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1. Recent Advances in the Temple University Digital Pathology Corpus

   https://doi.org/10.1109/SPMB47826.2019.9037859  

   Hunt, I. ; Husain, S. ; Simon, J. ; Obeid, I. ; Picone, J. ( December 2019 , IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   Obeid, Iyad ; Picone, Joseph ; Selesnick, Ivan (Ed.)

   The Neural Engineering Data Consortium (NEDC) is developing a large open source database of high-resolution digital pathology images known as the Temple University Digital Pathology Corpus (TUDP) [1]. Our long-term goal is to release one million images. We expect to release the first 100,000 image corpus by December 2020. The data is being acquired at the Department of Pathology at Temple University Hospital (TUH) using a Leica Biosystems Aperio AT2 scanner [2] and consists entirely of clinical pathology images. More information about the data and the project can be found in Shawki et al. [3]. We currently have a National Science Foundation (NSF) planning grant [4] to explore how best the community can leverage this resource. One goal of this poster presentation is to stimulate community-wide discussions about this project and determine how this valuable resource can best meet the needs of the public. 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. The data is organized by tissue type as shown below: Filenames: tudp/v1.0.0/svs/gastro/000001/00123456/2015_03_05/0s15_12345/0s15_12345_0a001_00123456_lvl0001_s000.svs tudp/v1.0.0/svs/gastro/000001/00123456/2015_03_05/0s15_12345/0s15_12345_00123456.docx Explanation: tudp: root directory of the corpus v1.0.0: version number of the release svs: the image data type gastro: the type of tissue 000001: six-digit sequence number used to control directory complexity 00123456: 8-digit patient MRN 2015_03_05: the date the specimen was captured 0s15_12345: the clinical case name 0s15_12345_0a001_00123456_lvl0001_s000.svs: the actual image filename consisting of a repeat of the case name, a site code (e.g., 0a001), the type and depth of the cut (e.g., lvl0001) and a token number (e.g., s000) 0s15_12345_00123456.docx: the filename for the corresponding case report We currently recognize fifteen tissue types in the first installment of the corpus. 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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2. SQLite: past, present, and future

   https://doi.org/10.14778/3554821.3554842  

   Gaffney, Kevin P. ; Prammer, Martin ; Brasfield, Larry ; Hipp, D. Richard ; Kennedy, Dan ; Patel, Jignesh M. ( August 2022 , Proceedings of the VLDB Endowment)

   In the two decades following its initial release, SQLite has become the most widely deployed database engine in existence. Today, SQLite is found in nearly every smartphone, computer, web browser, television, and automobile. Several factors are likely responsible for its ubiquity, including its in-process design, standalone codebase, extensive test suite, and cross-platform file format. While it supports complex analytical queries, SQLite is primarily designed for fast online transaction processing (OLTP), employing row-oriented execution and a B-tree storage format. However, fueled by the rise of edge computing and data science, there is a growing need for efficient in-process online analytical processing (OLAP). DuckDB, a database engine nicknamed "the SQLite for analytics", has recently emerged to meet this demand. While DuckDB has shown strong performance on OLAP benchmarks, it is unclear how SQLite compares. Furthermore, we are aware of no work that attempts to identify root causes for SQLite's performance behavior on OLAP workloads. In this paper, we discuss SQLite in the context of this changing workload landscape. We describe how SQLite evolved from its humble beginnings to the full-featured database engine it is today. We evaluate the performance of modern SQLite on three benchmarks, each representing a different flavor of in-process data management, including transactional, analytical, and blob processing. We delve into analytical data processing on SQLite, identifying key bottlenecks and weighing potential solutions. As a result of our optimizations, SQLite is now up to 4.2X faster on SSB. Finally, we discuss the future of SQLite, envisioning how it will evolve to meet new demands and challenges. 

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3. Data Engineering for HPC with Python

   https://doi.org/10.1109/PyHPC51966.2020.00007  

   Abeykoon, Vibhatha ; Perera, Niranda ; Widanage, Chathura ; Kamburugamuve, Supun ; Kanewala, Thejaka Amila ; Maithree, Hasara ; Wickramasinghe, Pulasthi ; Uyar, Ahmet ; Fox, Geoffrey ( November 2020 , 2020 IEEE/ACM 9th Workshop on Python for High-Performance and Scientific Computing (PyHPC))

   null (Ed.)

   Data engineering is becoming an increasingly important part of scientific discoveries with the adoption of deep learning and machine learning. Data engineering deals with a variety of data formats, storage, data extraction, transformation, and data movements. One goal of data engineering is to transform data from original data to vector/matrix/tensor formats accepted by deep learning and machine learning applications. There are many structures such as tables, graphs, and trees to represent data in these data engineering phases. Among them, tables are a versatile and commonly used format to load and process data. In this paper, we present a distributed Python API based on table abstraction for representing and processing data. Unlike existing state-of-the-art data engineering tools written purely in Python, our solution adopts high performance compute kernels in C++, with an in-memory table representation with Cython-based Python bindings. In the core system, we use MPI for distributed memory computations with a data-parallel approach for processing large datasets in HPC clusters. 

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4. Software and Data Resources to Advance Machine Learning Research in Electroencephalography

   https://doi.org/10.1109/SPMB47826.2019.9037851  

   Rahman, S. ; Miranda, M. ; Obeid, I. ; Picone, J. ( December 2019 , IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   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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5. The Temple University Digital Pathology Corpus: The Breast Tissue Subset

   https://doi.org/10.1109/SPMB52430.2021.9672275  

   Wevodau, Z. ; Doshna, B. ; Jhala, N. ; Akhtar, I. ; Obeid, I. ; Picone, J. ( December 2021 , Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   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. 

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