Imaging of intranasal drug delivery to the brain: updated review 2.0

Since the first review on imaging of intranasal drug delivery (INDD) was published in 2020, interest in the topic has increased, necessitating an update, which is the basis of the current review. INDD is a promising alternative for treating central nervous system (CNS) diseases. In vivo imaging is also important for therapy assessment, both clinically and preclinically. This review details studies that further our understanding of INDD and the fate of these therapies in the CNS using in vivo imaging. We performed a literature search using the keywords "Intranasal delivery" and "Imaging" from 2020 to 2025 and summarized these findings in the current updated review. This review is not comprehensive but provides examples of recent publications that explore the various treatments under development for nose-to-brain (N2B) therapeutic delivery through imaging. Imaging will include magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), gamma scintigraphy, and computed tomography (CT) for both humans and animals. Additional specialty topics pursued experimentally in animals include in vivo optical imaging techniques, including bioluminescence and fluorescence imaging. Finally, we discuss image-guided therapeutic techniques such as focused ultrasound and conclude with future directions. In this review, we introduce each imaging modality, describe its utilization, and outline its strengths and weaknesses, specifically in the context of N2B therapeutics.