Optical imaging of the brain has expanded dramatically in the past two decades. New optics, indicators, and experimental paradigms are now enabling in-vivo imaging from the synaptic to the cortex-wide scales. To match the resulting flood of data across scales, computational methods are continuously being developed to meet the need of extracting biologically relevant information. In this pursuit challenges arise in some domains (e.g., SNR and resolution limits in micron-scale data) that require specialized algorithms. These algorithms can, for example, make use of state-of-the-art machine learning to maximally learn the details of a given scale to optimize the processing pipeline. In contrast, other methods, however, such as graph signal processing, seek to abstract away from some of the details that are scale-specific to provide solution to specific sub-problems common across scales of neuroimaging. Here we discuss limitations and tradeoffs in algorithmic design with the goal of identifying how data quality and variability can hamper algorithm use and dissemination.