Pre-clinical phase-contrast imaging of the whole brain in situ: from traumatic to diffuse white matter injury

X-ray computed tomography (CT) has been a mainstay of clinical neuroimaging since the 1970s. Its quick scans, high spatial resolution, ease of availability, and relatively low cost make it essential for the diagnosis and monitoring of injury and disease. However, low contrast resolution relative to magnetic resonance imaging (MRI) has limited its use in resolving subtle variations between different soft tissue types and between inflamed and healthy tissues. While clinical CT exploits the attenuation of X-rays through the body, phase contrast X-ray imaging (PCXI) additionally uses refraction and diffraction, increasing sensitivity to subtle inhomogeneities in tissue composition. Most PCXI-CT research has focused on lung and breast tissue, where the sparsely-distributed surrounding bone does not significantly obscure soft tissues. However, neuroimaging with X-rays poses unique challenges, since the brain is fully encased within the highly-attenuating skull, making soft-tissue segmentation difficult and creating artifacts that can obscure the underlying anatomy. We have previously demonstrated that PCXI-CT can resolve anatomical structures within the brains of small animals in situ at micron-scale resolution (Croton et al., 2018) and have developed new correction methods to address the key artifacts that appear when capturing these soft-tissue images (Croton et al., 2019). Here, we present recent progress in the detection of brain injury with PCXI-CT, including direct comparisons to MRI of the same injured brains. Our project aims to spatially resolve injuries that elude MRI, including both traumatic and diffuse injury, in order to better understand the progression of cerebral palsy near birth.