The Optical Imaging Laboratory has developed a hand-held optical imaging system that is capable of 3D tomographic imaging. However, the imaging system is limited by longer imaging times, and inaccuracy in the positional tracking of the handheld probe. Hence, the objective is to improve the performance of the imaging system by Table 3.3 Positions collected in the 2D tracking study for the second generation probe heads. Both probe heads were moved in the same positions on separate phantoms where (0,0) is the bottom right position of the phantom. Therefore each of these positions was repeated 5 times per probe head. ……………………………………………………………………………………....58 Table 4.1 Error comparison of the tracking devices in two dimensional tracking. The averages of the errors are shown here as well as the average distance from the true measured position as calculated using Equations 3 -6…………………………………………………………...…………………….…..67 Table 4.2 Comparison of the target location and errors of the probe location for both trackers. The location of the target was taken from the images that were collected in the 2D studies with a 2% Liposyn filled cubical phantom. The true location of the target was compared to the location found in the images giving the errors shown above.……………………………………………………………………………….71 Table 4.3 Table showing the error of the acoustic, optical, and multiple objects with optical. Each of the co-registration software's accuracy was compared in a study where the probe head with the tracker attached was moved along the face of a cubical phantom. The positions at which the probe(s) head was/were located were measured physically and through the co-registration software to provide an accurate comparison of the accuracy of each tracker……………………………………………………………………….…….. A above is a large bed manufactured by Imaging Diagnostic Systems, Inc. It involves the breast to be imaged through transillumination while placed in a hole on the imaging bed. B above is also a transillumination imager that requires compression of the breast for imaging [Wang, et al, 2010]. C above is a hand held imager, however is for spectroscopic measurements [Bevilacqua, et al, 2000] [Chance, et al. 2005;Chen, et al. 2004;Sao, et a. 2003;Tromberg, et al. 2005;Xu, et al. 2007;Zhu, et al. 1999]. Recently, the Optical Imaging Laboratory (OIL) has developed a hand held optical imaging system that is capable of 3D tomography. To obtain measurements relevant for 3D tomographic imaging, a co-registration technique is employed, that allows registering the positional information of the hand-held probe on the tissue geometry during imaging studies. The feasibility of co-registered imaging and 3D tomography studies on tissue phantoms have been demonstrated in the past. [Ge, et al. 2008;Jayachandran, et al. 2007]. However, there are limitations in our hand-held optical imaging system in the path of our ongoing clinical translational efforts. These include:(i) Longer imaging times: The optical imaging system and the positional tracking device are operated independently via ...