Department of Electrical and Computer Engineering, University of Rochester, Rochester, New York.
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Clin Cancer Res. 2019 Apr 1;25(7):2136-2143. doi: 10.1158/1078-0432.CCR-18-2684. Epub 2018 Oct 23.
High tissue pressure prevents chemotherapeutics from reaching the core of pancreatic tumors. Therefore, targeted therapies have been developed to reduce this pressure. While point probes have shown the effectiveness of these pressure-reducing therapies via single-location estimates, ultrasound elastography is now widely available as an imaging technique to provide real-time spatial maps of shear modulus (tissue stiffness). However, the relationship between shear modulus and the underlying tumor microenvironmental causes of high tissue pressure has not been investigated. In this work, elastography was used to investigate how shear modulus influences drug delivery , and how it correlates with collagen density, hyaluronic acid content, and patent vessel density-features of the tumor microenvironment known to influence tissue pressure.
Intravenous injection of verteporfin, an approved human fluorescent drug, was used in two pancreatic cancer xenograft models [AsPC-1 ( = 25) and BxPC-3 ( = 25)].
Fluorescence intensity was higher in AsPC-1 tumors than in BxPC-3 tumors ( < 0.0001). Comparing drug uptake images and shear wave elastographic images with histologic images revealed that: (i) drug delivery and shear modulus were inversely related, (ii) shear modulus increased linearly with increasing collagen density, and (iii) shear modulus was marginally correlated with the local assessment of hyaluronic acid content.
These results demonstrate that elastography could guide targeted therapy and/or identify patients with highly elevated tissue pressure..
高组织压力阻止化疗药物到达胰腺肿瘤的核心部位。因此，已经开发了靶向疗法来降低这种压力。虽然点探针通过单点估计显示了这些减压疗法的有效性，但超声弹性成像现在作为一种成像技术广泛应用于提供剪切模量（组织硬度）的实时空间图谱。然而，剪切模量与导致高组织压力的肿瘤微环境的潜在原因之间的关系尚未得到研究。在这项工作中，弹性成像被用于研究剪切模量如何影响药物输送，以及它如何与胶原密度、透明质酸含量和已知影响组织压力的有功能血管密度相关。
静脉注射批准的人荧光药物维替泊芬，用于两种胰腺癌细胞异种移植模型[AsPC-1（=25）和 BxPC-3（=25）]。
与 BxPC-3 肿瘤相比，AsPC-1 肿瘤中的荧光强度更高（<0.0001）。将药物摄取图像和剪切波弹性成像图像与组织学图像进行比较表明：（i）药物输送与剪切模量呈负相关，（ii）剪切模量随胶原密度的增加呈线性增加，（iii）剪切模量与局部透明质酸含量评估呈边缘相关。
这些结果表明，弹性成像可以指导靶向治疗和/或识别组织压力高度升高的患者。
