IRON MAN interacts with BRUTUS to maintain iron homeostasis in Arabidopsis.

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.

Fe deficiency-induced ethylene synthesis confers resistance to Botrytis cinerea.

Although iron (Fe) deficiency is an adverse condition to growth and development of plants, it increases the resistance to pathogens. How Fe deficiency induces the resistance to pathogens is still unclear. Here, we reveal that the inoculation of Botrytis cinerea activates the Fe deficiency response of plants, which further induces ethylene synthesis and then resistance to B. cinerea. FIT and bHLH Ib are a pair of bHLH transcription factors, which control the Fe deficiency response. Both the Fe deficiency-induced ethylene synthesis and resistance are blocked in fit-2 and bhlh4x-1 (a quadruple mutant for four bHLH Ib members). SAM1 and SAM2, two ethylene synthesis-associated genes, are induced by Fe deficiency in a FIT-bHLH Ib-dependent manner. Moreover, SAM1 and SAM2 are required for the increased ethylene and resistance to B. cinerea under Fe-deficient conditions. Our findings suggest that the FIT-bHLH Ib module activates the expression of SAM1 and SAM2, thereby inducing ethylene synthesis and resistance to B. cinerea. This study uncovers that Fe signaling also functions as a part of the plant immune system against pathogens.

Automated Age-Related Macular Degeneration Detector on Optical Coherence Tomography Images Using Slice-Sum Local Binary Patterns and Support Vector Machine.

Artificial intelligence has revolutionised smart medicine, resulting in enhanced medical care. This study presents an automated detector chip for age-related macular degeneration (AMD) using a support vector machine (SVM) and three-dimensional (3D) optical coherence tomography (OCT) volume. The aim is to assist ophthalmologists by reducing the time-consuming AMD medical examination. Using the property of 3D OCT volume, a modified feature vector connected method called slice-sum is proposed, reducing computational complexity while maintaining high detection accuracy. Compared to previous methods, this method significantly reduces computational complexity by at least a hundredfold. Image adjustment and noise removal steps are excluded for classification accuracy, and the feature extraction algorithm of local binary patterns is determined based on hardware consumption considerations. Through optimisation of the feature vector connection method after feature extraction, the computational complexity of SVM detection is significantly reduced, making it applicable to similar 3D datasets. Additionally, the design supports model replacement, allowing users to train and update classification models as needed. Using TSMC 40 nm CMOS technology, the proposed detector achieves a core area of 0.12 mm2 while demonstrating a classification throughput of 8.87 decisions/s at a maximum operating frequency of 454.54 MHz. The detector achieves a final testing classification accuracy of 92.31%.

Emotion Self-Regulation in Neurotic Students: A Pilot Mindfulness-Based Intervention to Assess Its Effectiveness through Brain Signals and Behavioral Data.

Neuroticism has recently received increased attention in the psychology field due to the finding of high implications of neuroticism on an individual's life and broader public health. This study aims to investigate the effect of a brief 6-week breathing-based mindfulness intervention (BMI) on undergraduate neurotic students' emotion regulation. We acquired data of their psychological states, physiological changes, and electroencephalogram (EEG), before and after BMI, in resting states and tasks. Through behavioral analysis, we found the students' anxiety and stress levels significantly reduced after BMI, with p-values of 0.013 and 0.027, respectively. Furthermore, a significant difference between students in emotion regulation strategy, that is, suppression, was also shown. The EEG analysis demonstrated significant differences between students before and after MI in resting states and tasks. Fp1 and O2 channels were identified as the most significant channels in evaluating the effect of BMI. The potential of these channels for classifying (single-channel-based) before and after BMI conditions during eyes-opened and eyes-closed baseline trials were displayed by a good performance in terms of accuracy (~77%), sensitivity (76-80%), specificity (73-77%), and area-under-the-curve (AUC) (0.66-0.8) obtained by k-nearest neighbor (KNN) and support vector machine (SVM) algorithms. Mindfulness can thus improve the self-regulation of the emotional state of neurotic students based on the psychometric and electrophysiological analyses conducted in this study.

WPO-Net: Windowed Pose Optimization Network for Monocular Visual Odometry Estimation.

Visual odometry is the process of estimating incremental localization of the camera in 3-dimensional space for autonomous driving. There have been new learning-based methods which do not require camera calibration and are robust to external noise. In this work, a new method that do not require camera calibration called the "windowed pose optimization network" is proposed to estimate the 6 degrees of freedom pose of a monocular camera. The architecture of the proposed network is based on supervised learning-based methods with feature encoder and pose regressor that takes multiple consecutive two grayscale image stacks at each step for training and enforces the composite pose constraints. The KITTI dataset is used to evaluate the performance of the proposed method. The proposed method yielded rotational error of 3.12 deg/100 m, and the training time is 41.32 ms, while inference time is 7.87 ms. Experiments demonstrate the competitive performance of the proposed method to other state-of-the-art related works which shows the novelty of the proposed technique.

Automatic Polyp Segmentation in Colonoscopy Images Using a Modified Deep Convolutional Encoder-Decoder Architecture.

Colorectal cancer has become the third most commonly diagnosed form of cancer, and has the second highest fatality rate of cancers worldwide. Currently, optical colonoscopy is the preferred tool of choice for the diagnosis of polyps and to avert colorectal cancer. Colon screening is time-consuming and highly operator dependent. In view of this, a computer-aided diagnosis (CAD) method needs to be developed for the automatic segmentation of polyps in colonoscopy images. This paper proposes a modified SegNet Visual Geometry Group-19 (VGG-19), a form of convolutional neural network, as a CAD method for polyp segmentation. The modifications include skip connections, 5 × 5 convolutional filters, and the concatenation of four dilated convolutions applied in parallel form. The CVC-ClinicDB, CVC-ColonDB, and ETIS-LaribPolypDB databases were used to evaluate the model, and it was found that our proposed polyp segmentation model achieved an accuracy, sensitivity, specificity, precision, mean intersection over union, and dice coefficient of 96.06%, 94.55%, 97.56%, 97.48%, 92.3%, and 95.99%, respectively. These results indicate that our model performs as well as or better than previous schemes in the literature. We believe that this study will offer benefits in terms of the future development of CAD tools for polyp segmentation for colorectal cancer diagnosis and management. In the future, we intend to embed our proposed network into a medical capsule robot for practical usage and try it in a hospital setting with clinicians.

Development of Rheumatoid Arthritis Classification from Electronic Image Sensor Using Ensemble Method.

Rheumatoid arthritis (RA) is an autoimmune illness that impacts the musculoskeletal system by causing chronic, inflammatory, and systemic effects. The disease often becomes progressive and reduces physical function, causes suffering, fatigue, and articular damage. Over a long period of time, RA causes harm to the bone and cartilage of the joints, weakens the joints' muscles and tendons, eventually causing joint destruction. Sensors such as accelerometer, wearable sensors, and thermal infrared camera sensor are widely used to gather data for RA. In this paper, the classification of medical disorders based on RA and orthopaedics datasets using Ensemble methods are discussed. The RA dataset was gathered from the analysis of white blood cell classification using features extracted from the image of lymphocytes acquired from a digital microscope with an electronic image sensor. The orthopaedic dataset is a benchmark dataset for this study, as it posed a similar classification problem with several numerical features. Three ensemble algorithms such as bagging, Adaboost, and random subspace were used in the study. These ensemble classifiers use k-NN (K-nearest neighbours) and Random forest (RF) as the base learners of the ensemble classifiers. The data classification is accessed using holdout and 10-fold cross-validation evaluation methods. The assessment was based on set of performance measures such as precision, recall, F-measure, and receiver operating characteristic (ROC) curve. The performance was also measured based on the comparison of the overall classification accuracy rate between different ensembles classifiers and the base learners. Overall, it was found that for Dataset 1, random subspace classifier with k-NN shows the best results in terms of overall accuracy rate of 97.50% and for Dataset 2, bagging-RF shows the highest overall accuracy rate of 94.84% over different ensemble classifiers. The findings indicate that the efficiency of the base classifiers with ensemble classifier have substantially improved.

Pulse waveform analysis on temporal changes in ocular blood flow due to caffeine intake: a comparative study between habitual and non-habitual groups.

PURPOSE: To evaluate and compare the temporal changes in pulse waveform parameters of ocular blood flow (OBF) between non-habitual and habitual groups due to caffeine intake. METHOD: This study was conducted on 19 healthy subjects (non-habitual 8; habitual 11), non-smoking and between 21 and 30 years of age. Using laser speckle flowgraphy (LSFG), three areas of optical nerve head were analyzed which are vessel, tissue, and overall, each with ten pulse waveform parameters, namely mean blur rate (MBR), fluctuation, skew, blowout score (BOS), blowout time (BOT), rising rate, falling rate, flow acceleration index (FAI), acceleration time index (ATI), and resistive index (RI). Two-way mixed ANOVA was used to determine the difference between every two groups where p < 0.05 is considered significant. RESULT: There were significant differences between the two groups in several ocular pulse waveform parameters, namely MBR (overall, vessel, tissue), BOT (overall), rising rate (overall), and falling rate (vessel), all with p < 0.05. In addition, the ocular pulse waveform parameters, i.e., MBR (overall), skew (tissue), and BOT (tissue) showed significant temporal changes within the non-habitual group, but not within the habitual group. The temporal changes in parameters MBR (vessel, tissue), skew (overall, vessel), BOT (overall, vessel), rising rate (overall), falling rate (overall, vessel), and FAI (tissue) were significant for both groups (habitual and non-habitual) in response to caffeine intake. CONCLUSION: The experiment results demonstrated caffeine does modulate OBF significantly and response differently in non-habitual and habitual groups. Among all ten parameters, MBR and BOT were identified as the suitable biomarkers to differentiate between the two groups.

Detection of Low Resilience Using Data-Driven Effective Connectivity Measures.

Conventional thresholding techniques for graph theory analysis, such as absolute, proportional and mean degree, have often been used in characterizing human brain networks under different mental disorders, such as mental stress. However, these approaches may not always be reliable as conventional thresholding approaches are subjected to human biases. Using a mental resilience study, we investigate if data-driven thresholding techniques such as Global Cost Efficiency (GCE-abs) and Orthogonal Minimum Spanning Trees (OMSTs) could provide equivalent results, whilst eliminating human biases. We implemented Phase Slope Index (PSI) to compute effective brain connectivity, and applied data-driven thresholding approaches to filter the brain networks in order to identify key features of low resilience within a cohort of healthy individuals. Our dataset encompassed resting-state EEG recordings gathered from a total of 36 participants (31 females and 5 males). Relevant features were extracted to train and validate a classifier model (Support Vector Machine, SVM). The detection of low stress resilience among healthy individuals using the SVM model scores an accuracy of 80.6% with GCE-abs, and 75% with OMSTs, respectively.

Classification of Prefrontal Cortex Activity Based on Functional Near-Infrared Spectroscopy Data upon Olfactory Stimulation.

The sense of smell is one of the most important organs in humans, and olfactory imaging can detect signals in the anterior orbital frontal lobe. This study assessed olfactory stimuli using support vector machines (SVMs) with signals from functional near-infrared spectroscopy (fNIRS) data obtained from the prefrontal cortex. These data included odor stimuli and air state, which triggered the hemodynamic response function (HRF), determined from variations in oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) levels; photoplethysmography (PPG) of two wavelengths (raw optical red and near-infrared data); and the ratios of data from two optical datasets. We adopted three SVM kernel functions (i.e., linear, quadratic, and cubic) to analyze signals and compare their performance with the HRF and PPG signals. The results revealed that oxyHb yielded the most efficient single-signal data with a quadratic kernel function, and a combination of HRF and PPG signals yielded the most efficient multi-signal data with the cubic function. Our results revealed superior SVM analysis of HRFs for classifying odor and air status using fNIRS data during olfaction in humans. Furthermore, the olfactory stimulation can be accurately classified by using quadratic and cubic kernel functions in SVM, even for an individual participant data set.

Automatic colonic polyp detection using integration of modified deep residual convolutional neural network and ensemble learning approaches.

BACKGROUND AND OBJECTIVE: The increased incidence of colorectal cancer (CRC) and its mortality rate have attracted interest in the use of artificial intelligence (AI) based computer-aided diagnosis (CAD) tools to detect polyps at an early stage. Although these CAD tools have thus far achieved a good accuracy level to detect polyps, they still have room to improve further (e.g. sensitivity). Therefore, a new CAD tool is developed in this study to detect colonic polyps accurately. METHODS: In this paper, we propose a novel approach to distinguish colonic polyps by integrating several techniques, including a modified deep residual network, principal component analysis and AdaBoost ensemble learning. A powerful deep residual network architecture, ResNet-50, was investigated to reduce the computational time by altering its architecture. To keep the interference to a minimum, median filter, image thresholding, contrast enhancement, and normalisation techniques were exploited on the endoscopic images to train the classification model. Three publicly available datasets, i.e., Kvasir, ETIS-LaribPolypDB, and CVC-ClinicDB, were merged to train the model, which included images with and without polyps. RESULTS: The proposed approach trained with a combination of three datasets achieved Matthews Correlation Coefficient (MCC) of 0.9819 with accuracy, sensitivity, precision, and specificity of 99.10%, 98.82%, 99.37%, and 99.38%, respectively. CONCLUSIONS: These results show that our method could repeatedly classify endoscopic images automatically and could be used to effectively develop computer-aided diagnostic tools for early CRC detection.

Detection of Emotional Sensitivity Using fNIRS Based Dynamic Functional Connectivity.

In this study, we proposed an analytical framework to identify dynamic task-based functional connectivity (FC) features as new biomarkers of emotional sensitivity in nursing students, by using a combination of unsupervised and supervised machine learning techniques. The dynamic FC was measured by functional Near-Infrared Spectroscopy (fNIRS), and computed using a sliding window correlation (SWC) analysis. A k -means clustering technique was applied to derive four recurring connectivity states. The states were characterized by both graph theory and semi-metric analysis. Occurrence probability and state transition were extracted as dynamic FC network features, and a Random Forest (RF) classifier was implemented to detect emotional sensitivity. The proposed method was trialled on 39 nursing students and 19 registered nurses during decision-making, where we assumed registered nurses have developed strategies to cope with emotional sensitivity. Emotional stimuli were selected from International Affective Digitized Sound System (IADS) database. Experiment results showed that registered nurses demonstrated single dominant connectivity state of task-relevance, while nursing students displayed in two states and had higher level of task-irrelevant state connectivity. The results also showed that students were more susceptive to emotional stimuli, and the derived dynamic FC features provided a stronger discriminating power than heart rate variability (accuracy of 81.65% vs 71.03%) as biomarkers of emotional sensitivity. This work forms the first study to demonstrate the stability of fNIRS based dynamic FC states as a biomarker. In conclusion, the results support that the state distribution of dynamic FC could help reveal the differentiating factors between the nursing students and registered nurses during decision making, and it is anticipated that the biomarkers might be used as indicators when developing professional training related to emotional sensitivity.

Optimizing Mental Workload Estimation by Detecting Baseline State Using Vector Phase Analysis Approach.

Improper baseline return from the previous task-evoked hemodynamic response (HR) can contribute to a large variation in the subsequent HR, affecting the estimation of mental workload in brain-computer interface systems. In this study, we proposed a method using vector phase analysis to detect the baseline state as being optimal or suboptimal. We hypothesize that selecting neuronal-related HR as observed in the optimal-baseline blocks can lead to an improvement in estimating mental workload. Oxygenated and deoxygenated hemoglobin concentration changes were integrated as parts of the vector phase. The proposed method was applied to a block-design functional near-infrared spectroscopy dataset (total blocks = 1384), measured on 24 subjects performing multiple difficulty levels of mental arithmetic task. Significant differences in hemodynamic signal change were observed between the optimal- and suboptimal-baseline blocks detected using the proposed method. This supports the effectiveness of the proposed method in detecting baseline state for better estimation of mental workload. The results further highlight the need of customized recovery duration. In short, the proposed method offers a practical approach to detect task-evoked signals, without the need of extra probes.

Automated Thresholding Method for fNIRS-Based Functional Connectivity Analysis: Validation With a Case Study on Alzheimer's Disease.

While functional integration has been suggested to reflect brain health, non-standardized network thresholding methods complicate network interpretation. We propose a new method to analyze functional near-infrared spectroscopy-based functional connectivity (fNIRS-FC). In this study, we employed wavelet analysis for motion correction and orthogonal minimal spanning trees (OMSTs) to derive the brain connectivity. The proposed method was applied to an Alzheimer's disease (AD) dataset and was compared with a number of well-known thresholding techniques. The results demonstrated that the proposed method outperformed the benchmarks in filtering cost-effective networks and in differentiation between patients with mild AD and healthy controls. The results also supported the proposed method as a feasible technique to analyze fNIRS-FC, especially with cost-efficiency, assortativity and laterality as a set of effective features for the diagnosis of AD.

fNIRS-based functional connectivity estimation using semi-metric analysis to study decision making by nursing students and registered nurses.

This study aims to investigate the generalizability of the semi-metric analysis of the functional connectivity (FC) for functional near-infrared spectroscopy (fNIRS) by applying it to detect the dichotomy in differential FC under affective and neutral emotional states in nursing students and registered nurses during decision making. The proposed method employs wavelet transform coherence to construct FC networks and explores semi-metric analysis to extract network redundancy features, which has not been considered in conventional fNIRS-based FC analyses. The trials of the proposed method were performed on 19 nursing students and 19 registered nurses via a decision-making task under different emotional states induced by affective and neutral emotional stimuli. The cognitive activities were recorded using fNIRS, and the emotional stimuli were adopted from the International Affective Digitized Sound System (IADS). The induction of emotional effects was validated by heart rate variability (HRV) analysis. The experimental results by the proposed method showed significant difference (FDR-adjusted p = 0.004) in the nursing students' cognitive FC network under the two different emotional conditions, and the semi-metric percentage (SMP) of the right prefrontal cortex (PFC) was found to be significantly higher than the left PFC (FDR-adjusted p = 0.036). The benchmark method (a typical weighted graph theory analysis) gave no significant results. In essence, the results support that the semi-metric analysis can be generalized and extended to fNIRS-based functional connectivity estimation.

A Unified Analytical Framework With Multiple fNIRS Features for Mental Workload Assessment in the Prefrontal Cortex.

Knowing the actual level of mental workload is important to ensure the efficacy of brain-computer interface (BCI) based cognitive training. Extracting signals from limited area of a brain region might not reveal the actual information. In this study, a functional near-infrared spectroscopy (fNIRS) device equipped with multi-channel and multi-distance measurement capability was employed for the development of an analytical framework to assess mental workload in the prefrontal cortex (PFC). In addition to the conventional features, e.g. hemodynamic slope, we introduced a new feature - deep contribution ratio which is the proportion of cerebral hemodynamics to the fNIRS signals. Multiple sets of features were examined by a simple logical operator to suppress the false detection rate in identifying the activated channels. Using the number of activated channels as input to a linear support vector machine (SVM), the performance of the proposed analytical framework was assessed in classifying three levels of mental workload. The best set of features involves the combination of hemodynamic slope and deep contribution ratio, where the identified number of activated channels returned an average accuracy of 80.6% in predicting mental workload, compared to a single conventional feature (accuracy: 59.8%). This suggests the feasibility of the proposed analytical framework with multiple features as a means towards a more accurate assessment of mental workload in fNIRS-based BCI applications.

Assessing Neural Compensation With Visuospatial Working Memory Load Using Near-Infrared Imaging.

Alzheimer's disease is characterized by the progressive deterioration of cognitive abilities particularly working memory while mild cognitive impairment (MCI) represents its prodrome. It is generally believed that neural compensation is intact in MCI but absent in Alzheimer's disease. This study investigated the effects of increasing task load as a means to induce neural compensation through a novel visual working memory (VSWM) task using functional near-infrared spectroscopy (fNIRS). The bilateral prefrontal cortex (PFC) was explored due to its relevance in VSWM and neural compensation. A total of 31 healthy controls (HC), 12 patients with MCI and 18 patients with mild Alzheimer's disease (mAD) were recruited. Although all groups showed sensitivity in terms of behavioral performance (i.e. score) towards increasing task load (level 1 to 3), only in MCI load effect on cortical response (as measured by fNIRS) was significant. At lower task load, bilateral PFC activation did not differ between MCI and HC. Neural compensation in the form of hyperactivation was only noticeable in MCI with a moderate task load. Lack of hyperactivation in mAD, coupled with significantly poorer task performance across task loads, suggested the inability to compensate due to a greater degree of neurodegeneration. Our findings provided an insight into the interaction of cognitive load theory and neural compensatory mechanisms. The experiment results demonstrated the feasibility of inducing neural compensation with the proposed VSWM task at the right amount of cognitive load. This may provide a promising avenue to develop an effective cognitive training and rehabilitation for dementia population.

Forward genetic screen for auxin-deficient mutants by cytokinin.

Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis.

Parapapillary atrophy and optic disc region assessment (PANDORA): retinal imaging tool for assessment of the optic disc and parapapillary atrophy.

We describe a computer-aided measuring tool, named parapapillary atrophy and optic disc region assessment (PANDORA), for automated detection and quantification of both the parapapillary atrophy (PPA) and the optic disc (OD) regions in two-dimensional color retinal fundus images. The OD region is segmented using a combination of edge detection and ellipse fitting methods. The PPA region is identified by the presence of bright pixels in the temporal zone of the OD, and it is segmented using a sequence of techniques, including a modified Chan-Vese approach, thresholding, scanning filter, and multiseed region growing. PANDORA has been tested with 133 color retinal images (82 with PPA; 51 without PPA) drawn randomly from the Lothian Birth Cohort (LBC) database, together with a "ground truth" estimate from an ophthalmologist. The PPA detection rate is 89.47% with a sensitivity of 0.83 and a specificity of 1. The mean accuracy in defining the OD region is 81.31% (SD=10.45) when PPA is present and 95.32% (SD=4.36) when PPA is absent. The mean accuracy in defining the PPA region is 73.57% (SD=11.62). PANDORA demonstrates for the first time how to quantify the OD and PPA regions using two-dimensional fundus images, enabling ophthalmologists to study ocular diseases related to PPA using a standard fundus camera.

Quantification of parapapillary atrophy and optic disc.

PURPOSE: A computer-aided measuring tool was devised to automatically detect and quantify both the parapapillary atrophy (PPA) and the optic disc (OD) regions in two-dimensional color fundus images of the retina. METHODS: The OD region was segmented using the Chan-Vese model with a shape restraint. This region was then removed from the image (OD+PPA), which was cropped in a modified Chan-Vese approach, producing a first-order estimation of the PPA region. Its boundary is subsequently refined by using thresholding, a scanning filter, and multiseed region-growing methods. Dual channels (blue and red) in the red-green-blue space are used to minimize the interference effects of blood vessels and artifacts. RESULTS: The software was tested on 94 randomly selected images of eyes with PPA from 66 subjects of a well-characterized cohort database. Our proposed algorithm achieved a mean accuracy level of 93.8% (SD 5.26) and 94.0% (SD 5.88) in estimating the size of the PPA and OD respectively, compared with the ground estimate defined by an ophthalmologist. In terms of correlation between the data of the ground estimate and our estimation, we obtained a correlation coefficient of 0.98 for both the PPA and the OD. CONCLUSIONS: This software offers a means of quantifying the size of PPA on two-dimensional fundus images for the first time. The proposed algorithm is capable of detecting and quantifying PPA and OD regions repeatedly, with a mean accuracy of >93%, and could also provide additional information, such as the transverse and conjugate diameter of OD, which may be useful in eye-screening.