Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Sci Rep. 2020 Feb 12;10(1):2478. doi: 10.1038/s41598-020-59338-z.
Ultrasound localization microscopy (ULM) permits the reconstruction of super-resolved microvascular images at clinically relevant penetration depths, which can be potentially leveraged to provide non-invasive quantitative measures of tissue hemodynamics and hypoxic status. We demonstrate that ULM microbubble data processing methods, applied to images acquired with a Verasonics Vantage 256 system, can provide a non-invasive imaging surrogate biomarker of tissue oxygenation status. This technique was applied to evaluate the microvascular structure, vascular perfusion, and hypoxia of a renal cell carcinoma xenograft model grown in the chorioallantoic membrane of chicken embryos. Histological microvascular density was significantly correlated to ULM measures of intervessel distance (R = -0.92, CI = [-0.99,-0.42], p = 0.01). The Distance Metric, a measure of vascular tortuosity, was found to be significantly correlated to hypoxyprobe quantifications (R = 0.86, CI = [0.17, 0.99], p = 0.03). ULM, by providing non-invasive in vivo microvascular structural information, has the potential to be a crucial clinical imaging modality for the diagnosis and therapy monitoring of solid tumors.
超声定位显微镜（ULM）可在临床相关的穿透深度重建超分辨率微血管图像，这可潜在地用于提供组织血液动力学和缺氧状态的非侵入性定量测量。我们证明，应用于 Verasonics Vantage 256 系统获取的图像的 ULM 微泡数据处理方法，可以提供组织氧合状态的非侵入性成像替代生物标志物。该技术应用于评估在鸡胚脉络膜卵黄囊中生长的肾癌细胞异种移植模型的微血管结构、血管灌注和缺氧。组织学微血管密度与 ULM 血管间距离测量值呈显著负相关（R=-0.92，CI=[-0.99，-0.42]，p=0.01）。距离度量（一种血管迂曲度的测量方法）与缺氧探针定量呈显著正相关（R=0.86，CI=[0.17，0.99]，p=0.03）。ULM 通过提供非侵入性的体内微血管结构信息，有潜力成为诊断和治疗监测实体瘤的重要临床成像方式。
