MRI Radiomics: Tumor Identification and Reverse Image Search Using Convolutional Neural Network
In This White Paper
Magnetic Resonance Imaging (MRI) is commonly used in the diagnosis of brain tumors. Traditionally, physicians are trained to use their eyes when interpreting the scans; as the old saying goes, "a radiologist looking for a ruler is a radiologist in trouble." The recent emergence of the field of radiomics – which quantifies tumor features in MRI scans to create mineable high-dimensional data – is changing the game and creating new clinical decision support tools for identifying cases with tumor similarities. This paper leverages deep learning to match MRI tumor images to scans with similar features with the goal of providing clinicians a tool to increase accuracy and speed to diagnosis. The methodology presented herein involves combining multiple artificial neural networks in order to identify tumor regions and then match the tumor in question to those with the highest degree of similarities.
Magnetic resonance imaging (MRI) is a common medical imaging tool used to diagnose a variety of conditions, such as brain cancer1. The rich information composed in MRI imaging data can reveal valuable insights into diagnosis and recommended treatment options. When first introduced into clinical practice, MRI images were manually interpreted by radiologist in a time intensive visual review process. Recently, the field of radiomics has emerged which transforms MRI images into mineable high-dimensional data, enabling physicians to harness quantitative image analysis that aid the clinical decision process2,3.
While radiomics can provide quantitative patient information, the timely step of isolating specific regions (segmentation) is required to improve the features extracted by radiometric methods4. For example, in interpreting scans for cancer diagnosis, the physician is often interested in tumor characteristics and not the surrounding healthy tissue. Therefore, physicians must first select a region of interest (ROI) so that the radiomic quantitative metrics have clinical relevance to the tumor and not the entire imaging area. With the current lack of trained radiologists, especially in rural areas, the automation of the ROI segmentation process could prove beneficial to tumor identification and the radiomics pipeline5.
Convolutional neural networks (CNNs) have been shown as a promising automated solution to the ROI selection process and radiometrics4–6. CNNs extract image features through multiple layers of convolution with trainable weights7. The CNN is trained to identify ROIs by learning from human-labeled segmented images, placing ROI segmentation CNNs in a type of deep learning called supervised learning (i.e., supplying the CNN with labels is required). Once trained, the CNN can rapidly identify ROIs on images it was not trained on. Common CNN architectures to perform ROI selection are YOLO (You only look once) and U-nets, among others. On an average, it takes a physician about one hour to segment a brain tumor; however CNNs have been shown to segment brain tumors in under one minute with similar accuracy to physicians8. Therefore, it can be seen how CNNs are crucial to the ROI selection process for radiomics and can help to address the radiologist shortage problem.
In addition to segmentation, CNNs can also allow clinically relevant features to be extracted from the ROIs for radiomics. A popular CNN architecture for extracting relevant features is a CNN autoencoder. Autoencoders compress images down into an encoding, which contain the relevant clinical features. For example, when supplied with an ROI of a tumor the autoencoder compresses the image down to an encoding which contains clinically relevant features such as texture that can be later used for prognosis analysis9. Unlike ROI segmentation CNNs, autoencoders are a type of unsupervised learning and only need to be supplied with an image for training, reducing the cost and time associated with relevant feature extraction in the radiomics pipeline.
The extracted features from CNN autoencoders can often be abstract and difficult for a human to interpret. To obtain useful information to aid in clinical decisions, the extracted features must be analyzed and compared with other patient data in a large database. For example, the embedding of a patient of interest can be compared against the embeddings of other patients to find similar cases. By comparing treatments and outcomes of similar cases the feature analysis can aid the physician in a clinical decision. Feature analysis takes just seconds, whereas a physician can spend up to an hour comparing similar cases (and always with the possibility of missing relevant cases based on nuanced feature similarities). Feature analysis is a large area of research and can be performed using a variety of machine learning techniques such as deep learning, support vector machines or decision trees9.
In this paper an MRI brain tumor radiomics pipeline solution is described that can provide physicians with a similar patient case in under a minute, potentially saving physicians hours of work and creating a meaningful mechanism for clinical decision support. A YOLO CNN is employed to identify brain tumors, and two CNN autoencoders to identify patients with similar tumors. For training of the CNNs and generating a lookup database the 2020 BraTS (Brain Tumor Image Segmentation Benchmark) database was utilized. Provided by the Perelman School of Medicine at University of Pennsylvania, the BraTS database is an image database that contains brain tumor segmentations and four MRI modalities per patient10–12.
Experimental Setup and Methodology
The BraTS 2020 dataset consists of 494 patients, each with a full MRI brain scan across four different MRI modalities: T1, T1Gd, T2 and T2-FLAIR (Fluid Attenuated Inversion Recovery). In brief, MRI obtains image contrast by applying a variety of magnetic pulses to tissue and sensing the resulting changes to proton particles' spin. T1, T2 and T2-FLAIR each apply different magnetic pulses to look at tissue proton spin changes, while T1Gd applies a T1 pulse after intravenously infusing the patient with the contrast agent Gadolinium10. Since each modality applies a different magnetic pulse or uses a contrast agent, they each reveal different clinically relevant structural and molecular contrast information about the tissue. The BraTS dataset was created to allow data scientists to compete in developing the best radiomic algorithms. So, for 369 patients in the dataset there are three-dimensional (3D) segmentations of the tumor (if one is present and manual generated by human experts), as well as additional metadata such as overall patient survival and tumor characteristics. For the remaining 125 patients this additional information is left out and only known by the providers of the BraTS dataset. For the purposes of this work, only the MRI brain scans and tumor segmentations were used for training of CNNs and the 125 patients with missing segmentation information were used for testing. Each MRI modality and tumor segmentation contains a 155x240x240 pixel data cube in NIFTY format. All modalities and segmentations are co-registered for each patient. An example of different modalities and the segmented tumor are provided in the Figure 2.
While the dataset contained 3D data for each modality, the CNNs only use one slice at a time along the second and third dimensions (Transverse Plane) of the data cube. So, for each patient and modality there are 155 slices or images of size 240x240 pixels.
RADIOMICS PIPELINE ARCHITECTURE
The objective of the radiomics pipeline (Figure 3) presented in this paper is to take a patient MRI slice, identify if a tumor is present, and if one is present find a patient slice with a similar tumor. The user supplies the pipeline with a patient MRI slice, where YOLO will then detect a tumor ROI if one is present. If no tumor is present, the pipeline finishes. If a tumor is present, autoencoder 1 (AE1) extracts the relevant image features across the whole slice and compares it with other patient slice features in the database. Notice that in the autoencoder approach, features are automatically generated as a result of the autoencoder's inherent dimensional reduction, without necessitating explicit definition or selection. The top 200 slice results are then identified. Next, the tumor is segmented from the supplied slice using YOLO and the features are extracted with autoencoder 2 (AE2). The tumor features are then compared with the tumor features from the top 200 slice results of AE1, and the top five results from unique patients are output.
It is common practice in medicine to use different MRI modalities in a complementary way to extract maximum and highly useful features6. Therefore, YOLO and the autoencoders were supplied with multi-modal images to maximize relevant feature extraction and radiomic performance. YOLO is supplied with T1, T2, T1Gd slices, while AE1 and AE2 are supplied with all modalities. YOLO only used three modalities so prebuilt YOLO models (which typically take red, green, blue three channel images) can be used and transfer learning can be taken advantage of to speed up training. For the autoencoders, custom networks were built to accept all four MRI modalities.
YOLO, which expands to "You Only Look Once," is an object detection and identification algorithm that is based on CNNs. One of YOLO's key benefits is that it can detect multiple objects of different categories by only scanning the image one time, hence the name "you only look once." This allows YOLO to infer object detection quickly, ~50 milliseconds on a graphical processing unit (GPU). In this project, YOLOv3 model was used which was supplied with pretrained weights to expedite training time and available at this GitHub location: github.com/AntonMu/TrainYourOwnYOLO/tree/master13. All the YOLO training was performed on Amazon Web Services (AWS) p3.8xlarge instance using a dockerized TensorFlow image. The docker image used was tensorflow/tensorflow:nightly-custom-op-gpu-ubuntu16 and was pulled from the docker hub (hub.docker.com).
In this project, YOLO is used to detect and locate brain tumors from the MRIs. To train YOLO it needs to be supplied with MRI images and their respective tumor bounding box locations. The BraTS dataset supplied a binary 3D tumor mask. Each mask consists of complex 3D shapes that are often disconnected. These masks need to be converted into a bounding box to train YOLO for each slice. To do this the following steps were taken:
- A slice of the binary tumor mask is read and dilated with 5x5 kernel to connect sparse tumor masks.
- Connected component analysis is performed to find all tumor locations in the slice. Connected components with less than 300 pixels are filtered out to allow for sufficient signal in YOLO training.
- For each connected component or tumor the contour extremes are found and used to calculate the bounding box coordinates.
As discussed earlier in the pipeline architecture, the training images for YOLO were created using three modalities, T2, T1 and T1Gd. YOLOv3 takes Red-Green-Blue channel images as input, thus 240x240x3 arrays for each slice were created using the three modalities for the third dimension. Labels for training YOLO were supplied in CSV (comma separated values) format with the following information: multi-modal slice image name, bounding box coordinates, and the object name (in this application only 1 category was used: Brain Tumor). The bounding box coordinates were created for the CSV using the tumor mask to bounding box steps described above.
YOLO was trained on a total of 24,422 multi-modal MRI images. Out of training data (228,780 images), approximately 10.6% images had tumor(s) in them. The validation loss after training was 7.84. Once trained when supplied with the three-channel multi-modal MRI image, YOLO was able to identify where a tumor was located along with the probability of it being a tumor (as shown in Figure 4 below).
The purpose of autoencoders in the radiomics pipeline was to extract relevant image features needed to find similar images in the BraTS database. The autoencoders compressed multi-modal MRI images into an encoded vector which contained the relevant image features. Both autoencoders, AE1 and AE2, were built on the same architecture (Figure 5). The input was a 240x240x4 image where the third dimension was the different MRI modalities. The encoded vector, which contained the relevant image features, was 19200x1. Therefore, the autoencoder compressed the input multi-modal MRI images into encodings with a compression ratio of 12.
The Python package Keras was used to construct and train the autoencoders. Unlike YOLO, the autoencoders used the input image as a label and compared it with the image output by the autoencoder to train weights. The autoencoder architecture consisted of 12 layers: six layers for the encoder and six layers for the decoder parts of the network (as shown in Figure 5 below). Each layer had two convolutional layers, followed by batch normalization and max pooling for encoding or up-sampling for decoding. Batch normalization was performed to expedite training14. To obtain the encoded vector, flattening was performed in the final layer of the encoder. This resulted in a large network with a total of 21 million trainable parameters.
These Keras callbacks were used for model tuning:
- ModelCheckpoint: For saving the weights for each epoch of training and monitoring the validation loss. 14
- EarlyStopping: To avoid overfitting, the validation loss was monitored. If the validation loss did not improve over 10 epochs the training was terminated.
- Both the autoencoders were compiled with Adadelta optimizer and binary cross-entropy loss. A mini-batch size of 100 images was used.
The autoencoder was trained on an AWS p3.8xlarge instance using two Tesla V100 GPUs, one for each autoencoder. It took about 50 hours to complete the autoencoder training. However, it should be noted that the validation loss did not stagnate and even after 50 hours of training further improvement could potentially be realized.
AE1 was used to identify similar MRI slices. After training AE1, the validation loss reached a value of 0.12. The generated image from the decoder can be compared with the input image to visualize how the autoencoder was performing (as shown in Figure 6). The autoencoder successfully extracted some relevant image features. While the decoded image is blurry there appears to be similarities between the input and output image modality intensity regions and the outline of the brain is consistent.
To find similar slices of a test multi-modal MRI image, its compressed vector from AE1 is compared with other slices' compressed vectors in the BraTS database. Cosine similarity ranking was used to measure the similarity between the input test image and the compressed vectors in the database. Cosine similarity takes a maximum value of one, and the higher the value, the more similar the two compressed vectors are. To expedite lookup of test images, all the BraTS training images were pre-compressed into their encoded vectors. Cosine similarity was then calculated between the test image and all the training images using batches of 100 compressed vectors and TensorFlow's cosine similarity function utilizing a GPU. We found that the top similar slice results would often be from the same patient. Since the end goal of the pipeline was to find patients with a similar tumor, the top ranked slices from the top 200 MRI slices were filtered to be fed into AE2. Among these 200 slices, the top five individual patients are obtained that have the highest similarity in full-MRIs.
AE2 was used to find similar tumors within the top ranked slices from the top 200 MRI slices obtained from section above. The generated image from the decoder can be compared with the input image to visualize how the autoencoder was performing (as shown in Figure 6). After training AE2, the validation loss reached a value of 0.03. Like AE1, the performance of AE2 can be visualized by comparing the input and output image. AE2 successfully extracted some relevant features which allowed similar tumors to be identified.
To prepare the data fed into AE2, the tumors were cropped using the bounding boxes from YOLO and centered in a 240x240x4 array of zeros. This ensured that the tumors fed into AE2 were all the same size and the autoencoder input layer could remain constant.
To find similar tumors, the input test image was cropped according to YOLO output and fed into AE2 to obtain the encoding vectors. The test image was then compared and ranked against the top 200 encoded vectors using cosine similarity. The top five results from individual patients were then output that had similar tumors as that of the input.
After training, the validation losses of both autoencoders were as follows:
- AE1: 0.12
- AE2: 0.03
These relatively low values for the binary cross entropy from the autoencoders indicate that the encoders are able to successfully compress the information contained in the MRI's while maintaining a faithful description of the original image.
TUMOR DETECTION RESULTS
After training, the validation loss for the YOLO model reached 7.84. The trained YOLO model was used to detect tumors in 9165 new MRIs. The model found tumors in 6014 of these MRIs. The mean of the confidence scores by which the YOLO model detected tumor(s) is 85.7%. Out of all the MRIs in which the algorithm detected tumors, more than 60% of them had a confidence score of at least 95%.
IMAGE LOOKUP RESULTS
The image lookup code was built to identify MRIs that showed similarities, both, in the complete MRI slice and in the tumor image (if any). This code was run on AWS using p2.xlarge instance and on average, it took 47.6 seconds to execute completely. These results demonstrate the impact our model can have in segmenting brain tumors and in providing MRI and tumor slices that are most similar to the input MRI.
Figure 7 is an example of the inputs and outputs of the image lookup code:
In these examples, we observe qualitative similarity of the brain MRI slices in the images returned in Figure 7(a) as well as the tumors shape and size for the images in Figure 7(b). These results indicate to us that the two autoencoders are producing good representations of the brain MRI's which allows for successful reverse image lookup.
We developed an MRI brain tumor radiomics pipeline solution that could increase accuracy and speed to diagnosis by providing physicians with a similar patient MRI images in under a minute. This pipeline employs a YOLO CNN to identify brain tumors, and two CNN autoencoders to first identify similar patient MRI slices, and then within those similar patient slices, to identify patients with similar tumors. The YOLO CNN produced a validation loss of 7.84, and the two autoencoders produced validation losses of 0.12 and 0.03 respectively.
There are several important considerations that need to be made when deploying a robust implementation of this pipeline. For example, our pipeline employs the black box approach--images are inputted, and similar images are received as output, but the actual decisions made by the algorithm are opaque to the user. The pipeline would benefit from an increase in interpretability, perhaps, by including the feature importance in the model decision making process. Also, as noted above, the autoencoder loss was not stagnating. Further increase in performance can be obtained by training the autoencoders for a longer period. Finally, a U-Net CNN can be more accurate than YOLO because U-Net produces a well-defined border around the tumor, while YOLO produces a bounding box.
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