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Photoacoustic imaging (PAI) uniquely integrates scalable spatial resolution, deep penetration, and non\u2010ionizing excitation, which enables multi\u2010scale visualization from subcellular structures to the whole brain. This review systematically summarizes the fundamental principles of PAI, commonly used contrast agents, and key system components, and provides a comparative analysis of the major imaging modalities\u2014optical\u2010resolution and acoustic\u2010resolution photoacoustic microscopy (OR\u2010\/AR\u2010PAM), photoacoustic computed tomography (PACT), and photoacoustic endoscopy (PAE). PACT offers superior penetration depth and field of view, whereas OR\u2010\/AR\u2010PAM provides higher spatial resolution at molecular scales. By aligning disease\u2010specific imaging requirements with the functional strengths of each modality, PAI has enabled integrated structural and functional imaging in glioblastoma, neurodegenerative disorders, traumatic brain injury, and cerebrovascular diseases, highlighting its integrated advantages for multiscale brain imaging. Finally, the review discusses key challenges for clinical translation of PAI, including motion artifacts, blood\u2013brain barrier constraints, contrast agent approval, limitations of single\u2010modality approaches, and technical limitations, and proposes corresponding strategies to address these obstacles. This review provides forward\u2010looking guidance for the clinical translation of multiscale brain imaging technologies.<\/jats:p>","DOI":"10.1002\/adhm.202505743","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:22:21Z","timestamp":1776057741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Photoacoustic Imaging for Brain Diseases: Principles, Applications, and Clinical Translation Challenges"],"prefix":"10.1002","volume":"15","author":[{"given":"Xixi","family":"Hu","sequence":"first","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing P. R. 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