skip to main content


Title: EMIXER: End-to-end Multimodal X-ray Generation via Self-supervision
Deep generative models have enabled the automated synthesis of high-quality data for diverse applications. However, the most effective generative models are specialized to data from a single domain (e.g., images or text). Real-world applications such as healthcare require multi-modal data from multiple domains (e.g., both images and corresponding text), which are difficult to acquire due to limited availability and privacy concerns and are much harder to synthesize. To tackle this joint synthesis challenge, we propose an End-to-end MultImodal X-ray genERative model (EMIXER) for jointly synthesizing x-ray images and corresponding free-text reports, all conditional on diagnosis labels. EMIXER is an conditional generative adversarial model by 1) generating an image based on a label, 2) encoding the image to a hidden embedding, 3) producing the corresponding text via a hierarchical decoder from the image embedding, and 4) a joint discriminator for assessing both the image and the corresponding text. EMIXER also enables self-supervision to leverage vast amount of unlabeled data. Extensive experiments with real X-ray reports data illustrate how data augmentation using synthesized multimodal samples can improve the performance of a variety of supervised tasks including COVID-19 X-ray classification with very limited samples. The quality of generated images and reports are also confirmed by radiologists. We quantitatively show that EMIXER generated synthetic datasets can augment X-ray image classification, report generation models to achieve 5.94% and 6.9% improvement on models trained only on real data samples. Taken together, our results highlight the promise of state of generative models to advance clinical machine learning.  more » « less
Award ID(s):
1909577 2046795
NSF-PAR ID:
10387024
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Proceedings of Machine Learning Research
Volume:
182
ISSN:
2640-3498
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Obeid, I. (Ed.)
    The Neural Engineering Data Consortium (NEDC) is developing the Temple University Digital Pathology Corpus (TUDP), an open source database of high-resolution images from scanned pathology samples [1], as part of its National Science Foundation-funded Major Research Instrumentation grant titled “MRI: High Performance Digital Pathology Using Big Data and Machine Learning” [2]. The long-term goal of this project is to release one million images. We have currently scanned over 100,000 images and are in the process of annotating breast tissue data for our first official corpus release, v1.0.0. This release contains 3,505 annotated images of breast tissue including 74 patients with cancerous diagnoses (out of a total of 296 patients). In this poster, we will present an analysis of this corpus and discuss the challenges we have faced in efficiently producing high quality annotations of breast tissue. It is well known that state of the art algorithms in machine learning require vast amounts of data. Fields such as speech recognition [3], image recognition [4] and text processing [5] are able to deliver impressive performance with complex deep learning models because they have developed large corpora to support training of extremely high-dimensional models (e.g., billions of parameters). Other fields that do not have access to such data resources must rely on techniques in which existing models can be adapted to new datasets [6]. A preliminary version of this breast corpus release was tested in a pilot study using a baseline machine learning system, ResNet18 [7], that leverages several open-source Python tools. The pilot corpus was divided into three sets: train, development, and evaluation. Portions of these slides were manually annotated [1] using the nine labels in Table 1 [8] to identify five to ten examples of pathological features on each slide. Not every pathological feature is annotated, meaning excluded areas can include focuses particular to these labels that are not used for training. A summary of the number of patches within each label is given in Table 2. To maintain a balanced training set, 1,000 patches of each label were used to train the machine learning model. Throughout all sets, only annotated patches were involved in model development. The performance of this model in identifying all the patches in the evaluation set can be seen in the confusion matrix of classification accuracy in Table 3. The highest performing labels were background, 97% correct identification, and artifact, 76% correct identification. A correlation exists between labels with more than 6,000 development patches and accurate performance on the evaluation set. Additionally, these results indicated a need to further refine the annotation of invasive ductal carcinoma (“indc”), inflammation (“infl”), nonneoplastic features (“nneo”), normal (“norm”) and suspicious (“susp”). This pilot experiment motivated changes to the corpus that will be discussed in detail in this poster presentation. To increase the accuracy of the machine learning model, we modified how we addressed underperforming labels. One common source of error arose with how non-background labels were converted into patches. Large areas of background within other labels were isolated within a patch resulting in connective tissue misrepresenting a non-background label. In response, the annotation overlay margins were revised to exclude benign connective tissue in non-background labels. Corresponding patient reports and supporting immunohistochemical stains further guided annotation reviews. The microscopic diagnoses given by the primary pathologist in these reports detail the pathological findings within each tissue site, but not within each specific slide. The microscopic diagnoses informed revisions specifically targeting annotated regions classified as cancerous, ensuring that the labels “indc” and “dcis” were used only in situations where a micropathologist diagnosed it as such. Further differentiation of cancerous and precancerous labels, as well as the location of their focus on a slide, could be accomplished with supplemental immunohistochemically (IHC) stained slides. When distinguishing whether a focus is a nonneoplastic feature versus a cancerous growth, pathologists employ antigen targeting stains to the tissue in question to confirm the diagnosis. For example, a nonneoplastic feature of usual ductal hyperplasia will display diffuse staining for cytokeratin 5 (CK5) and no diffuse staining for estrogen receptor (ER), while a cancerous growth of ductal carcinoma in situ will have negative or focally positive staining for CK5 and diffuse staining for ER [9]. Many tissue samples contain cancerous and non-cancerous features with morphological overlaps that cause variability between annotators. The informative fields IHC slides provide could play an integral role in machine model pathology diagnostics. Following the revisions made on all the annotations, a second experiment was run using ResNet18. Compared to the pilot study, an increase of model prediction accuracy was seen for the labels indc, infl, nneo, norm, and null. This increase is correlated with an increase in annotated area and annotation accuracy. Model performance in identifying the suspicious label decreased by 25% due to the decrease of 57% in the total annotated area described by this label. A summary of the model performance is given in Table 4, which shows the new prediction accuracy and the absolute change in error rate compared to Table 3. The breast tissue subset we are developing includes 3,505 annotated breast pathology slides from 296 patients. The average size of a scanned SVS file is 363 MB. The annotations are stored in an XML format. A CSV version of the annotation file is also available which provides a flat, or simple, annotation that is easy for machine learning researchers to access and interface to their systems. Each patient is identified by an anonymized medical reference number. Within each patient’s directory, one or more sessions are identified, also anonymized to the first of the month in which the sample was taken. These sessions are broken into groupings of tissue taken on that date (in this case, breast tissue). A deidentified patient report stored as a flat text file is also available. Within these slides there are a total of 16,971 total annotated regions with an average of 4.84 annotations per slide. Among those annotations, 8,035 are non-cancerous (normal, background, null, and artifact,) 6,222 are carcinogenic signs (inflammation, nonneoplastic and suspicious,) and 2,714 are cancerous labels (ductal carcinoma in situ and invasive ductal carcinoma in situ.) The individual patients are split up into three sets: train, development, and evaluation. Of the 74 cancerous patients, 20 were allotted for both the development and evaluation sets, while the remain 34 were allotted for train. The remaining 222 patients were split up to preserve the overall distribution of labels within the corpus. This was done in hope of creating control sets for comparable studies. Overall, the development and evaluation sets each have 80 patients, while the training set has 136 patients. In a related component of this project, slides from the Fox Chase Cancer Center (FCCC) Biosample Repository (https://www.foxchase.org/research/facilities/genetic-research-facilities/biosample-repository -facility) are being digitized in addition to slides provided by Temple University Hospital. This data includes 18 different types of tissue including approximately 38.5% urinary tissue and 16.5% gynecological tissue. These slides and the metadata provided with them are already anonymized and include diagnoses in a spreadsheet with sample and patient ID. We plan to release over 13,000 unannotated slides from the FCCC Corpus simultaneously with v1.0.0 of TUDP. Details of this release will also be discussed in this poster. Few digitally annotated databases of pathology samples like TUDP exist due to the extensive data collection and processing required. The breast corpus subset should be released by November 2021. By December 2021 we should also release the unannotated FCCC data. We are currently annotating urinary tract data as well. We expect to release about 5,600 processed TUH slides in this subset. We have an additional 53,000 unprocessed TUH slides digitized. Corpora of this size will stimulate the development of a new generation of deep learning technology. In clinical settings where resources are limited, an assistive diagnoses model could support pathologists’ workload and even help prioritize suspected cancerous cases. ACKNOWLEDGMENTS This material is supported by the National Science Foundation under grants nos. CNS-1726188 and 1925494. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. REFERENCES [1] N. Shawki et al., “The Temple University Digital Pathology Corpus,” in Signal Processing in Medicine and Biology: Emerging Trends in Research and Applications, 1st ed., I. Obeid, I. Selesnick, and J. Picone, Eds. New York City, New York, USA: Springer, 2020, pp. 67 104. https://www.springer.com/gp/book/9783030368432. [2] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning.” Major Research Instrumentation (MRI), Division of Computer and Network Systems, Award No. 1726188, January 1, 2018 – December 31, 2021. https://www. isip.piconepress.com/projects/nsf_dpath/. [3] A. Gulati et al., “Conformer: Convolution-augmented Transformer for Speech Recognition,” in Proceedings of the Annual Conference of the International Speech Communication Association (INTERSPEECH), 2020, pp. 5036-5040. https://doi.org/10.21437/interspeech.2020-3015. [4] C.-J. Wu et al., “Machine Learning at Facebook: Understanding Inference at the Edge,” in Proceedings of the IEEE International Symposium on High Performance Computer Architecture (HPCA), 2019, pp. 331–344. https://ieeexplore.ieee.org/document/8675201. [5] I. Caswell and B. Liang, “Recent Advances in Google Translate,” Google AI Blog: The latest from Google Research, 2020. [Online]. Available: https://ai.googleblog.com/2020/06/recent-advances-in-google-translate.html. [Accessed: 01-Aug-2021]. [6] V. Khalkhali, N. Shawki, V. Shah, M. Golmohammadi, I. Obeid, and J. Picone, “Low Latency Real-Time Seizure Detection Using Transfer Deep Learning,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2021, pp. 1 7. https://www.isip. piconepress.com/publications/conference_proceedings/2021/ieee_spmb/eeg_transfer_learning/. [7] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning,” Philadelphia, Pennsylvania, USA, 2020. https://www.isip.piconepress.com/publications/reports/2020/nsf/mri_dpath/. [8] I. Hunt, S. Husain, J. Simons, I. Obeid, and J. Picone, “Recent Advances in the Temple University Digital Pathology Corpus,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2019, pp. 1–4. https://ieeexplore.ieee.org/document/9037859. [9] A. P. Martinez, C. Cohen, K. Z. Hanley, and X. (Bill) Li, “Estrogen Receptor and Cytokeratin 5 Are Reliable Markers to Separate Usual Ductal Hyperplasia From Atypical Ductal Hyperplasia and Low-Grade Ductal Carcinoma In Situ,” Arch. Pathol. Lab. Med., vol. 140, no. 7, pp. 686–689, Apr. 2016. https://doi.org/10.5858/arpa.2015-0238-OA. 
    more » « less
  2. Text-to-image generative models have achieved unprecedented success in generating high-quality images based on natural language descriptions. However, it is shown that these models tend to favor specific social groups when prompted with neutral text descriptions (e.g., ‘a photo of a lawyer’). Following Zhao et al. (2021), we study the effect on the diversity of the generated images when adding ethical intervention that supports equitable judgment (e.g., ‘if all individuals can be a lawyer irrespective of their gender’) in the input prompts. To this end, we introduce an Ethical NaTural Language Interventions in Text-to-Image GENeration (ENTIGEN) benchmark dataset to evaluate the change in image generations conditional on ethical interventions across three social axes – gender, skin color, and culture. Through CLIP-based and human evaluation on minDALL.E, DALL.E-mini and Stable Diffusion, we find that the model generations cover diverse social groups while preserving the image quality. In some cases, the generations would be anti-stereotypical (e.g., models tend to create images with individuals that are perceived as man when fed with prompts about makeup) in the presence of ethical intervention. Preliminary studies indicate that a large change in the model predictions is triggered by certain phrases such as ‘irrespective of gender’ in the context of gender bias in the ethical interventions. We release code and annotated data at https://github.com/Hritikbansal/entigen_emnlp. 
    more » « less
  3. The past decade has witnessed the rising dominance of deep learning and artificial intelligence in a wide range of applications. In particular, the ocean of wireless smartphones and IoT devices continue to fuel the tremendous growth of edge/cloudbased machine learning (ML) systems including image/speech recognition and classification. To overcome the infrastructural barrier of limited network bandwidth in cloud ML, existing solutions have mainly relied on traditional compression codecs such as JPEG that were historically engineered for humanend users instead of ML algorithms. Traditional codecs do not necessarily preserve features important to ML algorithms under limited bandwidth, leading to potentially inferior performance. This work investigates application-driven optimization of programmable commercial codec settings for networked learning tasks such as image classification. Based on the foundation of variational autoencoders (VAEs), we develop an end-to-end networked learning framework by jointly optimizing the codec and classifier without reconstructing images for given data rate (bandwidth). Compared with standard JPEG codec, the proposed VAE joint compression and classification framework achieves classification accuracy improvement by over 10% and 4%, respectively, for CIFAR-10 and ImageNet-1k data sets at data rate of 0.8 bpp. Our proposed VAE-based models show 65%􀀀99% reductions in encoder size,  1.5􀀀 13.1 improvements in inference speed and 25%􀀀99% savings in power compared to baseline models. We further show that a simple decoder can reconstruct images with sufficient quality without compromising classification accuracy. 
    more » « less
  4. Rutkowski L. ; Scherer R. ; Korytkowski M. ; Pedrycz W. ; Tadeusiewicz R. ; Zurada J. (Ed.)
    In this work, we investigate the impact of class imbalance on the accuracy and diversity of synthetic samples generated by conditional generative adversarial networks (CGAN) models. Though many studies utilizing GANs have seen extraordinary success in producing realistic image samples, these studies generally assume the use of well-processed and balanced benchmark image datasets, including MNIST and CIFAR-10. However, well-balanced data is uncommon in real world applications such as detecting fraud, diagnosing diabetes, and predicting solar flares. It is well known that when class labels are not distributed uniformly, the predictive ability of classification algorithms suffers significantly, a phenomenon known as the "class-imbalance problem." We show that the imbalance in the training set can also impact sample generation of CGAN models. We utilize the well known MNIST datasets, controlling the imbalance ratio of certain classes within the data through sampling. We are able to show that both the quality and diversity of generated samples suffer in the presence of class imbalances and propose a novel framework named Two-stage CGAN to produce high-quality synthetic samples in such cases. Our results indicate that the proposed framework provides a significant improvement over typical oversampling and undersampling techniques utilized for class imbalance remediation. 
    more » « less
  5. Image retrieval relies heavily on the quality of the data modeling and the distance measurement in the feature space. Building on the concept of image manifold, we first propose to represent the feature space of images, learned via neural networks, as a graph. Neighborhoods in the feature space are now defined by the geodesic distance between images, represented as graph vertices or manifold samples. When limited images are available, this manifold is sparsely sampled, making the geodesic computation and the corresponding retrieval harder. To address this, we augment the manifold samples with geometrically aligned text, thereby using a plethora of sentences to teach us about images. In addition to extensive results on standard datasets illustrating the power of text to help in image retrieval, a new public dataset based on CLEVR is introduced to quantify the semantic similarity between visual data and text data. The experimental results show that the joint embedding manifold is a robust representation, allowing it to be a better basis to perform image retrieval given only an image and a textual instruction on the desired modifications over the image. 
    more » « less