VisR Ultrasound for Noninvasively Interrogating Stromal Collagen Organization in Women as a Breast Cancer Biomarker

VisR 超声无创检查女性基质胶原蛋白组织作为乳腺癌生物标志物

基本信息

批准号：
10680931
负责人：
Caterina M Gallippi
金额：
$ 59.35万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-15 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10680931
关键词：
Acoustics Adjuvant Chemotherapy Adverse effects Anisotropy Benign Biological Markers Biopsy Breast Cancer Detection Cessation of life Clinical Collagen Collagen Fiber Complex Custom Data Data Collection Death Rate Dependence Development Diagnosis Diagnostic Neoplasm Staging Diagnostic Sensitivity Digital Breast Tomosynthesis Digital Mammography Disease Progression Early Diagnosis Feasibility Studies Functional disorder Goals Imaging technology In complete remission Investigation Learning Lesion Magnetic Resonance Imaging Malignant - descriptor Malignant Neoplasms Manuals Mass in breast Measurement Monitor Neoadjuvant Therapy Neoplasm Metastasis Outcome Pathologic Patients Pattern Performance Prognosis Public Health Radiation Radiation Dose Unit Reporting Sensitivity and Specificity Specificity Stress Technology Tissues Woman Women&apos s Health Work breast cancer diagnosis cancer biomarkers cancer diagnosis cancer therapy cancer type clinically relevant contrast enhanced cost elastography histological studies improved in silico in vivo interest malignant breast neoplasm radiological imaging response restraint screening success treatment response trend ultrasound viscoelasticity

项目摘要

PROJECT SUMMARY Breast cancer is now the most prevalent cancer, with 2.3 million women diagnosed and 685,000 deaths globally. Although, the death rate has declined by about 1% per year over the last decade due in large part to earlier detection through screening, the current screening standard, digital mammography, lacks sensitivity and is challenged in radiographically dense breasts. Sensitivity in dense breasts is improved by magnetic resonance imaging (MRI), but required contrast enhancement and substantial additional cost are drawbacks. A non-contrast, low-cost alternative, ultrasound strain elastography (SE) has been shown to achieve high sensitivity and specificity for breast cancer diagnosis. However, while SE diagnoses suspicious breast massed by interrogating tissue stiffness, the underlying cause of stiffening is not discerned. Among the many possible causes, stromal collagen organization is newly a focus of intense interest due to its recently proven association with breast cancer stage, prognosis, treatment response, and other clinical features. Therefore, delineating stromal collagen organization in vivo would not only improve breast cancer diagnosis and treatment management but also help to elucidate the complex and poorly understood pathophysiology of breast cancer development, progression, and aggressiveness. One approach to noninvasively evaluating stromal collagen organization in the breast is ultrasound shear wave elastography (SWE), but shear wave propagation is inhibited in 63% of malignant breast masses, leading to low-quality measurements. The lack of a robust ultrasound approach to interrogating stromal collagen organization represents a major gap in exploiting a rapidly emerging and highly promising biomarker for breast cancer. To fill this gap, our group has developed Viscoelastic Response (VisR) ultrasound, an on-axis approach to interrogating collagen fiber organization via stiffness anisotropy in breast masses and surrounding stroma without observing shear wave propagation. Our preliminary in vivo data, acquired in 30 women with BIRADS-4 or -5 masses, demonstrate that VisR-derived ratio of mass-to-surrounding tissue stiffness anisotropy (RMSA) differentiated biopsy-confirmed malignant (n=9) from benign (n=21) breast masses with a sensitivity of 95% and a specificity of 89%. Further, in our pilot feasibility study of four women monitored serially while undergoing neoadjuvant chemotherapy (NAC), VisR RMSA trended from malignant to benign indication with response to treatment. The success of our investigations motivates further advancement of VisR RMSA measurement technology, its extension to revealing the relationship between VisR RMSA outcomes and stromal collagen organization, and broader application to cancer detection and treatment monitoring. We hypothesize: Advanced VisR RMSA correlates to stromal collagen fiber organization, which is relevant to differentiating malignant from benign breast masses and predicting pathologic complete response (pCR) to NAC in women, in vivo.

项目摘要乳腺癌现在是最普遍的癌症，有230万妇女被诊断出和685,000人死亡全球。虽然，在过去的十年中，死亡率每年下降约1％，这在很大程度上是由于通过筛查，当前筛查标准，数字乳房X线摄影，缺乏灵敏度和在射线照相密集的乳房中受到挑战。磁性的敏感性通过磁性提高共振成像（MRI），但需要增强对比度和大量额外成本是缺点。一个已证明非对比度，低成本替代性，超声菌株弹性图（SE）可实现高乳腺癌诊断的敏感性和特异性。但是，尽管SE诊断出可疑的乳房通过询问组织刚度，无法分辨出僵硬的根本原因。在许多可能的原因是，由于其最近经过证明的关联乳腺癌阶段，预后，治疗反应和其他临床特征。因此，描绘体内基质胶原蛋白组织不仅会改善乳腺癌的诊断和治疗管理，但也有助于阐明乳腺癌的复杂且知之甚少的病理生理学发展，进步和侵略性。一种非侵入性评估基质胶原蛋白的方法乳房中的组织是超声剪切波弹性图（SWE），但剪切波传播是抑制63％的恶性乳房肿块，导致低质量的测量。缺乏强大的超声询问基质胶原蛋白组织的超声方法是利用A的主要差距迅速出现的乳腺癌生物标志物。为了填补这一空白，我们的小组已经发展了粘弹性响应（VISR）超声，这是一种通过乳房和周围基质中的刚度各向异性，而无需观察剪切波的传播。我们的初步的体内数据，在30名患有Birads-4或-5群众的女性中获得质量与刺激组织刚度各向异性（RMSA）的比率分化了活检证实的恶性肿瘤（n = 9）来自良性（n = 21）的乳腺肿块，灵敏度为95％，特异性为89％。此外，在我们的飞行员中对新辅助化疗（NAC），VISR进行了连续监测的四名妇女的可行性研究 RMSA从恶性趋向于良性指示，并响应治疗。我们的成功调查激发了Visr RMSA测量技术的进一步发展，其扩展为揭示Visr RMSA结果与基质胶原蛋白组织之间的关系，更广泛应用于癌症检测和治疗监测。我们假设：高级Visr RMSA与基质胶原蛋白纤维组织，这与良性乳腺肿块区分开并预测体内女性NAC的病理完全反应（PCR）。