Microscopic multifrequency MR elastography for mapping viscoelasticity in zebrafish.

PURPOSE: The zebrafish (Danio rerio) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness of the role of biomechanical properties in tumor progression and neuronal development has led to an increasing interest in the noninvasive mapping of the viscoelastic properties of zebrafish by elastography methods applicable to bulky and nontranslucent tissues. METHODS: Microscopic multifrequency MR elastography is introduced for mapping shear wave speed (SWS) and loss angle (φ) as markers of stiffness and viscosity of muscle, brain, and neuroblastoma tumors in postmortem zebrafish with 60 µm in-plane resolution. Experiments were performed in a 7 Tesla MR scanner at 1, 1.2, and 1.4 kHz driving frequencies. RESULTS: Detailed zebrafish viscoelasticity maps revealed that the midbrain region (SWS = 3.1 ± 0.7 m/s, φ = 1.2 ± 0.3 radian [rad]) was stiffer and less viscous than telencephalon (SWS = 2.6 ± 0. 5 m/s, φ = 1.4 ± 0.2 rad) and optic tectum (SWS = 2.6 ± 0.5 m/s, φ = 1.3 ± 0.4 rad), whereas the cerebellum (SWS = 2.9 ± 0.6 m/s, φ = 0.9 ± 0.4 rad) was stiffer but less viscous than both (all p < .05). Overall, brain tissue (SWS = 2.9 ± 0.4 m/s, φ = 1.2 ± 0.2 rad) had similar stiffness but lower viscosity values than muscle tissue (SWS = 2.9 ± 0.5 m/s, φ = 1.4 ± 0.2 rad), whereas neuroblastoma (SWS = 2.4 ± 0.3 m/s, φ = 0.7 ± 0.1 rad, all p < .05) was the softest and least viscous tissue. CONCLUSION: Microscopic multifrequency MR elastography-generated maps of zebrafish show many details of viscoelasticity and resolve tissue regions, of great interest in neuromechanical and oncological research and for which our study provides first reference values.

The influence of static portal pressure on liver biophysical properties.

The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH2O). Our experiments demonstrated that, with increasing portal pressure, rat livers showed higher water content, water diffusivity, and increased vessel sizes quantified by the vessel tissue volume fraction (VTVF). These effects were most pronounced in native, unconfined livers (VTVF: 300±120%, p<0.05, ADC: 88±29%, p<0.01), while still significant under confinement (confined: VTVF: 53±32%, p<0.01, ADC: 28±19%, p<0.05; confined-fixed: VTVF: 52±20%, p<0.001, ADC: 11±2%, p<0.01; confined-viscous: VTVF: 210±110%, p<0.01, ADC: 26±9%, p<0.001). Softening with elevated portal pressure (-12±5, p<0.05) occurred regardless of confinement and fixation. However, the liver stiffened when exposed to a more viscous inflow fluid (11±4%, p<0.001). Taken together, our results elucidate the complex relationship between macroscopic-biophysical parameters of liver tissue measured by mpMRI and vascular-fluid properties. Influenced by portal pressure, vascular permeability, and matrix crosslinking, liver stiffness is sensitive to intrinsic poroelastic properties, which, alongside vascular architecture and water diffusivity, may aid in the differential diagnosis of liver disease. STATEMENT OF SIGNIFICANCE: Using highly controllable ex vivo rat liver phantoms, hepatic biophysical properties such as tissue-vascular structure, stiffness, and water diffusivity were investigated using multiparametric MRI including multifrequency magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). Through elaborate tuning of the experimental conditions such as the static portal pressure, flow viscosity, amount and distribution of fluid content in the liver, we identified the contributions of the fluid component to the overall imaging-based biophysical properties of the liver. Our finding demonstrated the sensitivity of liver stiffness to the hepatic poroelastic properties, which may aid in the differential diagnosis of liver diseases.