Qinetiq Limited

Anastasios Kesidis

Margaret Jai Varga

Maria Petrou

Paul Gerard Ducksbury

Roberto Cipolla

Christelle Marie Guittet

Michael J Hamer

A method of histological assessment of nuclear pleomorphism to identify potential cell nuclei divides image data into overlapping sub-images. It uses principal component analysis to derive monochromatic image data, followed by Otsu thresholding to produce a binary image. It removes image regions at sub-image boundaries, unsuitably small image regions and holes in relatively large image regions. It then reassembles the resulting sub-images into a single image. Perimeters (P) and areas (A) of image regions which are potential cell nuclei are determined and used in calculating nuclear shape factors P/A. Nuclear pleomorphism is assessed as relatively low, moderate or high according to whether predetermined shape factor thresholds indicate a mean cell nucleus shape factor for an image is relatively low, moderate or high.

Histological assessment of nuclear pleomorphism

A method of measurement of mitotic activity from histopathological specimen images initially identifies image pixels with luminances corresponding to mitotic figures and selects from them a reference pixel to provide a reference color. Pixels similar to the reference color are located; image regions are grown on located pixels by adding pixels satisfying thresholds of differences to background and image region luminances. Grown regions are thresholded in area, compactness, width/height ratio, luminance ratio to background and difference between areas grown with perturbed thresholds. Grown regions are counted as indicating mitotic figures by thresholding region number, area and luminance. An alternative method of measuring mitotic activity measures a profile of an image region and counts the image region as corresponding to a mitotic figure if its profile is above a threshold at an intensity associated with mitotic figures. A mitotic figure is also indicated if the profile does not meet the previous criterion but has three other values satisfying respective threshold criteria.

Measurement of mitotic activity

A method of measuring oestrogen or progesterone receptor (ER or PR) comprises identifying in histopathological specimen image data pixel groups indicating cell nuclei, and deriving image hue and saturation. The image is thresholded using hue and saturation and preferentially stained cells identified. ER or PR status is determined from normalised average saturation and proportion of preferentially stained cells. A method of measuring C-erb-2 comprises correlating window functions with pixel sub-groups to identify cell boundaries, computing measures of cell boundary brightness and sharpness and brightness extent around cell boundaries, and comparing the measures with comparison images associated with different values of C-erb-2. A C-erb-2 value associated with a comparison image having similar brightness-related measures is assigned. A method of measuring vascularity comprises deriving image hue and saturation, producing a segmented image by hue and saturation thresholding and identifying contiguous pixels. Vascularity is determined from contiguous pixel area corresponding to vascularity expressed as a proportion of total image area.

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Athens, Greece

Anastasios Kesidis