Erik H. Clayton

Quantitative Imaging Methods for the Development and Validation of Brain Biomechanics Models

Rapid deformation of brain tissue in response to head impact or acceleration can lead to numerous pathological changes, both immediate and delayed. Modeling and simulation hold promise for illuminating the mechanisms of traumatic brain injury (TBI) and for developing preventive devices and strategies. However, mathematical models have predictive value only if they satisfy two conditions. First, they must capture the biomechanics of the brain as both a material and a structure, including the mechanics of brain tissue and its interactions with the skull. Second, they must be validated by direct comparison with experimental data. Emerging imaging technologies and recent imaging studies provide important data for these purposes. This review describes these techniques and data, with an emphasis on magnetic resonance imaging approaches. In combination, these imaging tools promise to extend our understanding of brain biomechanics and improve our ability to study TBI in silico.

Transmission, attenuation and reflection of shear waves in the human brain

Traumatic brain injuries (TBIs) are caused by acceleration of the skull or exposure to explosive blast, but the processes by which mechanical loads lead to neurological injury remain poorly understood. We adapted motion-sensitive magnetic resonance imaging methods to measure the motion of the human brain in vivo as the skull was exposed to harmonic pressure excitation (45, 60 and 80 Hz). We analysed displacement fields to quantify the transmission, attenuation and reflection of distortional (shear) waves as well as viscoelastic material properties. Results suggest that internal membranes, such as the falx cerebri and the tentorium cerebelli, play a key role in reflecting and focusing shear waves within the brain. The skull acts as a low-pass filter over the range of frequencies studied. Transmissibility of pressure waves through the skull decreases and shear wave attenuation increases with increasing frequency. The skull and brain function mechanically as an integral structure that insulates internal anatomic features; these results are valuable for building and validating mathematical models of this complex and important structural system.

Damage Detection and Correlation-Based Localization Using Wireless Mote Sensors

This study focuses on an experimental damage detection and correlation-based localization demonstration using wireless sensors. A simple cantilever beam has been constructed in the laboratory to serve as a test bed for measuring acceleration responses with these devices. The goal of this preliminary investigation is to test the feasibility and functionality of a wireless sensor network (WSN) to detect and localize damage utilizing current wireless mote technology

Mechanical properties of viscoelastic media by local frequency estimation of divergence-free wave fields.

Magnetic resonance elastography (MRE) is an imaging modality with which mechanical properties can be noninvasively measured in living tissue. Magnetic resonance elastography relies on the fact that the elastic shear modulus determines the phase velocity and, hence the wavelength, of shear waves which are visualized by motion-sensitive MR imaging. Local frequency estimation (LFE) has been used to extract the local wavenumber from displacement wave fields recorded by MRE. LFE -based inversion is attractive because it allows material parameters to be estimated without explicitly invoking the equations governing wave propagation, thus obviating the need to numerically compute the Laplacian. Nevertheless, studies using LFE have not explicitly addressed three important issues: (1) tissue viscoelasticity; (2) the effects of longitudinal waves and rigid body motion on estimates of shear modulus; and (3) mechanical anisotropy. In the current study we extend the LFE technique to (1) estimate the (complex) viscoelastic shear modulus in lossy media; (2) eliminate the effects of longitudinal waves and rigid body motion; and (3) determine two distinct shear moduli in anisotropic media. The extended LFE approach is demonstrated by analyzing experimental data from a previously-characterized, isotropic, viscoelastic, gelatin phantom and simulated data from a computer model of anisotropic (transversely isotropic) soft material.

A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9-19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

Wave Propagation in the Human Brain and Skull Imaged in vivo by MR Elastography

Traumatic brain injuries (TBI) are common, and often lead to permanent physical, cognitive, and/or behavioral impairment. TBI arises in vehicle accidents, assaults, athletic competition, and in battle (due to both impact and blast). Despite the prevalence and severity of TBI, the condition remains poorly understood and difficult to diagnose. Computer simulations of injury mechanics offer enormous potential for the study of TBI; however, computer models require accurate descriptions of tissue constitutive behavior and brain-skull boundary conditions. Lacking such data, numerical predictions of brain deformation remain uncertain. Brain tissue is heterogeneous, anisotropic, nonlinear, and viscoelastic. The viscoelastic properties are particularly important for TBI, which usually involves rapid deformation due to impact.

Shear Wave Propagation of the Ferret Brain at Multiple Frequencies In Vivo

Mathematical modeling and computer simulations are widely used for understanding traumatic brain injury (TBI). However, accurate tissue parameters are needed, especially for the brain in vivo. In this study, we used the ferret as the animal model because it is the smallest mammal with a folded brain and significant white matter tracts. Magnetic resonance elastography (MRE) has proven useful for in vivo measurement of biological tissue properties. Mechanical properties of the ferret brain over a range of frequencies from 400–800 Hz were studied using MRE. Experiment results show both that storage and loss modulus increases with frequency and that dissipative effects in the white matter (characterized by the loss modulus G″) were significant larger than in gray matter.Copyright

Brain Response to Extracranial Pressure Excitation Imaged in vivo by MR Elastography

Traumatic brain injuries (TBI) are common, and often lead to permanent cognitive impairment. Despite the prevalence and severity of TBI, the condition remains poorly understood. Computer simulations of injury mechanics offer enormous potential for the study of TBI; however, computer models require accurate descriptions of tissue constitutive behavior and brain-skull boundary conditions. Magnetic resonance elastography (MRE) is a non-invasive imaging modality that provides quantitative spatial maps of tissue stiffness in vivo. MRE is performed by inducing micron-amplitude propagating shear waves into tissue and imaging the resulting motion with a specialized “motion-sensitive” MRI pulse sequence. Invoking a restricted form of Navier’s equation these data can be inverted to estimate material stiffness. As such, clinical interest in MRE has largely been driven by the direct empirical relationship between tissue stiffness and health. However, the so-called “raw” MRE data themselves (3-D displacement measurements) and calculated strains can elucidate loading paths, anatomic boundaries and the dynamic response of the intact human head. In this study, we use the MRE imaging technique to measure in vivo displacement fields of brain motion as the cranium is exposed to acoustic frequency pressure excitation (45, 60, 80 Hz) and calculate the resulting shear-strain fields (2-D).

Magnetic Resonance Elastography of the Mouse Vitreous Humor In Vivo

Magnetic resonance elastography (MRE) is a novel experimental technique for estimating the dynamic shear modulus of biological tissue in vivo and non-invasively. Propagating acoustic frequency shear waves are launched into biologic tissue via external mechanical actuator and a conventional magnetic resonance imaging (MRI) scanner is used to acquire spatial-temporal measurements of the wave displacement field with micron precision. Local shear modulus estimates are obtained by inverting the equations governing shear wave motion. Changes in tissue pathology may be accompanied by a stark change in tissue elasticity. As a result, MRE has appeal to healthcare practitioners as a non-invasive diagnostic tool. Recently, MRE-based modulus estimates have been obtained in animal liver, brain, and heart [2-7]. Here, for the first time, MRE was used to probe the shear modulus of mouse eye vitreous humor in vivo and non-invasively.

Characterization of Murine Glioma by Magnetic Resonance Elastography: Preliminary Results

Magnetic resonance elastography (MRE) is a non-invasive imaging technique that permits quantitative measurement of the mechanical properties of biological tissue. In MRE, coherent tissue displacements are induced by a mechanical actuator and images are collected in synchrony with these mechanical motions. Components of displacement in any direction can be measured by applying the motion-encoding gradients along that direction. The mechanical properties of tissue are derived by fitting measured displacement data to the equations governing wave propagation. A number of groups have explored the diagnostic value of MRE in the clinical setting, driven largely by the empirically observed relationship between tissue health and stiffness. The investigation of MRI methods as biomarkers of tumor progression and early therapeutic response remains an extremely active and important area of research. In this regard, MRE has considerable potential for staging cancer and monitoring the effects of therapy. We seek to demonstrate the utility of MRE for cancer staging by tracking the viscoelastic properties of brain tumor in a mouse model of high-grade glioma. Brain tissue viscoelasticity cannot be probed in vivo by any other known imaging technique, yet is suspected to contain valuable information about tissue health. Preliminary results indicate elastographic sensitivity to the presence of brain tumors in the living mouse.