Multi-spectral and Fluorescence Diffuse Optical Tomography of Breast Cancer

Multi-spectral and Fluorescence Diffuse Optical Tomography of Breast Cancer Alper Corlu Arjun G. Yodh Multi-spectral and fluorescence diffuse optical tomography (DOT) techniques are explored and applied to image human breast cancer in vivo. Image reconstruction algorithms that utilize first and second order gradient information are described in detail. Breast DOT requires large computational memory and long run times. To this end, parallel computation techniques were developed appropriate to each reconstruction algorithm. A parallel plate DOT instrument developed for breast cancer imaging is described. The system relies heavily on continuous-wave (CW) transmission measurements and utilizes frequency domain (FD) measurements on the reemission side. However, traditional DOT image reconstruction methods based on CW measurements fail to separate tissue absorption and scattering uniquely. In this manuscript, multi-spectral DOT is shown to be capable of minimizing cross-talk and retrieving spectral parameters almost uniquely when the measurement wavelengths are optimized. A theoretical framework to select optimum wavelengths is provided, and tested with computer simulations. Results from phantom spectroscopy experiments and in vivo patient measurements support the notion that multi-spectral methods are superior to traditional DOT image reconstruction schemes. The same breast DOT instrument is improved and utilized to obtain the first in vivo images of human breast cancer based on fluorescence DOT (FDOT). To this end the fluorophore Indocyanine vii Green (ICG) is injected intravenously and fluorescence excitation and detection are accomplished in the soft-compression, parallel-plane, transmission geometry using laser sources at 786 nm and spectrally filtered CCD detection. Careful phantom and in vivo measurements are carried on to assure that the signals are due to ICG fluorescence, rather than tissue autofluorescence and excitation light leakage. An in vivo measurement protocol is designed to maximize the ICG contrast by acquiring full fluorescence tomographic scan during the tail of ICG temporal decay curve. The image reconstruction method used to obtain 3D contrast image of ICG concentration is described. Intrinsic and fluorescence contrast images of three cancer patients are presented, and it is found that tumor-to-normal tissue contrast based on ICG fluorescence is two-to-four-fold higher than contrast based on hemoglobin and scattering parameters.