Microstructural MRI Evolution During Adult Mouse Brain Maturation and Concussion Recovery
Abstract
Mild traumatic brain injury (mTBI), also called concussion, has become a significant public health concern. Current clinical neuroimaging techniques lack the sensitivity and specificity required to reliably detect signs of concussion, as large-scale changes are absent. Diffusion magnetic resonance imaging (dMRI) has arguably had the greatest influence to-date of neuroimaging modalities in mTBI, but previous studies have reported inconsistent findings, as standard dMRI lacks specificity and provides a limited model of neuroanatomy. This thesis explores the application of microstructural MR methods, that go beyond standard dMRI to improve sensitivity and specificity, to a preclinical model of mTBI and adult brain maturation. These methods include: frequency-dependent dMRI, which can probe smaller spatial scales than standard dMRI; tensor-valued dMRI, which removes the confound of fiber orientation dispersion on the diffusion measurement; and magnetization transfer saturation (MTsat) MRI, which provides specificity to myelin content.
We first characterize the reproducibility of the microstructural MR metrics applied and provide preclinical sample sizes required to detect relevant effect sizes. Given feasible sample sizes (10-15), tensor-valued and frequency-dependent dMRI metrics may provide sensitivity to subtle microstructural changes (4-8%) and moderate changes (>6%), respectively, while MTsat could detect small changes (in vivoevidence of changes post-mTBI detectable with microstructural MR methods in subacute and chronic stages, while the standard dMRI metrics did not show changes. The sexually dimorphic patterns observed here, both during brain maturation and concussion recovery, may motivate more sex-dependent mTBI research, as females remain underrepresented in mTBI research.