Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Department of Biophysics, Johns Hopkins University, Baltimore, MD, 21205, USA.
Sci Rep. 2020 Feb 11;10(1):2372. doi: 10.1038/s41598-020-58918-3.
Abnormal tumor hemodynamics are a critical determinant of a tumor's microenvironment (TME), and profoundly affect drug delivery, therapeutic efficacy and the emergence of drug and radio-resistance. Since multiple hemodynamic variables can simultaneously exhibit transient and spatiotemporally heterogeneous behavior, there is an exigent need for analysis tools that employ multiple variables to characterize the anomalous hemodynamics within the TME. To address this, we developed a new toolkit called HemoSYS for quantifying the hemodynamic landscape within angiogenic microenvironments. It employs multivariable time-series data such as in vivo tumor blood flow (BF), blood volume (BV) and intravascular oxygen saturation (Hb) acquired concurrently using a wide-field multicontrast optical imaging system. The HemoSYS toolkit consists of propagation, clustering, coupling, perturbation and Fourier analysis modules. We demonstrate the utility of each module for characterizing the in vivo hemodynamic landscape of an orthotropic breast cancer model. With HemoSYS, we successfully described: (i) the propagation dynamics of acute hypoxia; (ii) the initiation and dissolution of distinct hemodynamic niches; (iii) tumor blood flow regulation via local vasomotion; (iv) the hemodynamic response to a systemic perturbation with carbogen gas; and (v) frequency domain analysis of hemodynamic heterogeneity in the TME. HemoSYS (freely downloadable via the internet) enables vascular phenotyping from multicontrast in vivo optical imaging data. Its modular design also enables characterization of non-tumor hemodynamics (e.g. brain), other preclinical disease models (e.g. stroke), vascular-targeted therapeutics, and hemodynamic data from other imaging modalities (e.g. MRI).
异常肿瘤血液动力学是肿瘤微环境（TME）的关键决定因素，它深刻地影响着药物输送、治疗效果以及药物和放射抗性的出现。由于多个血液动力学变量可以同时表现出瞬态和时空异质性的行为，因此迫切需要使用多个变量来分析工具来描述 TME 内异常血液动力学的特征。为了解决这个问题，我们开发了一个名为 HemoSYS 的新工具包，用于量化血管生成微环境中的血液动力学景观。它采用多变量时间序列数据，如使用宽场多对比光学成像系统同时获得的体内肿瘤血流（BF）、血液体积（BV）和血管内氧饱和度（Hb）。HemoSYS 工具包由传播、聚类、耦合、扰动和傅里叶分析模块组成。我们展示了每个模块用于描述正交乳腺癌模型体内血液动力学景观的能力。使用 HemoSYS，我们成功描述了：（i）急性缺氧的传播动力学；（ii）不同血液动力学小生境的启动和溶解；（iii）通过局部血管运动调节肿瘤血流；（iv）用碳化氧气体对全身扰动的血液动力学反应；（v）TME 中血液动力学异质性的频域分析。HemoSYS（可通过互联网免费下载）能够从多对比体内光学成像数据中进行血管表型分析。其模块化设计还能够对非肿瘤血液动力学（如大脑）、其他临床前疾病模型（如中风）、血管靶向治疗以及来自其他成像模式（如 MRI）的血液动力学数据进行特征描述。
