Abstract

Breast cancer is the most prevalent cancer and the main cause of cancer-related death in women worldwide. There are limitations associated with the existing clinical tools for breast cancer detection and alternative modalities for early detection and classification of breast cancer are urgently needed. Here we describe an optical imaging technique, called multispectral diffuse optical tomography (DOT), and demonstrate its ability of non-invasively evaluating nuclear morphometry for differentiating benign from malignant lesions. Photon densities along the surface of the breast were measured to allow for the extraction of three statistical parameters including the size, elongation and density of nuclei inside the breast tissue. The results from 14 patients (4 malignant and 10 benign lesions) show that there exist significant contrasts between the diseased and surrounding normal nuclei and that the recovered nuclear morphological parameters agree well the pathological findings. We found that the nuclei of cancer cells were less-spherical compared with those of surrounding normal cells, while the nuclear density or volume fraction provided the highest contrast among the three statistical parameters recovered. This pilot study demonstrates the potential of multispectral DOT as a cellular imaging method for accurate determination of breast cancer.

Highlights

  • Alterations in nuclear morphology are a hallmark of cancer cells

  • The changes in cellular and nuclear morphology correlate with tumor grade

  • In a significant step further to utilize a more realistic scattering model, we demonstrate here that more reasonable morphological parameters are obtained upon modeling nuclei as spheroidal particles, randomly oriented in the breast tissue

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Summary

Introduction

Alterations in nuclear morphology are a hallmark of cancer cells. Nuclei of cancer cells divide out of control and contain extra chromosomes. Compared with nuclei in non-cancerous cells, nuclei in cancer cells are larger, closer together and more irregular in morphology [1,2,3,4,5,6,7]. The changes in cellular and nuclear morphology correlate with tumor grade. Most of the relevant diagnostic techniques for evaluating breast lesiosn are invasive and require biopsy sampling of the breast tissue and subsequent pathologic analysis. The ability to assess changes in nuclear morphology non-invasively would represent a major step forward in the development of strategies to non-invasively evaluate indeterminate breast lesions and detect breast cancer

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