Viscoelasticity of children and adolescent brains through MR elastography.

Magnetic Resonance Elastography (MRE) is an elasticity imaging technique that allows a safe, fast, and non-invasive evaluation of the mechanical properties of biological tissues in vivo. Since mechanical properties reflect a tissue's composition and arrangement, MRE is a powerful tool for the investigation of the microstructural changes that take place in the brain during childhood and adolescence. The goal of this study was to evaluate the viscoelastic properties of the brain in a population of healthy children and adolescents in order to identify potential age and sex dependencies. We hypothesize that because of myelination, age dependent changes in the mechanical properties of the brain will occur during childhood and adolescence. Our sample consisted of 26 healthy individuals (13 M, 13 F) with age that ranged from 7-17 years (mean: 11.9 years). We performed multifrequency MRE at 40, 60, and 80 Hz actuation frequencies to acquire the complex-valued shear modulus G = G' + iG″ with the fundamental MRE parameters being the storage modulus (G'), the loss modulus (G″), and the magnitude of complex-valued shear modulus (|G|). We fitted a springpot model to these frequency-dependent MRE parameters in order to obtain the parameter α, which is related to tissue's microstructure, and the elasticity parameter k, which was converted to a shear modulus parameter (µ) through viscosity (η). We observed no statistically significant variation in the parameter µ, but a significant increase of the microstructural parameter α of the white matter with increasing age (p < 0.05). Therefore, our MRE results suggest that subtle microstructural changes such as neural tissue's enhanced alignment and geometrical reorganization during childhood and adolescence could result in significant biomechanical changes. In line with previously reported MRE data for adults, we also report significantly higher shear modulus (µ) for female brains when compared to males (p < 0.05). The data presented here can serve as a clinical baseline in the analysis of the pediatric and adolescent brain's viscoelasticity over this age span, as well as extending our understanding of the biomechanics of brain development.

Isolation and Immunofluorescent Staining of Fresh Rat Pia-Arachnoid Complex Tissue for Micromechanical Characterization.

In this article, we describe a protocol for the isolation and staining of fresh tissue of the inner rat meningeal layers, or pia-arachnoid complex (PAC). The PAC is believed to act as a mechanical damper offering a fundamental layer of protection against brain injury; however, its overall mechanical properties are still rather unexplored. In order to perform micromechanical measurements on the PAC, the tissue must be extracted and characterized while maintaining its native mechanical properties (i.e., avoiding any chemical or physical modification that could alter it). In light of this need, we developed a protocol for the immunofluorescent staining of fresh PAC tissue that does not require any fixation or permeabilization step. This approach will allow researchers to investigate important properties of the anatomy of ex vivo PAC tissue while at the same time offering a platform for the mechanical analysis of this complex material. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Isolation of fresh rat pia-arachnoid complex tissue Basic Protocol 2: Fresh immunofluorescent staining of rat pia-arachnoid complex tissue Alternate Protocol: Adhesion of pia-arachnoid complex tissue to glass slides for micromechanical characterization.

Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain.

BACKGROUND AND PURPOSE: The brain's stiffness measurements from magnetic resonance elastography (MRE) strongly depend on actuation frequencies, which makes cross-study comparisons challenging. We performed a preliminary study to acquire optimal sets of actuation frequencies to accurately obtain rheological parameters for the whole brain (WB), white matter (WM), and gray matter (GM). METHODS: Six healthy volunteers aged between 26 and 72 years old went through MRE with a modified single-shot spin-echo echo planar imaging pulse sequence embedded with motion encoding gradients on a 3T scanner. Frequency-independent brain material properties and best-fit material model were determined from the frequency-dependent brain tissue response data (20 -80 Hz), by comparing four different linear viscoelastic material models (Maxwell, Kelvin-Voigt, Springpot, and Zener). During the material fitting, spatial averaging of complex shear moduli (G*) obtained under single actuation frequency was performed, and then rheological parameters were acquired. Since clinical scan time is limited, a combination of three actuation frequencies that would provide the most accurate approximation and lowest fitting error was determined for WB, WM, and GM by optimizing for the lowest Bayesian information criterion (BIC). RESULTS: BIC scores for the Zener and Springpot models showed these models approximate the multifrequency response of the tissue best. The best-fit frequency combinations for the reference Zener and Springpot models were identified to be 30-60-70 and 30-40-80 Hz, respectively, for the WB. CONCLUSIONS: Optimal sets of actuation frequencies to accurately obtain rheological parameters for WB, WM, and GM were determined from shear moduli measurements obtained via 3-dimensional direct inversion. We believe that our study is a first-step in developing a region-specific multifrequency MRE protocol for the human brain.