Design and characterization of a digital image acquisition system for whole-specimen breast histopathology

We have developed a digital histopathology imaging system capable of producing a three-dimensional (3D) representation of histopathology from an entire lumpectomy specimen. The system has the potential to improve the accuracy of surgical margin assessment in the treatment of breast cancer by providing finer sampling and 3D visualization. A scanning light microscope was modified to allow digital photomicrography of a stack of large (up to 120x170 mm2) histology slides cut serially through the entire specimen. The images are registered and displayed in 2D and 3D. The design of the system, which reduces or eliminates the appearance of 'tiling' and 'seam' artefacts inherent in the scanning method, is described and its resolution, contrast/noise and coverage properties are characterized through measurements of the modulation transfer function (MTF), depth of field (DOF) and signal difference to noise ratio (SDNR). The imaging task requires a lateral resolution of 5 microm, an SDNR of 5 between relevant features, 'tiling artefact' at a level below the detectability threshold of the eye, and 'seam artefact' of less than 5-10 microm. The tests demonstrate that the system is largely adequate for the imaging task, although further optimizations are required to reduce the degradation of coverage incurred by seam artefact.