Quantitative evaluation of image registration algorithms is a difficult and under-addressed issue due to the lack of a reference standard in most registration problems. In this work a method is presented whereby detailed reference standard data may be constructed in an efficient semi-automatic fashion. A well-distributed set of n landmarks is detected fully automatically in one scan of a pair to be registered. Using a custom-designed interface, observers define corresponding anatomic locations in the second scan for a specified subset of s of these landmarks. The remaining n-s landmarks are matched fully automatically by a thin-plate-spline based system using the s manual landmark correspondences to model the relationship between the scans. The method is applied to 47 pairs of temporal thoracic CT scans, three pairs of brain MR scans and five thoracic CT datasets with synthetic deformations. Interobserver differences are used to demonstrate the accuracy of the matched points. The utility of the reference standard data as a tool in evaluating registration is shown by the comparison of six sets of registration results on the 47 pairs of thoracic CT data.

Numerous studies have shown the prognostic significance of nuclear morphometry in breast cancer patients. Wide acceptance of morphometric methods has, however, been hampered by the tedious and time consuming nature of the manual segmentation of nuclei and the lack of equipment for high throughput digitization of slides. Recently, whole slide imaging became more affordable and widely available, making fully digital pathology archives feasible. In this study, we employ an automatic nuclei segmentation algorithm to extract nuclear morphometry features related to size and we analyze their prognostic value in male breast cancer. The study population comprised 101 male breast cancer patients for whom survival data was available (median follow-up of 5.7 years). Automatic segmentation was performed on digitized tissue microarray slides, and for each patient, the mean nuclear area and the standard deviation of the nuclear area were calculated. In univariate survival analysis, a significant difference was found between patients with low and high mean nuclear area (P ¼ 0.022), while nuclear atypia score did not provide prognostic value. In Cox regression, mean nuclear area had independent additional prognostic value (P ¼ 0.032) to tumor size and tubule formation. In conclusion, we present an automatic method for nuclear morphometry and its application in male breast cancer prognosis. The automatically extracted mean nuclear area proved to be a significant prognostic indicator. With the increasing availability of slide scanning equipment in pathology labs, these kinds of quantitative approaches can be easily integrated in the workflow of routine pathology practice.

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A serious challenge in image registration is the accurate alignment of two images in which a certain structure is present in only one of the two. Such topological changes are problematic for conventional non-rigid registration algorithms. We propose to incorporate in a conventional free-form registration framework a geometrical penalty term that minimizes the volume of the missing structure in one image. We demonstrate our method on cervical MR images for brachytherapy. The intrapatient registration problem involves one image in which a therapy applicator is present and one in which it is not. By including the penalty term, a substantial improvement in the surface distance to the gold standard anatomical position and the residual volume of the applicator void are obtained. Registration of neighboring structures, i.e. the rectum and the bladder is generally improved as well, albeit to a lesser degree.