C02 Wideband dispersion mMRE for the detection of tissue fluidity in precancerous niches

越来越多的证据表明，有利于实体瘤形成的软组织改变往往与炎症、基质积累和血管渗漏引起的组织粘度和流动性异常有关。在二氧化碳中，我们将利用软组织的粘弹性分散作为异常组织流动性的生物物理特征来识别癌前生态位，这些生态位有肿瘤休眠和转移性定植的风险。与其他固体材料相比，柔软的生物组织具有独特的粘弹性分散特性，这意味着材料在低机械振动频率下类似于液体，在高机械振动频率下类似于刚性固体。然而，与低频剪切波的一致激发和反演相关的技术问题阻碍了在体内流体组织行为动态范围内成功实施MRE。此外，低振动频率从未与MRE中的经典频率范围相结合，无论是体内还是体外，用于全宽带分析粘弹性弥散，作为肿瘤形成和恶性转化的预测指标。我们的主要假设是，根据宽带粘弹性色散分析显示的组织流动性，包括低振动频率，可以在体内检测到癌前生态位的形成。为了验证这一假设，我们将首先开发一种方法，在患者的1至80 Hz和小组织样本的80 Hz至kHz范围内的扩展频段内，以高空间分辨率一致地绘制软组织粘弹性色散。利用这种新型的多频MRE （mMRE）技术，我们将研究A02分析的不同程度炎症、纤维化和代谢能力患者的肝脏，并将其与健康对照组和C01研究的肝脏肿瘤患者进行比较。此外，我们将开发高分辨率微观宽带MRE（µMRE）方法，以获取和分析从C01和B02接收的肿瘤标本和肿瘤环境中的粘弹性分散数据，并建立流动性作为早期肿瘤形成的标志。在这个研究单位内，C02将负责(i)开发宽带mmre成像硬件和临床和临床前扫描仪的序列，这些将提供给B01， B02和C01；（ii）为A01、B01、B02、B03和C01提供体内和体外粘弹性分散数据分析工具；（iii）建立mre测量的流动性，用于检测癌症的生物力学特征，该特征与肿瘤细胞运动和解除干扰过渡（与A03和C03）密切相关。C02关注肝脏炎症、纤维化、代谢变化（A02）和早期肿瘤形成（C01），结合肝组织的组织病理学变化，旨在揭示软实体组织形成癌前生态位的流体特征。

There is growing evidence that soft tissue alterations in favor of solid tumor formation are often associated with abnormal viscosity and tissue fluidity caused by inflammation, matrix accumulation and vascular leakage. In C02, we will leverage the viscoelastic dispersion of soft tissue as biophysical signature of abnormal tissue fluidity to identify precancerous niches, which are at risk of tumor dormancy and metastatic colonialization. Compared with other solid materials, soft biological tissues possess unique viscoelastic dispersion properties, meaning that the materials resemble those of liquids at low mechanical vibration frequencies and rigid solids at higher frequencies. However, technical issues related to consistent excitation and inversion of low-frequency shear waves have prevented successful implementation of MRE in the dynamic range of fluid tissue behavior in vivo. Furthermore, low vibration frequencies have never been combined with the classical frequency ranges in MRE, both in vivo and ex vivo, for full wideband analysis of viscoelastic dispersion as predictive marker for tumor formation and malignant transformation. Our main hypothesis underlying this project is that the formation of precancerous niches can be detected in vivo based on tissue fluidity as revealed by wideband viscoelastic dispersion analysis, including low vibration frequencies. To test this hypothesis, we will first develop methods that consistently map soft tissue viscoelastic dispersion with high spatial resolution in an extended frequency band from 1 to 80 Hz in patients and from 80 Hz to the kHz range in small tissue samples. Using this novel multifrequency MRE (mMRE) technology, we will study the livers of patients with various degrees of inflammation, fibrosis and metabolic capacities as analyzed by A02 in comparison to healthy controls and patients with liver tumors investigated in C01. Moreover, we will develop the methods for high-resolution microscopic wideband MRE (µMRE) to acquire and analyze viscoelastic dispersion data in specimens of tumors and tumor environment received from C01 and B02 and to establish fluidity as a marker for early tumor formation. Within this research unit, C02 will be responsible for (i) the development of wideband-mMRE imaging hardware and sequences in clinical and preclinical scanners which will be provided to B01, B02 and C01; (ii) provision of analysis tools for viscoelastic dispersion data in vivo and ex vivo to A01, B01, B02, B03 and C01; and (iii) establishment of mMRE-measured fluidity for detecting the biomechanical hallmark of cancer that is critically linked to tumor cell motility and unjamming transitions (with A03 and C03). Focused on liver inflammation, fibrosis, metabolic changes (A02) and early tumor formation (C01) in combination with histopathological changes of hepatic tissues, C02 aims to reveal the fluid signature of soft solid tissue forming a precancerous niche.