An interpretable classifier for high-resolution breast cancer screening images utilizing weakly supervised localization

Introduction

This is an implementation of the Globally-Aware Multiple Instance Classifier (GMIC) model as described in our paper. The architecture of the proposed model is shown below.

Highlights of GMIC:

• High Accuracy: GMIC outperformed ResNet-34 and Faster R-CNN.
• High Efficiency: Compared to ResNet-34, GMIC has 28.8% fewer parameters, uses 78.43% less GPU memory and is 4.1x faster during inference and 5.6x faster during training.
• Weakly Supervised Lesion Localization: Despite being trained with only image-level labels indicating the presence of any benign or malignant lesion, GMIC is able to generate pixel-level saliency maps (shown below) that provide additional interpretability.

The implementation allows users to obtain breast cancer predictions and visualization of saliency maps by applying one of our pretrained models. We provide weights for 5 GMIC-ResNet-18 models. The model is implemented in PyTorch.

• Input: A mammography image that is cropped to 2944 x 1920 and are saved as 16-bit png files. As a part of this repository, we provide 4 sample exams (in sample_data/images directory and exam list stored in sample_data/exam_list_before_cropping.pkl), each of which includes 2 CC view images and 2 MLO view images. Those exams contain original mammogrphy images and therefore need to be preprocessed (see the Preprocessing section).

• Output: The GMIC model generates one prediction for each image: probability of benign and malignant findings. All predictions are saved into a csv file $OUTPUT_PATH/predictions.csv that contains the following columns: image_index, benign_pred, malignant_pred, benign_label, malignant_label. In addition, each input image is associated with a visualization file saved under $OUTPUT_PATH/visualization. An exemplar visualization file is illustrated below. The images (from left to right) represent:

  • input mammography with ground truth annotation (green=benign, red=malignant),
  • patch map that illustrates the locations of ROI proposal patches (blue squares),
  • saliency map for benign class,
  • saliency map for malignant class,
  • 6 ROI proposal patches with the associated attention score on top.

Update (2021/03/08): Updated the documentation

Update (2020/12/15): Added the preprocessing pipeline.

Update (2020/12/16): Added the example notebook.

Prerequisites

• Python (3.6)
• PyTorch (1.1.0)
• torchvision (0.2.2)
• NumPy (1.14.3)
• SciPy (1.0.0)
• H5py (2.7.1)
• imageio (2.4.1)
• pandas (0.22.0)
• opencv-python (3.4.2)
• tqdm (4.19.8)
• matplotlib (3.0.2)

License

This repository is licensed under the terms of the GNU AGPLv3 license.

How to run the code

You need to first install conda in your environment. Before running the code, please run pip install -r requirements.txt first. Once you have installed all the dependencies, run.sh will automatically run the entire pipeline and save the prediction results in csv. Note that you need to first cd to the project directory and then execute . ./run.sh. When running the individual Python scripts, please include the path to this repository in your PYTHONPATH.

We recommend running the code with a GPU. To run the code with CPU only, please change DEVICE_TYPE in run.sh to 'cpu'.

The following variables defined in run.sh can be modified as needed:

• MODEL_PATH: The path where the model weights are saved.
• CROPPED_IMAGE_PATH: The directory where cropped mammograms are saved.
• SEG_PATH: The directory where ground truth segmenations are saved.
• EXAM_LIST_PATH: The path where the exam list is stored.
• OUTPUT_PATH: The path where visualization files and predictions will be saved.
• DEVICE_TYPE: Device type to use in heatmap generation and classifiers, either 'cpu' or 'gpu'.
• GPU_NUMBER: GPUs number multiple GPUs are available.
• MODEL_INDEX: Which one of the five models to use. Valid values include {'1', '2', '3', '4', '5','ensemble'}.
• visualization-flag: Whether to generate visualization.

You should obtain the following outputs for the sample exams provided in the repository (found in sample_output/predictions.csv by default).

image_index	benign_pred	malignant_pred	benign_label	malignant_label
0_L-CC	0.1356	0.0081	0	0
0_R-CC	0.8929	0.3259	1	0
0_L-MLO	0.2368	0.0335	0	0
0_R-MLO	0.9509	0.1812	1	0
1_L-CC	0.0546	0.0168	0	0
1_R-CC	0.5986	0.9910	0	1
1_L-MLO	0.0414	0.0139	0	0
1_R-MLO	0.5383	0.9308	0	1
2_L-CC	0.0678	0.0227	0	0
2_R-CC	0.1917	0.0603	1	0
2_L-MLO	0.1210	0.0093	0	0
2_R-MLO	0.2440	0.0231	1	0
3_L-CC	0.6295	0.9326	0	1
3_R-CC	0.2291	0.1603	0	0
3_L-MLO	0.6304	0.7496	0	1
3_R-MLO	0.0622	0.0507	0	0

Data

sample_data/images contains 4 exams each of which includes 4 the original mammography images (L-CC, L-MLO, R-CC, R-MLO). All mammography images are saved in png format. The original 12-bit mammograms are saved as rescaled 16-bit images to preserve the granularity of the pixel intensities, while still being correctly displayed in image viewers.

sample_data/segmentation contains the binary pixel-level segmentation labels for some exams. All segmentations are saved as png images.

sample_data/exam_list_before_cropping.pkl contains a list of exam information. Each exam is represented as a dictionary with the following format:

{'horizontal_flip': 'NO',
  'L-CC': ['0_L-CC'],
  'L-MLO': ['0_L-MLO'],
  'R-MLO': ['0_R-MLO'],
  'R-CC': ['0_R-CC'],
  'best_center': {'R-CC': [(1136.0, 158.0)],
   'R-MLO': [(1539.0, 252.0)],
   'L-MLO': [(1530.0, 307.0)],
   'L-CC': [(1156.0, 262.0)]},
  'cancer_label': {'benign': 1,
   'right_benign': 0,
   'malignant': 0,
   'left_benign': 1,
   'unknown': 0,
   'right_malignant': 0,
   'left_malignant': 0},
  'L-CC_benign_seg': ['0_L-CC_benign'],
  'L-CC_malignant_seg': ['0_L-CC_malignant'],
  'L-MLO_benign_seg': ['0_L-MLO_benign'],
  'L-MLO_malignant_seg': ['0_L-MLO_malignant'],
  'R-MLO_benign_seg': ['0_R-MLO_benign'],
  'R-MLO_malignant_seg': ['0_R-MLO_malignant'],
  'R-CC_benign_seg': ['0_R-CC_benign'],
  'R-CC_malignant_seg': ['0_R-CC_malignant']}

In their original formats, images from L-CC and L-MLO views face right, and images from R-CC and R-MLO views face left. We horizontally flipped R-CC and R-MLO images so that all four views face right. Values for L-CC, R-CC, L-MLO, and R-MLO are list of image filenames without extensions and directory name.

Preprocessing

Run the following commands to crop mammograms and calculate information about augmentation windows.

Crop mammograms

python3 src/cropping/crop_mammogram.py \
    --input-data-folder $DATA_FOLDER \
    --output-data-folder $CROPPED_IMAGE_PATH \
    --exam-list-path $INITIAL_EXAM_LIST_PATH  \
    --cropped-exam-list-path $CROPPED_EXAM_LIST_PATH  \
    --num-processes $NUM_PROCESSES

src/import_data/crop_mammogram.py crops the mammogram around the breast and discards the background in order to improve image loading time and time to run segmentation algorithm and saves each cropped image to $PATH_TO_SAVE_CROPPED_IMAGES/short_file_path.png using h5py. In addition, it adds additional information for each image and creates a new image list to $CROPPED_IMAGE_LIST_PATH while discarding images which it fails to crop. Optional --verbose argument prints out information about each image. The additional information includes the following:

• window_location: location of cropping window w.r.t. original dicom image so that segmentation map can be cropped in the same way for training.
• rightmost_points: rightmost nonzero pixels after correctly being flipped.
• bottommost_points: bottommost nonzero pixels after correctly being flipped.
• distance_from_starting_side: records if zero-value gap between the edge of the image and the breast is found in the side where the breast starts to appear and thus should have been no gap. Depending on the dataset, this value can be used to determine wrong value of horizontal_flip.

Calculate optimal centers

python3 src/optimal_centers/get_optimal_centers.py \
    --cropped-exam-list-path $CROPPED_EXAM_LIST_PATH \
    --data-prefix $CROPPED_IMAGE_PATH \
    --output-exam-list-path $EXAM_LIST_PATH \
    --num-processes $NUM_PROCESSES

src/optimal_centers/get_optimal_centers.py outputs new exam list with additional metadata to $EXAM_LIST_PATH. The additional information includes the following:

• best_center: optimal center point of the window for each image. The augmentation windows drawn with best_center as exact center point could go outside the boundary of the image. This usually happens when the cropped image is smaller than the window size. In this case, we pad the image and shift the window to be inside the padded image in augmentation. Refer to the data report for more details.

Outcomes of preprocessing

After the preprocessing step, you should have the following files in the $OUTPUT_PATH directory (default is sample_output):

• cropped_images: a folder that contains the cropped images corresponding to all images in the sample_data/images.
• data.pkl: the pickle file of a data list that includes the preprocessing metadata for each image and exam.

Reference

If you found this code useful, please cite our paper:

An interpretable classifier for high-resolution breast cancer screening images utilizing weakly supervised localization
Yiqiu Shen, Nan Wu, Jason Phang, Jungkyu Park, Kangning Liu, Sudarshini Tyagi, Laura Heacock, S. Gene Kim, Linda Moy, Kyunghyun Cho and Krzysztof J. Geras
Medical Image Analysis 2020

@article{shen2020interpretable, 
title={An interpretable classifier for high-resolution breast cancer screening images utilizing weakly supervised localization},
author={Shen, Yiqiu and Wu, Nan and Phang, Jason and Park, Jungkyu and Liu, Kangning and Tyagi, Sudarshini and Heacock, Laura and Kim, S Gene and Moy, Linda and Cho, Kyunghyun and others},
journal={Medical Image Analysis},
pages={101908},
year={2020},
publisher={Elsevier}

}

Reference to previous GMIC version:

Globally-Aware Multiple Instance Classifier for Breast Cancer Screening
Yiqiu Shen, Nan Wu, Jason Phang, Jungkyu Park, S. Gene Kim, Linda Moy, Kyunghyun Cho and Krzysztof J. Geras
Machine Learning in Medical Imaging - 10th International Workshop, MLMI 2019, Held in Conjunction with MICCAI 2019, Proceedings. Springer , 2019. p. 18-26 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 11861 LNCS).

@inproceedings{shen2019globally, 
title={Globally-Aware Multiple Instance Classifier for Breast Cancer Screening},
    author={Shen, Yiqiu and Wu, Nan and Phang, Jason and Park, Jungkyu and Kim, Gene and Moy, Linda and Cho, Kyunghyun and Geras, Krzysztof J},
    booktitle={Machine Learning in Medical Imaging: 10th International Workshop, MLMI 2019, Held in Conjunction with MICCAI 2019, Shenzhen, China, October 13, 2019, Proceedings},
    volume={11861},
    pages={18-26},
    year={2019},
    organization={Springer Nature}}