Probing physiology and molecular function using optical imaging: applications to breast cancer

Abstract

The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring.

Figure 1

Breast transillumination. Craniocaudal (cc) and oblique (ob) views of the left (L) breast of a 72-year-old patient affected by invasive ductal carcinoma. The cancer diameter is 2.5 cm. The cancer appears with high contrast in both views of the breast. From Fantini et al [20], with permission.

Figure 2

DOT of ICG enhancement obtained simultaneously with gadolinium-enhanced MRI of the same breast affected by an 8-mm ductal carcinoma. (a) Sagittal magnetic resonance image of the breast (in grayscale) superimposed with the gadolinium enhancement (in color). The cancerous lesion appears enhanced in the center of the image because of gadolinium administration. (b) Coronal DOT image of the absorption coefficient change due to ICG distribution. This image is perpendicular to the plane of the MRI image in (a) and is obtained for the volume of interest indicated on (a) with the dashed line box. (c) Functional magnetic resonance coronal reslicing of the volume of interest with the same dimensions as (b). Gadolinium enhancement is averaged over the volume of interest and appears in color. The cancer appears in the right upper corner of the coronal image and has high spatial congruence with its appearance on the DOT image. A secondary lesion on the left, middle part of the image also coregisters well with the DOT image. A third lesion, which appears on the lower boundary of the DOT image, is probably an artifact. Although single slices through the breast volume are shown here, both MRI and DOT retrieve three-dimensional information of the volume of investigation. Published with permission from Ntziachristos et al [7]; © 2000 National Academy of Sciences, USA.

Figure 3

DOT of intrinsic breast contrast at 754 nm. The figures display the distribution of (a) the absorption and (b) reduced scattering coefficient from a patient with a well-localized 3.4-cm fibroadenoma in the upper central region of her breast. The geometry is a single plane transecting the location of the abnormality, in a craniocaudal view. The lesion appears to have higher absorption than the average background breast absorption, possibly due to increased vascularization. No significant scattering contrast is obtained. Spectral information, namely the combination of such images at multiple wavelengths, can quantify the vascularization and oxygenation level of breast lesions. From Pogue et al [27], with permission of the Radiological Society of North America.

Figure 4

Imaging molecular function. (a) Light (baseline) image and (b) the contrast-enhanced fluorescence image of an LX-1 tumor implanted into the mammary fat pad of a nude mouse, as indicated by the white arrow. Significant contrast appears between cancer and background on the fluorescence image. The contrast agent used was a synthetic graft copolymer with Cy5.5-quenched fluorochromes, which was activated in the presence of cathepsin D. (c) Dissected tumor in the mammary pad and (d) histology. Published with permission from Weissleder et al [13].