Chakraborty Debamitra, Mills Bradley N, Cheng Jing, Komissarov Ivan, Gerber Scott A, Sobolewski Roman
Materials Science Graduate Program, University of Rochester, Rochester, New York 14627-1299, USA.
Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623, USA.
ACS Omega. 2023 Mar 8;8(11):9925-9933. doi: 10.1021/acsomega.2c07080. eCollection 2023 Mar 21.
Pancreatic ductal adenocarcinoma (PDAC) is one of the significant reasons for cancer-related death in the United States due to a lack of timely prognosis and the poor efficacy of the standard treatment protocol. Immunotherapy-based neoadjuvant therapy, such as stereotactic body radiotherapy (SBRT), has shown promising results compared to conventional radiotherapy in strengthening the antitumor response in PDAC. To probe and quantify the antitumor response with SBRT, we propose to study the tumor microenvironment using terahertz time-domain spectroscopy (THz-TDS). Since the tumor's complex microenvironment plays a key role in disease progression and treatment supervision, THz-TDS can be a revolutionary tool to help in treatment planning by probing the changes in the tissue microenvironment. This paper presents THz-TDS of paraffin-embedded PDAC samples utilizing a clinically relevant genetically engineered mouse model. This Article aims to develop and validate a novel time-domain approximation method based on maximum probability (MAP) estimation to extract terahertz parameters, namely, the refractive index and the absorption coefficient, from THz-TDS. Unlike the standard frequency-domain (FD) analysis, the parameters extracted from MAP construct better-conserved tissue parameters estimates, since the FD optimization often incorporates errors due to numerical instabilities during phase unwrapping, especially when propagating in lossy media. The THz-range index of refraction extracted from MAP and absorption coefficient parameters report a statistically significant distinction between PDAC tissue regions and their healthy equivalents. The coefficient of variation of the refractive index extracted by MAP is one order of magnitude lower compared to the one extracted from FD analysis. The index of refraction and absorption coefficient extracted from the MAP are suggested as the best imaging markers to reconstruct THz images of biological tissues to reflect their physical properties accurately and reproducibly. The obtained THz scans were validated using standard histopathology.
胰腺导管腺癌（PDAC）是美国癌症相关死亡的重要原因之一，因为缺乏及时的预后评估且标准治疗方案疗效不佳。基于免疫疗法的新辅助治疗，如立体定向体部放疗（SBRT），与传统放疗相比，在增强PDAC的抗肿瘤反应方面已显示出有前景的结果。为了探究和量化SBRT的抗肿瘤反应，我们提议使用太赫兹时域光谱（THz-TDS）研究肿瘤微环境。由于肿瘤复杂的微环境在疾病进展和治疗监测中起关键作用，THz-TDS可以成为一种革命性工具，通过探测组织微环境的变化来辅助治疗规划。本文利用临床相关的基因工程小鼠模型展示了石蜡包埋的PDAC样本的THz-TDS。本文旨在开发并验证一种基于最大概率（MAP）估计的新型时域近似方法，以从THz-TDS中提取太赫兹参数，即折射率和吸收系数。与标准频域（FD）分析不同，从MAP提取的参数构建了更保守的组织参数估计值，因为FD优化在相位展开过程中常常因数值不稳定而引入误差，尤其是在有损介质中传播时。从MAP提取的太赫兹范围折射率和吸收系数参数显示，PDAC组织区域与其健康对应区域之间存在统计学上的显著差异。与从FD分析中提取的折射率相比，MAP提取的折射率变异系数低一个数量级。建议将从MAP提取的折射率和吸收系数作为最佳成像标记，以准确且可重复地重建生物组织的THz图像，反映其物理特性。使用标准组织病理学对获得的THz扫描结果进行了验证。
