Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Department of Small Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA.
J Ultrasound Med. 2024 Jun;43(6):1099-1107. doi: 10.1002/jum.16438. Epub 2024 Feb 27.
Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA).
A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross-section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash-in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels.
SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P > .09), both SRUS-derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P = .03 and P = .05, respectively) and 24 hours (P = .02 and P = .01, respectively), but not in control group tumors (P > .22). Similarly, SRUS derived microvascular maps were not different at baseline (P = .81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P < .04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R > .09, P < .03).
SRUS imaging is a new modality for assessing tumor response to treatment using a VDA.
评估使用超分辨率超声（SRUS）成像技术检测血管破坏剂（VDA）治疗肿瘤反应的早期变化。
将 28 只雌性无胸腺裸鼠（Charles River Laboratories）种植人乳腺癌细胞（MDA-MB-231，ATCC）于乳腺脂肪垫，待其生长。使用 Vevo 3100 扫描仪（FUJIFILM VisualSonics Inc）进行超声成像，配备 MX250 线阵换能器，在尾静脉内推注微泡（MB）造影剂（Definity，Lantheus Medical Imaging）前后进行。基线超声成像后，通过放置的导管注射 VDA 药物（康普瑞汀 A4 磷酸盐，CA4P，Sigma Aldrich）或对照生理盐水。4 或 24 小时后，对同一肿瘤横切面进行重复超声成像。使用校准传感器直接测量肿瘤内压。所有原始超声数据均保存在线处理和使用自定义 MATLAB 软件（MathWorks Inc）进行 SRUS 图像重建。从包含肿瘤空间和整个后处理超声图像序列的区域生成时间 MB 计数（TMC）曲线，以及反映每个像素位置 MB 计数的传统 SRUS 图。从这些 TMC 曲线中提取峰值增强（PE）和流入率（WIR）。在结束时，使用番茄凝集素标记显影的血管对肿瘤内微血管密度（MVD）进行量化。
SRUS 图像在对照和治疗肿瘤之间显示出明显差异。虽然在基线时（0 小时，P>0.09）各组参数无差异，但 VDA 治疗的肿瘤的 SRUS 衍生的 PE 和 WIR 测量值在 4 小时（P=0.03 和 P=0.05）和 24 小时（P=0.02 和 P=0.01）时均显著降低，但在对照组肿瘤中没有差异（P>0.22）。同样，基线时 SRUS 衍生的微血管图无差异（P=0.81），但治疗后肿瘤的血管密度测量值在 4 小时和 24 小时时均较低（P<0.04）。在对照组肿瘤中发现肿瘤内压与 PE 和 WIR 参数之间呈负相关（R>0.09，P<0.03）。
SRUS 成像技术是一种新的评估血管破坏剂治疗肿瘤反应的方法。
