Computerized detection and segmentation of mitochondria on electron microscope images

Mitochondrial function plays an important role in the regulation of cellular life and death, including disease states. Disturbance in mitochondrial function and distribution can be accompanied by significant morphological alterations. Electron microscopy tomography (EMT) is a powerful technique to study the 3D structure of mitochondria, but the automatic detection and segmentation of mitochondria in EMT volumes has been challenging due to the presence of subcellular structures and imaging artifacts. Therefore, the interpretation, measurement and analysis of mitochondrial distribution and features have been time consuming, and development of specialized software tools is very important for high-throughput analyses needed to expedite the myriad studies on cellular events. Typically, mitochondrial EMT volumes are segmented manually using special software tools. Automatic contour extraction on large images with multiple mitochondria and many other subcellular structures is still an unaddressed problem. The purpose of this work is to develop computer algorithms to detect and segment both fully and partially seen mitochondria on electron microscopy images. The detection method relies on mitochondria's approximately elliptical shape and double membrane boundary. Initial detection results are first refined using active contours. Then, our seed point selection method automatically selects reliable seed points along the contour, and segmentation is finalized by automatically incorporating a live-wire graph search algorithm between these seed points. In our evaluations on four images containing multiple mitochondria, 52 ellipses are detected among which 42 are true and 10 are false detections. After false ellipses are eliminated manually, 14 out of 15 fully seen mitochondria and 4 out of 7 partially seen mitochondria are successfully detected. When compared with the segmentation of a trained reader, 91% Dice similarity coefficient was achieved with an average 4.9 nm boundary error.