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Quantitative diagnosis of tissue microstructure with wide-field high spatial frequency domain imaging

机译：宽视野高空间频域成像定量诊断组织微观结构

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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 (>1cm2). 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 ex vivo 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.
机译：非接触式微创内窥镜光学成像是用于组织检查和癌症筛查的宝贵诊断工具。对组织微环境高度敏感的点采样技术既耗时，又常常在临床上无法承受。对于大型视野（FOV）快速筛查方法以突出微妙的组织微结构改变，临床上存在重大需求。为了满足这一未满足的需求，我们开发了高空间频域成像（HSFDI）–一种非接触式成像方式，可以在大视野（> 1cm 2 ）上对组织的微观散射结构进行空间映射。 HSFDI基于来自前向高散射介质的亚散射光的解析反射模型，根据结构光的反射率对光散射相位函数的空间分辨参数（即后向散射概率和光扩散长度）进行量化在高空间频率下进行调制。借助单快照多频率解调（SSMD），即使在超高调制频率下也可实现增强的信噪比（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的散射结构（李子）形态。在通过光学体模进行验证后，对新鲜离体组织样品的测量显示出不同类型和疾病状态（正常，炎性和癌性）组织之间相功能参数的显着对比和差异，而组织吸收和散射系数降低仅显示出适度的变化。 HSFDI可以提供通过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记物的宽视野图像。潜在的临床应用包括在手术过程中对切除的组织进行快速筛查以及对可疑病变进行无创检查。

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