Informatics, digital & computational pathology

Machine learning & deep learning

Computer aided detection

Editor-in-Chief: Debra L. Zynger, M.D.
Po-Hsuan Cameron Chen, Ph.D.
David F. Steiner, M.D., Ph.D.

Topic Completed: 30 May 2019

Minor changes: 14 May 2021

Copyright: 2019-2021,, Inc.

PubMed Search: Computer aided detection[TI] pathology

Po-Hsuan Cameron Chen, Ph.D.
David F. Steiner, M.D., Ph.D.
Page views in 2020: 142
Page views in 2021 to date: 110
Cite this page: Chen PHC, Liu Y, Steiner DF. Computer aided detection. website. Accessed November 27th, 2021.
Definition / general
  • System to assist with locating histologic or cytologic findings of interest
  • May be particularly relevant for:
    • Small or sparse pathologic findings that could potentially be missed
    • Quantitation tasks in which miscounting may be likely
  • By contrast, a computer aided diagnosis system is meant to help with diagnostic interpretation, such as tumor grading or subtyping a histologic or cytologic feature (i.e. "what" as opposed to "where")
Essential features
  • System that assists with detection or localization of findings of interest
  • Requires an algorithm to detect findings and a user interface to assist the pathologist in the diagnosis
  • Typically most useful for increasing sensitivity, efficiency or quantitation
Key components
  • Computer aided detection (CADe): technology or system that detects findings of interest on medical images, typically with the goal of reducing the false negative rate
  • Computer aided diagnosis (CADx): technology or system that characterizes or interprets findings on medical images (such as tumor grade)
  • Model: the machine learning algorithm underlying the CADe system
  • Receiver operating characteristic (ROC) curve: a plot that represents the tradeoffs between sensitivity and specificity across a range of decision thresholds
  • Operating point: a specific point along a receiver operating characteristic curve, thus representing the specific diagnostic tradeoff of sensitivity and specificity at that point
    • Human diagnostic performance is often represented as a single operating point for each individual
    • Diagnostic algorithms often have continuous output (for example, a number between 0 and 1)
      • Thus, a threshold corresponding to a specific operating point must be chosen in order to decide which regions to highlight
Steps in building
  • Development: develop a computer algorithm to accurately identify a finding of interest, which typically involves
    • Collecting data: slides / images with expert labels for the findings of interest
    • Training model: supervised learning if expert labels provided
    • Evaluating model: using a set of images not used for training
  • Inference: application of the algorithm to the images of interest (i.e. running the algorithm on the image)
    • Requires digitized slides or computer integration with a microscope
    • Operating points (thresholds for algorithm output) are applied to determine which finding(s) should be highlighted (typically based on validation data)
  • Integration: integration with the clinical workflow is often a key challenge for an effective system and is likely unique for different uses
  • Evaluation: an accurate computer algorithm may not translate directly into a useful system; its effectiveness in improving clinical workflows or patient outcomes must be evaluated
  • Improving efficiency: by highlighting regions of interest and reducing review time
  • Improving accuracy: by highlighting small or rare lesions or cells that are easily missed
  • Improving consistency: by helping to count histologic features of interest, such as immunohistochemistry quantitation, mitoses or centroblasts
Uses by pathologists
Pap smear screening
Peripheral blood smear counting
  • One of the original CADe applications in pathology (Ann N Y Acad Sci 1966;128:1035)
  • Clinical task: differential cell count of peripheral blood smear slides
  • Algorithm methodology: convolutional neural networks (Clin Lab Haematol 2003;25:139, Am J Clin Pathol 2005;124:770)
  • Evaluation: comparison of classification accuracy between automated systems (Cellavision Diffmaster Octavia and DM96) and manual differential cell counts (J Clin Pathol 2007;60:72, Clin Lab Med 2002;22:299)
    • Both systems correlated well with manual counts
    • Shortened review time compared with an experienced clinical laboratory scientist
    • Both automated systems met the hematological lab requirements in terms of reliability and efficiency

Mitotic counting in breast cancer
  • Clinical task: mitotic counting for the histological review of breast cancer specimens
  • Algorithm methodology: decision trees that distinguish between mitosis and nonmitosis using image based statistical and morphological features (J Pathol Inform 2013;4:10)
  • Evaluation: automated versus manual and relabeling of manual reads (Med Image Anal 2015;20:237)
    • Error rate comparable to interobserver pathologist agreement

Classification of follicular lymphoma
  • Clinical task: centroblast counting for the histological grading of follicular lymphoma
  • Algorithm methodology: k-nearest neighbor classifier identifies high power fields of interest and classifies low versus high risk categories using a color coded map (BMC Med Inform Decis Mak 2015;15:115)
  • Evaluation: comparison of accuracy and interrater variability with and without model assistance
    • Improved accuracy, especially among residents
    • Improved consistency (reduced variability) across both experts and residents
    • Residents were more likely to change scores after using the computer system

Metastatic cancer detection in lymph nodes
  • Clinical task: finding metastatic breast cancer in sentinel lymph node biopsies
  • Algorithm methodology: convolutional neural network identifies and highlights tumor cells in lymph nodes (Arch Pathol Lab Med 2018 Oct 8 [Epub ahead of print])
  • Evaluation: board certified pathologists digitally reviewed slides in assisted versus unassisted modes (Am J Surg Pathol 2018;42:1636)
    • Increased sensitivity for micrometastases
    • Shorter review time per image for micrometastases and negative images
    • Image review of micrometastases considered to be easier with assistance
Microscopic (histologic) images

Contributed by David F. Steiner, M.D., Ph.D.

Detection of metastatic tumor in lymph nodes

Board review style question #1
Which of the following is an example of computer aided detection (CADe) in pathology?

  1. An algorithm that can accurately grade prostate cancer
  2. Comparison of algorithm performance to pathologist performance for classification of follicular lymphoma
  3. A system that uses an algorithm to identify mitoses on a digital pathology image and highlights those regions for review by a pathologist
  4. A tool that uses a machine learning algorithm to identify and report lymph node metastases without review by a pathologist
Board review style answer #1
C. Computer aided detection (CADe) systems in pathology utilize an algorithm to identify features or regions of interest but also must communicate that information back to the human experts in a useful way

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Reference: Computer aided detection
Board review style question #2
Which of the following is a required element of a computer aided detection (CADe) in pathology?

  1. The ability to apply an algorithm to pathology images
  2. An algorithm that can identify all possible features of interest for a given image
  3. Choosing an operating point for the model that is superior to pathologists for both sensitivity and specificity
  4. A convolutional neural network (CNN) trained to classify pathology images
Board review style answer #2
A. The only required element above is the ability to apply the algorithm to the image, either via slide digitization or computer integration with a microscope. Computer aided detection (CADe) systems might only identify a single feature for a given image, other types of algorithms can be used and CADe systems do not necessarily need to be more sensitive or specific than pathologists in all cases in order to be useful.

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Reference: Computer aided detection
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