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1. A personalized classification of behavioral severity of autism spectrum disorder using a comprehensive machine learning framework

   https://doi.org/10.1038/s41598-023-43478-z  

   Ali, Mohamed T. ; Gebreil, Ahmad ; ElNakieb, Yaser ; Elnakib, Ahmed ; Shalaby, Ahmed ; Mahmoud, Ali ; Sleman, Ahmed ; Giridharan, Guruprasad A. ; Barnes, Gregory ; Elbaz, Ayman S. ( October 2023 , Scientific Reports)

   Autism Spectrum Disorder (ASD) is characterized as a neurodevelopmental disorder with a heterogeneous nature, influenced by genetics and exhibiting diverse clinical presentations. In this study, we dissect Autism Spectrum Disorder (ASD) into its behavioral components, mirroring the diagnostic process used in clinical settings. Morphological features are extracted from magnetic resonance imaging (MRI) scans, found in the publicly available dataset ABIDE II, identifying the most discriminative features that differentiate ASD within various behavioral domains. Then, each subject is categorized as having severe, moderate, or mild ASD, or typical neurodevelopment (TD), based on the behavioral domains of the Social Responsiveness Scale (SRS). Through this study, multiple artificial intelligence (AI) models are utilized for feature selection and classifying each ASD severity and behavioural group. A multivariate feature selection algorithm, investigating four different classifiers with linear and non-linear hypotheses, is applied iteratively while shuffling the training-validation subjects to find the set of cortical regions with statistically significant association with ASD. A set of six classifiers are optimized and trained on the selected set of features using 5-fold cross-validation for the purpose of severity classification for each behavioural group. Our AI-based model achieved an average accuracy of 96%, computed as the mean accuracy across the top-performing AI models for feature selection and severity classification across the different behavioral groups. The proposed AI model has the ability to accurately differentiate between the functionalities of specific brain regions, such as the left and right caudal middle frontal regions. We propose an AI-based model that dissects ASD into behavioral components. For each behavioral component, the AI-based model is capable of identifying the brain regions which are associated with ASD as well as utilizing those regions for diagnosis. The proposed system can increase the speed and accuracy of the diagnostic process and result in improved outcomes for individuals with ASD, highlighting the potential of AI in this area.

    

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2. Merging fNIRS-EEG Brain Monitoring and Body Motion Capture to Distinguish Parkinson’s Disease

   https://doi.org/10.1109/TNSRE.2020.2987888  

   Abtahi, Mohammadreza ; Borgheai, Seyed Bahram ; Jafari, Roohollah ; Constant, Nicholas ; Diouf, Rassoul ; Shahriari, Yalda ; Mankodiya, Kunal ( January 2020 , IEEE Transactions on Neural Systems and Rehabilitation Engineering)

   Functional connectivity between the brain and body kinematics has largely not been investigated due to the requirement of motionlessness in neuroimaging techniques such as functional magnetic resonance imaging (fMRI). However, this connectivity is disrupted in many neurodegenerative disorders, including Parkinson’s Disease (PD), a neurological progressive disorder characterized by movement symptoms including slowness of movement, stiffness, tremors at rest, and walking and standing instability. In this study, brain activity is recorded through functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), and body kinematics were captured by a motion capture system (Mocap) based on an inertial measurement unit (IMU) for gross movements (large movements such as limb kinematics), and the WearUp glove for fine movements (small range movements such as finger kinematics). PD and neurotypical (NT) participants were recruited to perform 8 different movement tasks. The recorded data from each modality have been analyzed individually, and the processed data has been used for classification between the PD and NT groups. The average changes in oxygenated hemoglobin (HbO2) from fNIRS, EEG power spectral density in the Theta, Alpha, and Beta bands, acceleration vector from Mocap, and normalized WearUp flex sensor data were used for classification. 12 different support vector machine (SVM) classifiers have been used on different datasets such as only fNIRS data, only EEG data, hybrid fNIRS/EEG data, and all the fused data for two classification scenarios: classifying PD and NT based on individual activities, and all activity data fused together. The PD and NT group could be distinguished with more than 83% accuracy for each individual activity. For all the fused data, the PD and NT groups are classified with 81.23%, 92.79%, 92.27%, and 93.40% accuracy for the fNIRS only, EEG only, hybrid fNIRS/EEG, and all fused data, respectively. The results indicate that the overall performance of classification in distinguishing PD and NT groups improves when using both brain and body data. 

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3. 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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4. Prediction of isometric handgrip force from graded event-related desynchronization of the sensorimotor rhythm

   https://doi.org/10.1088/1741-2552/ac23c0  

   Haddix, Chase ; Al-Bakri, Amir F ; Sunderam, Sridhar ( September 2021 , Journal of Neural Engineering)

   Abstract Objective . Brain–computer interfaces (BCIs) show promise as a direct line of communication between the brain and the outside world that could benefit those with impaired motor function. But the commands available for BCI operation are often limited by the ability of the decoder to differentiate between the many distinct motor or cognitive tasks that can be visualized or attempted. Simple binary command signals (e.g. right hand at rest versus movement) are therefore used due to their ability to produce large observable differences in neural recordings. At the same time, frequent command switching can impose greater demands on the subject’s focus and takes time to learn. Here, we attempt to decode the degree of effort in a specific movement task to produce a graded and more flexible command signal. Approach. Fourteen healthy human subjects (nine male, five female) responded to visual cues by squeezing a hand dynamometer to different levels of predetermined force, guided by continuous visual feedback, while the electroencephalogram (EEG) and grip force were monitored. Movement-related EEG features were extracted and modeled to predict exerted force. Main results. We found that event-related desynchronization (ERD) of the 8–30 Hz mu-beta sensorimotor rhythm of the EEG is separable for different degrees of motor effort. Upon four-fold cross-validation, linear classifiers were found to predict grip force from an ERD vector with mean accuracies across subjects of 53% and 55% for the dominant and non-dominant hand, respectively. ERD amplitude increased with target force but appeared to pass through a trough that hinted at non-monotonic behavior. Significance. Our results suggest that modeling and interactive feedback based on the intended level of motor effort is feasible. The observed ERD trends suggest that different mechanisms may govern intermediate versus low and high degrees of motor effort. This may have utility in rehabilitative protocols for motor impairments. 

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5. Assaying neural activity of children during video game play in public spaces: a deep learning approach

   https://doi.org/10.1088/1741-2552/ab1876  

   Sujatha Ravindran, Akshay ; Mobiny, Aryan ; Cruz-Garza, Jesus G. ; Paek, Andrew ; Kopteva, Anastasiya ; Contreras Vidal, José L. ( May 2019 , Journal of Neural Engineering)

   Objective. Understanding neural activity patterns in the developing brain remains one of the grand challenges in neuroscience. Developing neural networks are likely to be endowed with functionally important variability associated with the environmental context, age, gender, and other variables. Therefore, we conducted experiments with typically developing children in a stimulating museum setting and tested the feasibility of using deep learning techniques to help identify patterns of brain activity associated with different conditions.Approach. A four-channel dry EEG-based Mobile brain-body imaging data of children at rest and during videogame play (VGP) was acquired at the Children’s Museum of Houston. A data-driven approach based on convolutional neural networks (CNN) was used to describe underlying feature representations in the EEG and their ability to discern task and gender. The variability of the spectral features of EEG during the rest condition as a function of age was also analyzed.Main results. Alpha power (7–13 Hz) was higher during rest whereas theta power (4–7 Hz) was higher during VGP. Beta (13–18 Hz) power was the most significant feature, higher in females, when differentiating between males and females. Using data from both temporoparietal channels to classify between VGP and rest condition, leave-one-subject-out cross-validation accuracy of 67% was obtained. Age-related changes in EEG spectral content during rest were consistent with previous developmental studies conducted in laboratory settings showing an inverse relationship between age and EEG power.Significance. These findings are the first to acquire, quantify and explain brain patterns observed during VGP and rest in freely behaving children in a museum setting using a deep learning framework. The study shows how deep learning can be used as a data driven approach to identify patterns in the data and explores the issues and the potential of conducting experiments involving children in a natural and engaging environment.

    

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