Variation in nuclear size and shape is an important criterion of malignancy
for many tumor types; however, categorical estimates by pathologists have poor
reproducibility. Measurements of nuclear characteristics (morphometry) can
improve reproducibility, but manual methods are time consuming. In this study,
we evaluated fully automated morphometry using a deep learning-based algorithm
in 96 canine cutaneous mast cell tumors with information on patient survival.
Algorithmic morphometry was compared with karyomegaly estimates by 11
pathologists, manual nuclear morphometry of 12 cells by 9 pathologists, and the
mitotic count as a benchmark. The prognostic value of automated morphometry was
high with an area under the ROC curve regarding the tumor-specific survival of
0.943 (95% CI: 0.889 - 0.996) for the standard deviation (SD) of nuclear area,
which was higher than manual morphometry of all pathologists combined (0.868,
95% CI: 0.737 - 0.991) and the mitotic count (0.885, 95% CI: 0.765 - 1.00). At
the proposed thresholds, the hazard ratio for algorithmic morphometry (SD of
nuclear area $\geq 9.0 \mu m^2$) was 18.3 (95% CI: 5.0 - 67.1), for manual
morphometry (SD of nuclear area $\geq 10.9 \mu m^2$) 9.0 (95% CI: 6.0 - 13.4),
for karyomegaly estimates 7.6 (95% CI: 5.7 - 10.1), and for the mitotic count
30.5 (95% CI: 7.8 - 118.0). Inter-rater reproducibility for karyomegaly
estimates was fair ($\kappa$ = 0.226) with highly variable
sensitivity/specificity values for the individual pathologists. Reproducibility
for manual morphometry (SD of nuclear area) was good (ICC = 0.654). This study
supports the use of algorithmic morphometry as a prognostic test to overcome
the limitations of estimates and manual measurements.

通过深度学习算法的自动形态测量，该研究支持使用自动形态测量作为一种预后测试，以克服估计和手动测量的限制。

基于深度学习算法的核形态测量对犬皮肤鳞状细胞癌具有预后意义

Nuclear Morphometry using a Deep Learning-based Algorithm has Prognostic  Relevance for Canine Cutaneous Mast Cell Tumors

The size of nuclei in histological preparations from excised breast tumors is
predictive of patient outcome (large nuclei indicate poor outcome).
Pathologists take into account nuclear size when performing breast cancer
grading. In addition, the mean nuclear area (MNA) has been shown to have
independent prognostic value. The straightforward approach to measuring nuclear
size is by performing nuclei segmentation. We hypothesize that given an image
of a tumor region with known nuclei locations, the area of the individual
nuclei and region statistics such as the MNA can be reliably computed directly
from the image data by employing a machine learning model, without the
intermediate step of nuclei segmentation. Towards this goal, we train a deep
convolutional neural network model that is applied locally at each nucleus
location, and can reliably measure the area of the individual nuclei and the
MNA. Furthermore, we show how such an approach can be extended to perform
combined nuclei detection and measurement, which is reminiscent of
granulometry.

使用卷积神经网络从肿瘤图像数据直接测量肿瘤区域内的核大小和核平均面积，并实现混合核检测和测量，以提高乳腺肿瘤诊断精度。