Project Details
Projekt
C02 Wideband dispersion mMRE for the detection of tissue fluidity in precancerous niches
Subject Area
Medical Physics, Biomedical Technology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 513752256
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.
DFG Programme
Research Units
