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.

项目概要乳腺癌现在是最常见的癌症，有 230 万名女性被诊断出乳腺癌，685,000 人死亡全球。尽管如此，死亡率在过去十年中每年下降约 1%，这在很大程度上是由于通过筛查进行早期检测，目前的筛查标准数字乳房X线摄影缺乏敏感性和在放射学上致密的乳房中面临挑战。通过磁力提高致密乳房的敏感性磁共振成像（MRI），但需要增强对比度和大量额外成本是缺点。一个非对比、低成本替代方案超声应变弹性成像 (SE) 已被证明可以实现高乳腺癌诊断的敏感性和特异性。然而，虽然 SE 诊断出可疑的乳房肿块通过询问组织僵硬度，无法识别僵硬的根本原因。在众多的可能中由于其最近被证明的关联性，基质胶原蛋白组织最近成为人们强烈关注的焦点与乳腺癌分期、预后、治疗反应和其他临床特征有关。因此，划定体内基质胶原组织不仅可以改善乳腺癌的诊断和治疗管理，还有助于阐明乳腺癌复杂且知之甚少的病理生理学发展、进步和进取性。一种无创评估基质胶原的方法乳房组织是超声剪切波弹性成像（SWE），但剪切波传播是 63% 的恶性乳腺肿块受到抑制，导致测量结果质量低下。缺乏稳健的超声方法询问基质胶原组织代表了利用胶原蛋白的主要差距快速新兴且极具前景的乳腺癌生物标志物。为了填补这一空白，我们小组开发了粘弹性响应 (VisR) 超声，一种通过轴检查胶原纤维组织的方法乳腺肿块和周围基质的硬度各向异性，无需观察剪切波传播。我们的在 30 名患有 BIRADS-4 或 -5 肿块的女性中获得的初步体内数据表明，VisR 衍生的肿块与周围组织硬度各向异性 (RMSA) 的比率区分活检证实的恶性 (n=9) 来自良性 (n=21) 乳腺肿块，敏感性为 95%，特异性为 89%。此外，在我们的试点中对四名女性在接受新辅助化疗 (NAC)、VisR 期间进行连续监测的可行性研究随着治疗的反应，RMSA 从恶性指标趋向于良性指标。我们的成功研究推动 VisR RMSA 测量技术的进一步发展，将其扩展到揭示 VisR RMSA 结果与基质胶原组织之间的关系，以及更广泛的应用于癌症检测和治疗监测。我们假设：Advanced VisR RMSA 与基质胶原纤维组织，与区分恶性和良性乳腺肿块有关并预测女性体内 NAC 的病理完全缓解 (pCR)。