Noninvasive high-resolution deep-brain photoacoustic imaging with a negatively focused fiber-laser ultrasound transducer

Noninvasive high-resolution deep-brain imaging is essential to fundamental cognitive process study and neuroprotective drugs development. Although optical microscopes can resolve fine biological structures with good contrast without exposure to ionizing radiation or a strong magnetic field, the optical scattering limits the penetration depth and hinders its capability for deep-brain imaging. Here, in vivo high-resolution imaging of the whole mouse brain is demonstrated by using a photoacoustic computed tomography system with a negatively focused fiber-laser ultrasound transducer. By leveraging the high flexibility and low bending loss of the optical fiber, a rationally designed negatively focused fiber laser cavity exhibits a low detection limit down to 5.4 Pa and a broad view angle of ∼120 deg , enabling mouse brain imaging with a penetration larger than 7 mm and a nearly isotropic spatial resolution of ∼130 μm . In addition, the negative curvature of the fiber laser reduces the working distance, which facilitates the development of a compact and portable linear scanning imaging system. In vivo imaging of a mouse model with intracerebral hemorrhage is also showcased to demonstrate its capability for potential biomedical and clinical applications. With high spatial resolution and large tissue penetration, the system may provide a noninvasive, user-friendly, and high-performance imaging solution for biomedical research and preclinical/clinical diagnosis.