This thesis is devoted to solving the inverse source problem arising in image reconstruction problems. In general, the solution is non-unique and the problem is severely ill-posed. Therefore, small perturbations, such as the noise in the data, and the modeling error in the forward problem, will cause huge errors in the computations. In practice, the most widely used method to tackle the problem is based on Tikhonov-type regularizations, which minimizes a cost function combining a regularization term and a data fitting term. However, because the two tasks, namely regularization and data fitting, are coupled together in Tikhonov regularization, they are difficult to solve. It happens even if each task can be efficiently solved when they are separate. We propose a method to overcome the major difficulties, namely the non-uniqueness of the solution and noisy data fitting, separately. First we find a particular solution called the orthogonal solution that satisfies the data fitting term. Then we add to it a correction function in the kernel space so that the final solution fulfills the regularization and other physical requirements. The key idea is that the correction function in the kernel has no impact to the data fitting, and the regularization is imposed in a smaller space. Moreover, there is no parameter needed to balance the data fitting and regularization terms. As a case study, we apply the proposed method to Fluorescence Tomography (FT), an emerging imaging technique well known for its ill-posedness and low image resolution in existing reconstruction techniques. We demonstrate by theory and examples that the proposed algorithm can drastically improve the computation speed and the image resolution over existing methods.