Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies

Abstract

Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm(3) single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8x8x8 cm(3)) in response to area illumination (12 cm(2)) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.

Magnetic resonance–coupled fluorescence tomography scanner for molecular imaging of tissue

“…[1][2][3][4][5][6] Other studies have focused on the systematic development and assessment of diffuse optical fluorescence tomographic ͑DOFT͒ imaging techniques in tissue volumes relevant to human imaging, if targeted probes earn clinical approval. [7][8][9][10][11] Most previous work involving human breast imaging has been completed using tissue simulating phantoms, though fluorescence tomography images of human breast using the nontargeted fluorophore indocyanine green ͑ICG͒ have very recently been published. 7 Pursuing noninvasive optical molecular imaging at depth implies that the interrogating photons are measured only at the tissue surface, making the image inversion problem severely underdetermined and ill posed, even with dense source and detector configurations.…”

Spectral distortion in diffuse molecular luminescence tomography in turbid media

“…[27][28][29][30][31][32][33] Systems have been developed to collect fluorescence intensities from an array of source-detector positions surrounding the tissue of interest and model-based reconstruction techniques have been used to recover fluorescence activity by matching the modeled and measured data using optimization techniques. Most experimental systems employ band-pass or long-pass filters to separate the excitation signal from the fluorescence emission, but rarely has the capability to resolve the fluorescence spectrum been incorporated.…”

A novel fuzzy clustering algorithm for the analysis of axillary lymph node tissue sections

“…However, traditional histology remains a subjective technique and significant problems are often encountered including missed lesions and an unsatisfactory discrepancy between pathologists. These problems in diagnosis have led to considerable interest in investigating the application of spectroscopic approaches for disease diagnosis [1,2]. Fourier transform infrared (FTIR) spectroscopic imaging provides a chemical fingerprint of microscopic areas within a tissue sample [3][4][5][6].…”