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  1. Michielli N, Acharya UR, Molinari F
    Comput Biol Med, 2019 03;106:71-81.
    PMID: 30685634 DOI: 10.1016/j.compbiomed.2019.01.013
    Automated evaluation of a subject's neurocognitive performance (NCP) is a relevant topic in neurological and clinical studies. NCP represents the mental/cognitive human capacity in performing a specific task. It is difficult to develop the study protocols as the subject's NCP changes in a known predictable way. Sleep is time-varying NCP and can be used to develop novel NCP techniques. Accurate analysis and interpretation of human sleep electroencephalographic (EEG) signals is needed for proper NCP assessment. In addition, sleep deprivation may cause prominent cognitive risks in performing many common activities such as driving or controlling a generic device; therefore, sleep scoring is a crucial part of the process. In the sleep cycle, the first stage of non-rapid eye movement (NREM) sleep or stage N1 is the transition between wakefulness and drowsiness and becomes relevant for the study of NCP. In this study, a novel cascaded recurrent neural network (RNN) architecture based on long short-term memory (LSTM) blocks, is proposed for the automated scoring of sleep stages using EEG signals derived from a single-channel. Fifty-five time and frequency-domain features were extracted from the EEG signals and fed to feature reduction algorithms to select the most relevant ones. The selected features constituted as the inputs to the LSTM networks. The cascaded architecture is composed of two LSTM RNNs: the first network performed 4-class classification (i.e. the five sleep stages with the merging of stages N1 and REM into a single stage) with a classification rate of 90.8%, and the second one obtained a recognition performance of 83.6% for 2-class classification (i.e. N1 vs REM). The overall percentage of correct classification for five sleep stages is found to be 86.7%. The objective of this work is to improve classification performance in sleep stage N1, as a first step of NCP assessment, and at the same time obtain satisfactory classification results in the other sleep stages.
  2. Meiburger KM, Acharya UR, Molinari F
    Comput Biol Med, 2018 01 01;92:210-235.
    PMID: 29247890 DOI: 10.1016/j.compbiomed.2017.11.018
    B-mode ultrasound imaging is used extensively in medicine. Hence, there is a need to have efficient segmentation tools to aid in computer-aided diagnosis, image-guided interventions, and therapy. This paper presents a comprehensive review on automated localization and segmentation techniques for B-mode ultrasound images. The paper first describes the general characteristics of B-mode ultrasound images. Then insight on the localization and segmentation of tissues is provided, both in the case in which the organ/tissue localization provides the final segmentation and in the case in which a two-step segmentation process is needed, due to the desired boundaries being too fine to locate from within the entire ultrasound frame. Subsequenly, examples of some main techniques found in literature are shown, including but not limited to shape priors, superpixel and classification, local pixel statistics, active contours, edge-tracking, dynamic programming, and data mining. Ten selected applications (abdomen/kidney, breast, cardiology, thyroid, liver, vascular, musculoskeletal, obstetrics, gynecology, prostate) are then investigated in depth, and the performances of a few specific applications are compared. In conclusion, future perspectives for B-mode based segmentation, such as the integration of RF information, the employment of higher frequency probes when possible, the focus on completely automatic algorithms, and the increase in available data are discussed.
  3. Molinari F, Raghavendra U, Gudigar A, Meiburger KM, Rajendra Acharya U
    Med Biol Eng Comput, 2018 Sep;56(9):1579-1593.
    PMID: 29473126 DOI: 10.1007/s11517-018-1792-5
    Atherosclerosis is a type of cardiovascular disease which may cause stroke. It is due to the deposition of fatty plaque in the artery walls resulting in the reduction of elasticity gradually and hence restricting the blood flow to the heart. Hence, an early prediction of carotid plaque deposition is important, as it can save lives. This paper proposes a novel data mining framework for the assessment of atherosclerosis in its early stage using ultrasound images. In this work, we are using 1353 symptomatic and 420 asymptomatic carotid plaque ultrasound images. Our proposed method classifies the symptomatic and asymptomatic carotid plaques using bidimensional empirical mode decomposition (BEMD) and entropy features. The unbalanced data samples are compensated using adaptive synthetic sampling (ADASYN), and the developed method yielded a promising accuracy of 91.43%, sensitivity of 97.26%, and specificity of 83.22% using fourteen features. Hence, the proposed method can be used as an assisting tool during the regular screening of carotid arteries in hospitals. Graphical abstract Outline for our efficient data mining framework for the characterization of symptomatic and asymptomatic carotid plaques.
  4. Acharya UR, Sree SV, Molinari F, Saba L, Nicolaides A, Suri JS
    J Clin Ultrasound, 2015 Jun;43(5):302-11.
    PMID: 24909942 DOI: 10.1002/jcu.22183
    To test a computer-aided diagnostic method for differentiating symptomatic from asymptomatic carotid B-mode ultrasonographic images.
  5. Sudarshan VK, Mookiah MR, Acharya UR, Chandran V, Molinari F, Fujita H, et al.
    Comput Biol Med, 2016 Feb 1;69:97-111.
    PMID: 26761591 DOI: 10.1016/j.compbiomed.2015.12.006
    Ultrasound is an important and low cost imaging modality used to study the internal organs of human body and blood flow through blood vessels. It uses high frequency sound waves to acquire images of internal organs. It is used to screen normal, benign and malignant tissues of various organs. Healthy and malignant tissues generate different echoes for ultrasound. Hence, it provides useful information about the potential tumor tissues that can be analyzed for diagnostic purposes before therapeutic procedures. Ultrasound images are affected with speckle noise due to an air gap between the transducer probe and the body. The challenge is to design and develop robust image preprocessing, segmentation and feature extraction algorithms to locate the tumor region and to extract subtle information from isolated tumor region for diagnosis. This information can be revealed using a scale space technique such as the Discrete Wavelet Transform (DWT). It decomposes an image into images at different scales using low pass and high pass filters. These filters help to identify the detail or sudden changes in intensity in the image. These changes are reflected in the wavelet coefficients. Various texture, statistical and image based features can be extracted from these coefficients. The extracted features are subjected to statistical analysis to identify the significant features to discriminate normal and malignant ultrasound images using supervised classifiers. This paper presents a review of wavelet techniques used for preprocessing, segmentation and feature extraction of breast, thyroid, ovarian and prostate cancer using ultrasound images.
  6. Faust O, Acharya UR, Sudarshan VK, Tan RS, Yeong CH, Molinari F, et al.
    Phys Med, 2017 Jan;33:1-15.
    PMID: 28010920 DOI: 10.1016/j.ejmp.2016.12.005
    The diagnosis of Coronary Artery Disease (CAD), Myocardial Infarction (MI) and carotid atherosclerosis is of paramount importance, as these cardiovascular diseases may cause medical complications and large number of death. Ultrasound (US) is a widely used imaging modality, as it captures moving images and image features correlate well with results obtained from other imaging methods. Furthermore, US does not use ionizing radiation and it is economical when compared to other imaging modalities. However, reading US images takes time and the relationship between image and tissue composition is complex. Therefore, the diagnostic accuracy depends on both time taken to read the images and experience of the screening practitioner. Computer support tools can reduce the inter-operator variability with lower subject specific expertise, when appropriate processing methods are used. In the current review, we analysed automatic detection methods for the diagnosis of CAD, MI and carotid atherosclerosis based on thoracic and Intravascular Ultrasound (IVUS). We found that IVUS is more often used than thoracic US for CAD. But for MI and carotid atherosclerosis IVUS is still in the experimental stage. Furthermore, thoracic US is more often used than IVUS for computer aided diagnosis systems.
  7. Raghavendra U, Rajendra Acharya U, Gudigar A, Hong Tan J, Fujita H, Hagiwara Y, et al.
    Ultrasonics, 2017 05;77:110-120.
    PMID: 28219805 DOI: 10.1016/j.ultras.2017.02.003
    Thyroid is a small gland situated at the anterior side of the neck and one of the largest glands of the endocrine system. The abrupt cell growth or malignancy in the thyroid gland may cause thyroid cancer. Ultrasound images distinctly represent benign and malignant lesions, but accuracy may be poor due to subjective interpretation. Computer Aided Diagnosis (CAD) can minimize the errors created due to subjective interpretation and assists to make fast accurate diagnosis. In this work, fusion of Spatial Gray Level Dependence Features (SGLDF) and fractal textures are used to decipher the intrinsic structure of benign and malignant thyroid lesions. These features are subjected to graph based Marginal Fisher Analysis (MFA) to reduce the number of features. The reduced features are subjected to various ranking methods and classifiers. We have achieved an average accuracy, sensitivity and specificity of 97.52%, 90.32% and 98.57% respectively using Support Vector Machine (SVM) classifier. The achieved maximum Area Under Curve (AUC) is 0.9445. Finally, Thyroid Clinical Risk Index (TCRI) a single number is developed using two MFA features to discriminate the two classes. This prototype system is ready to be tested with huge diverse database.
  8. Acharya UR, Molinari F, Sree SV, Swapna G, Saba L, Guerriero S, et al.
    Technol Cancer Res Treat, 2015 Jun;14(3):251-61.
    PMID: 25230716 DOI: 10.1177/1533034614547445
    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given.
  9. Raghavendra U, Gudigar A, Maithri M, Gertych A, Meiburger KM, Yeong CH, et al.
    Comput Biol Med, 2018 04 01;95:55-62.
    PMID: 29455080 DOI: 10.1016/j.compbiomed.2018.02.002
    Ultrasound imaging is one of the most common visualizing tools used by radiologists to identify the location of thyroid nodules. However, visual assessment of nodules is difficult and often affected by inter- and intra-observer variabilities. Thus, a computer-aided diagnosis (CAD) system can be helpful to cross-verify the severity of nodules. This paper proposes a new CAD system to characterize thyroid nodules using optimized multi-level elongated quinary patterns. In this study, higher order spectral (HOS) entropy features extracted from these patterns appropriately distinguished benign and malignant nodules under particle swarm optimization (PSO) and support vector machine (SVM) frameworks. Our CAD algorithm achieved a maximum accuracy of 97.71% and 97.01% in private and public datasets respectively. The evaluation of this CAD system on both private and public datasets confirmed its effectiveness as a secondary tool in assisting radiological findings.
  10. Loh HW, Ooi CP, Oh SL, Barua PD, Tan YR, Molinari F, et al.
    Comput Methods Programs Biomed, 2023 Nov;241:107775.
    PMID: 37651817 DOI: 10.1016/j.cmpb.2023.107775
    BACKGROUND AND OBJECTIVE: Attention Deficit Hyperactivity problem (ADHD) is a common neurodevelopment problem in children and adolescents that can lead to long-term challenges in life outcomes if left untreated. Also, ADHD is frequently associated with Conduct Disorder (CD), and multiple research have found similarities in clinical signs and behavioral symptoms between both diseases, making differentiation between ADHD, ADHD comorbid with CD (ADHD+CD), and CD a subjective diagnosis. Therefore, the goal of this pilot study is to create the first explainable deep learning (DL) model for objective ECG-based ADHD/CD diagnosis as having an objective biomarker may improve diagnostic accuracy.

    METHODS: The dataset used in this study consist of ECG data collected from 45 ADHD, 62 ADHD+CD, and 16 CD patients at the Child Guidance Clinic in Singapore. The ECG data were segmented into 2 s epochs and directly used to train our 1-dimensional (1D) convolutional neural network (CNN) model.

    RESULTS: The proposed model yielded 96.04% classification accuracy, 96.26% precision, 95.99% sensitivity, and 96.11% F1-score. The Gradient-weighted class activation mapping (Grad-CAM) function was also used to highlight the important ECG characteristics at specific time points that most impact the classification score.

    CONCLUSION: In addition to achieving model performance results with our suggested DL method, Grad-CAM's implementation also offers vital temporal data that clinicians and other mental healthcare professionals can use to make wise medical judgments. We hope that by conducting this pilot study, we will be able to encourage larger-scale research with a larger biosignal dataset. Hence allowing biosignal-based computer-aided diagnostic (CAD) tools to be implemented in healthcare and ambulatory settings, as ECG can be easily obtained via wearable devices such as smartwatches.

  11. Acharya UR, Raghavendra U, Koh JEW, Meiburger KM, Ciaccio EJ, Hagiwara Y, et al.
    Comput Methods Programs Biomed, 2018 Nov;166:91-98.
    PMID: 30415722 DOI: 10.1016/j.cmpb.2018.10.006
    BACKGROUND AND OBJECTIVE: Liver fibrosis is a type of chronic liver injury that is characterized by an excessive deposition of extracellular matrix protein. Early detection of liver fibrosis may prevent further growth toward liver cirrhosis and hepatocellular carcinoma. In the past, the only method to assess liver fibrosis was through biopsy, but this examination is invasive, expensive, prone to sampling errors, and may cause complications such as bleeding. Ultrasound-based elastography is a promising tool to measure tissue elasticity in real time; however, this technology requires an upgrade of the ultrasound system and software. In this study, a novel computer-aided diagnosis tool is proposed to automatically detect and classify the various stages of liver fibrosis based upon conventional B-mode ultrasound images.

    METHODS: The proposed method uses a 2D contourlet transform and a set of texture features that are efficiently extracted from the transformed image. Then, the combination of a kernel discriminant analysis (KDA)-based feature reduction technique and analysis of variance (ANOVA)-based feature ranking technique was used, and the images were then classified into various stages of liver fibrosis.

    RESULTS: Our 2D contourlet transform and texture feature analysis approach achieved a 91.46% accuracy using only four features input to the probabilistic neural network classifier, to classify the five stages of liver fibrosis. It also achieved a 92.16% sensitivity and 88.92% specificity for the same model. The evaluation was done on a database of 762 ultrasound images belonging to five different stages of liver fibrosis.

    CONCLUSIONS: The findings suggest that the proposed method can be useful to automatically detect and classify liver fibrosis, which would greatly assist clinicians in making an accurate diagnosis.

  12. Rajendra Acharya U, Meiburger KM, Wei Koh JE, Vicnesh J, Ciaccio EJ, Shu Lih O, et al.
    Artif Intell Med, 2019 09;100:101724.
    PMID: 31607348 DOI: 10.1016/j.artmed.2019.101724
    Cardiovascular diseases are the primary cause of death globally. These are often associated with atherosclerosis. This inflammation process triggers important variations in the coronary arteries (CA) and can lead to coronary artery disease (CAD). The presence of CA calcification (CAC) has recently been shown to be a strong predictor of CAD. In this clinical setting, computed tomography angiography (CTA) has begun to play a crucial role as a non-intrusive imaging method to characterize and study CA plaques. Herein, we describe an automated algorithm to classify plaque as either normal, calcified, or non-calcified using 2646 CTA images acquired from 73 patients. The automated technique is based on various features that are extracted from the Gabor transform of the acquired CTA images. Specifically, seven features are extracted from the Gabor coefficients : energy, and Kapur, Max, Rényi, Shannon, Vajda, and Yager entropies. The features were then ordered based on the F-value and input to numerous classification methods to achieve the best classification accuracy with the least number of features. Moreover, two well-known feature reduction techniques were employed, and the features acquired were also ranked according to F-value and input to several classifiers. The best classification results were obtained using all computed features without the employment of feature reduction, using a probabilistic neural network. An accuracy, positive predictive value, sensitivity, and specificity of 89.09%, 91.70%, 91.83% and 83.70% was obtained, respectively. Based on these results, it is evident that the technique can be helpful in the automated classification of plaques present in CTA images, and may become an important tool to reduce procedural costs and patient radiation dose. This could also aid clinicians in plaque diagnostics.
  13. Gudigar A, Kadri NA, Raghavendra U, Samanth J, Maithri M, Inamdar MA, et al.
    Comput Biol Med, 2024 Apr;172:108207.
    PMID: 38489986 DOI: 10.1016/j.compbiomed.2024.108207
    Artificial Intelligence (AI) techniques are increasingly used in computer-aided diagnostic tools in medicine. These techniques can also help to identify Hypertension (HTN) in its early stage, as it is a global health issue. Automated HTN detection uses socio-demographic, clinical data, and physiological signals. Additionally, signs of secondary HTN can also be identified using various imaging modalities. This systematic review examines related work on automated HTN detection. We identify datasets, techniques, and classifiers used to develop AI models from clinical data, physiological signals, and fused data (a combination of both). Image-based models for assessing secondary HTN are also reviewed. The majority of the studies have primarily utilized single-modality approaches, such as biological signals (e.g., electrocardiography, photoplethysmography), and medical imaging (e.g., magnetic resonance angiography, ultrasound). Surprisingly, only a small portion of the studies (22 out of 122) utilized a multi-modal fusion approach combining data from different sources. Even fewer investigated integrating clinical data, physiological signals, and medical imaging to understand the intricate relationships between these factors. Future research directions are discussed that could build better healthcare systems for early HTN detection through more integrated modeling of multi-modal data sources.
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