Classification of polyhedral shapes from individual anisotropically resolved cryo-electron tomography reconstructions.

BACKGROUND: Cryo-electron tomography (cryo-ET) enables 3D imaging of macromolecular structures. Reconstructed cryo-ET images have a "missing wedge" of data loss due to limitations in rotation of the mounting stage. Most current approaches for structure determination improve cryo-ET resolution either by some form of sub-tomogram averaging or template matching, respectively precluding detection of shapes that vary across objects or are a priori unknown. Various macromolecular structures possess polyhedral structure. We propose a classification method for polyhedral shapes from incomplete individual cryo-ET reconstructions, based on topological features of an extracted polyhedral graph (PG). RESULTS: We outline a pipeline for extracting PG from 3-D cryo-ET reconstructions. For classification, we construct a reference library of regular polyhedra. Using geometric simulation, we construct a non-parametric estimate of the distribution of possible incomplete PGs. In studies with simulated data, a Bayes classifier constructed using these distributions has an average test set misclassification error of < 5 % with upto 30 % of the object missing, suggesting accurate polyhedral shape classification is possible from individual incomplete cryo-ET reconstructions. We also demonstrate how the method can be made robust to mis-specification of the PG using an SVM based classifier. The methodology is applied to cryo-ET reconstructions of 30 micro-compartments isolated from E. coli bacteria. CONCLUSIONS: The predicted shapes aren't unique, but all belong to the non-symmetric Johnson solid family, illustrating the potential of this approach to study variation in polyhedral macromolecular structures.

Characterizing search, recognition, and decision in the detection of lung nodules on CT scans: elucidation with eye tracking.

PURPOSE: To determine the effectiveness of radiologists' search, recognition, and acceptance of lung nodules on computed tomographic (CT) images by using eye tracking. MATERIALS AND METHODS: This study was performed with a protocol approved by the institutional review board. All study subjects provided informed consent, and all private health information was protected in accordance with HIPAA. A remote eye tracker was used to record time-varying gaze paths while 13 radiologists interpreted 40 lung CT images with an average of 3.9 synthetic nodules (5-mm diameter) embedded randomly in the lung parenchyma. The radiologists' gaze volumes ( GV gaze volume s) were defined as the portion of the lung parenchyma within 50 pixels (approximately 3 cm) of all gaze points. The fraction of the total lung volume encompassed within the GV gaze volume s, the fraction of lung nodules encompassed within each GV gaze volume (search effectiveness), the fraction of lung nodules within the GV gaze volume detected by the reader (recognition-acceptance effectiveness), and overall sensitivity of lung nodule detection were measured. RESULTS: Detected nodules were within 50 pixels of the nearest gaze point for 990 of 992 correct detections. On average, radiologists searched 26.7% of the lung parenchyma in 3 minutes and 16 seconds and encompassed between 86 and 143 of 157 nodules within their GV gaze volume s. Once encompassed within their GV gaze volume , the average sensitivity of nodule recognition and acceptance ranged from 47 of 100 nodules to 103 of 124 nodules (sensitivity, 0.47-0.82). Overall sensitivity ranged from 47 to 114 of 157 nodules (sensitivity, 0.30-0.73) and showed moderate correlation (r = 0.62, P = .02) with the fraction of lung volume searched. CONCLUSION: Relationships between reader search, recognition and acceptance, and overall lung nodule detection rate can be studied with eye tracking. Radiologists appear to actively search less than half of the lung parenchyma, with substantial interreader variation in volume searched, fraction of nodules included within the search volume, sensitivity for nodules within the search volume, and overall detection rate.