Mesoscopic Quantification of Cortical Architecture in the Living Human Brain

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for a comprehensive understanding of brain structure and function. However, in vivo techniques for mesoscopic imaging have been hampered by the sensitivity challenges of acquiring data at very high resolutions and the lack of analysis tools that can retain fine-scale detail while also accurately positioning measurements relative to the complex folded structure of the cerebral cortex. Here, we present an experimental dataset in which we image the anatomical structure of the visual and auditory cortices of five participants at 0.35 × 0.35 × 0.35 mm3 resolution. To analyze this challenging dataset, we design and implement two sets of novel methodology: a method for mitigating imaging artifacts related to blood motion and a suite of software tools for accurate quantification and visualization of the mesoscopic structure of the cortical surface. Applying these methods, we demonstrate the ability to clearly identify structures that are visible only at the mesoscopic scale, including cortical layers and intracortical blood vessels. We freely share our dataset and tools with the research community, thereby enabling investigations of fine-scale neurobiological structures in both the current and future datasets. Overall, our results demonstrate the viability of mesoscopic imaging as a quantitative tool for studying the living human brain.