MOTIVATION: Membrane fusion constitutes a key stage in cellular processes such as synaptic neurotransmission and infection by enveloped viruses. Current experimental assays for fusion have thus far been unable to resolve early fusion events in fine structural detail. We have previously used molecular dynamics simulations to develop mechanistic models of fusion by small lipid vesicles. Here, we introduce a novel structural measurement of vesicle topology and fusion geometry: persistent voids. RESULTS: Persistent voids calculations enable systematic measurement of structural changes in vesicle fusion by assessing fusion stalk widths. They also constitute a generally applicable technique for assessing lipid topological change. We use persistent voids to compute dynamic relationships between hemifusion neck widening and formation of a full fusion pore in our simulation data. We predict that a tightly coordinated process of hemifusion neck expansion and pore formation is responsible for the rapid vesicle fusion mechanism, while isolated enlargement of the hemifusion diaphragm leads to the formation of a metastable hemifused intermediate. These findings suggest that rapid fusion between small vesicles proceeds via a small hemifusion diaphragm rather than a fully expanded one. AVAILABILITY: Software available upon request pending public release. SUPPLEMENTARY INFORMATION: Supplementary data are available on Bioinformatics online.