The reliable and reproducible quantitative image analysis of digital micrographs from high resolution transmission electron microscopy (HRTEM) of soot has been an area of interest since the early nineties. Since the resolution of HRTEM images is usually sufficient to carry out structural measurements at the atomic level, the information obtained from these images is very valuable as it potentially yields insight into very specific soot oxidation processes; however, extracting physically meaningful, reliable, accurate and statistically robust data from HRTEM images is not an easy process. Data extraction is hindered by the presence of overlapping structures, varying focus, contrast, illumination levels and noise in the images. In this paper a novel image analysis framework is presented to address these issues and explore the possibility of the extraction of high-fidelity structural data from HRTEM soot images. Emphasis is on the analysis of images of mostly amorphous, poorly ordered soot structures, as these are the most difficult to analyze. Published by Elsevier Inc. on behalf of The Combustion Institute.