Development of Terahertz Imaging Markers for Pancreatic Ductal Adenocarcinoma using Maximum A Posteriori Probability (MAP) Estimation.
Development of Terahertz Imaging Markers for Pancreatic Ductal Adenocarcinoma using Maximum A Posteriori Probability (MAP) Estimation.
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DOI：
10.1021/acsomega.2c07080
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发表时间：
2023-03-21
期刊：
影响因子：
4.1
通讯作者：
Sobolewski, Roman
中科院分区：
文献类型：
--
作者：
Chakraborty, Debamitra;Mills, Bradley N.;Cheng, Jing;Komissarov, Ivan;Gerber, Scott A.;Sobolewski, Roman
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和标准治疗方案的疗效差。与常规放疗相比，基于免疫疗法的新辅助疗法（如立体定向体部放疗（SBRT））在增强PDAC的抗肿瘤反应方面显示出有希望的结果。为了探测和量化SBRT的抗肿瘤反应，我们建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督中起着关键作用，THz-TDS可以成为一种革命性的工具，通过探测组织微环境的变化来帮助制定治疗计划。本文介绍了THZ-TDS的石蜡包埋的PDAC样品利用临床相关的基因工程小鼠模型。本文旨在开发并验证一种基于最大后验概率（MAP）估计的时域近似方法，从太赫兹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中提取的参数构建了更好的保守组织参数估计，因为FD优化通常包含由于相位展开期间数值不稳定性引起的误差，特别是在有损介质中传播时。从MAP和吸收系数参数中提取的THZ范围折射率报告了PDAC组织区域与其健康等效物之间的统计学显著差异。通过MAP提取的折射率的变化系数比从FD分析提取的折射率的变化系数低一个数量级。从MAP中提取的折射率和吸收系数是重建生物组织THz图像的最佳成像标记，以准确和可重复地反映其物理特性。使用标准组织病理学验证所获得的THz扫描。
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 a posteriori 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.
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