Innovations in preclinical MR elastography and applications in rat models of neurological disorders
Date
2025
Authors
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Publisher
University of Delaware
Abstract
Magnetic resonance elastography (MRE) is a quantitative MRI technique used to estimate the mechanical properties of tissue. While still relatively new, MRE has become the gold standard for diagnosing liver fibrosis and has shown great promise as a noninvasive, quantitative, evaluation technique in a multitude of physiological settings. This is due to MRE’s unique sensitivity to small variations in mechanical properties and its ability to reflect microstructural integrity. Mechanical properties are impacted by variations in microstructural composition and organization including cell density, myelination, vasculature, fiber alignment, and extracellular matrix (ECM) integrity. Thus, mechanical properties indirectly measure tissue health. Using brain MRE, we can detect tumors, assess cognitive health and memory performance, differentiate between brain structures, and monitor neurodegeneration and the natural aging process. Despite the numerous applications, there is much we do not fully understand about the microstructural contributions to the property changes we observe. Treatment development and benchmarking are also difficult in clinical settings. Human MRE studies are restricted by the availability of subjects, large variability between subjects, and ethical considerations. Thus, there is a need for advancements in preclinical MRE research to fill these knowledge gaps. ☐ MRE in preclinical models (preclinical MRE) is an emerging field motivated by the need to improve our understanding of the microstructure and its effects on the mechanical property measurements we find in humans. Through rodent models, we can monitor disease progression and correlate findings with histology. Animal models are also necessary for treatment development and allow for faster, more controlled longitudinal studies. To facilitate translatability, we must use the same MRE process in animals with comparable quality and resolution to humans. The field of rodent MRE is expanding, and several studies describe similar findings to humans and have verified their results with histology. However, mechanical property ranges and trends vary due to differences in data acquisition, scanner strength, inversion algorithm, and age of the rodents. Rat models are advantageous over mice in that mechanical properties from smaller structures may be recovered at similarly high field strengths and resolutions. Rat models are also more translatable to human neuroscience, yet the vast majority of preclinical brain MRE work has been done on mice. This thesis presents a series of experiments aimed at improving the capabilities, translatability, and applications of preclinical MRE with an emphasis on rat models of neurological disorders. ☐ The first aim focuses on the development of novel protocols for benchmarking MRE experiments and performing rat brain MRE with translatable quality and resolution to human MRE. This foundational work is then leveraged to establish the in vivo rat brain MRE protocol. In Aim 2, we develop a viscoelastic MRE phantom with tunable damping ratio independent of shear stiffness. This linear polyacrylamide (LPAA) phantom is used to improve benchmarking capabilities and to assess the sensitivity of our preclinical MRE protocol to small variations in mechanical properties. In the third aim, we apply the established preclinical MRE protocol to assess brain mechanical property alterations and recovery in a rat model of fetal alcohol spectrum disorders (FASD). This work evaluates whether MRE can reflect microstructural changes due to alcohol exposure and response to therapeutic intervention. In Aim four, we adopt a multimodal MRE and sodium MRI approach to assess the feasibility and sensitivity of detecting variations in brain mechanical properties and sodium concentration in a rat model of acute inflammation. ☐ Collectively, this work contributes improvements to the quality and translatability of preclinical MRE, combined with novel benchmarking tools and applications of MRE in rat models of neurological disorders. Future research in this field should strive to further our knowledge of microstructural components and their relationships to the mechanical properties we measure, and to explore multimodal imaging approaches to comprehensively assess tissue health.
Description
Keywords
Magnetic resonance elastography, Mechanical properties, Magnetic resonance imaging, Preclinical, Rodent