1-Norm waveform analysis for MR elastography-based quantification of inhomogeneity: Effects of the freeze-thaw cycle and Alzheimer's disease.

BACKGROUND: Despite its success in the mechanical characterization of biological tissues, magnetic resonance elastography (MRE) uses ill-posed wave inversions to estimate tissue stiffness. 1-Norm has been recently introduced as a mathematical measure for the scattering of mechanical waves due to inhomogeneities based on an analysis of the delineated contours of wave displacement. PURPOSE: To investigate 1-Norm as an MRE-based quantitative biomarker of mechanical inhomogeneities arising from microscopic structural tissue alterations caused by the freeze-thaw cycle (FTC) or Alzheimer's disease (AD). METHODS: In this proof-of-concept study, we prospectively investigated excised porcine kidney (n = 6), liver (n = 6), and muscle (n = 6) before vs. after the FTC at 500-2000 Hz and excised murine brain of healthy controls (n = 3) vs. 5xFAD species with AD (n = 3) at 1200-1800 Hz using 0.5 T tabletop MRE. 1-Norm analysis was compared with conventional wave inversion. RESULTS: While the FTC reduced both stiffness and inhomogeneity in kidney, liver, and muscle tissue, AD led to lower brain stiffness but more pronounced mechanical inhomogeneity. CONCLUSION: Our preliminary results show that 1-Norm is sensitive to tissue mechanical inhomogeneity due to FTC and AD without relying on ill-posed wave inversion techniques. 1-Norm has the potential to be used as an MRE-based diagnostic biomarker independent of stiffness to characterize abnormal conditions that involve changes in tissue mechanical inhomogeneity.

Sound transmission in human thorax through airway insonification: an experimental and computational study with diagnostic applications.

Pulmonary diseases and injury lead to structural and functional changes in the lung parenchyma and airways, often resulting in measurable sound transmission changes on the chest wall surface. Additionally, noninvasive imaging of externally driven mechanical wave motion in the chest (e.g., using magnetic resonance elastography) can provide information about lung stiffness and other structural property changes which may be of diagnostic value. In the present study, a comprehensive computational simulation (in silico) model was developed to simulate sound wave propagation in the airways, parenchyma, and chest wall under normal and pathological conditions that create distributed structural (e.g., pneumothoraces) and diffuse material (e.g., fibrosis) changes, as well as a localized structural and material changes as may be seen with a neoplasm. Experiments were carried out in normal subjects to validate the baseline model. Sound waves with frequency content from 50 to 600 Hz were introduced into the airways of three healthy human subjects through the mouth, and transthoracic transmitted waves were measured by scanning laser Doppler vibrometry at the chest wall surface. The computational model predictions of a frequency-dependent decreased sound transmission due to pneumothorax were consistent with experimental measurements reported in previous work. Predictions for the case of fibrosis show that while shear wave motion is altered, changes to compression wave propagation are negligible, and thus, insonification, which primarily drives compression waves, is not ideal to detect the presence of fibrosis. Results from the numerical simulation of a tumor show an increase in the wavelength of propagating waves in the immediate vicinity of the tumor region. Graphical abstract.

An investigation into the relationship between inhomogeneity and wave shapes in phantoms and ex vivo skeletal muscle using Magnetic Resonance Elastography and finite element analysis.

Soft biological tissues such as skeletal muscle and brain white matter can be inhomogeneous and anisotropic due to the presence of fibers. Unlike biological tissue, phantoms with known microstructure and defined mechanical properties enable a quantitative assessment and systematic investigation of the influence of inhomogeneities on the nature of shear wave propagation. This study introduces a mathematical measure for the wave shape, which the authors call as the 1-Norm, to determine the conditions under which homogenization may be a valid approach. This is achieved through experimentation using the Magnetic Resonance Elastography technique on 3D printed inhomogeneous fiber phantoms as well as on ex-vivo porcine lumbus muscle. In addition, Finite Element Analysis is used as a tool to decouple the effects of directional anisotropy from those of inhomogeneity. A correlation is then established between the values of 1-Norm derived from the wave front geometry, and the spacing (d) between neighboring inhomogeneities (spherical inclusions or fibers and fiber intersections in phantoms and muscle). Smaller values of 1-Norm indicate less wave scattering at the locations of fiber intersections, which implies that the wave propagation may be approximated to that of a homogeneous medium; homogenization may not be a valid approximation when significant scattering occurs at the locations of inhomogeneities. In conclusion, the current study proposes 1-Norm as a quantitative measure of the magnitude of wave scattering in a medium, which can potentially be used as a homogeneity index of a biological tissue.