A Study On Combined Time Domain Diffuse Fluorescence―Optical Tomography For Breast Tumor Diagnosis

The endogenouse-contrast-based diffuse optical tomography, referred ashemoglobin-DOT, is emerging as a potential imaging technique for breast cancerdetection. Hemoglobin-DOT provides not only the structural information, but also thefunctional images including oxy-hemoglobin, deoxy-hemoglobin, lipid and watercontent as well as the morphological images including nucleus size and volumefraction. It discloses the pathological and physiological abnormalities of in vivotissues by measuring its hemodynamic patterns is more preferred for differentiationbetween benign and malignant lesions as well as for tumor staging. However,hemoglobin-DOT suffers from low spatial resolution and quantitative reconstruction,that it is still clinically difficult to use hemoglobin-DOT. DOT with the use ofexogenous fluorescence dyes, referred to as fluorescence diffuse optical tomography(FDOT), not only inherits the advantages of DOT in detection depth andthree-dimension (3D) imaging, but also improves detection sensitivity as well as itspotential to simultaneously access tissue functionality and micro-environment indicessuch as pO2, pH etc. FDOT can markedly enhance detection sensitivity of breasttumor imaging and is reliable in tumor localization. Due to the high specificity ofFDOT, in the study, a combination of FDOT and hemoglobin-DOT is proposed forimproving the reliability of hemoglobin-DOT for early breast tumor diagnosis.The goal of this study is to make use of the advantages of FDOT andhemoglobin-DOT, a combination of both approaches is pursued, and that thequantitative accuracy of hemoglobin-DOT is improved and the capability of detectingearly lesions is enhanced. Compared with other multi-modality imaging systems, thishybrid scheme has the potential of cost-effectiveness of instrumentation and a highcapability of detection. This study involves imaging hardware implementation andsoftware development necessary for achieving the goal, and a combined time-domainfluorescence and hemoglobin-DOT image reconstruction scheme. The detail tasksinclude:(1) A time-domain32channels time resolved system based on thetime-correlated single photon counting technique (TCSPC) is developed. A highfrequence pico-second pulsed diode lasers at the wavelengths of780nm and830nm is employed as the source, a4-channel TCSPC module is applied to acquire the2-wavelength outward time-resolved flux.(2) Instrument calibration is used to eliminate the time-origins drifting anddifferences between system channels, which have a significant impact onreconstruction image quality. The3-D measurement is performed in a layered2-Dmeasuring way, and a counting threshold strategy is adopted to further optimize themeasurement performance and reduce the data-acquisition time.(3) A fluorescence-guided hemoglobin image reconstruction shceme within theframework of the generalized pulse spectrum technique (GPST) is proprosed. Thefluorescence yield image is segmented to extract the region of interest, which couldprovide a priori information to instruct hemoglobin-DOT reconstruction.(4) The linearity and sensitivity of the system responses to optical andfluorescence inclusions of various concentrations are assessed by using2-D scheme,respectively. The feasibility of3-D fluorescence-and hemoglobin-DOT is justifiedusing a realistic layered2D measuring and full3-D reconstructing strategy.Fluorescence-guided hemoglobin-DOT experiment is performed and demonstratedthat the reconstruction accuracy in hemoglobin-DOT could be significantly improvedby the regularization of a priori fluorescence location.(5) Clinicaly3-D hemoglobin-DOT has been studied.3-D2-wavelength DOTmeasurement is implemented to the MRI confirmed breast tumor, and reported thelesions could be identified by the hemoglobin concentration and oxygen saturationinformations, which prove that3-D hemoglobin-DOT is a useful technique for earlybreast tumor diagnosis.The existing multi-modality systems are usually structure complicated and veryexpensive in clinic usage. Moreover, traditional structure imaging modals are notsensitive to early tumor, that it is difficult to offer a priori information tohemoglobin-DOT. To cope with these limitations metioned above, a hybrid scheme oftime-domain fluorescence and hemoglobin tomographic imaging system based on thetime-correlated single photon counting technique is developed for early breast tumordiagnosis.A fluorescence-guided hemoglobin image reconstruction shceme is proposed, forthe reason that hemoglobin-DOT is low in sensitivity and reconstruction quanlity.Under this algorithm framework, fluorescence yield image is segmented to extract the region of interest, which could provide a priori information to instructhemoglobin-DOT reconstruction.In vivo3-D hemoglobin-DOT based on GPST could offer functional information,is tested an usful tool for early breast tumor diagnosis.