Lin Weihao, Zeng Bixin, Cao Zili, Chen Xinlin, Yang Kaiyan, Xu Min
Institute of Lasers and Biophotonics, Department of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
Department of Pathology and Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
Biomed Opt Express. 2018 Jun 4;9(7):2905-2916. doi: 10.1364/BOE.9.002905. eCollection 2018 Jul 1.
Non-contact and minimally invasive endoscopic optical imaging is an invaluable diagnostic tool for tissue examination and cancer screening. The point sampling techniques with high sensitivity to the tissue microenvironment are time consuming and often not affordable in clinics. There is a major clinical need for a large field-of-view (FOV) rapid screening method to highlight subtle tissue microstructural alterations. To address this unmet need, we have developed High Spatial Frequency Domain Imaging (HSFDI)-a non-contact imaging modality that spatially maps the tissue microscopic scattering structures over a large field of view (>1cm). Based on an analytical reflectance model of sub-diffusive light from forward-peaked highly scattering media, HSFDI quantifies the spatially-resolved parameters of the light scattering phase function (i.e., the backscattering probability and the light spreading length) from the reflectance of structured light modulated at high spatial frequencies. Enhanced signal to noise ratio (SNR) is achieved at even ultra-high modulation frequencies with single snapshot multiple frequency demodulation (SSMD). The variations in tissue microstructures, including the strength of the background (pudding) refractive index fluctuation and the prominent scattering structure (plum) morphology, can then be inferred. After validation with optical phantoms, measurements of fresh tissue samples revealed significant contrast and differentiation of the phase function parameters between different types and disease states (normal, inflammatory, and cancerous) of tissue whereas tissue absorption and reduced scattering coefficients only show modest changes. HSFDI may provide wide-field images of microscopic structural biomarkers unobtainable with either diffuse light imaging or point-based optical sampling. Potential clinical applications include the rapid screening of excised tissue and the noninvasive examination of suspicious lesions during operation.
非接触式微创内镜光学成像对于组织检查和癌症筛查而言是一种非常重要的诊断工具。对组织微环境具有高灵敏度的点采样技术耗时较长，而且在临床上往往成本过高。临床上迫切需要一种大视野（FOV）快速筛查方法，以突出细微的组织微观结构改变。为了满足这一未被满足的需求，我们开发了高空间频率域成像（HSFDI）——一种非接触式成像模式，可在大视野（>1厘米）范围内对组织微观散射结构进行空间映射。基于来自前向峰值高散射介质的亚扩散光的解析反射模型，HSFDI通过对高空间频率调制的结构光的反射率来量化光散射相位函数的空间分辨参数（即后向散射概率和光传播长度）。通过单快照多频解调（SSMD），即使在超高调制频率下也能实现增强的信噪比（SNR）。然后可以推断出组织微观结构的变化，包括背景（布丁）折射率波动的强度和突出散射结构（李子）的形态。在用光学模型进行验证后，对新鲜组织样本的测量揭示了不同类型和疾病状态（正常、炎症和癌性）组织之间相位函数参数的显著对比度和差异，而组织吸收和约化散射系数仅显示出适度变化。HSFDI可能提供漫射光成像或基于点的光学采样无法获得的微观结构生物标志物的宽视野图像。潜在的临床应用包括对切除组织的快速筛查以及手术期间对可疑病变的无创检查。
