Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
J Ultrasound Med. 2024 Jan;43(1):137-150. doi: 10.1002/jum.16347. Epub 2023 Oct 24.
Quantitative ultrasound (QUS) is a noninvasive imaging technique that can be used for assessing response to anticancer treatment. In the present study, tumor cell death response to the ultrasound-stimulated microbubbles (USMB) and hyperthermia (HT) treatment was monitored in vivo using QUS.
Human breast cancer cell lines (MDA-MB-231) were grown in mice and were treated with HT (10, 30, 50, and 60 minutes) alone, or in combination with USMB. Treatment effects were examined using QUS with a center frequency of 25 MHz (bandwidth range: 16 to 32 MHz). Backscattered radiofrequency (RF) data were acquired from tumors subjected to treatment. Ultrasound parameters such as average acoustic concentration (AAC) and average scatterer diameter (ASD), were estimated 24 hours prior and posttreatment. Additionally, texture features: contrast (CON), correlation (COR), energy (ENE), and homogeneity (HOM) were extracted from QUS parametric maps. All estimated parameters were compared with histopathological findings.
The findings of our study demonstrated a significant increase in QUS parameters in both treatment conditions: HT alone (starting from 30 minutes of heat exposure) and combined treatment of HT plus USMB finally reaching a maximum at 50 minutes of heat exposure. Increase in AAC for 50 minutes HT alone and USMB +50 minutes was found to be 5.19 ± 0.417% and 5.91 ± 1.11%, respectively, compared to the control group with AAC value of 1.00 ± 0.44%. Furthermore, between the treatment groups, ΔASD-ENE values for USMB +30 minutes HT significantly reduced, depicting 0.00062 ± 0.00096% compared to 30 minutes HT only group, showing 0.0058 ± 0.0013%. Further, results obtained from the histological analysis indicated greater cell death and reduced nucleus size in both HT alone and HT combined with USMB.
The texture-based QUS parameters indicated a correlation with microstructural changes obtained from histological data. This work demonstrated the use of QUS to detect HT treatment effects in breast cancer tumors in vivo.
定量超声（QUS）是一种非侵入性成像技术，可用于评估抗癌治疗的效果。在本研究中，我们使用 QUS 技术在体监测超声刺激微泡（USMB）和热疗（HT）治疗对肿瘤细胞死亡的反应。
人乳腺癌细胞系（MDA-MB-231）在小鼠中生长，并单独接受 HT（10、30、50 和 60 分钟）治疗，或与 USMB 联合治疗。使用中心频率为 25 MHz（带宽范围：16 至 32 MHz）的 QUS 检查治疗效果。从接受治疗的肿瘤中获取反向散射射频（RF）数据。在治疗前 24 小时和治疗后，估计超声参数，如平均声强（AAC）和平均散射体直径（ASD）。此外，从 QUS 参数图中提取纹理特征：对比度（CON）、相关性（COR）、能量（ENE）和均匀性（HOM）。比较所有估计参数与组织病理学发现。
我们的研究结果表明，在 HT 单独治疗（从 30 分钟的热暴露开始）和 HT 联合 USMB 治疗的两种治疗条件下，QUS 参数均显著增加，最终在 50 分钟的热暴露时达到最大值。单独 HT 治疗 50 分钟和 USMB+50 分钟的 AAC 增加分别为 5.19±0.417%和 5.91±1.11%，与 AAC 值为 1.00±0.44%的对照组相比。此外，在治疗组之间，USMB+30 分钟 HT 的 ΔASD-ENE 值显著降低，为 0.00062±0.00096%，而仅 30 分钟 HT 组为 0.0058±0.0013%。此外，组织学分析结果表明，单独 HT 治疗和 HT 联合 USMB 治疗均可导致细胞死亡增加和细胞核缩小。
基于纹理的 QUS 参数与组织学数据中获得的微观结构变化相关。本研究证明了 QUS 在体内检测乳腺癌肿瘤 HT 治疗效果的应用。
