Multi-photon microscopy was used to determine the differential response to radiation at multiple time points between radiation-resistant and -susceptible human head and neck cancer tumor xenografts grown in a cohort of 60 athymic mice. Mice were randomly divided into groups for cell line, treatment or control, and time points relative to treatment — baseline, 1 hour-, 24 hours-, and 48 hours-post-treatment. We quantified the optical redox ratio, lifetime of NAD(P)H, and heterogeneity in ORR and lifetime endpoints. We saw a significant effect of cell line, treatment, and the interaction of all three factors — line, treatment, and time point.
KEYWORDS: Tumors, Optical spectroscopy, Breast, Raman spectroscopy, Breast cancer, Scattering, Raman scattering, In vivo imaging, Diffuse reflectance spectroscopy, Data modeling
We used Diffuse Reflectance spectroscopy (DRS) and Raman spectroscopy to investigate functional differences between murine breast tumor xenografts of varying metastatic potential. Once tumors volume reached 200mm3, in-vivo DRS and ex-vivo Raman spectroscopy were performed. Spectra and optical properties were used to train and test a leave-one-out random forest classifier. Significant differences between metastatic and non-metastatic tumors were observed. The study shows that random forest classifiers coupled with optical spectroscopy provides consistent predictions of metastatic phenotype and metastatic abilities from the primary tumor that can be translated into clinic.
Purpose: The objective of this study is to quantitatively evaluate terahertz (THz) imaging for differentiating cancerous from non-cancerous tissues in mammary tumors developed in response to injection of N-ethyl-N-nitrosourea (ENU) in Sprague Dawley rats.
Approach: While previous studies have investigated the biology of mammary tumors of this model, the current work is the first study to employ an imaging modality to visualize these tumors. A pulsed THz imaging system is utilized to experimentally collect the time-domain reflection signals from each pixel of the rat’s excised tumor. A statistical segmentation algorithm based on the expectation-maximization (EM) classification method is implemented to quantitatively assess the obtained THz images. The model classification of cancer is reported in terms of the receiver operating characteristic (ROC) curves and the areas under the curves.
Results: The obtained low-power microscopic images of 17 ENU-rat tumor sections exhibited the presence of healthy connective tissue adjacent to cancerous tissue. The results also demonstrated that high reflection THz signals were received from cancerous compared with non-cancerous tissues. Decent tumor classification was achieved using the EM method with values ranging from 83% to 96% in fresh tissues and 89% to 96% in formalin-fixed paraffin-embedded tissues.
Conclusions: The proposed ENU breast tumor model of Sprague Dawley rats showed a potential to obtain cancerous tissues, such as human breast tumors, adjacent to healthy tissues. The implemented EM classification algorithm quantitatively demonstrated the ability of THz imaging in differentiating cancerous from non-cancerous tissues.
We used diffuse reflectance spectroscopy to assess the effects of different radiation therapy doses on tumor microenvironment. We injected 4T1 cells into the flanks of 25 mice to develop tumor xenografts, and randomly distributed the animals into control and radiation groups, which received a dose of either 1, 2, or 4 Gy. Treatment started when tumors reached a volume of 200 mm3. DRS measurements were obtained prior to and 1 hour after radiation on the five days of treatment, and once a day thereafter. Our data demonstrates that DRS is sensitive to tumor microenvironmental changes after low doses of radiation.
We used Diffuse Reflectance spectroscopy (DRS) to investigate functional changes within the tumor microenvironment when treated with different immunotherapy drugs. We injected the CT26 cell line into the flank of 35 mice that were assigned to 4 different groups: anti-PD-1, anti-CTLA-4, combination treatment, and IgG. The 4 groups were injected intraperitoneally on days 1, 4 and 7 (Day 1 – tumor at 80-120 mm3). DRS spectra were acquired simultaneously for 9 consecutive days and a lookup table (LUT)-based inverse model was implemented to decompose the spectral data. We found statistically significant differences in functional changes among the different immunotherapy groups.
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