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1. 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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2. Hierarchical Neural Dynamic Policies

   https://doi.org/10.15607/rss.2021.xvii.023  

   Bahl, Shikhar ; Gupta, Abhinav ; Pathak, Deepak ( July 2021 , Robotics: Science and Systems)

   We tackle the problem of generalization to unseen configurations for dynamic tasks in the real world while learning from high-dimensional image input. The family of nonlinear dynamical system-based methods have successfully demonstrated dynamic robot behaviors but have difficulty in generalizing to unseen configurations as well as learning from image inputs. Recent works approach this issue by using deep network policies and reparameterize actions to embed the structure of dynamical systems but still struggle in domains with diverse configurations of image goals, and hence, find it difficult to generalize. In this paper, we address this dichotomy by leveraging embedding the structure of dynamical systems in a hierarchical deep policy learning framework, called Hierarchical Neural Dynamical Policies (H-NDPs). Instead of fitting deep dynamical systems to diverse data directly, H-NDPs form a curriculum by learning local dynamical system-based policies on small regions in state-space and then distill them into a global dynamical system-based policy that operates only from high-dimensional images. H-NDPs additionally provide smooth trajectories, a strong safety benefit in the real world. We perform extensive experiments on dynamic tasks both in the real world (digit writing, scooping, and pouring) and simulation (catching, throwing, picking). We show that H-NDPs are easily integrated with both imitation as well as reinforcement learning setups and achieve state-of-the-art results. 

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3. Data-Driven Control of Markov Jump Systems: Sample Complexity and Regret Bounds

   https://doi.org/10.23919/ACC53348.2022.9867863  

   Du, Zhe ; Sattar, Yahya ; Tarzanagh, Davoud Ataee ; Balzano, Laura ; Ozay, Necmiye ; Oymak, Samet ( January 2022 , 2022 American Control Conference)

   Learning how to effectively control unknown dynamical systems from data is crucial for intelligent autonomous systems. This task becomes a significant challenge when the underlying dynamics are changing with time. Motivated by this challenge, this paper considers the problem of controlling an unknown Markov jump linear system (MJS) to optimize a quadratic objective in a data-driven way. By taking a model-based perspective, we consider identification-based adaptive control for MJS. We first provide a system identification algorithm for MJS to learn the dynamics in each mode as well as the Markov transition matrix, underlying the evolution of the mode switches, from a single trajectory of the system states, inputs, and modes. Through mixing-time arguments, sample complexity of this algorithm is shown to be O(1/T−−√). We then propose an adaptive control scheme that performs system identification together with certainty equivalent control to adapt the controllers in an episodic fashion. Combining our sample complexity results with recent perturbation results for certainty equivalent control, we prove that when the episode lengths are appropriately chosen, the proposed adaptive control scheme achieves O(T−−√) regret. Our proof strategy introduces innovations to handle Markovian jumps and a weaker notion of stability common in MJSs. Our analysis provides insights into system theoretic quantities that affect learning accuracy and control performance. Numerical simulations are presented to further reinforce these insights. 

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4. Numerical Assessment of Polynomial Nonlinear State-Space and Nonlinear-Mode Models for Near-Resonant Vibrations

   https://doi.org/10.3390/vibration3030022  

   Balaji, Nidish Narayanaa ; Lian, Shuqing ; Scheel, Maren ; Brake, Matthew R. ; Tiso, Paolo ; Noël, Jean-Philippe ; Krack, Malte ( September 2020 , Vibration)

   null (Ed.)

   In the present article, we follow up our recent work on the experimental assessment of two data-driven nonlinear system identification methodologies. The first methodology constructs a single nonlinear-mode model from periodic vibration data obtained under phase-controlled harmonic excitation. The second methodology constructs a state-space model with polynomial nonlinear terms from vibration data obtained under uncontrolled broadband random excitation. The conclusions drawn from our previous work (experimental) were limited by uncertainties inherent to the specimen, instrumentation, and signal processing. To avoid these uncertainties in the present work, we pursued a completely numerical approach based on synthetic measurement data obtained from simulated experiments. Three benchmarks are considered, which feature geometric, unilateral contact, and dry friction nonlinearity, respectively. As in our previous work, we assessed the prediction accuracy of the identified models with a focus on the regime near a particular resonance. This way, we confirmed our findings on the strengths and weaknesses of the two methodologies and derive several new findings: First, the state-space method struggles even for polynomial nonlinearities if the training data is chaotic. Second, the polynomial state-space models can reach high accuracy only in a rather limited range of vibration levels for systems with non-polynomial nonlinearities. Such cases demonstrate the sensitivity to training data inherent in the method, as model errors are inevitable here. Third, although the excitation does not perfectly isolate the nonlinear mode (exciter-structure interaction, uncontrolled higher harmonics, local instead of distributed excitation), the modal properties are identified with high accuracy. 

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5. Quasistatic Control of Dynamical Systems

   https://doi.org/10.1109/CDC51059.2022.9993345  

   Komaee, Arash ( December 2022 , 2022 IEEE 61st Conference on Decision and Control (CDC))

   This paper investigates a control strategy in which the state of a dynamical system is driven slowly along a trajectory of stable equilibria. This trajectory is a continuum set of points in the state space, each one representing a stable equilibrium of the system under some constant control input. Along the continuous trajectory of such constant control inputs, a slowly varying control is then applied to the system, aimed to create a stable quasistatic equilibrium that slowly moves along the trajectory of equilibria. As a stable equilibrium attracts the state of system within its vicinity, by moving the equilibrium slowly along the trajectory of equilibria, the state of system travels near this trajectory alongside the equilibrium. Despite the disadvantage of being slow, this control strategy is attractive for certain applications, as it can be implemented based only on partial knowledge of the system dynamics. This feature is in particular important for the complex systems for which detailed dynamical models are not available. 

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