We propose a flexible approach for the detection of features in images with ultra low signal-to-noise ratio using cubical persistent homology. Our main application is in the detection of atomic columns and other features in transmission electron microscopy (TEM) images. Cubical persistent homology is used to identify local minima in subregions in the frames of nanoparticle videos, which are hypothesized to correspond to relevant atomic features. We compare the performance of our algorithm to other employed methods for the detection of columns and their intensity. Additionally, Monte Carlo goodness-of-fit testing using real-valued summaries of persistence diagrams$\unicode{8212}$including the novel ALPS statistic$\unicode{8212}$derived from smoothed images (generated from pixels residing in the vacuum region of an image) is developed and employed to identify whether or not the proposed atomic features generated by our algorithm are due to noise. Using these summaries derived from the generated persistence diagrams, one can produce univariate time series for the nanoparticle videos, thus providing a means for assessing fluxional behavior. A guarantee on the false discovery rate for multiple Monte Carlo testing of identical hypotheses is also established.