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

项目总结 乳腺癌现在是最常见的癌症，有230万妇女确诊，685,000人死亡 全球范围内。尽管，在过去的十年中，死亡率每年下降约1%，很大程度上是由于 通过筛查更早地发现，目前的筛查标准，数字乳房X光检查，缺乏敏感性和 在放射影像上致密的乳房中受到了挑战。通过磁疗提高致密乳房的敏感度 磁共振成像(MRI)，但需要对比度增强和大量额外的成本是缺点。一个 无对比度、低成本的替代超声应变弹性成像(SE)已被证明达到高 乳腺癌诊断的敏感性和特异性。然而，当SE诊断可疑乳房聚集时 通过询问组织僵硬，无法辨别僵硬的潜在原因。在许多可能的情况下 原因，间质胶原组织由于其最近被证实的相关性而成为新的关注焦点 具有乳腺癌分期、预后、治疗反应等临床特点。因此，划定 体内间质胶原组织不仅可以改善乳腺癌的诊断和治疗 管理，但也有助于阐明复杂的和鲜为人知的乳腺癌的病理生理学 发展、进步和进取。一种无创性评价基质胶原蛋白的方法 乳腺中的组织是超声剪切波弹性成像(SWE)，但剪切波传播是 在63%的恶性乳腺肿块中被抑制，导致低质量的测量。缺乏一个健壮的 超声方法询问间质胶原组织是利用 迅速崛起、前景看好的乳腺癌生物标记物。为了填补这一空白，我们团队开发了 粘弹性反应(VISR)超声，一种轴向检查胶原纤维组织结构的方法 在没有观察到剪切波传播的情况下，乳腺肿块和周围间质中的僵硬各向异性。我们的 在30名患有BIRADS-4或-5肿块的女性中获得的初步活体数据表明，VISR来源的 肿块与周围组织硬度各向异性的比率(RMSA)分化活检证实为恶性 乳腺良性肿块9例，敏感性为95%，特异性为89%。此外，在我们的试点中 对4名接受新辅助化疗(NAC)的妇女进行连续监测的可行性研究 RMSA指征由恶性向良性发展，对治疗有反应。我们的成功 调查推动VisR RMSA测量技术的进一步进步，其扩展到 揭示VisR RMSA结果与间质胶原组织和更广泛的关系 应用于癌症检测和治疗监测。我们假设：高级VisR RMSA与 间质胶原纤维组织与乳腺良恶性肿块的鉴别 以及在活体内预测女性对NAC的病理完全应答(PCR)。

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.