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Title: The Temple University Digital Pathology Corpus: The Breast Tissue Subset
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
Award ID(s):
1726188
NSF-PAR ID:
10322452
Author(s) / Creator(s):
; ; ; ; ;
Editor(s):
Obeid, I.
Date Published:
Journal Name:
Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB)
Volume:
1
Issue:
1
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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Two major concerns that were raised when v1.5.2 of TUSZ was released for the Neureka 2020 Epilepsy Challenge were: (1) the subjects contained in the training, development (validation) and blind evaluation sets were not mutually exclusive, and (2) high frequency seizures were not accurately annotated in all files. Regarding (1), there were 50 subjects in dev, 50 subjects in eval, and 592 subjects in train. There was one subject common to dev and eval, five subjects common to dev and train, and 13 subjects common between eval and train. Though this does not substantially influence performance for the current generation of technology, it could be a problem down the line as technology improves. Therefore, we have rebuilt the partitions of the data so that this overlap was removed. This required augmenting the evaluation and development data sets with new subjects that had not been previously annotated so that the size of these subsets remained approximately the same. Since these annotations were done by a new group of annotators, special care was taken to make sure the new annotators followed the same practices as the previous generations of annotators. Part of our quality control process was to have the new annotators review all previous annotations. This rigorous training coupled with a strict quality control process where annotators review a significant amount of each other’s work ensured that there is high interrater agreement between the two groups (kappa statistic greater than 0.8) [6]. In the process of reviewing this data, we also decided to split long files into a series of smaller segments to facilitate processing of the data. Some subscribers found it difficult to process long files using Python code, which tends to be very memory intensive. We also found it inefficient to manipulate these long files in our annotation tool. In this release, the maximum duration of any single file is limited to 60 mins. This increased the number of edf files in the dev set from 1012 to 1832. Regarding (2), as part of discussions of several issues raised by a few subscribers, we discovered some files only had low frequency epileptiform events annotated (defined as events that ranged in frequency from 2.5 Hz to 3 Hz), while others had events annotated that contained significant frequency content above 3 Hz. Though there were not many files that had this type of activity, it was enough of a concern to necessitate reviewing the entire corpus. An example of an epileptiform seizure event with frequency content higher than 3 Hz is shown in Figure 1. Annotating these additional events slightly increased the number of seizure events. In v1.5.2, there were 673 seizures, while in v1.5.3 there are 1239 events. One of the fertile areas for technology improvements is artifact reduction. Artifacts and slowing constitute the two major error modalities in seizure detection [3]. This was a major reason we developed TUAR. It can be used to evaluate artifact detection and suppression technology as well as multimodal background models that explicitly model artifacts. An issue with TUAR was the practicality of the annotation tags used when there are multiple simultaneous events. An example of such an event is shown in Figure 2. In this section of the file, there is an overlap of eye movement, electrode artifact, and muscle artifact events. We previously annotated such events using a convention that included annotating background along with any artifact that is present. The artifacts present would either be annotated with a single tag (e.g., MUSC) or a coupled artifact tag (e.g., MUSC+ELEC). When multiple channels have background, the tags become crowded and difficult to identify. This is one reason we now support a hierarchical annotation format using XML – annotations can be arbitrarily complex and support overlaps in time. Our annotators also reviewed specific eye movement artifacts (e.g., eye flutter, eyeblinks). Eye movements are often mistaken as seizures due to their similar morphology [7][8]. We have improved our understanding of ocular events and it has allowed us to annotate artifacts in the corpus more carefully. In this poster, we will present statistics on the newest releases of these corpora and discuss the impact these improvements have had on machine learning research. We will compare TUSZ v1.5.3 and TUAR v2.0.0 with previous versions of these corpora. We will release v1.5.3 of TUSZ and v2.0.0 of TUAR in Fall 2021 prior to the symposium. ACKNOWLEDGMENTS Research reported in this publication was most recently supported by the National Science Foundation’s Industrial Innovation and Partnerships (IIP) Research Experience for Undergraduates award number 1827565. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the official views of any of these organizations. REFERENCES [1] I. Obeid and J. Picone, “The Temple University Hospital EEG Data Corpus,” in Augmentation of Brain Function: Facts, Fiction and Controversy. Volume I: Brain-Machine Interfaces, 1st ed., vol. 10, M. A. Lebedev, Ed. Lausanne, Switzerland: Frontiers Media S.A., 2016, pp. 394 398. https://doi.org/10.3389/fnins.2016.00196. [2] V. Shah et al., “The Temple University Hospital Seizure Detection Corpus,” Frontiers in Neuroinformatics, vol. 12, pp. 1–6, 2018. https://doi.org/10.3389/fninf.2018.00083. [3] A. Hamid et, al., “The Temple University Artifact Corpus: An Annotated Corpus of EEG Artifacts.” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2020, pp. 1-3. https://ieeexplore.ieee.org/document/9353647. [4] Y. Roy, R. Iskander, and J. Picone, “The NeurekaTM 2020 Epilepsy Challenge,” NeuroTechX, 2020. [Online]. Available: https://neureka-challenge.com/. [Accessed: 01-Dec-2021]. [5] S. Rahman, A. Hamid, D. Ochal, I. Obeid, and J. Picone, “Improving the Quality of the TUSZ Corpus,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2020, pp. 1–5. https://ieeexplore.ieee.org/document/9353635. [6] V. Shah, E. von Weltin, T. Ahsan, I. Obeid, and J. Picone, “On the Use of Non-Experts for Generation of High-Quality Annotations of Seizure Events,” Available: https://www.isip.picone press.com/publications/unpublished/journals/2019/elsevier_cn/ira. [Accessed: 01-Dec-2021]. [7] D. Ochal, S. Rahman, S. Ferrell, T. Elseify, I. Obeid, and J. Picone, “The Temple University Hospital EEG Corpus: Annotation Guidelines,” Philadelphia, Pennsylvania, USA, 2020. https://www.isip.piconepress.com/publications/reports/2020/tuh_eeg/annotations/. [8] D. Strayhorn, “The Atlas of Adult Electroencephalography,” EEG Atlas Online, 2014. [Online]. Availabl 
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  2. Obeid, Iyad ; Picone, Joseph ; Selesnick, Ivan (Ed.)
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The computing infrastructure required to support this database is extensive [5] and includes two HIPAA-secure computer networks, dual petabyte file servers, and Aperio’s eSlide Manager (eSM) software [6]. We currently have digitized over 50,000 slides from 2,846 patients and 2,942 clinical cases. There is an average of 12.4 slides per patient and 10.5 slides per case with one report per case. 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The raw image data is stored in Aperio’s “.svs” format, which is a multi-layered compressed JPEG format [3,7]. Pathology reports containing a summary of how a pathologist interpreted the slide are also provided in a flat text file format. A more complete summary of the demographics of this pilot corpus will be presented at the conference. Another goal of this poster presentation is to share our experiences with the larger community since many of these details have not been adequately documented in scientific publications. There are quite a few obstacles in collecting this data that have slowed down the process and need to be discussed publicly. Our backlog of slides dates back to 1997, meaning there are a lot that need to be sifted through and discarded for peeling or cracking. Additionally, during scanning a slide can get stuck, stalling a scan session for hours, resulting in a significant loss of productivity. Over the past two years, we have accumulated significant experience with how to scan a diverse inventory of slides using the Aperio AT2 high-volume scanner. We have been working closely with the vendor to resolve many problems associated with the use of this scanner for research purposes. This scanning project began in January of 2018 when the scanner was first installed. The scanning process was slow at first since there was a learning curve with how the scanner worked and how to obtain samples from the hospital. From its start date until May of 2019 ~20,000 slides we scanned. In the past 6 months from May to November we have tripled that number and how hold ~60,000 slides in our database. This dramatic increase in productivity was due to additional undergraduate staff members and an emphasis on efficient workflow. The Aperio AT2 scans 400 slides a day, requiring at least eight hours of scan time. The efficiency of these scans can vary greatly. When our team first started, approximately 5% of slides failed the scanning process due to focal point errors. We have been able to reduce that to 1% through a variety of means: (1) best practices regarding daily and monthly recalibrations, (2) tweaking the software such as the tissue finder parameter settings, and (3) experience with how to clean and prep slides so they scan properly. Nevertheless, this is not a completely automated process, making it very difficult to reach our production targets. With a staff of three undergraduate workers spending a total of 30 hours per week, we find it difficult to scan more than 2,000 slides per week using a single scanner (400 slides per night x 5 nights per week). The main limitation in achieving this level of production is the lack of a completely automated scanning process, it takes a couple of hours to sort, clean and load slides. We have streamlined all other aspects of the workflow required to database the scanned slides so that there are no additional bottlenecks. To bridge the gap between hospital operations and research, we are using Aperio’s eSM software. Our goal is to provide pathologists access to high quality digital images of their patients’ slides. eSM is a secure website that holds the images with their metadata labels, patient report, and path to where the image is located on our file server. Although eSM includes significant infrastructure to import slides into the database using barcodes, TUH does not currently support barcode use. Therefore, we manage the data using a mixture of Python scripts and manual import functions available in eSM. The database and associated tools are based on proprietary formats developed by Aperio, making this another important point of community-wide discussion on how best to disseminate such information. Our near-term goal for the TUDP Corpus is to release 100,000 slides by December 2020. We hope to continue data collection over the next decade until we reach one million slides. We are creating two pilot corpora using the first 50,000 slides we have collected. The first corpus consists of 500 slides with a marker stain and another 500 without it. This set was designed to let people debug their basic deep learning processing flow on these high-resolution images. We discuss our preliminary experiments on this corpus and the challenges in processing these high-resolution images using deep learning in [3]. We are able to achieve a mean sensitivity of 99.0% for slides with pen marks, and 98.9% for slides without marks, using a multistage deep learning algorithm. While this dataset was very useful in initial debugging, we are in the midst of creating a new, more challenging pilot corpus using actual tissue samples annotated by experts. The task will be to detect ductal carcinoma (DCIS) or invasive breast cancer tissue. There will be approximately 1,000 images per class in this corpus. Based on the number of features annotated, we can train on a two class problem of DCIS or benign, or increase the difficulty by increasing the classes to include DCIS, benign, stroma, pink tissue, non-neoplastic etc. Those interested in the corpus or in participating in community-wide discussions should join our listserv, nedc_tuh_dpath@googlegroups.com, to be kept informed of the latest developments in this project. You can learn more from our project website: https://www.isip.piconepress.com/projects/nsf_dpath. 
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  3. Obeid, Iyad Selesnick (Ed.)
    Electroencephalography (EEG) is a popular clinical monitoring tool used for diagnosing brain-related disorders such as epilepsy [1]. As monitoring EEGs in a critical-care setting is an expensive and tedious task, there is a great interest in developing real-time EEG monitoring tools to improve patient care quality and efficiency [2]. However, clinicians require automatic seizure detection tools that provide decisions with at least 75% sensitivity and less than 1 false alarm (FA) per 24 hours [3]. Some commercial tools recently claim to reach such performance levels, including the Olympic Brainz Monitor [4] and Persyst 14 [5]. In this abstract, we describe our efforts to transform a high-performance offline seizure detection system [3] into a low latency real-time or online seizure detection system. An overview of the system is shown in Figure 1. The main difference between an online versus offline system is that an online system should always be causal and has minimum latency which is often defined by domain experts. The offline system, shown in Figure 2, uses two phases of deep learning models with postprocessing [3]. The channel-based long short term memory (LSTM) model (Phase 1 or P1) processes linear frequency cepstral coefficients (LFCC) [6] features from each EEG channel separately. We use the hypotheses generated by the P1 model and create additional features that carry information about the detected events and their confidence. The P2 model uses these additional features and the LFCC features to learn the temporal and spatial aspects of the EEG signals using a hybrid convolutional neural network (CNN) and LSTM model. Finally, Phase 3 aggregates the results from both P1 and P2 before applying a final postprocessing step. The online system implements Phase 1 by taking advantage of the Linux piping mechanism, multithreading techniques, and multi-core processors. To convert Phase 1 into an online system, we divide the system into five major modules: signal preprocessor, feature extractor, event decoder, postprocessor, and visualizer. The system reads 0.1-second frames from each EEG channel and sends them to the feature extractor and the visualizer. The feature extractor generates LFCC features in real time from the streaming EEG signal. Next, the system computes seizure and background probabilities using a channel-based LSTM model and applies a postprocessor to aggregate the detected events across channels. The system then displays the EEG signal and the decisions simultaneously using a visualization module. The online system uses C++, Python, TensorFlow, and PyQtGraph in its implementation. The online system accepts streamed EEG data sampled at 250 Hz as input. The system begins processing the EEG signal by applying a TCP montage [8]. Depending on the type of the montage, the EEG signal can have either 22 or 20 channels. To enable the online operation, we send 0.1-second (25 samples) length frames from each channel of the streamed EEG signal to the feature extractor and the visualizer. Feature extraction is performed sequentially on each channel. The signal preprocessor writes the sample frames into two streams to facilitate these modules. In the first stream, the feature extractor receives the signals using stdin. In parallel, as a second stream, the visualizer shares a user-defined file with the signal preprocessor. This user-defined file holds raw signal information as a buffer for the visualizer. The signal preprocessor writes into the file while the visualizer reads from it. Reading and writing into the same file poses a challenge. The visualizer can start reading while the signal preprocessor is writing into it. To resolve this issue, we utilize a file locking mechanism in the signal preprocessor and visualizer. Each of the processes temporarily locks the file, performs its operation, releases the lock, and tries to obtain the lock after a waiting period. The file locking mechanism ensures that only one process can access the file by prohibiting other processes from reading or writing while one process is modifying the file [9]. The feature extractor uses circular buffers to save 0.3 seconds or 75 samples from each channel for extracting 0.2-second or 50-sample long center-aligned windows. The module generates 8 absolute LFCC features where the zeroth cepstral coefficient is replaced by a temporal domain energy term. For extracting the rest of the features, three pipelines are used. The differential energy feature is calculated in a 0.9-second absolute feature window with a frame size of 0.1 seconds. The difference between the maximum and minimum temporal energy terms is calculated in this range. Then, the first derivative or the delta features are calculated using another 0.9-second window. Finally, the second derivative or delta-delta features are calculated using a 0.3-second window [6]. The differential energy for the delta-delta features is not included. In total, we extract 26 features from the raw sample windows which add 1.1 seconds of delay to the system. We used the Temple University Hospital Seizure Database (TUSZ) v1.2.1 for developing the online system [10]. The statistics for this dataset are shown in Table 1. A channel-based LSTM model was trained using the features derived from the train set using the online feature extractor module. A window-based normalization technique was applied to those features. In the offline model, we scale features by normalizing using the maximum absolute value of a channel [11] before applying a sliding window approach. Since the online system has access to a limited amount of data, we normalize based on the observed window. The model uses the feature vectors with a frame size of 1 second and a window size of 7 seconds. We evaluated the model using the offline P1 postprocessor to determine the efficacy of the delayed features and the window-based normalization technique. As shown by the results of experiments 1 and 4 in Table 2, these changes give us a comparable performance to the offline model. The online event decoder module utilizes this trained model for computing probabilities for the seizure and background classes. These posteriors are then postprocessed to remove spurious detections. The online postprocessor receives and saves 8 seconds of class posteriors in a buffer for further processing. It applies multiple heuristic filters (e.g., probability threshold) to make an overall decision by combining events across the channels. These filters evaluate the average confidence, the duration of a seizure, and the channels where the seizures were observed. The postprocessor delivers the label and confidence to the visualizer. The visualizer starts to display the signal as soon as it gets access to the signal file, as shown in Figure 1 using the “Signal File” and “Visualizer” blocks. Once the visualizer receives the label and confidence for the latest epoch from the postprocessor, it overlays the decision and color codes that epoch. The visualizer uses red for seizure with the label SEIZ and green for the background class with the label BCKG. Once the streaming finishes, the system saves three files: a signal file in which the sample frames are saved in the order they were streamed, a time segmented event (TSE) file with the overall decisions and confidences, and a hypotheses (HYP) file that saves the label and confidence for each epoch. The user can plot the signal and decisions using the signal and HYP files with only the visualizer by enabling appropriate options. For comparing the performance of different stages of development, we used the test set of TUSZ v1.2.1 database. It contains 1015 EEG records of varying duration. The any-overlap performance [12] of the overall system shown in Figure 2 is 40.29% sensitivity with 5.77 FAs per 24 hours. For comparison, the previous state-of-the-art model developed on this database performed at 30.71% sensitivity with 6.77 FAs per 24 hours [3]. The individual performances of the deep learning phases are as follows: Phase 1’s (P1) performance is 39.46% sensitivity and 11.62 FAs per 24 hours, and Phase 2 detects seizures with 41.16% sensitivity and 11.69 FAs per 24 hours. We trained an LSTM model with the delayed features and the window-based normalization technique for developing the online system. Using the offline decoder and postprocessor, the model performed at 36.23% sensitivity with 9.52 FAs per 24 hours. The trained model was then evaluated with the online modules. The current performance of the overall online system is 45.80% sensitivity with 28.14 FAs per 24 hours. Table 2 summarizes the performances of these systems. The performance of the online system deviates from the offline P1 model because the online postprocessor fails to combine the events as the seizure probability fluctuates during an event. The modules in the online system add a total of 11.1 seconds of delay for processing each second of the data, as shown in Figure 3. In practice, we also count the time for loading the model and starting the visualizer block. When we consider these facts, the system consumes 15 seconds to display the first hypothesis. The system detects seizure onsets with an average latency of 15 seconds. Implementing an automatic seizure detection model in real time is not trivial. We used a variety of techniques such as the file locking mechanism, multithreading, circular buffers, real-time event decoding, and signal-decision plotting to realize the system. A video demonstrating the system is available at: https://www.isip.piconepress.com/projects/nsf_pfi_tt/resources/videos/realtime_eeg_analysis/v2.5.1/video_2.5.1.mp4. The final conference submission will include a more detailed analysis of the online performance of each module. ACKNOWLEDGMENTS Research reported in this publication was most recently supported by the National Science Foundation Partnership for Innovation award number IIP-1827565 and the Pennsylvania Commonwealth Universal Research Enhancement Program (PA CURE). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the official views of any of these organizations. REFERENCES [1] A. Craik, Y. He, and J. L. Contreras-Vidal, “Deep learning for electroencephalogram (EEG) classification tasks: a review,” J. Neural Eng., vol. 16, no. 3, p. 031001, 2019. https://doi.org/10.1088/1741-2552/ab0ab5. [2] A. C. Bridi, T. Q. Louro, and R. C. L. Da Silva, “Clinical Alarms in intensive care: implications of alarm fatigue for the safety of patients,” Rev. Lat. Am. Enfermagem, vol. 22, no. 6, p. 1034, 2014. https://doi.org/10.1590/0104-1169.3488.2513. [3] M. Golmohammadi, V. Shah, I. Obeid, and J. Picone, “Deep Learning Approaches for Automatic Seizure Detection from Scalp Electroencephalograms,” 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, New York, USA: Springer, 2020, pp. 233–274. https://doi.org/10.1007/978-3-030-36844-9_8. [4] “CFM Olympic Brainz Monitor.” [Online]. Available: https://newborncare.natus.com/products-services/newborn-care-products/newborn-brain-injury/cfm-olympic-brainz-monitor. [Accessed: 17-Jul-2020]. [5] M. L. Scheuer, S. B. Wilson, A. Antony, G. Ghearing, A. Urban, and A. I. Bagic, “Seizure Detection: Interreader Agreement and Detection Algorithm Assessments Using a Large Dataset,” J. Clin. Neurophysiol., 2020. https://doi.org/10.1097/WNP.0000000000000709. [6] A. Harati, M. Golmohammadi, S. Lopez, I. Obeid, and J. Picone, “Improved EEG Event Classification Using Differential Energy,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium, 2015, pp. 1–4. https://doi.org/10.1109/SPMB.2015.7405421. [7] V. Shah, C. Campbell, I. Obeid, and J. Picone, “Improved Spatio-Temporal Modeling in Automated Seizure Detection using Channel-Dependent Posteriors,” Neurocomputing, 2021. [8] W. Tatum, A. Husain, S. Benbadis, and P. Kaplan, Handbook of EEG Interpretation. New York City, New York, USA: Demos Medical Publishing, 2007. [9] D. P. Bovet and C. Marco, Understanding the Linux Kernel, 3rd ed. O’Reilly Media, Inc., 2005. https://www.oreilly.com/library/view/understanding-the-linux/0596005652/. [10] V. Shah et al., “The Temple University Hospital Seizure Detection Corpus,” Front. Neuroinform., vol. 12, pp. 1–6, 2018. https://doi.org/10.3389/fninf.2018.00083. [11] F. Pedregosa et al., “Scikit-learn: Machine Learning in Python,” J. Mach. Learn. Res., vol. 12, pp. 2825–2830, 2011. https://dl.acm.org/doi/10.5555/1953048.2078195. [12] J. Gotman, D. Flanagan, J. Zhang, and B. Rosenblatt, “Automatic seizure detection in the newborn: Methods and initial evaluation,” Electroencephalogr. Clin. Neurophysiol., vol. 103, no. 3, pp. 356–362, 1997. https://doi.org/10.1016/S0013-4694(97)00003-9. 
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  4. Obeid, Iyad ; Selesnick, Ivan ; Picone, Joseph (Ed.)
    The Temple University Hospital Seizure Detection Corpus (TUSZ) [1] has been in distribution since April 2017. It is a subset of the TUH EEG Corpus (TUEG) [2] and the most frequently requested corpus from our 3,000+ subscribers. It was recently featured as the challenge task in the Neureka 2020 Epilepsy Challenge [3]. A summary of the development of the corpus is shown below in Table 1. The TUSZ Corpus is a fully annotated corpus, which means every seizure event that occurs within its files has been annotated. The data is selected from TUEG using a screening process that identifies files most likely to contain seizures [1]. Approximately 7% of the TUEG data contains a seizure event, so it is important we triage TUEG for high yield data. One hour of EEG data requires approximately one hour of human labor to complete annotation using the pipeline described below, so it is important from a financial standpoint that we accurately triage data. A summary of the labels being used to annotate the data is shown in Table 2. Certain standards are put into place to optimize the annotation process while not sacrificing consistency. Due to the nature of EEG recordings, some records start off with a segment of calibration. This portion of the EEG is instantly recognizable and transitions from what resembles lead artifact to a flat line on all the channels. For the sake of seizure annotation, the calibration is ignored, and no time is wasted on it. During the identification of seizure events, a hard “3 second rule” is used to determine whether two events should be combined into a single larger event. This greatly reduces the time that it takes to annotate a file with multiple events occurring in succession. In addition to the required minimum 3 second gap between seizures, part of our standard dictates that no seizure less than 3 seconds be annotated. Although there is no universally accepted definition for how long a seizure must be, we find that it is difficult to discern with confidence between burst suppression or other morphologically similar impressions when the event is only a couple seconds long. This is due to several reasons, the most notable being the lack of evolution which is oftentimes crucial for the determination of a seizure. After the EEG files have been triaged, a team of annotators at NEDC is provided with the files to begin data annotation. An example of an annotation is shown in Figure 1. A summary of the workflow for our annotation process is shown in Figure 2. Several passes are performed over the data to ensure the annotations are accurate. Each file undergoes three passes to ensure that no seizures were missed or misidentified. The first pass of TUSZ involves identifying which files contain seizures and annotating them using our annotation tool. The time it takes to fully annotate a file can vary drastically depending on the specific characteristics of each file; however, on average a file containing multiple seizures takes 7 minutes to fully annotate. This includes the time that it takes to read the patient report as well as traverse through the entire file. Once an event has been identified, the start and stop time for the seizure is stored in our annotation tool. This is done on a channel by channel basis resulting in an accurate representation of the seizure spreading across different parts of the brain. Files that do not contain any seizures take approximately 3 minutes to complete. Even though there is no annotation being made, the file is still carefully examined to make sure that nothing was overlooked. In addition to solely scrolling through a file from start to finish, a file is often examined through different lenses. Depending on the situation, low pass filters are used, as well as increasing the amplitude of certain channels. These techniques are never used in isolation and are meant to further increase our confidence that nothing was missed. Once each file in a given set has been looked at once, the annotators start the review process. The reviewer checks a file and comments any changes that they recommend. This takes about 3 minutes per seizure containing file, which is significantly less time than the first pass. After each file has been commented on, the third pass commences. This step takes about 5 minutes per seizure file and requires the reviewer to accept or reject the changes that the second reviewer suggested. Since tangible changes are made to the annotation using the annotation tool, this step takes a bit longer than the previous one. Assuming 18% of the files contain seizures, a set of 1,000 files takes roughly 127 work hours to annotate. Before an annotator contributes to the data interpretation pipeline, they are trained for several weeks on previous datasets. A new annotator is able to be trained using data that resembles what they would see under normal circumstances. An additional benefit of using released data to train is that it serves as a means of constantly checking our work. If a trainee stumbles across an event that was not previously annotated, it is promptly added, and the data release is updated. It takes about three months to train an annotator to a point where their annotations can be trusted. Even though we carefully screen potential annotators during the hiring process, only about 25% of the annotators we hire survive more than one year doing this work. To ensure that the annotators are consistent in their annotations, the team conducts an interrater agreement evaluation periodically to ensure that there is a consensus within the team. The annotation standards are discussed in Ochal et al. [4]. An extended discussion of interrater agreement can be found in Shah et al. [5]. The most recent release of TUSZ, v1.5.2, represents our efforts to review the quality of the annotations for two upcoming challenges we hosted: an internal deep learning challenge at IBM [6] and the Neureka 2020 Epilepsy Challenge [3]. One of the biggest changes that was made to the annotations was the imposition of a stricter standard for determining the start and stop time of a seizure. Although evolution is still included in the annotations, the start times were altered to start when the spike-wave pattern becomes distinct as opposed to merely when the signal starts to shift from background. This cuts down on background that was mislabeled as a seizure. For seizure end times, all post ictal slowing that was included was removed. The recent release of v1.5.2 did not include any additional data files. Two EEG files had been added because, originally, they were corrupted in v1.5.1 but were able to be retrieved and added for the latest release. The progression from v1.5.0 to v1.5.1 and later to v1.5.2, included the re-annotation of all of the EEG files in order to develop a confident dataset regarding seizure identification. Starting with v1.4.0, we have also developed a blind evaluation set that is withheld for use in competitions. The annotation team is currently working on the next release for TUSZ, v1.6.0, which is expected to occur in August 2020. It will include new data from 2016 to mid-2019. This release will contain 2,296 files from 2016 as well as several thousand files representing the remaining data through mid-2019. In addition to files that were obtained with our standard triaging process, a part of this release consists of EEG files that do not have associated patient reports. Since actual seizure events are in short supply, we are mining a large chunk of data for which we have EEG recordings but no reports. Some of this data contains interesting seizure events collected during long-term EEG sessions or data collected from patients with a history of frequent seizures. It is being mined to increase the number of files in the corpus that have at least one seizure event. We expect v1.6.0 to be released before IEEE SPMB 2020. The TUAR Corpus is an open-source database that is currently available for use by any registered member of our consortium. To register and receive access, please follow the instructions provided at this web page: https://www.isip.piconepress.com/projects/tuh_eeg/html/downloads.shtml. The data is located here: https://www.isip.piconepress.com/projects/tuh_eeg/downloads/tuh_eeg_artifact/v2.0.0/. 
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  5. Obeid, I. ; Selesnick, I. (Ed.)
    The Neural Engineering Data Consortium at Temple University has been providing key data resources to support the development of deep learning technology for electroencephalography (EEG) applications [1-4] since 2012. We currently have over 1,700 subscribers to our resources and have been providing data, software and documentation from our web site [5] since 2012. In this poster, we introduce additions to our resources that have been developed within the past year to facilitate software development and big data machine learning research. Major resources released in 2019 include: ● Data: The most current release of our open source EEG data is v1.2.0 of TUH EEG and includes the addition of 3,874 sessions and 1,960 patients from mid-2015 through 2016. ● Software: We have recently released a package, PyStream, that demonstrates how to correctly read an EDF file and access samples of the signal. This software demonstrates how to properly decode channels based on their labels and how to implement montages. Most existing open source packages to read EDF files do not directly address the problem of channel labels [6]. ● Documentation: We have released two documents that describe our file formats and data representations: (1) electrodes and channels [6]: describes how to map channel labels to physical locations of the electrodes, and includes a description of every channel label appearing in the corpus; (2) annotation standards [7]: describes our annotation file format and how to decode the data structures used to represent the annotations. Additional significant updates to our resources include: ● NEDC TUH EEG Seizure (v1.6.0): This release includes the expansion of the training dataset from 4,597 files to 4,702. Calibration sequences have been manually annotated and added to our existing documentation. Numerous corrections were made to existing annotations based on user feedback. ● IBM TUSZ Pre-Processed Data (v1.0.0): A preprocessed version of the TUH Seizure Detection Corpus using two methods [8], both of which use an FFT sliding window approach (STFT). In the first method, FFT log magnitudes are used. In the second method, the FFT values are normalized across frequency buckets and correlation coefficients are calculated. The eigenvalues are calculated from this correlation matrix. The eigenvalues and correlation matrix's upper triangle are used to generate feature. ● NEDC TUH EEG Artifact Corpus (v1.0.0): This corpus was developed to support modeling of non-seizure signals for problems such as seizure detection. We have been using the data to build better background models. Five artifact events have been labeled: (1) eye movements (EYEM), (2) chewing (CHEW), (3) shivering (SHIV), (4) electrode pop, electrostatic artifacts, and lead artifacts (ELPP), and (5) muscle artifacts (MUSC). The data is cross-referenced to TUH EEG v1.1.0 so you can match patient numbers, sessions, etc. ● NEDC Eval EEG (v1.3.0): In this release of our standardized scoring software, the False Positive Rate (FPR) definition of the Time-Aligned Event Scoring (TAES) metric has been updated [9]. The standard definition is the number of false positives divided by the number of false positives plus the number of true negatives: #FP / (#FP + #TN). We also recently introduced the ability to download our data from an anonymous rsync server. The rsync command [10] effectively synchronizes both a remote directory and a local directory and copies the selected folder from the server to the desktop. It is available as part of most, if not all, Linux and Mac distributions (unfortunately, there is not an acceptable port of this command for Windows). To use the rsync command to download the content from our website, both a username and password are needed. An automated registration process on our website grants both. An example of a typical rsync command to access our data on our website is: rsync -auxv nedc_tuh_eeg@www.isip.piconepress.com:~/data/tuh_eeg/ Rsync is a more robust option for downloading data. We have also experimented with Google Drive and Dropbox, but these types of technology are not suitable for such large amounts of data. All of the resources described in this poster are open source and freely available at https://www.isip.piconepress.com/projects/tuh_eeg/downloads/. We will demonstrate how to access and utilize these resources during the poster presentation and collect community feedback on the most needed additions to enable significant advances in machine learning performance. 
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