Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography

Abstract

We have developed a novel parallel-plate diffuse optical tomography (DOT) system for threedimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, total-hemoglobin concentration, blood oxygen saturation, and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and Magnetic Resonance Imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-NIH Public Access hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than one week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT.

Direct measurement of tissue blood flow and metabolism with diffuse optics

“…The feasibility of DCS/NIRS for this type of application in humans has been demonstrated for breast [33,36,38], head and neck tumours [34,37] and for basal cell carcinomas [39]. The early flow changes that were found may be significant in affecting drug-delivery efficacy and/or tumour oxygenation during chemoradiation therapy.…”

“…Such effects will be small and can be accounted for by independent NIRS/DOS measurements. For the mean-square particle displacement, in practice, the Brownian model, Dr 2 (t) = 6D B t, fits the observed correlation decay curves fairly well over a wide range of tissue types and source-detector separations, including rat brain [18][19][20][21][22]; mouse tumours [23][24][25][26]; piglet brain [27]; and human skeletal muscle [28][29][30][31][32], human tumours [33][34][35][36][37][38][39] and human brain [40][41][42][43][44][45][46][47][48] (figure 1c). Here, D B is an effective diffusion coefficient that is a few orders of magnitude larger than the traditional thermal Brownian diffusion coefficient of cells in blood given by the Einstein-Smoluchowski relation [49].…”

Multiparametric Monitoring of Chemotherapy Treatment Response in Locally Advanced Breast Cancer Using Quantitative Ultrasound and Diffuse Optical Spectroscopy

“…Since the absorption peaks for lipids were beyond the spectral range of the imaging system, lipid content (%Lipid) was estimated using the linear relationship with the scatter power, previously described by Cerussi et al, and Intes et al [10,51]. Lastly, the TOI has been defined in a variety of ways [42,56,57] and previously described by Cerussi et al to give maximum tissue contrast in breast as:…”

Near-infrared diffuse correlation spectroscopy in cancer diagnosis and therapy monitoring

“…Endogenous tumor-to-normal contrasts available to NIRS include: tissue absorption; scattering; concentrations of oxy-, deoxy-, and total-hemoglobin, water and lipids; and blood oxygen saturation. [7][8][9][10][11][12][13][14][15] A relatively new dynamic NIR technique, namely diffuse correlation spectroscopy (DCS) 16,17 or diffuse wave spectroscopy (DWS), [18][19][20] has been developed which can directly measure the motions of red blood cells in biological tissues while also maintaining all the advantages of NIRS. DCS flow measurements are accomplished by monitoring speckle fluctuations of photons induced by the moving scatterers in tissues.…”