Yang Fan, Yang Zhengduo, Zhu Zheng, Zhu Siwei, Song Wei, Yang Yong, Yuan Xiaocong
Research Center for Frontier Fundamental Studies, Zhejiang Laboratory, Hangzhou 311100, China.
Nanophotonics Research Center, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen 518060, China.
Photoacoustics. 2025 Mar 4;43:100712. doi: 10.1016/j.pacs.2025.100712. eCollection 2025 Jun.
Accurate and rapid intraoperative diagnosis of micro-infiltration in early-stage tumors presents a formidable challenge for decades. Here, we propose a novel diagnostic approach, that combines Photoacoustic Morphological Imaging (PAMI) with an broadband Photoacoustic Spectral Analysis (PASA), to implement intraoperative assessment of early-stage tumor while its high-frequencies between 50 and 150 MHz respond to various nuclei specifically. Our system, a broadband Ultraviolet Photoacoustic Microscopy (bUV-PAM), uniquely integrates ultraviolet laser-induced nucleus-specific photoacoustic excitation with broadband photoacoustic detection (up to 176 MHz at -6 dB) via an optical surface wave sensor. This approach facilitates the simultaneous acquisition of morphological and spectral information from unstained tissue sections, yielding a comprehensive dual-modality virtual slice within a single raster scan. Using human colorectal tissue samples, we applied the joint PAMI and PASA approach across 6 case groups. Morphological features in PAMI showed a high concordance with Hematoxylin and Eosin (H&E) staining, whereas micro-infiltrative features were too indistinct to be identified in both PAMI and H&E images. In contrast, the PASA effectively distinguishes between micro-infiltrated and non-infiltrated tissues, a finding validated by subsequent Immunohistochemical (IHC) assessments. The preliminary results suggest that the joint approach holds potential to enhance intraoperative detection of micro-infiltration, thereby offering a promising avenue for accurate and rapid surgical margin assessment.
几十年来，对早期肿瘤微浸润进行准确、快速的术中诊断一直是一项艰巨的挑战。在此，我们提出一种新颖的诊断方法，即将光声形态成像（PAMI）与宽带光声光谱分析（PASA）相结合，以实现对早期肿瘤的术中评估，同时其50至150MHz的高频能特异性地响应各种细胞核。我们的系统，即宽带紫外光声显微镜（bUV-PAM），通过光学表面波传感器将紫外激光诱导的细胞核特异性光声激发与宽带光声检测（-6dB时高达176MHz）独特地整合在一起。这种方法有助于从未染色的组织切片中同时获取形态和光谱信息，在单次光栅扫描中生成全面的双模态虚拟切片。我们使用人类结肠组织样本，在6个病例组中应用了联合PAMI和PASA方法。PAMI中的形态特征与苏木精和伊红（H&E）染色高度一致，而微浸润特征在PAMI和H&E图像中都过于模糊难以识别。相比之下，PASA能有效区分微浸润组织和未浸润组织，这一发现得到了后续免疫组织化学（IHC）评估的验证。初步结果表明，这种联合方法有潜力增强术中对微浸润的检测，从而为准确、快速的手术切缘评估提供一条有前景的途径。
