Clinton J.V. Campbell

Ricardo Gonzalez, Ashirbani Saha, Clinton J. V. Campbell et al.

This paper discusses some overlooked challenges faced when working with machine learning models for histopathology and presents a novel opportunity to support "Learning Health Systems" with them. Initially, the authors elaborate on these challenges after separating them according to their mitigation strategies: those that need innovative approaches, time, or future technological capabilities and those that require a conceptual reappraisal from a critical perspective. Then, a novel opportunity to support "Learning Health Systems" by integrating hidden information extracted by ML models from digitalized histopathology slides with other healthcare big data is presented.

Ricardo Gonzalez, Peyman Nejat, Ashirbani Saha et al.

Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2-2.6) and 1.8 (95% CI, 1.3-2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11-3.29) for recurrence, and between 0.09 (95% CI, 0.01-0.70) and 0.65 (95% CI, 0.43-0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results (...)

Rohollah Moosavi Tayebi, Youqing Mu, Taher Dehkharghanian et al.

Bone marrow cytology is required to make a hematological diagnosis, influencing critical clinical decision points in hematology. However, bone marrow cytology is tedious, limited to experienced reference centers and associated with high inter-observer variability. This may lead to a delayed or incorrect diagnosis, leaving an unmet need for innovative supporting technologies. We have developed the first ever end-to-end deep learning-based technology for automated bone marrow cytology. Starting with a bone marrow aspirate digital whole slide image, our technology rapidly and automatically detects suitable regions for cytology, and subsequently identifies and classifies all bone marrow cells in each region. This collective cytomorphological information is captured in a novel representation called Histogram of Cell Types (HCT) quantifying bone marrow cell class probability distribution and acting as a cytological "patient fingerprint". The approach achieves high accuracy in region detection (0.97 accuracy and 0.99 ROC AUC), and cell detection and cell classification (0.75 mAP, 0.78 F1-score, Log-average miss rate of 0.31). HCT has potential to revolutionize hematopathology diagnostic workflows, leading to more cost-effective, accurate diagnosis and opening the door to precision medicine.

Shivam Kalra, H. R. Tizhoosh, Sultaan Shah et al.

The emergence of digital pathology has opened new horizons for histopathology and cytology. Artificial-intelligence algorithms are able to operate on digitized slides to assist pathologists with diagnostic tasks. Whereas machine learning involving classification and segmentation methods have obvious benefits for image analysis in pathology, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologist a novel approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas [TCGA] program by National Cancer Institute, USA) of whole slide images from almost 11,000 patients depicting different types of malignancies. For the first time, we successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000x1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative "majority voting" to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen sections slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.