Quantitative cell nuclear imaging by dual-view optical-resolution photoacoustic microscopy

An estimated ~250,000 new cases of both invasive and non-invasive breast cancer were diagnosed in US women almost every year. To reduce the local recurrence rate, the breast conserving surgery (BCS) is widely used as the initial therapy, which is to excise the tumor with a rim of normal surrounding tissue such that no cancer cells remain at the cut margin, Patients with positive margin commonly require a second surgical procedure to obtain clear margins. To this end, optical-resolution photoacoustic microscopy (OR-PAM) with ultraviolet (UV) laser illumination (OR-UV-PAM) has been developed for providing label-free, high-resolution, and histology like imaging of fixed, unprocessed breast tissue. To further improve the performance of OR-UV-PAM, here, we introduce dual-view UV-PAM (DV-UV-PAM) to significantly improve the axial resolution, achieving three-dimensional (3D) resolution isotropy. We first use 0.5 μm polystyrene beads and carbon fibers to validate the resolution isotropy improvement. Imaging of mouse brain slices further demonstrates the improved resolution isotropy, revealing the 3D structure of cell nuclei in detail, which facilitates quantitative cell nuclear analysis.