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

C02 宽带色散 mMRE 用于检测癌前微环境中的组织流动性

• 批准号: 530849360
• 负责人: Privatdozent Dr. Rolf Otto Reiter
• 金额: --
• 依托单位: Klinik für Radiologie (mit dem Bereich Kinderradiologie) (CCM)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/530849360?language=en
• 关键词: C02; Wideband; dispersion; mMRE; detection

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.

越来越多的证据表明，有利于实体瘤形成的软组织改变通常与炎症、基质积聚和血管渗漏引起的异常粘度和组织流动性有关。在C 02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处于肿瘤休眠和转移性定殖的风险中的癌前小生境。与其他固体材料相比，软生物组织具有独特的粘弹性分散特性，这意味着该材料在低机械振动频率下类似于液体，在较高频率下类似于刚性固体。然而，与低频剪切波的一致激励和反转相关的技术问题已经阻止了在体内流体组织行为的动态范围中成功实施MRE。此外，低振动频率从未与MRE中的经典频率范围结合，无论是在体内还是体外，用于粘弹性分散体的全宽带分析，作为肿瘤形成和恶性转化的预测标记。本项目的主要假设是，癌前壁龛的形成可以在体内检测的基础上，通过宽带粘弹性色散分析，包括低振动频率揭示的组织流动性。为了检验这一假设，我们将首先开发出一种方法，该方法在患者中从1 Hz到80 Hz的扩展频带中以及在小组织样本中从80 Hz到kHz的范围内以高空间分辨率一致地映射软组织粘弹性色散。使用这种新的多频率MRE（mMRE）技术，我们将研究A02分析的具有不同程度炎症、纤维化和代谢能力的患者的肝脏，并与C 01中研究的健康对照和肝肿瘤患者进行比较。此外，我们将开发高分辨率显微宽带MRE（µMRE）的方法，以获取和分析从C 01和B 02接收的肿瘤和肿瘤环境样本中的粘弹性分散数据，并将流动性作为早期肿瘤形成的标志。在该研究单位内，C 02将负责（i）开发临床和临床前扫描仪中的宽带mMRE成像硬件和序列，并将其提供给B 01、B 02和C 01;（ii）为A01、B 01、B 02、B 03和C 01提供体内和体外粘弹性分散数据的分析工具;和（iii）建立mMRE测量的流动性，用于检测与肿瘤细胞运动性和不干扰转变（用A03和C 03）密切相关的癌症生物力学标志。C 02聚焦于肝脏炎症、纤维化、代谢变化（A02）和早期肿瘤形成（C 01），结合肝组织的组织病理学变化，旨在揭示形成癌前生态位的软固体组织的流体特征。