Advances in Photoacoustic Imaging for Brain Diseases: Principles, Applications, and Clinical Translation Challenges

Area of Science:

• Neuroimaging
• Biomedical Optics
• Medical Physics

Background:

• Increasing prevalence of brain diseases necessitates advanced imaging solutions.
• Existing brain imaging techniques face limitations in resolution, penetration, and biocompatibility.
• Photoacoustic imaging (PAI) offers a unique combination of scalable resolution, deep penetration, and non-ionizing excitation for multiscale brain visualization.

Purpose of the Study:

• To systematically review the principles, contrast agents, and system components of PAI.
• To comparatively analyze major PAI modalities: optical-resolution and acoustic-resolution photoacoustic microscopy (OR-PAM/AR-PAM), photoacoustic computed tomography (PACT), and photoacoustic endoscopy (PAE).
• To highlight PAI's application in various brain diseases and discuss challenges and strategies for clinical translation.

Main Methods:

• Systematic review of fundamental PAI principles and technologies.
• Comparative analysis of OR-/AR-PAM, PACT, and PAE based on penetration depth, resolution, and field of view.
• Literature synthesis on PAI applications in glioblastoma, neurodegenerative disorders, traumatic brain injury, and cerebrovascular diseases.

Main Results:

• PACT provides superior penetration depth and field of view for whole-brain imaging.
• OR-/AR-PAM offer higher spatial resolution for subcellular and molecular-scale imaging.
• PAI enables integrated structural and functional imaging across multiple brain diseases.

Conclusions:

• PAI is a versatile multiscale imaging technology with significant advantages for brain imaging.
• Key challenges for clinical translation include motion artifacts, blood-brain barrier crossing, contrast agent approval, and technical limitations.
• Addressing these challenges through strategic approaches will facilitate the clinical adoption of PAI for brain disease diagnosis and management.