融合荧光与光声成像，实现深层肿瘤精准定位。
Combined fluorescence and photoacoustic imaging of tozuleristide in muscle tissue in vitro -- toward optically-guided solid tumor surgery: feasibility studies
- 用快速扫描光声超声补足近红外荧光成像深度不足缺陷。
- 在34毫米深处仍可检测到20微摩尔的靶向造影剂。
- 适合需要术前规划与术中广范围切除的肿瘤手术。
近红外荧光（NIRF）可实现高对比度、视频速率、非接触式肿瘤靶向造影剂成像，有望指导实体瘤切除手术。然而，由于组织深度超过约5毫米时灵敏度和分辨率下降，其在大范围切除中的应用受到质疑。为此，本文提出用快速扫描光声超声（PAUS）成像弥补NIRF的局限性。在暗红色牛肌肉组织的体外探索性可行性研究中，发现PAUS可在高达约34毫米的深度下，从背景中识别出浓度为20 μM的tozuleristide（一种临床阶段研究性成像剂），显著拓展了NIRF的探测能力。通过直接注射20 μM tozuleristide至约8毫米深度的牛肌肉组织，验证了光谱PAUS成像性能：激光能量补偿与强杂波抑制得益于快速扫描方法的独特优势，大幅提升了光谱精度与检测极限，并显著减少图像伪影。因此，NIRF-PAUS联合策略在光学引导实体瘤手术中，具备实现术前（以PA）与术中（以NIRF）全面肿瘤检测及广范围切除的潜力。
原文摘要 · Abstract (English)
Near-infrared fluorescence (NIRF) can deliver high-contrast, video-rate, non-contact imaging of tumor-targeted contrast agents with the potential to guide surgeries excising solid tumors. However, it has been met with skepticism for wide-margin excision due to sensitivity and resolution limitations at depths larger than ~5 mm in tissue. To address this limitation, fast-sweep photoacoustic-ultrasound (PAUS) imaging is proposed to complement NIRF. In an exploratory in vitro feasibility study using dark-red bovine muscle tissue, we observed that PAUS scanning can identify tozuleristide, a clinical stage investigational imaging agent, at a concentration of 20 uM from the background at depths of up to ~34 mm, highly extending the capabilities of NIRF alone. The capability of spectroscopic PAUS imaging was tested by direct injection of 20 uM tozuleristide into bovine muscle tissue at a depth of ~ 8 mm. It is shown that laser-fluence compensation and strong clutter suppression enabled by the unique capabilities of the fast-sweep approach greatly improve spectroscopic accuracy and the PA detection limit, and strongly reduce image artifacts. Thus, the combined NIRF-PAUS approach can be promising for comprehensive pre- (with PA) and intra- (with NIRF) operative solid tumor detection and wide-margin excision in optically guided solid tumor surgery.
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