Monte Carlo Modeling of Shortwave-Infrared Fluorescence Photon Migration in Voxelized Media for the Detection of Breast Cancer

Abstract

Recent progress regarding shortwave-infrared (SWIR) molecular imaging technology has inspired another modality of noninvasive diagnosis for early breast cancer detection in which previous mammography or sonography would be compensated. Although a SWIR fluorescence image of a small breast cancer of several millimeters was obtained from experiments with small animals, detailed numerical analyses before clinical application were required, since various parameters such as size as well as body hair differed between humans and small experimental animals. In this study, the feasibility of SWIR was compared against visible (VIS) and near-infrared (NIR) region, using the Monte Carlo simulation in voxelized media. In this model, due to the implementation of the excitation gradient, fluorescence is based on rational mechanisms, whereas fluorescence within breast cancer is spatially proportional to excitation intensity. The fluence map of SWIR simulation with excitation gradient indicated signals near the upper surface of the cancer, and stronger than those of the NIR. Furthermore, there was a dependency on the fluence signal distribution on the contour of the breast tissue, as well as the internal structure, due to the implementation of digital anatomical data for the Visible Human Project. The fluorescence signal was observed to become weaker in all regions including the VIS, the NIR, and the SWIR region, when fluorescence-labeled cancer either became smaller or was embedded in a deeper area. However, fluorescence in SWIR alone from a cancer of 4 mm diameter was judged to be detectable at a depth of 1.4 cm.

Keywords: Monte Carlo simulation; breast cancer; duct; fluorescence; near-infrared light; shortwave-infrared light; visible human project; visible light; voxelized media.

Figure 1

Visualization of the internal structure of the female breasts from the Visible Human Project (VHP). (A) Slice of the upper body. (B) Three-dimensional reconstruction of the upper body. (C) Internal structure in the reconstruction. (D) Enlarged internal structure with fluorescence-labeled cancer with 1 cm diameter. (E) The 3-D vision of the enlarged structure is observed from a different angle. (F) 3-D vision from another different angle. See text.

Figure 2

Implementation of the contour and the internal structures derived from breast anatomical data of the Visible Human Project (VHP). (A) Cropped image from a slice. (B) Allocation of the fat, the duct and the skin based on pixel value. (C) Reconstruction of a 3-D voxel model. (D) Setting of coordinate system in the slice containing the center and top of nipple (x = 0, z = 0). The depth denotes the distance from z = 0 to the upper surface of the cancer.

Figure 3

Flowchart of the Monte Carlo simulation in voxelized media for breast tissue. (A) Implementation of the breast anatomical data of the VHP. (B) Excitation part of the simulation. (C) Computation routines were based on Wang et al. [25]. (D) Emission part.

Figure 4

Effect of the excitation gradient in the SWIR (A,B), the NIR (C,D) and the VIS (E,F). Fluence maps without excitation gradient (A,C,E) and with gradient (B,D,F). Fluorescence-labeled cancer with a diameter of 1 cm in the duct were embedded x = 0 at a depth of 2 cm, denoted by circles of the white broken line. All maps share the values on the x and the z-axis of (E) and the scale bar, which shows the logarithmic scale of intensity (W/cm²) in (B).

Figure 5

Fluence maps of photons associated with excitation (A,C,E) and emission (B,D,F) in the SWIR (A,B), the NIR (C,D), and the VIS (E,F). Fluorescence-labeled cancer with a diameter of 1 mm in the duct was embedded x = 0 at a depth of 3 cm. All maps share values on the x and z-axis of (E). (A,C,E) share the scale bar which shows the logarithmic scale in (A) and (B,D,F) share the scale bar in (B).

Figure 6

Effect on the detected fluorescence intensity of cancer size (A, 0.1–1.0 cm) and cancer depth (B, 1–2 cm). Insert is enlarged on the axis of the intensity. Closed circles: SWIR, Open squares: NIR, Closed triangles: VIS. The red broken line denotes the detectable intensity of 10 nW/cm².