Noninvasive Pressure Estimation in Breast Cancer using Ultrasound

项目总结 众所周知，肿瘤间质压力(TIP)高的乳腺癌对化疗的反应很差。 因为药物输送不良(即，高压阻止药物进入肿瘤组织)。 最近的数据表明，TIP是一个潜在的有用的参数，用于评估特定的乳腺癌 事实上会对全身抗癌治疗有反应。此外，我们的团队有令人兴奋的数据， 提示乳腺癌组织中的非侵入性压力评估可以使用一种新的 造影剂和定制技术，我们称之为TIP评估使用US(TIPE-US)。 该项目的第一个目标是开发一种单分散相变造影剂(PCCA)，它是一种 在环境条件下稳定的液体纳米液滴，但可以使用美国能量触发 相变为高度回声的微泡(MB)。重要的是，这种相变是敏感的 受周围流体静压的控制，并与之呈线性关系。然后我们将确定最优的 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) 在一系列生理上相关的数值上的压力。一台可编程的美国扫描仪将被定制为 启动并检测PCCA激活，然后将所用的US能量转换为相应的压力值 通过查找表。在第二个目标中，我们将评估TIPE-US在监测早期肿瘤方面的潜力 使用乳腺癌动物模型对抗癌治疗的反应(或缺乏反应)。 拟议的实验结果将确定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 测量癌症患者的TIP和监测新辅助治疗环境中的治疗以区分 应答者和非应答者之间的差异，这反过来将允许更好的、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.