Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice

Abstract

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.

Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish

“…14 MR elastography (MRE) is a versatile method that allows the noninvasive and 3D, spatially resolved mapping of viscoelasticity parameters in soft tissues for clinical diagnosis, 15 and biomedical research. [16][17][18][19][20] High-field MRE in small animal scanners has been applied to a wide variety of animal models, including Yucatan mini-pigs, 21 ferrets, 22 mice, 18,[23][24][25] rats, 26,27 and frog oocytes. 28 In small animal models, MRE can provide maps of viscoelasticity with a pixel size on the order of 180 µm.…”

MR Elastography in Cancer

“…30,42,97 On the other hand, stiffness is a critical parameter that is related to solid stress when supplemented by additional information. 40,41…”

“…Although the first represents a perfect soft solid, the second has strongly attenuating properties. 27 Magnetic resonance elastography holds great potential for the mechanical, noninvasive characterization of tumors in patients, 39 particularly for image-based quantification of solid stress 40,41 and tissue fluidity. 30,42 Current limits of MRE are related to its relatively low spatial resolution for the assessment of tumor heterogeneity as well as stability issues due to noise and possible negative interferences of propagating waves.…”

“…101 Magnetic resonance elastography quantification of solid stress has been demonstrated in controlled compression tests in animals; however, such tests are less well applicable in patients. 40,41 Sensitization of MRE to solid stress and tumor compression requires repeat MRE at different levels of prestress or assessment of tissue deformation induced by the growing mass. 102,103 Tissue deformation resulting from a displacing tumor mass can be derived from 3D MRI data based on the assumed undeformed geometry of the host tissue.…”

Added Value of Viscoelasticity for MRI-Based Prediction of Ki-67 Expression of Hepatocellular Carcinoma Using a Deep Learning Combined Radiomics (DLCR) Model

“…Higher Ki-67 expression is associated with faster progression and poorer prognosis for HCC patients. During tumor progression, increased vascularity and cellularity, a denser extracellular matrix, and higher interstitial pressure influenced the tumor stiffness and fluidity [ 33 , 34 ]. Moreover, constant elevating blood supply for maintaining tumor growth and development also had an impact on the tumor fluidity.…”