Abstract-Permeabilization, when observed on a tissue level, is a dynamic process resulting from changes in membrane permeability when exposing biological cells to external electric field (E).In this paper we present a sequential finite element model of E distribution in tissue which considers local changes in tissue conductivity due to permeabilization. These changes affect the pattern of the field distribution during the high voltage pulse application.The presented model consists of a sequence of static models (steps), which describe E distribution at discrete time intervals during tissue permeabilization and in this way present the dynamics of electropermeabilization. The tissue conductivity for each static model in a sequence is determined based on E distribution from the previous step by considering a sigmoid dependency between specific conductivity and E intensity. Such a dependency was determined by parameter estimation on a set of current measurements, obtained by in vivo experiments. Another set of measurements was used for model validation. All experiments were performed on rabbit liver tissue with inserted needle electrodes. Model validation was carried out in four different ways: 1) by comparing reversibly permeabilized tissue computed by the model and the reversibly permeabilized area of tissue as obtained in the experiments; 2) by comparing the area of irreversibly permeabilized tissue computed by the model and the area where tissue necrosis was observed in experiments; 3) through the comparison of total current at the end of pulse and computed current in the last step of sequential electropermeabilization model; 4) by comparing total current during the first pulse and current computed in consecutive steps of a modeling sequence.The presented permeabilization model presents the first approach of describing the course of permeabilization on tissue level. Despite some approximations (ohmic tissue behavior) the model can predict the permeabilized volume of tissue, when exposed to electrical treatment. Therefore, the most important contribution and novelty of the model is its potentiality to be used as a tool for determining parameters for effective tissue permeabilization.

A crucial part of image-guided therapy is registration of preoperative and intraoperative images, by which the precise position and orientation of the patient's anatomy is determined in three dimensions. This paper presents a novel approach to register three-dimensional (3-D) computed tomography (CT) or magnetic resonance (MR) images to one or more two-dimensional (2-D) X-ray images. The registration is based solely on the information present in 2-D and 3-D images. It does not require fiducial markers, intraoperative X-ray image segmentation, or timely construction of digitally reconstructed radiographs. The originality of the approach is in using normals to bone surfaces, preoperatively defined in 3-D MR or CT data, and gradients of intraoperative X-ray images at locations defined by the X-ray source and 3-D surface points. The registration is concerned with finding the rigid transformation of a CT or MR volume, which provides the best match between surface normals and back projected gradients, considering their amplitudes and orientations. We have thoroughly validated our registration method by using MR, CT, and X-ray images of a cadaveric lumbar spine phantom for which "gold standard" registration was established by means of fiducial markers, and its accuracy assessed by target registration error. Volumes of interest, containing single vertebrae L1-L5, were registered to different pairs of X-ray images from different starting positions, chosen randomly and uniformly around the "gold standard" position. CT/X-ray (MR/ X-ray) registration, which is fast, was successful in more than 91% (82% except for L1) of trials if started from the "gold standard" translated or rotated for less than 6 mm or 17 degrees (3 mm or 8.6 degrees), respectively. Root-mean-square target registration errors were below 0.5 mm for the CT to X-ray registration and below 1.4 mm for MR to X-ray registration.

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