Using Optical Spectroscopy to Longitudinally Monitor Physiological Changes within Solid Tumors

Abstract

The feasibility of using quantitative diffuse reflectance spectroscopy to longitudinally monitor physiological response to cancer therapy was evaluated in a preclinical model. This study included two groups of nude mice bearing 4T1 flank tumors (N = 50), half of which were treated with a maximum tolerated dose of doxorubicin (DOX). Diffuse reflectance spectra were collected from tumors during a period of 2 weeks using a fiber-optic probe coupled to a spectrometer. These spectra were quantified using an inverse scalable Monte Carlo model of light transport in tissue to extract the concentrations of oxygenated, deoxygenated hemoglobin (dHb), and a wavelength mean reduced scattering coefficient (<micro(s)'>). The tumor growth rates of the treated and control groups were nearly identical, as were changes in the scattering parameter <micro(s)'> during this time frame. However, tumors treated with DOX showed a transient but significant increase in blood oxygen saturation. A comparison between the optically derived and immunohistochemical end points in a subset of the 50 animals showed that the temporal kinetics of dHb concentration and <micro(s)'> were highly concordant with those of hypoxic and necrotic fractions, respectively. In conclusion, optical methods could function as a "screening" technology in longitudinal studies of small animal tumor models to accelerate development and testing of new anticancer drugs. This technique could isolate specific landmark time points at which more expensive and sophisticated imaging methods or immunohistochemistry could be performed.

In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts

“…Decreased sO 2 in treated tumors agrees with the DOSI-measured decrease in sO 2 in patient tumors one week after initiation of therapy [19], as well as with immunohistochemical study of hypoxia in HER2 overexpressing xenograft tumors [12]. Decreased sO 2 has also been shown in non-treated control mice over a 13 day timecourse with diffuse reflectance imaging [36]. Additionally, BT474 tumors exhibited a significant decrease in sO 2 with treatment compared to all other groups on day 5.…”

Performance of a lookup table-based approach for measuring tissue optical properties with diffuse optical spectroscopy

“…24 Indeed, researchers have used DOS and diffuse optical tomography (DOT) to predict longterm response in preclinical models and patients based on oxygen saturation of hemoglobin. 25,26 The LUT accurately measured the hemoglobin saturation to within 4 percent of the expected value, again indicating the robustness of the model. We found the magnitude of the reflectance for the deoxygenated state to be consistently less compared to the initial oxygenated state.…”

Experimental validation of an inverse fluorescence Monte Carlo model to extract concentrations of metabolically relevant fluorophores from turbid phantoms and a murine tumor model

“…The value of the optical absorption and scattering properties used here were based on our previous estimates of optical properties of murine tumors (μ a ≈ 3.5 cm −1 , μ 0 s ≈ 10 cm −1 , averaged between 350 to 650 nm). 50 Each phantom set contained two subsets: these two subsets either had two different HbO 2 absorption levels with same scattering, or two levels of scattering with the same HbO 2 absorption level. Each subset contained a phantom with increasing fluorophore concentrations through sequential additions of small volumes of fluorophore stock solution.…”