High-Density Polyethylene Custom Focusing Lenses for High-Resolution Transient Terahertz Biomedical Imaging Sensors.

Transient terahertz time-domain spectroscopy (THz-TDS) imaging has emerged as a novel non-ionizing and noninvasive biomedical imaging modality, designed for the detection and characterization of a variety of tissue malignancies due to their high signal-to-noise ratio and submillimeter resolution. We report our design of a pair of aspheric focusing lenses using a commercially available lens-design software that resulted in about 200 × 200-µm2 focal spot size corresponding to the 1-THz frequency. The lenses are made of high-density polyethylene (HDPE) obtained using a lathe fabrication and are integrated into a THz-TDS system that includes low-temperature GaAs photoconductive antennae as both a THz emitter and detector. The system is used to generate high-resolution, two-dimensional (2D) images of formalin-fixed, paraffin-embedded murine pancreas tissue blocks. The performance of these focusing lenses is compared to the older system based on a pair of short-focal-length, hemispherical polytetrafluoroethylene (TeflonTM) lenses and is characterized using THz-domain measurements, resulting in 2D maps of the tissue refractive index and absorption coefficient as imaging markers. For a quantitative evaluation of the lens effect on the image resolution, we formulated a lateral resolution parameter, R2080, defined as the distance required for a 20-80% transition of the imaging marker from the bare paraffin region to the tissue region in the same image frame. The R2080 parameter clearly demonstrates the advantage of the HDPE lenses over TeflonTM lenses. The lens-design approach presented here can be successfully implemented in other THz-TDS setups with known THz emitter and detector specifications.

Development of Terahertz Imaging Markers for Pancreatic Ductal Adenocarcinoma using Maximum A Posteriori Probability (MAP) Estimation.

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.