PEARL: projection-estimation accelerated Richardson-Lucy deconvolution for rapid volumetric imaging

Three-dimensional imaging of biological specimens requires high spatiotemporal resolution, but the intensive computational demands of processing continuously recorded images hinder the real-time reconstruction of millisecond cellular events. Here, we introduce projection-estimation accelerated Richardson-Lucy (PEARL) Deconvolution, an accelerated 3D reconstruction technique that significantly reduces iteration requirements for image reconstruction based on Richardson-Lucy deconvolution. We validate PEARL's capabilities by imaging immuno-stained mitochondria, GFP-labeled peroxisomes, and human pluripotent stem cell-derived organoids, demonstrating enhanced reconstruction speed and accuracy across diverse biological applications.