Pulsed terahertz reflection imaging of tumors in a spontaneous model of breast cancer

Abstract

We report the use of reflection-mode terahertz (THz) imaging in a transgenic mouse model of breast cancer. Unlike tumor xenografts that are grown from established cell lines, these tumors were spontaneously generated in the mammary fat pad of mice, and are a better representation of human breast cancer. THz imaging results from 7 tumors that recapitulate the compartmental complexity of breast cancer are presented here. Imaging was first performed on freshly excised tumors within an hour of excision and then repeated after fixation with formalin and paraffin. These THz images were then compared with histopathology to determine reflection-mode signals from specific regions within tumor. Our results demonstrate that the THz signal was consistently higher in cancerous tissue compared with fat, muscle, and fibrous tissue. Almost all tumors presented in this work demonstrated advanced stages where cancer infiltrated other tissues like fat and fibrous stroma. As the first known THz investigation in a transgenic model, these results hold promise for THz imaging at different stages of breast cancer.

Terahertz Imaging and Characterization Protocol for Freshly Excised Breast Cancer Tumors

“…This led to a false positive result, suggesting a larger presence of cancer in the tumor. DMEM showed a similarly high refractive index and absorption coefficient to water, as seen in Figure 10C 19 and 10D 19 , so it is highly recommended to dry the tumor properly before imaging.…”

“…The protocol for the freshly excised breast cancer tumors can also be used for the characterization and imaging of any other type of freshly excised solid tumor 8,9,10,11 . While this manuscript focuses on imaging freshly excised breast tumors following the described protocol, THz imaging of the associated formalin-fixed paraffin-embedded tissue blocks has also been successfully validated with pathology 14,15,16,17,19 . Imaging protocols similar to the one proposed here could be developed for pathology support in analyzing embedded tissues as well.…”

“…As a result, THz imaging and spectroscopy has been used to classify and differentiate various tissue features such as water content to indicate burn damage and healing 4 , liver cirrhosis 5 , and cancer in excised tissues 6,7 . Cancer assessment in particular covers a broad range of potential clinical and surgical applications, and has been investigated for cancers of the brain 8 , liver 9 , ovaries 10 , gastrointestinal tract 11 , and breast 7,12,13,14,15,16,17,18,19 .…”

“…The objective of this work is to provide a guideline for THz application for freshly excised tissue using a commercial THz system. The protocol was developed on a THz imaging and spectroscopy system 26 for murine breast cancer tumors 13,17,19 and was extended to human surgical tissue obtained from biobanks 7,18 . While the protocol was generated for breast cancer, the same concepts can be applied to similar THz imaging systems and other types of solid-tumor cancers that are treated with surgery where success depends on margin assessment 27 .…”

“…Normalize the sample data with the reference data and perform the power spectra based on the integration of the normalized data over the frequency range from f 1 = 0.5 THz to f 2 = 1.0 THz using the following equation 19 :…”