Noninvasive Pressure Estimation in Breast Cancer using Ultrasound

项目摘要 已知具有高肿瘤间质压（TIP）的乳腺癌对化疗反应差 由于药物输送差（即，高压防止药物进入肿瘤组织）。 最近的数据表明，TIP是一个潜在的有用参数，用于评估特定的乳腺癌是否 对全身性抗癌治疗有反应。此外，我们的团队有令人兴奋的数据， 所提出在乳腺癌组织中的无创压力估计可以使用一种新的 造影剂和定制技术，我们称之为使用US的TIP估计（TIPE-US）。 本项目的第一个目标是开发一种单分散相变造影剂（PCCA）， 在环境条件下稳定的液体纳米液滴，但可以使用US能量触发以经历 相变为高回声微泡（MB）。重要的是，这种相变是敏感的 受周围流体静压力控制，并与之线性相关。然后我们将确定最佳的 在精确改变周围流体的同时激活这些PCCA所需的US参数（能量） 在生理相关值的范围内的压力。将定制可编程US扫描仪， 启动并检测PCCA激活，然后将所使用的US能量转换为相应的压力值 通过查找表。第二个目的是评价TIPE-US在早期肿瘤监测中的应用价值 使用乳腺癌的动物模型来评估对抗癌疗法的应答（或缺乏应答）。 拟议实验的结果将确定TIPE-US是否是一种可行的新方法， 测量癌组织中的肿瘤内压力。这项创新技术最终可能被用于 均测量癌症患者的TIP，并监测新辅助治疗情况下的治疗，以区分 反应者和非反应者之间的差异，这反过来又将允许更好的，个性化的治疗选择， 被选中。

PROJECT SUMMARY It is known that breast cancers with high tumor interstitial pressure (TIP) respond poorly to chemotherapy because of poor drug delivery (i.e., the high pressure prevents the drug from entering the tumorous tissue). Recent data suggests TIP is a potentially useful parameter for assessing whether a particular breast cancer will in fact ever respond to systemic anticancer treatment. Moreover, our group has exciting data that would suggest noninvasive pressure estimation in breast cancer tissue can be performed in real-time using a novel contrast agent and custom technology we have termed TIP estimation using US (TIPE-US). The first aim of this project is to develop a monodisperse phase-change contrast agent (PCCA) that is a stabilized liquid nanodroplet under ambient conditions but can be triggered using US energy to undergo a phase transition into a highly echogenic microbubble (MB). Importantly, this phase transition is sensitively governed, and linearly related to, the surrounding hydrostatic fluid pressure. We will then determine the optimal US parameters (energy) required for activating these PCCA while precisely varying the surrounding fluid pressure across a range of physiologically relevant values. A programmable US scanner will be customized to initiate and detect PCCA activation and then convert the US energy used into a corresponding pressure value via lookup tables. In the second aim, we will evaluate the potential of TIPE-US for monitoring early tumor response (or lack thereof) to anticancer therapy using an animal model of breast cancer. The outcome of the proposed experiments will establish whether TIPE-US is a viable new method for measuring intratumoral pressure in cancerous tissue. This innovative technology may ultimately be utilized to both measure TIP in cancer patients and for monitoring treatment in the neoadjuvant setting to differentiate between responders and non-responders, which in turn will allow for better, individualized treatment options to be selected.