Changes in tissue structure, such as to the boundaries of cancerous tumors, occur in many disease processes. Terahertz (THz) waves demonstrate the potential to detect these changes. The ability to identify and characterize microscopic structural changes in tissue using THz imaging could enable earlier detection of cancer, improving patient outcomes. While polarization measurements of reflected THz waves are thought to have diagnostic value, the underlying mechanisms that create different polarization responses in tissues remain poorly understood. This gap in understanding underscores a need for computational models capable of explaining and predicting the phenomena that researchers have observed experimentally. Polarimetric measurements of terahertz (THz) scattering can detect subtle changes in tissue architecture that result from disease or damage. For example, THz measurements demonstrated signal contrast between burned and healthy skin regions. Courtesy of Heller et al., doi: 10.1117/1.JBO.30.6.066001. In a study led by professor Hassan Arbab, researchers at Stony Brook University analyzed Mie scattering of polarized THz light from cancerous tumor budding using Monte Carlo simulation. They compared the outcome of the simulation with experimental results obtained in phantom models, and performed an analysis of a polarization-sensitive THz scan of an ex vivo porcine burn injury. The results of the Stony Brook study indicate that polarimetric imaging using THz waves has the potential to detect structural changes due to disease progression. The team began by using Monte Carlo simulation to model how THz waves scatter from spherical particles embedded in highly absorbing biological media. Particles of varying diameters can be representative of disease-related structures like tumor clusters or hair follicles that have been destroyed due to burn injuries. The simulation revealed contrast in the Stokes vectors and Mueller Matrix elements for varying scattering particle sizes. The researchers compared the simulation results with experimental data from four phantoms consisting of polypropylene particles of varying sizes, suspended in gelatin. The phantoms mimicked the optical properties of actual tissue. They measured phantoms of moderately-sized tumor budding and poorly differentiated clusters. The results showed frequency-dependent patterns that clearly correlated with particle size, confirming the simulation predictions. As predicted, the larger scattering particles produced higher-intensity diffusely scattered light. The larger particles also produced distinct dips in polarization at specific frequencies. This finding could be used to assess the size of the scattering particles. These experimental results demonstrate the potential to use THz light — specifically, the degree of polarization and intensity of diffusely scattered light — as a diagnostic marker. The team further showed that a characterization of the tissue’s relevant polarization properties can be achieved using just one polarization measurement, unlike conventional approaches that require at least four measurements. Finally, the researchers induced a full-thickness burn injury in ex vivo porcine skin samples and compared the data captured over the burned and healthy regions of the tissue. The results showed contrast between the burned and healthy tissue regions, demonstrating the potential to use THz polarimetric imaging to distinguish between disease states in ex vivo tissue. Most existing THz imaging techniques use the differences in water content between healthy and diseased tissue as their main source of diagnostic contrast. This approach can be overly simplistic for many disease conditions. The ability to detect and characterize structural changes in tissue through THz polarimetric imaging could open new possibilities for timely detection of malignancies. For example, THz imaging could be used to identify tumor budding, where small clusters of cancer cells break away from the main tumor. THz polarimetric imaging offers a potentially simpler, more efficient way to detect these clusters than current methods that rely on tissue sampling and intricate staining procedures. The research team plans to extend its study by investigating actual cancer tissue samples and expanding its THz measurement capabilities to capture even smaller tissue features. THz systems with larger bandwidth, currently in development, could enable polarimetric techniques with the potential to resolve structures as small as 10-30 μm, enabling a wider range of disease-related tissue changes to be detected with THz light. As THz technology continues to advance, the results of the Stony Brook study could have a significant influence on the inclusion of THz imaging in routine medical diagnosis, potentially transforming the way clinicians detect and monitor disease progression. The research was published in the Journal of Biomedical Optics (www.doi.org/10.1117/1.JBO.30.6.066001).