Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA.
J Biomed Opt. 2013 Apr;18(4):046008. doi: 10.1117/1.JBO.18.4.046008.
Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.
亚表面荧光成像是医学应用所期望的，包括基于原卟啉 IX（PpIX）的皮肤肿瘤诊断、手术指导和光动力疗法中的剂量测定。虽然组织光学性质和非均质性使得真正的亚表面荧光测绘成为不适定问题，但超声引导荧光层析成像（USFT）提供了区域荧光测绘。在这里，通过荧光信号（自体荧光、PpIX、光产物）的光谱解耦和白光光谱确定的体光学性质来实现 USFT。分段 US 图像为使用基于区域的漫射 FT 进行荧光重建提供了先验空间信息。该方法在模拟、组织均匀和包含体模以及注射包含体的动物模型中进行了测试。重建的荧光产率与 PpIX 浓度呈线性关系，包括使用的最低浓度 0.025μg/ml。白光光谱提供了光学性质的信息，与使用固定的、基于文献的光学性质相比，这提高了荧光重建的准确性，分别将重建误差和重建荧光标准差降低了 8.9 倍和 2.0 倍。对于没有和有 2 毫米类似皮肤层的包含体模，恢复的对比度-背景误差分别为 25%和 74%。初步的小鼠模型成像证明了该 USFT 系统在体内光动力疗法中进行亚表面荧光测量的可行性。这些数据表明，这种 USFT 的实现能够在人类皮肤肿瘤的光动力治疗期间进行局部 PpIX 测绘，用于剂量评估。
