Brain age predicted using graph convolutional neural network explains neurodevelopmental trajectory in preterm neonates

OBJECTIVES: Dramatic brain morphological changes occur throughout the third trimester of gestation. In this study, we investigated whether the predicted brain age (PBA) derived from graph convolutional network (GCN) that accounts for cortical morphometrics in third trimester is associated with postnatal abnormalities and neurodevelopmental outcome. METHODS: In total, 577 T1 MRI scans of preterm neonates from two different datasets were analyzed; the NEOCIVET pipeline generated cortical surfaces and morphological features, which were then fed to the GCN to predict brain age. The brain age index (BAI; PBA minus chronological age) was used to determine the relationships among preterm birth (i.e., birthweight and birth age), perinatal brain injuries, postnatal events/clinical conditions, BAI at postnatal scan, and neurodevelopmental scores at 30 months. RESULTS: Brain morphology and GCN-based age prediction of preterm neonates without brain lesions (mean absolute error [MAE]: 0.96 weeks) outperformed conventional machine learning methods using no topological information. Structural equation models (SEM) showed that BAI mediated the influence of preterm birth and postnatal clinical factors, but not perinatal brain injuries, on neurodevelopmental outcome at 30 months of age. CONCLUSIONS: Brain morphology may be clinically meaningful in measuring brain age, as it relates to postnatal factors, and predicting neurodevelopmental outcome. CLINICAL RELEVANCE STATEMENT: Understanding the neurodevelopmental trajectory of preterm neonates through the prediction of brain age using a graph convolutional neural network may allow for earlier detection of potential developmental abnormalities and improved interventions, consequently enhancing the prognosis and quality of life in this vulnerable population. KEY POINTS: •Brain age in preterm neonates predicted using a graph convolutional network with brain morphological changes mediates the pre-scan risk factors and post-scan neurodevelopmental outcomes. •Predicted brain age oriented from conventional deep learning approaches, which indicates the neurodevelopmental status in neonates, shows a lack of sensitivity to perinatal risk factors and predicting neurodevelopmental outcomes. •The new brain age index based on brain morphology and graph convolutional network enhances the accuracy and clinical interpretation of predicted brain age for neonates

Machine learning for understanding and predicting neurodevelopmental outcomes in premature infants: a systematic review

BACKGROUND: Machine learning has been attracting increasing attention for use in healthcare applications, including neonatal medicine. One application for this tool is in understanding and predicting neurodevelopmental outcomes in preterm infants. In this study, we have carried out a systematic review to identify findings and challenges to date. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched in February 2022, with articles then screened in a non-blinded manner by two authors. RESULTS: The literature search returned 278 studies, with 11 meeting the eligibility criteria for inclusion. Convolutional neural networks were the most common machine learning approach, with most studies seeking to predict neurodevelopmental outcomes from images and connectomes describing brain structure and function. Studies to date also sought to identify features predictive of outcomes; however, results varied greatly. CONCLUSIONS: Initial studies in this field have achieved promising results; however, many machine learning techniques remain to be explored, and the consensus is yet to be reached on which clinical and brain features are most predictive of neurodevelopmental outcomes

Application and potential of artificial intelligence in neonatal medicine

Neonatal care is becoming increasingly complex with large amounts of rich, routinely recorded physiological, diagnostic and outcome data. Artificial intelligence (AI) has the potential to harness this vast quantity and range of information and become a powerful tool to support clinical decision making, personalised care, precise prognostics, and enhance patient safety. Current AI approaches in neonatal medicine include tools for disease prediction and risk stratification, neurological diagnostic support and novel image recognition technologies. Key to the integration of AI in neonatal medicine is the understanding of its limitations and a standardised critical appraisal of AI tools. Barriers and challenges to this include the quality of datasets used, performance assessment, and appropriate external validation and clinical impact studies. Improving digital literacy amongst healthcare professionals and cross-disciplinary collaborations are needed to harness the full potential of AI to help take the next significant steps in improving neonatal outcomes for high-risk infants

A COMPUTATIONAL FRAMEWORK FOR NEONATAL BRAIN MRI STRUCTURE SEGMENTATION AND CLASSIFICATION

Deep Learning is increasingly being used in both supervised and unsupervised learning to derive complex patterns from data. However, the successful implementation of deep learning using medical imaging requires careful consideration for the quality and availability of data. Infants diagnosed with CHD are at a higher risk for neurodevelopmental impairment. Many of these deficits may be attenuated by early detection and intervention. However, we currently lack effective diagnostic tools for the reliable detection of these disorders at the neonatal period. We believe that the structural correlates of the cognitive deficits associated with developmental abnormalities can be measured within the first few months of life. Based on this assumption, we hypothesize that we can use an atlas registration based structural segmentation pipeline to sufficiently reduce the search space of neonatal structural brain MRI to viably implement convolutional neural networks for dysplasia classification. Secondly, we hypothesize that convolutional neural networks can successfully identify morphological biomarkers capable of detecting structurally abnormal brain substructures. In this study, we develop a computational framework for the automated classification of dysplastic substructures from neonatal MRI. We validate our implementation on a dataset of neonates born with CHD, as this is a vulnerable population for structural dysmaturation. We chose the cerebellum as the initial test substructure because of its relatively simple structure and known vulnerability to structural dysplasia in infants born with CHD. We then apply the same method to the hippocampus, a more challenging substructure due to its complex morphological properties. We attempt to overcome the limited availability of clinical data in neonatal populations by first extracting each brain substructure of interest and individually registering them into a standard space. This greatly reduces the search space required to learn the subtle abnormalities associated with a given pathology, making it feasible to implement a 3-D CNN as the classification algorithm. We achieved excellent classification accuracy in detecting dysplastic cerebelli, and demonstrate a viable computational framework for search space reduction using limited clinical datasets. All methods developed in this work are designed to be extensible, reproducible, and generalizable diagnostic tools for future neuroimaging problems

Role of deep learning in infant brain MRI analysis

Deep learning algorithms and in particular convolutional networks have shown tremendous success in medical image analysis applications, though relatively few methods have been applied to infant MRI data due numerous inherent challenges such as inhomogenous tissue appearance across the image, considerable image intensity variability across the first year of life, and a low signal to noise setting. This paper presents methods addressing these challenges in two selected applications, specifically infant brain tissue segmentation at the isointense stage and presymptomatic disease prediction in neurodevelopmental disorders. Corresponding methods are reviewed and compared, and open issues are identified, namely low data size restrictions, class imbalance problems, and lack of interpretation of the resulting deep learning solutions. We discuss how existing solutions can be adapted to approach these issues as well as how generative models seem to be a particularly strong contender to address them

Prospects of deep learning for medical imaging

Machine learning techniques are essential components of medical imaging research. Recently, a highly flexible machine learning approach known as deep learning has emerged as a disruptive technology to enhance the performance of existing machine learning techniques and to solve previously intractable problems. Medical imaging has been identified as one of the key research fields where deep learning can contribute significantly. This review article aims to survey deep learning literature in medical imaging and describe its potential for future medical imaging research. First, an overview of how traditional machine learning evolved to deep learning is provided. Second, a survey of the application of deep learning in medical imaging research is given. Third, wellknown software tools for deep learning are reviewed. Finally, conclusions with limitations and future directions of deep learning in medical imaging are provided

GAMER MRI: Gated-attention mechanism ranking of multi-contrast MRI in brain pathology.

During the last decade, a multitude of novel quantitative and semiquantitative MRI techniques have provided new information about the pathophysiology of neurological diseases. Yet, selection of the most relevant contrasts for a given pathology remains challenging. In this work, we developed and validated a method, Gated-Attention MEchanism Ranking of multi-contrast MRI in brain pathology (GAMER MRI), to rank the relative importance of MR measures in the classification of well understood ischemic stroke lesions. Subsequently, we applied this method to the classification of multiple sclerosis (MS) lesions, where the relative importance of MR measures is less understood. GAMER MRI was developed based on the gated attention mechanism, which computes attention weights (AWs) as proxies of importance of hidden features in the classification. In the first two experiments, we used Trace-weighted (Trace), apparent diffusion coefficient (ADC), Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted (T1w) images acquired in 904 acute/subacute ischemic stroke patients and in 6,230 healthy controls and patients with other brain pathologies to assess if GAMER MRI could produce clinically meaningful importance orders in two different classification scenarios. In the first experiment, GAMER MRI with a pretrained convolutional neural network (CNN) was used in conjunction with Trace, ADC, and FLAIR to distinguish patients with ischemic stroke from those with other pathologies and healthy controls. In the second experiment, GAMER MRI with a patch-based CNN used Trace, ADC and T1w to differentiate acute ischemic stroke lesions from healthy tissue. The last experiment explored the performance of patch-based CNN with GAMER MRI in ranking the importance of quantitative MRI measures to distinguish two groups of lesions with different pathological characteristics and unknown quantitative MR features. Specifically, GAMER MRI was applied to assess the relative importance of the myelin water fraction (MWF), quantitative susceptibility mapping (QSM), T1 relaxometry map (qT1), and neurite density index (NDI) in distinguishing 750 juxtacortical lesions from 242 periventricular lesions in 47 MS patients. Pair-wise permutation t-tests were used to evaluate the differences between the AWs obtained for each quantitative measure. In the first experiment, we achieved a mean test AUC of 0.881 and the obtained AWs of FLAIR and the sum of AWs of Trace and ADC were 0.11 and 0.89, respectively, as expected based on previous knowledge. In the second experiment, we achieved a mean test F1 score of 0.895 and a mean AW of Trace = 0.49, of ADC = 0.28, and of T1w = 0.23, thereby confirming the findings of the first experiment. In the third experiment, MS lesion classification achieved test balanced accuracy = 0.777, sensitivity = 0.739, and specificity = 0.814. The mean AWs of T1map, MWF, NDI, and QSM were 0.29, 0.26, 0.24, and 0.22 (p < 0.001), respectively. This work demonstrates that the proposed GAMER MRI might be a useful method to assess the relative importance of MRI measures in neurological diseases with focal pathology. Moreover, the obtained AWs may in fact help to choose the best combination of MR contrasts for a specific classification problem

Intelligent monitoring and interpretation of preterm physiological signals using machine learning

Every year, more than one in ten babies are born prematurely. In Ireland of the 70000 babies delivered every year, 4500 are born too early. Premature babies are at a higher risk of complications, which may lead to both short-term and long-term adverse health outcomes. The neonatal population is especially vulnerable and a delay in the identification of medical conditions, as well as delays in the initiating the correct treatment, may be fatal. After birth, preterms are admitted to the neonatal intensive care unit (NICU), where a continuous flow of information in the form of physiological signals is available. Physiological signals can assist clinicians in decision making related to the diagnosis and treatment of various diseases. This information, however, can be highly complex, and usually requires expert analysis which may not be available at all times. The work conducted in this thesis develops a decision support systems for the intelligent monitoring of preterms in the NICU. This will allow for an accurate estimation of the current health status of the preterm neonate as well as the prediction of possible long-term complications. This thesis is comprised of three main work packages (WP), each addressing health complication of preterm on three different stages of life. At the first 12 hours of life the health status is quantified using the clinical risk index for babies (CRIB). This is followed by the assessment of the preterm’s well-being at discharge from the NICU using the clinical course score (CCS). Finally, the long-term neurodevelopmental follow-up is assessed using the Bayley III scales of development at two years. This is schematically represented in Figure 1 along with the main findings and contributions. Low blood pressure (BP) or hypotension is a recognised problem in preterm infants particularly during the first 72 hours of life. Hypotension may cause decreased cerebral perfusion, resulting in deprived oxygen delivery to the brain. Deciding when and whether to treat hypotension relies on our understanding of the relation between BP, oxygenation and brain activity. The electroencephalogram (EEG) is the most commonly used technology to assess the ‘brain health’ of a newborn. The first WP investigates the relationship between short-term dynamics in BP and EEG energy in the preterm on a large dataset of continuous multi-channel unedited EEG recordings in the context of the health status measured by the CRIB score. The obtained results indicate that a higher risk of mortality for the preterm is associated with a lower level of nonlinear interaction between EEG and BP. The level of coupling between these two systems can potentially serve as an additional source of information when deciding whether or not to intervene in the preterm. The electrocardiogram (ECG) is also routinely recorded in preterm infants. Analysis of heart rate variability (HRV) provides a non-invasive assessment of both the sympathetic and parasympathetic control of the heart rate. A novel automated objective decision support tool for the prediction of the short-term outcome (CCS) in preterm neonates who may have low BP is proposed in the second WP. Combining multiple HRV features extracted during hypotensive episodes, the classifier achieved an AUC of 0.97 for the task of short-term outcome prediction, using a leave-one-patient-out performance assessment. The developed system is based on the boosted decision tree classifier and allows for the continuous monitoring of the preterm. The proposed system is validated on a large clinically collected dataset of multimodal recordings from preterm neonates. If the correct treatment is initiated promptly after diagnosis, it can potentially improve the neurodevelopmental outcome of the preterm infant. The third WP presents a pilot study investigating the predictive capability of the early EEG recorded at discharge from the NICU with respect to the 2-year neurodevelopmental outcome using machine learning techniques. Two methods are used: 1) classical feature-based classifier, and 2) end-to-end deep learning. This is a fundamental study in this area, especially in the context of applying end-to-end learning to the preterm EEG for the problem of long-term outcome prediction. It is shown that for the available labelled dataset of 37 preterm neonates, the classical feature-based approach outperformed the end-to-end deep learning technique. A discussion of the obtained result as well as a section highlighting the possible limitations and areas that need to be investigated in the future are provided

Multimodal and multicontrast image fusion via deep generative models

Recently, it has become progressively more evident that classic diagnostic labels are unable to reliably describe the complexity and variability of several clinical phenotypes. This is particularly true for a broad range of neuropsychiatric illnesses (e.g., depression, anxiety disorders, behavioral phenotypes). Patient heterogeneity can be better described by grouping individuals into novel categories based on empirically derived sections of intersecting continua that span across and beyond traditional categorical borders. In this context, neuroimaging data carry a wealth of spatiotemporally resolved information about each patient's brain. However, they are usually heavily collapsed a priori through procedures which are not learned as part of model training, and consequently not optimized for the downstream prediction task. This is because every individual participant usually comes with multiple whole-brain 3D imaging modalities often accompanied by a deep genotypic and phenotypic characterization, hence posing formidable computational challenges. In this paper we design a deep learning architecture based on generative models rooted in a modular approach and separable convolutional blocks to a) fuse multiple 3D neuroimaging modalities on a voxel-wise level, b) convert them into informative latent embeddings through heavy dimensionality reduction, c) maintain good generalizability and minimal information loss. As proof of concept, we test our architecture on the well characterized Human Connectome Project database demonstrating that our latent embeddings can be clustered into easily separable subject strata which, in turn, map to different phenotypical information which was not included in the embedding creation process. This may be of aid in predicting disease evolution as well as drug response, hence supporting mechanistic disease understanding and empowering clinical trials

Automatic Detection of Hijaiyah Letters Pronunciation using Convolutional Neural Network Algorithm

Abstract— Speech recognition technology is used in learning to read letters in the Qur'an. This study aims to implement the CNN algorithm in recognizing the results of introducing the pronunciation of the hijaiyah letters. The pronunciation sound is extracted using the Mel-frequency cepstral coefficients (MFCC) model and then classified using a deep learning model with the CNN algorithm. This system was developed using the CRISP-DM model. Based on the results of testing 616 voice data of 28 hijaiyah letters, the best value was obtained for accuracy of 62.45%, precision of 75%, recall of 50% and f1-score of 58%