; Regulation; Research; Resolution; Rodent; Rodent Model; Role; Screening for cancer; Sensitivity and Specificity; Signal Transduction; Solid Neoplasm; Specificity; Structure; System; Technology; Testing; Time; Tissues; Training; Transducers; Translating; Translations; Tubular formation; Ultrasonography; Universities; Woman; Work; angiogenesis; base; breast lesion; clinically relevant; cost; density; design; gadolinium oxide; human subject; imaging probe; improved; in vivo; innovation; malignant breast neoplasm; mouse model; neoplastic cell; new technology; novel; parent grant; pre-clinical; psychosocial; public health relevance; radiologist; research clinical testing; response; screening; standard of care; tool; tumor; young woman; 3-Dimensional; Acoustics; Algorithms; Angiography; Biological Markers; Biopsy; Blood Vessels; Breast; Breast Cancer Early Detection; Caliber; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Contrast Media; Core Biopsy; Data; Detection; Development; Diagnosis; Diagnostic Imaging; Discriminant Analysis; Disease; Early Diagnosis; Equation; Evaluation; Excision; Fibrosis; Gadolinium; Genetic Engineering; Genetically Engineered Mouse; Goals; Gold; Grant; Gray unit of radiation dose; Growth; Guidelines; Human; Image; Imaging Techniques; Imaging technology; Impairment; Ionizing radiation; Kidney; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Gland Parenchyma; Mammography; Metric; Microscopy; Modeling; Morphology; Mus; Noise; North Carolina; Onset of illness; Operative Surgical Procedures; Optics; Output; Parents; Pathology; Pathology Report; Patient Care; Patients; Pilot Projects; Population; Predictive Value; Probability; Process; Radiology Specialty; Reader; Regulation; Research; Resolution; Rodent; Rodent Model; Role; Screening for cancer; Sensitivity and Specificity; Signal Transduction; Solid Neoplasm; Specificity; Structure; System; Technology; Testing; Time; Tissues; Training; Transducers; Translating; Translations; Tubular formation; Ultrasonography; Universities; Woman; Work; angiogenesis; base; breast lesion; clinically relevant; cost; density; design; gadolinium oxide; human subject; imaging probe; improved; in vivo; innovation; malignant breast neoplasm; mouse model; neoplastic cell; new technology; novel; parent grant; pre-clinical; psychosocial; public health relevance; radiologist; research clinical testing; response; screening; standard of care; tool; tumor; young woman

DESCRIPTION (provided by applicant): It is well known that tumors dramatically distort microvasculature throughout the angiogenic process. Data show that substantial changes in microvasculature structure occur after the arrival of only 100s of tumor cells, that these changes extend to vessels that are relatively large (hundreds of microns in diameter), and that microvascular changes extend well beyond tumor margins, even soon after the onset of disease. These unique microvascular "cancer signatures" are a biomarker which provides us with a means to overcome traditional resolution limitations which otherwise impair micro-tumor detection. Thus, our innovative response to improving imaging sensitivity to micro-cancers is to detect these microvascular changes, rather than the solid tumor itself. Prior groups have illustrated the potential for this concept using optical microscopy, however optical microscopy is inherently non-clinically translatable for this application, and hence we are using a novel ultrasound approach. Although previously, ultrasound has not provided utility in assessing changes in microvascular structure, our group has recently implemented a new US imaging technique called "Acoustic Angiography" which provides supreme signal-to-noise and high resolution for imaging microvessel structure. This new imaging technique thus enables microvessel segmentation and tortuosity quantification. Encouraging preliminary pre-clinical data in have already illustrated our ability use acoustic angiography to discriminate small tumors and healthy tissue based on an analysis of microvessel morphology alone. The parent grant involves a comprehensive development of this promising new technology, including both optimizations of the imaging technique, as well as preclinical in-vivo studies using clinically-relevant genetically engineered rodent models of breast cancer to establish sensitivity and specificity in assessing the biomarker of tumor associated angiogenesis as a function of tumor size for early detection. In this supplement/revision application, we propose to carry the technology from the parent grant into a pilot clinical trial. Our goal is to demonstrate that this new imaging technology, Acoustic Angiography, will be effective in human patients. Our approach involves a 60 patient clinical study on patients with suspected breast cancer. Results will be compared for sensitivity and specificity against traditional ultrasound imaging (standard of care), as well as gold standard pathology provided as each patient will receive a biopsy or excision of the lesion. Although this small clinical pilot study will not be able to fully evaluatethe role of Acoustic Angiography in early cancer detection, the results of this study will provide necessary comparison data against gold standards to evaluate the potential efficacy of this new biomarker imaging technique, and help us optimize the technology and design a larger scale clinical trial as we move towards translation.

描述（由申请人提供）：众所周知，在整个血管生成过程中，肿瘤会极大地扭曲微脉管系统。数据表明，仅100次肿瘤细胞到达后，微血管结构发生了实质性变化，这些变化延伸到相对较大的血管（直径数百微米），即使在疾病发作后不久，微血管变化也远远超出了肿瘤缘。这些独特的微血管“癌症特征”是一种生物标志物，它为我们提供了一种克服传统分辨率限制的方法，否则会损害微肿瘤检测。因此，我们对提高成像对微型癌症的敏感性的创新反应是检测这些微血管变化，而不是实体瘤本身。先前的组已经使用光学显微镜说明了这种概念的潜力，但是对于此应用程序，光学显微镜本质上是非链式翻译的，因此我们使用了一种新型的超声方法。尽管以前，超声尚未提供评估微血管结构变化的实用性，但我们的小组最近实施了一种称为“声学血管造影”的新型美国成像技术，该技术提供了最高的信号到噪声和高分辨率，可用于成像微型处理结构。因此，这种新的成像技术可以使微血管分割和曲折度定量。鼓励初步的临床前数据已经说明了我们的能力使用声血管造影，以基于微血管形态的分析来区分小肿瘤和健康组织。父母的赠款涉及对这项有希望的新技术的全面发展，包括成像技术的优化，以及临床前的体内研究，使用临床上相关的乳腺癌基因啮齿动物模型，以确立敏感性和特异性，以评估肿瘤相关的血管生成的生物标志物，以期与早期检测的功能相关的血管生成与肿瘤大小的功能。在此补充/修订申请中，我们建议将该技术从父母赠款运送到试点临床试验中。我们的目标是证明这种新的成像技术，即声血管造影，对人类患者有效。我们的方法涉及对可疑乳腺癌患者进行60项患者临床研究。将比较结果的敏感性和特异性对传统的超声成像（护理标准），以及提供的金标准病理学，因为每个患者将接受活检或切除病变。尽管这项小型临床试验研究将无法完全评估声学血管造影在早期癌症检测中的作用，但这项研究的结果将根据金标准提供必要的比较数据，以评估这种新的生物标志物成像技术的潜在功效，并帮助我们优化技术和设计更大范围的临床试验，因为我们走向翻译。