Noninvasive Pressure Estimation in Breast Cancer using Ultrasound

使用超声波对乳腺癌进行无创压力估计

基本信息

批准号：
9225468
负责人：
Kenneth Hoyt
金额：
$ 19.97万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-12 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9225468
关键词：
Acoustics Adopted Angiogenesis Inhibitors Animal Model Animals Antineoplastic Agents Blood Vessels Breast Cancer Cell Breast Cancer Model Breast Cancer Patient Cancer Patient Cancerous Clinical Management Contrast Media Custom Data Detection Development Drug Delivery Systems Extracellular Space Goals Gold Growth Human Hydrostatic Pressure Image Implant Liquid substance Measurement Measures Methods Microbubbles Monitor Morbidity - disease rate Mus Needles Neoadjuvant Therapy Normal tissue morphology Operative Surgical Procedures Outcome Paclitaxel Patient Monitoring Patients Pharmaceutical Preparations Phase Transition Physiologic pulse Physiological Publishing Research Project Grants Research Proposals Subgroup System Systemic Therapy Techniques Technology Testing Time Tissues Ultrasonic Therapy Ultrasonography Woman anticancer treatment base cancer therapy chemotherapy contrast enhanced experimental study improved in vivo individual patient individualized medicine innovation innovative technologies interstitial intravenous administration lymphatic drainage malignant breast neoplasm nanoDroplet nanoscale new technology next generation novel phase change pressure prevent programs responders and non-responders response technology development time use tumor tumor growth uptake vapor vaporization

项目摘要

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.

项目概要众所周知，肿瘤间质压力（TIP）高的乳腺癌对化疗的反应较差由于药物输送不良（即高压阻止药物进入肿瘤组织）。最近的数据表明，TIP 是评估特定乳腺癌是否存在的潜在有用参数。事实上，系统性抗癌治疗会对患者产生反应。此外，我们的团队拥有令人兴奋的数据建议可以使用一种新颖的方法实时进行乳腺癌组织中的无创压力估计我们将造影剂和定制技术称为使用 US 的 TIP 估计 (TIPE-US)。该项目的首要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滴，但可以使用美国能量触发以经历相转变为高回声微泡 (MB)。重要的是，这种相变是敏感的受周围静水压力的控制并与其线性相关。然后我们将确定最佳的激活这些 PCCA 同时精确改变周围流体所需的 US 参数（能量）一系列生理相关值的压力。可编程美国扫描仪将被定制启动并检测PCCA激活，然后将使用的US能量转换为相应的压力值通过查找表。第二个目标是评估 TIPE-US 监测早期肿瘤的潜力使用乳腺癌动物模型对抗癌治疗有反应（或缺乏反应）。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瘤内压力。这项创新技术最终可能用于两者都测量癌症患者的 TIP 并监测新辅助治疗中的治疗以区分反应者和非反应者之间的差异，这反过来又将为患者提供更好的、个性化的治疗选择被选中。