Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics.

Small animal models play a fundamental role in brain research by deepening the understanding of the physiological functions and mechanisms underlying brain disorders and are thus essential in the development of therapeutic and diagnostic imaging tracers targeting the central nervous system. Advances in structural, functional, and molecular imaging using MRI, PET, fluorescence imaging, and optoacoustic imaging have enabled the interrogation of the rodent brain across a large temporal and spatial resolution scale in a non-invasively manner. However, there are still several major gaps in translating from preclinical brain imaging to the clinical setting. The hindering factors include the following: (1) intrinsic differences between biological species regarding brain size, cell type, protein expression level, and metabolism level and (2) imaging technical barriers regarding the interpretation of image contrast and limited spatiotemporal resolution. To mitigate these factors, single-cell transcriptomics and measures to identify the cellular source of PET tracers have been developed. Meanwhile, hybrid imaging techniques that provide highly complementary anatomical and molecular information are emerging. Furthermore, deep learning-based image analysis has been developed to enhance the quantification and optimization of the imaging protocol. In this mini-review, we summarize the recent developments in small animal neuroimaging toward improved translational power, with a focus on technical improvement including hybrid imaging, data processing, transcriptomics, awake animal imaging, and on-chip pharmacokinetics. We also discuss outstanding challenges in standardization and considerations toward increasing translational power and propose future outlooks.