Digital pathology is the practice of pathology using digital images of tissue sections rather than glass slides. Whole slide imaging (WSI) scanners digitize entire slides at high resolution, producing virtual slides that can be viewed, analyzed, shared, and archived without a physical microscope.
Whole Slide Imaging Scanners
WSI scanners capture tissue sections at microscopic resolution (typically 0.25-0.5 µm per pixel, equivalent to 20x or 40x objectives). Line-scan scanners move the slide past a stationary line of sensors, capturing contiguous stripes assembled into a single image. Tile-scan scanners capture overlapping square fields stitched together by software. Array-scan scanners capture the entire slide at once using multiple sensors.
Scanning parameters include resolution (20x for most diagnostic work, 40x for detailed cytology and mitotic counting), focus method (single-point, multi-point, or real-time autofocus), z-stacking (multiple focal planes for thick sections), and compression (JPEG2000 at quality factor 70-90 for routine use; lossless for research). Scan time ranges from 30 seconds to 5 minutes per slide depending on size and resolution.
Image Formats and Storage
WSI files are enormous — a single 40x scan of a 15×15 mm tissue section generates 5-15 GB of uncompressed data. Compression reduces this to 500 MB-2 GB. The SVS format (Aperio/Leica) is the most widely adopted, storing multiple resolution levels (pyramid) for efficient viewing. Other formats include NDPI (Hamamatsu), CZI (Zeiss), MRXS (3DHistech), and the open DICOM standard for medical imaging. A typical pathology laboratory generates 1-5 TB of WSI data per year. Storage requires tiered solutions: fast SSD for recent cases, HDD for active archive, and tape or cloud for long-term archive.
Viewing and Reporting
Specialized whole slide viewers (Aperio ImageScope, QuPath, Sedeen, Sectra) mimic microscope navigation — pan, zoom, measuring tools, annotations. Integration with the laboratory information system (LIS) ensures that cases, images, and reports are linked. Pathologists report from the digital image using voice recognition, with the WSI viewer and LIS open simultaneously. Worklists prioritize cases and track turnaround time.
Remote Reporting and Telepathology
Digital pathology enables remote reporting — pathologists review cases from any location with adequate internet bandwidth (minimum 50 Mbps for smooth viewing). Teleconsultation allows second opinions from subspecialists worldwide. Frozen sections can be scanned and transmitted to a remote pathologist for intra-operative consultation. Regulatory requirements vary — FDA clearance for primary diagnosis on WSI (Philips IntelliSite, Leica Aperio AT2) was obtained in 2017, and many countries now permit digital primary diagnosis.
Validation for Primary Diagnosis
Validating WSI for primary diagnosis requires a validation study comparing digital and glass slide diagnosis on the same cases. CAP guidelines recommend at least 60 cases spanning the diagnostic spectrum, with a washout period between glass and digital review. Concordance should exceed 95%. Pathologists must complete training on the viewing software, including navigation, annotation, measurement, and integration with reporting tools.
Artificial Intelligence in Digital Pathology
Computer-aided diagnosis (CAD) algorithms detect regions of interest — mitotic figures, tumor areas, micro-metastases. Quantitative image analysis provides reproducible measurements: Ki-67 index, HER2 score, PD-L1 tumor proportion score. Machine learning classifiers distinguish benign from malignant lesions, grade tumors, and predict molecular subtypes from H&E alone. Deep learning algorithms require large, well-annotated training datasets. Regulatory approval of AI algorithms in pathology is emerging — several products have CE marking and FDA clearance for specific applications. The pathologist remains responsible for the final diagnosis, with AI serving as a decision-support tool.
