A Hematologist-Level Deep Learning Algorithm (BMSNet) for Assessing the Morphologies of Single Nuclear Balls in Bone Marrow Smears: Algorithm Development
Authors: Wu Yi-Ying , Huang Tzu-Chuan , Ye Ren-Hua , Fang Wen-Hui , Lai Shiue-Wei , Chang Ping-Ying , Liu Wei-Nung , Kuo Tai-Yu , Lee Cho-Hao , Tsai Wen-Chiuan , Lin Chin 
Published: April 2020

Background
Bone marrow aspiration and biopsy remain the gold standard for the diagnosis of hematological diseases despite the development of flow cytometry (FCM) and molecular and gene analyses. However, the interpretation of the results is laborious and operator dependent. Furthermore, the obtained results exhibit inter- and intravariations among specialists. Therefore, it is important to develop a more objective and automated analysis system. Several deep learning models have been developed and applied in medical image analysis but not in the field of hematological histology, especially for bone marrow smear applications.

Objective
The aim of this study was to develop a deep learning model (BMSNet) for assisting hematologists in the interpretation of bone marrow smears for faster diagnosis and disease monitoring.

Methods
From January 1, 2016, to December 31, 2018, 122 bone marrow smears were photographed and divided into a development cohort (N=42), a validation cohort (N=70), and a competition cohort (N=10). The development cohort included 17,319 annotated cells from 291 high-resolution photos. In total, 20 photos were taken for each patient in the validation cohort and the competition cohort. This study included eight annotation categories: erythroid, blasts, myeloid, lymphoid, plasma cells, monocyte, megakaryocyte, and unable to identify. BMSNet is a convolutional neural network with the YOLO v3 architecture, which detects and classifies single cells in a single model. Six visiting staff members participated in a human-machine competition, and the results from the FCM were regarded as the ground truth.

Results
In the development cohort, according to 6-fold cross-validation, the average precision of the bounding box prediction without consideration of the classification is 67.4%. After removing the bounding box prediction error, the precision and recall of BMSNet were similar to those of the hematologists in most categories. In detecting more than 5% of blasts in the validation cohort, the area under the curve (AUC) of BMSNet (0.948) was higher than the AUC of the hematologists (0.929) but lower than the AUC of the pathologists (0.985). In detecting more than 20% of blasts, the AUCs of the hematologists (0.981) and pathologists (0.980) were similar and were higher than the AUC of BMSNet (0.942). Further analysis showed that the performance difference could be attributed to the myelodysplastic syndrome cases. In the competition cohort, the mean value of the correlations between BMSNet and FCM was 0.960, and the mean values of the correlations between the visiting staff and FCM ranged between 0.952 and 0.990.

Conclusions
Our deep learning model can assist hematologists in interpreting bone marrow smears by facilitating and accelerating the detection of hematopoietic cells. However, a detailed morphological interpretation still requires trained hematologists.