Design considerations for a miniature multicontrast neuroimager

Traditional optical imaging systems are designed for imaging with a single contrast mechanism, and therefore can interrogate only a single neurophysiologic variable. However, the biological complexity underlying neurophysiological function and its alteration in neurodegenerative diseases, requires the simultaneous interrogation of multiple neurophysiologic variables to arrive at a better understanding. Today's multicontrast optical imaging systems satisfy this need, but suffer from some inherent limitations. Owing to the need to integrate multiple contrast mechanisms, these imaging systems tend to be benchtop-based and unportable, often requiring animals to be anesthetized, custom built and expensive. This limits their widespread adoption. Miniaturization, although technically challenging, remains a potential solution to these limitations. To address this unmet need, here we present the design considerations and practical guidelines for building inexpensive, miniaturized, and portable multicontrast optical neuroimaging systems that allow comprehensive interrogation of brain function in freely behaving rodents. We then showcase an example tri-contrast miniature neuroimaging system and demonstrate the implementation of our guidelines. We conclude by demonstrating the utility of such a miniature multicontrast neuroimaging system by interrogating in an awake rodent the tumor extent, angiogenic vascular sprouting, flow establishment in the newly formed vessels, as well as anomalies in resting-state microvascular fluctuations in a preclinical model of brain tumor progression.