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Munich, Germany

Patent
Definiens | Date: 2015-04-27

A method for determining whether a test biomarker is a stain for a type of cell component, such as membrane or nucleus, involves performing various segmentation processes on an image of tissue stained with the test biomarker. One segmentation process searches for a first cell component type, and another segmentation process searches for a second cell component type by segmenting only stained pixels. The test biomarker is identified as a stain for each component type if the process identifies the component based only on stained pixels. Whether the test biomarker is a membrane stain or nucleus stain is displayed on a graphical user interface. In addition, the method identifies stained pixels corresponding to a second cell component using pixels determined to correspond to a first cell component. An expression profile for the test biomarker is then displayed that indicates the proportion of stained pixels in each type of cell component.


Both object-oriented analysis and the faster pixel-oriented analysis are used to recognize patterns in an image of stained tissue. Object-oriented image analysis is used to segment a small portion of the image into object classes. Then the object class to which each pixel in the remainder of the image most probably belongs is determined using decision trees with pixelwise descriptors. The pixels in the remaining image are assigned object classes without segmenting the remainder of the image into objects. After the small portion is segmented into object classes, characteristics of object classes are determined. The pixelwise descriptors describe which pixels are associated with particular object classes by matching the characteristics of object classes to the comparison between pixels at predetermined offsets. A pixel heat map is generated by giving each pixel the color assigned to the object class that the pixelwise descriptors indicate is most probably associated with that pixel.


The coregistration of digital images of tissue slices is improved by updating landmarks based on the manual outlining of regions of interest on the images. A first image of a first slice is coarsely coregistered with a second image of a second slice using a first landmark on the first image and a second landmark on the second image. A user manually outlines a first region of interest on the first image. The outline is positioned over a second region of interest on the second image using the second landmark. The user manually moves a contour point of the outline on the second image to form a corrected outline. The second landmark is moved based on how the contour point was manually moved so that the first and second images are more finely coregistered after the second landmark is moved. Each state of corrected contour points and landmarks is saved.


An image-based biomarker is generated using image features obtained through object-oriented image analysis of medical images. The values of a first subset of image features are measured and weighted. The weighted values of the image features are summed to calculate the magnitude of a first image-based biomarker. The magnitude of the biomarker for each patient is correlated with a clinical endpoint, such as a survival time, that was observed for the patient whose medical images were analyzed. The correlation is displayed on a graphical user interface as a scatter plot. A second subset of image features is selected that belong to a second image-based biomarker such that the magnitudes of the second image-based biomarker for the patients better correlate with the clinical endpoints observed for those patients. The second biomarker can then be used to predict the clinical endpoint of other patients whose clinical endpoints have not yet been observed.


A system for computer-aided detection uses a computer-implemented network structure to analyze patterns present in digital image slices of a human body and to generate a three-dimensional anatomical model of a patient. The anatomical model is generated by detecting easily identifiable organs first and then using those organs as context objects to detect other organs. A user specifies membership functions that define which objects of the network structure belong to the various classes of human organs specified in a class hierarchy. A membership function of a potentially matching class determines whether a candidate object of the network structure belongs to the potential class based on the relation between a property of the voxels linked to the candidate object and a property of the context object. Some voxel properties used to classify an object are location, brightness and volume. The human organs are then measured to assist in the patients diagnosis.

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