Classification and 3D averaging with missing wedge correction in biological electron tomography.

Strategies for the determination of 3D structures of biological macromolecules using electron crystallography and single-particle electron microscopy utilize powerful tools for the averaging of information obtained from 2D projection images of structurally homogeneous specimens. In contrast, electron tomographic approaches have often been used to study the 3D structures of heterogeneous, one-of-a-kind objects such as whole cells where image-averaging strategies are not applicable. Complex entities such as cells and viruses, nevertheless, contain multiple copies of numerous macromolecules that can individually be subjected to 3D averaging. Here we present a complete framework for alignment, classification, and averaging of volumes derived by electron tomography that is computationally efficient and effectively accounts for the missing wedge that is inherent to limited-angle electron tomography. Modeling the missing data as a multiplying mask in reciprocal space we show that the effect of the missing wedge can be accounted for seamlessly in all alignment and classification operations. We solve the alignment problem using the convolution theorem in harmonic analysis, thus eliminating the need for approaches that require exhaustive angular search, and adopt an iterative approach to alignment and classification that does not require the use of external references. We demonstrate that our method can be successfully applied for 3D classification and averaging of phantom volumes as well as experimentally obtained tomograms of GroEL where the outcomes of the analysis can be quantitatively compared against the expected results.

A system for the generation of curves on 3D brain images.

In this study, a computational optimal system for the generation of curves on triangulated surfaces representing 3D brains is described. The algorithm is based on optimally computing geodesics on the triangulated surfaces following Kimmel and Sethian ([1998]: Proc Natl Acad Sci 95:15). The system can be used to compute geodesic curves for accurate distance measurements as well as to detect sulci and gyri. These curves are defined based on local surface curvatures that are computed following a novel approach presented in this study. The corresponding software is available to the research community.

Screening for developmental dysplasia of the hip: from theory to practice. Collaborative Group DDH Project.

OBJECTIVE: To evaluate an organizational model for neonatal population screening for developmental dysplasia of the hip. METHODS: In 4648 neonates born in six hospitals of the Lombardy region, screening for developmental dysplasia of the hip was done using the Ortolani-Barlow maneuver and ultrasonography. RESULTS: The frequency of positive results of clinical and ultrasound examinations carried out in the hospitals varied considerably as a result of difficulties in the Ortolani-Barlow test reproducibility and in the low sensitivity of the clinical examination when compared to ultrasonography. Neonatal screening results implied a large number of subjects with a IIa hip, according to Graf's system; as these subjects require follow-up, the cost of this type of screening is high. Ultrasound findings were normal at 69 days of life in 88% and 75% of subjects, respectively, with unilateral and bilateral type IIa hip. CONCLUSION: This study evaluated various organizational models for screening (for different time periods and for selected populations) in relation to the cost-benefit ratio and demonstrated the different problems that still impede identification of a correct screening model.