Virtual electron microscopy: a simple implementation creating a new paradigm in ultrastructural examination

Ultrastructural examination is a time-consuming and tiring process, requiring search for diagnostic features on a low-contrast screen in a dim environment. This article describes a method to circumvent these problems through the creation of a virtual ultrathin slide. This can be achieved by automated capturing of hundreds of images at high magnification and stitching them together into a digital image with a resolution of 4 nm/pixel. The pathologist can then navigate the virtual slide at his/her workstation computer. The image shows good contrast and resolution for diagnostic purposes, and most important, the pathologist can precisely note where the specific ultrastructural features are located. The setup required to implement virtual electron microscopy includes a transmission electron microscope equipped with motorized stage and automated digital image capture function, 2 free software components, self-developed software, and a desktop-grade computer. Besides use in daily diagnosis, virtual electron microscopy can open up many new applications such as undergraduate teaching, pathology resident training, external quality assurance program, and expert consultation.