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Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health—increased Nε-carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health—increased glucosepane; and impaired renal health—increased BCAAs and decreased Nε-(γ-glutamyl)lysine. Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively. In 2-step analysis, algorithms combining subject age, BMI, and urinary Nε-fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% (cf. random selection 33%). From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 – 7, 26 – 28, and 34 – 79, respectively. We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health. Other information Published in: Oxidative Medicine and Cellular Longevity License: http://creativecommons.org/licenses/by/4.0 See article on publisher's website: http://dx.doi.org/10.1155/2019/4851323

Background Clinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD. Methods Thirty-eight children with ASD (29 male, 9 female; age 7.6 ± 2.0 years) and 31 age-matched healthy controls (23 males, 8 females; 8.6 ± 2.0 years) were recruited for this study. Plasma protein glycation, oxidation, and nitration adducts and amino acid metabolome in plasma and urine were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning methods were then employed to explore and optimize combinations of analyte data for ASD diagnosis. Results We found that children with ASD had increased advanced glycation endproducts (AGEs), Nε-carboxymethyl-lysine (CML) and Nω-carboxymethylarginine (CMA), and increased oxidation damage marker, dityrosine (DT), in plasma protein, with respect to healthy controls. We also found that children with ASD had increased CMA free adduct in plasma ultrafiltrate and increased urinary excretion of oxidation free adducts, alpha-aminoadipic semialdehyde and glutamic semialdehyde. From study of renal handling of amino acids, we found that children with ASD had decreased renal clearance of arginine and CMA with respect to healthy controls. Algorithms to discriminate between ASD and healthy controls gave strong diagnostic performance with features: plasma protein AGEs—CML, CMA—and 3-deoxyglucosone-derived hydroimidazolone, and oxidative damage marker, DT. The sensitivity, specificity, and receiver operating characteristic area-under-the-curve were 92%, 84%, and 0.94, respectively. Conclusions Changes in plasma AGEs were likely indicative of dysfunctional metabolism of dicarbonyl metabolite precursors of AGEs, glyoxal and 3-deoxyglucosone. DT is formed enzymatically by dual oxidase (DUOX); selective increase of DT as an oxidative damage marker implicates increased DUOX activity in ASD possibly linked to impaired gut mucosal immunity. Decreased renal clearance of arginine and CMA in ASD is indicative of increased arginine transporter activity which may be a surrogate marker of disturbance of neuronal availability of amino acids. Data driven combination of these biomarkers perturbed by proteotoxic stress, plasma protein AGEs and DT, gave diagnostic algorithms of high sensitivity and specificity for ASD. Electronic supplementary material The online version of this article (10.1186/s13229-017-0183-3) contains supplementary material, which is available to authorized users.

The ability to record and analyse electrical behaviour across the heart using optical and electrode mapping has revolutionised cardiac research. However, wider uptake of these technologies is constrained by the lack of multi-functional and robustly characterised analysis and mapping software. We present ElectroMap, an adaptable, high-throughput, open-source software for processing, analysis and mapping of complex electrophysiology datasets from diverse experimental models and acquisition modalities. Key innovation is development of standalone module for quantification of conduction velocity, employing multiple methodologies, currently not widely available to researchers. ElectroMap has also been designed to support multiple methodologies for accurate calculation of activation, repolarisation, arrhythmia detection, calcium handling and beat-to-beat heterogeneity. ElectroMap implements automated signal segmentation, ensemble averaging and integrates optogenetic approaches. Here we employ ElectroMap for analysis, mapping and detection of pro-arrhythmic phenomena in silico, in cellulo, animal model and in vivo patient datasets. We anticipate that ElectroMap will accelerate innovative cardiac research and enhance the uptake, application and interpretation of mapping technologies leading to novel approaches for arrhythmia prevention.

BackgroundUltrasound images are difficult to segment because of their noisy and low contrast nature which makes it challenging to extract the important features. Typical intensity-gradient based approaches are not suitable for these low contrast images while it has been shown that the local phase based technique provides better results than intensity based methods for ultrasound images. The spatial feature extraction methods ignore the continuity in the heart cycle and may also capture spurious features. It is believed that the spurious features (noise) that are not consistent along the frames can be excluded by considering the temporal information. MethodsIn this paper, we present a local phase based 4D (3D+time) feature asymmetry (FA) measure using the monogenic signal. We have investigated the spatio-temporal feature extraction to explore the effect of adding time information in the feature extraction process. ResultsTo evaluate the impact of time dimension, the results of 4D based feature extraction are compared with the results of 3D based feature extraction which shows the favorable 4D feature extraction results when temporal resolution is good. The paper compares the band-pass filters (difference of Gaussian, Cauchy and Gaussian derivative) in terms of their feature extraction performance. Moreover, the feature extraction is further evaluated quantitatively by left ventricle segmentation using the extracted features. ConclusionsThe results demonstrate that the spatio-temporal feature extraction is promising in frames with good temporal resolution.

The advent of real-time 3-D echocardiography (RT3DE) promised dynamic 3-D image acquisition with the potential of a more objective and complete functional analysis. In spite of that, 2-D echocardiography remains the backbone of echocardiography imaging in current clinical practice, with RT3DE mainly used for clinical research. The uptake of RT3DE has been slow because of missing anatomic information, limited field-of-view (FOV) and tedious analysis procedures. This paper presents multiview fusion 3D echocardiography, where multiple images with complementary information are acquired from different probe positions. These multiple images are subsequently aligned and fused together for preserving salient structures in a single, multiview fused image. A novel and simple wavelet-based fusion algorithm is proposed that exploits the low- and high-frequency separation capability of the wavelet analysis. The results obtained show that the proposed multiview fusion considerably improves the contrast (31.1%), contrast-to-noise ratio (46.7%), signal-to-noise ratio (44.7%) and anatomic features (12%) in 3-D echocardiography, and enlarges the FOV (28.2%). This indicates that multiview fusion substantially enhances the image quality and information.

IntroductionContrast 3D echocardiography (C3DE) is commonly used to enhance the visual quality of ultrasound images in comparison with non-contrast 3D echocardiography (3DE). Although the image quality in C3DE is perceived to be improved for visual analysis, however it actually deteriorates for the purpose of automatic or semi-automatic analysis due to higher speckle noise and intensity inhomogeneity. Therefore, the LV endocardial feature extraction and segmentation from the C3DE images remains a challenging problem. MethodsTo address this challenge, this work proposes an adaptive pre-processing method to invert the appearance of C3DE image. The image inversion is based on an image intensity threshold value which is automatically estimated through image histogram analysis. ResultsIn the inverted appearance, the LV cavity appears dark while the myocardium appears bright thus making it similar in appearance to a 3DE image. Moreover, the resulting inverted image has high contrast and low noise appearance, yielding strong LV endocardium boundary and facilitating feature extraction for segmentation. ConclusionsOur results demonstrate that the inverse appearance of contrast image enables the subsequent LV segmentation. Contrast 3d echocardiography suffers from high speckle.The automated analysis from contrast 3d echocardiography is a difficult task.Contrast image inversion is proposed to match appearance with non-contrast image.An automatic threshold estimation method is proposed to enable image inversion.The contrast image inversion enables LV segmentation using non-contrast methods.

Real-time 3D echocardiography (RT3DE) promises a more objective and complete cardiac functional analysis by dynamic 3D image acquisition. Despite several efforts towards automation of left ventricle (LV) segmentation and tracking, these remain challenging research problems due to the poor-quality nature of acquired images usually containing missing anatomical information, speckle noise, and limited field-of-view (FOV). Recently, multi-view fusion 3D echocardiography has been introduced as acquiring multiple conventional single-view RT3DE images with small probe movements and fusing them together after alignment. This concept of multi-view fusion helps to improve image quality and anatomical information and extends the FOV. We now take this work further by comparing single-view and multi-view fused images in a systematic study. In order to better illustrate the differences, this work evaluates image quality and information content of single-view and multi-view fused images using image-driven LV endocardial segmentation and tracking. The image-driven methods were utilized to fully exploit image quality and anatomical information present in the image, thus purposely not including any high-level constraints like prior shape or motion knowledge in the analysis approaches. Experiments show that multi-view fused images are better suited for LV segmentation and tracking, while relatively more failures and errors were observed on single-view images.

Recent advances in four-dimensional (4-D) ultrasound enable the acquisition and visualisation of the entire fetal heart. However, getting consistent, shadow free, data remains problematic due to the uncontrollable nature of fetal orientation. This article presents the first investigation into the utility of image fusion to improve the quality of volumetric fetal cardiac imaging. Multiple volume scans are registered using a semiautomatic approach and five fusion methods are assessed for their ability to remove artefacts and improve image quality. Image quality is assessed in terms of signal-to-noise ratio, contrast and contrast-to-noise ratio. Qualitative results are presented for the ability to remove artefacts. The fusion methods assessed were found to be divided into those that reduce noise and those that increase contrast. The effect of fusion on left ventricle segmentation using commercial state-of-the-art software is also considered. The use of image fusion is shown to reduce the variability of volume estimates by about 50% relative to measurement on a single scan.

Real-time 3-dimensional echocardiography (RT3DE) permits the acquisition and visualization of the beating heart in 3D. Despite a number of efforts to automate the left ventricle (LV) delineation from RT3DE images, this remains a challenging problem due to the poor nature of the acquired images usually containing missing anatomical information and high speckle noise. Recently, there have been efforts to improve image quality and anatomical definition by acquiring multiple single-view RT3DE images with small probe movements and fusing them together after alignment. In this work, we evaluate the quality of the multiview fused images using an image-driven semiautomatic LV segmentation method. The segmentation method is based on an edge-driven level set framework, where the edges are extracted using a local-phase inspired feature detector for low-contrast echocardiography boundaries. This totally image-driven segmentation method is applied for the evaluation of end-diastolic (ED) and end-systolic (ES) single-view and multiview fused images. Experiments were conducted on 17 cases and the results show that multiview fused images have better image segmentation quality, but large failures were observed on ED (88.2%) and ES (58.8%) single-view images.

OBJECTIVES: This study assessed 3-dimensional fusion echocardiography (3DFE), combining several real-time 3-dimensional echocardiography (RT3DE) full volumes from different transducer positions, for improvement in quality and completeness of the reconstructed image. BACKGROUND: The RT3DE technique has limited image quality and completeness of datasets even with current matrix transducers. METHODS: RT3DE datasets were acquired in 32 participants (mean age 33.7 +/- 18.8 years; 27 men, 5 women). The 3DFE technique was also performed on a cardiac phantom. The endocardial border definition of RT3DE and 3DFE segments was graded for quality: good (2), intermediate (1), poor (0), or out of sector. Short-axis and apical images were compared in RT3DE and 3DFE, yielding 2,048 segments. The images were processed to generate 3DFE and then compared with cardiac magnetic resonance. RESULTS: In the heart phantom, fused datasets showed improved contrast to noise ratio from 49.4 +/- 25.1 (single dataset) to 125.4 +/- 25.1 (6 datasets fused together). In subjects, more segments were graded as good quality with 3DFE (805 vs. 435; p < 0.0001) and fewer as intermediate (184 vs. 283; p = 0.017), poor (31 vs. 265; p < 0.0001), or out of sector (4 vs. 41; p < 0.001) compared with the single 3-dimensional dataset. End-diastolic volume (EDV) and end-systolic volume (ESV) obtained from 3-dimensional fused datasets were equivalent to those from single datasets (EDV 118.2 +/- 39 ml vs. 119.7 +/- 43 ml; p = 0.41; ESV 48.1 +/- 30 ml vs. 48.4 +/- 35 ml; p = 0.87; ejection fraction [EF] 61.0 +/- 10% vs. 61.8 +/- 10%; p = 0.44). Bland-Altman analysis showed good 95% limits of agreement for the nonfused datasets (EDV +/-46 ml; ESV +/-36 ml; EF +/-14%) and the fused datasets (EDV +/-45 ml; ESV +/-35 ml; EF +/-16%), when compared with cardiac magnetic resonance. CONCLUSIONS: Fusion of full-volume datasets resulted in an improvement in endocardial borders, image quality, and completeness of the datasets.

The study of functional brain connectivity alterations induced by neurological disorders and their analysis from resting state functional Magnetic Resonance Imaging (rfMRI) is generally considered to be a challenging task. The main challenge lies in determining and interpreting the large-scale connectivity of brain regions when studying neurological disorders such as epilepsy. We tackle this challenging task by studying the cortical region connectivity using a novel approach for clustering the rfMRI time series signals and by identifying discriminant functional connections using a novel difference statistic measure. The proposed approach is then used in conjunction with the difference statistic to conduct automatic classification experiments for epileptic and healthy subjects using the rfMRI data. Our results show that the proposed difference statistic measure has the potential to extract promising discriminant neuroimaging markers. The extracted neuroimaging markers yield 93.08% classification accuracy on unseen data as compared to 80.20% accuracy on the same dataset by a recent state-of-the-art algorithm. The results demonstrate that for epilepsy the proposed approach confirms known functional connectivity alterations between cortical regions, reveals some new connectivity alterations, suggests potential neuroimaging markers, and predicts epilepsy with high accuracy from rfMRI scans. Scopus