Accuracy limits for efficiently determining shape and size of low-density lipoprotein macromolecules from cryogenic transmission electron microscope images

Document Type

Conference Proceeding

Date of Original Version



Previous research has shown that that the size (diameter) of LDL particles can have an effect on cardiovascular health and that LDL macromolecules may be non-spherical in shape. Some of these studies, however, used methods that are not conducive to automatic determination of the shape and size parameters of the particles. In particular, these prior methods used either centrifugal separations leading to mass/volume ratios or manual determination of parameters from scanned micrographs. This paper describes the investigation of methods of efficiently determining the geometric shape and size of LDL macromolecules from scanned micrographs. Variants of direct correlation of computer-generated geometric models to the orthonormal projection CTEM micrographs were investigated to determine applicability of determining pertinent geometric parameters of the expected discoid shape of the LDL. Analysis software was developed to analyze artificially generated discoid objects to determine the limits of the method. The results of this research show that the described method can be used to determine the shape and size of LDL particles to within a few pixels in both radius and height of the purported discoid shapes. By allowing for efficient generation of a histogram of LDL parameters in samples of blood, it is hoped that the pertinent parameters can then be correlated to observed cardiovascular state in order to assist in the determination of pertinent relationships between LDL geometry and overall cardiovascular health.

Publication Title, e.g., Journal

Progress in Biomedical Optics and Imaging - Proceedings of SPIE