A simultaneous magnetic resonance imaging (MRI) and Diffusion wave optical tomography characterization of tissue may contribute significantly to the great need to increase the sensitivity/specificity of the MRI breast examination for patients having a positive mammogram or a palpable breast mass. The increased concentration of gadolinium in the tumor volume with respect to the background tissue has afforded a significant sensitivity for the MRI examination. This application aims to utilize MRI guided information about the location, size and shape of relevant voxels in conjunction with DWOT to increase specificity. Time domain measurement of global u(a) and u(s') is of demonstrated feasibility in human breasts (600 measurements). The applicants propose a multisource, multidetector fiber optic coupling of time domain photon diffusion technology into the MRI magnet bore. The optical method affords four novel specificities related to the tumor characteristics in vivo that are expected to differ from the characteristics of the normal over 40 year breast. 1) increased blood concentration due to neo-vascularization region necessary for tumor growth; 2) relatively increased desaturation of hemoglobin due to the high oxygen demand of the tumor; 3) increased light scattering due to increased intracellular organelle content of the tumor mass; 4) increased absorption/fluorescence washin/washout of a contrast agent, cardiogreen, analogous to the gadolinium chelate for which the optical method has an extremely high sensitivity. This research proposes a detailed analysis of these four parameters in studies of all patients for which MRI/MRS of breast tumors is offered and for which identical simultaneous protocols are proposed. It is proposed that the sensitivities/specificities of the primary breast examination will be significantly enhanced over and above that of either the optical method alone or the MRI method alone as will be determined by appropriate statistical analysis of 57 patients per year. Twenty normal patients will be studied under similar conditions outside the MRI magnet in order to determine overlap between normal and tumor bearing breasts with respect to blood concentration, blood deoxygenation, organelle light scattering. Two theoretical approaches are to be employed to determine tumor optical properties. The first a MRI guided analytic approach on the exact solution for a sphere. This method, along with a more general virtual source procedure will directly utilize structural information from the MRI images do deduce optical properties. The analytic approaches will be sensitive to optical properties for objects of order 0.5 cm in diameter. Other imaging algorithms that do not rely on MRI images will also be employed. To achieve optimal sensitivity/specificity in breast tumor detection we will evaluate and apply comparative weights to the several optical criteria and to the imaging algorithms.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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University of Pennsylvania
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