Prediction of Parkinson's Disease Risk Based on Genetic Profile and Established Risk Factors.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder, and literature suggests that genetics and lifestyle/environmental factors may play a key role in the triggering of the disease. This study aimed to evaluate the predictive performance of a 12-Single Nucleotide Polymorphisms (SNPs) polygenic risk score (PRS) in combination with already established PD-environmental/lifestyle factors. METHODS: Genotypic and lifestyle/environmental data on 235 PD-patients and 464 controls were obtained from a previous study carried out in the Cypriot population. A PRS was calculated for each individual. Univariate logistic-regression analysis was used to assess the association of PRS and each risk factor with PD-status. Stepwise-regression analysis was used to select the best predictive model for PD combining genetic and lifestyle/environmental factors. RESULTS: The 12-SNPs PRS was significantly increased in PD-cases compared to controls. Furthermore, univariate analyses showed that age, head injury, family history, depression, and Body Mass Index (BMI) were significantly associated with PD-status. Stepwise-regression suggested that a model which includes PRS and seven other independent lifestyle/environmental factors is the most predictive of PD in our population. CONCLUSIONS: These results suggest an association between both genetic and environmental factors and PD, and highlight the potential for the use of PRS in combination with the classical risk factors for risk prediction of PD.

Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder affecting a substantial proportion of the elderly Cypriot population. The objective of this study was to evaluate PD risk variants that have been identified previously in Genome Wide Association Studies (GWAS) and to find environmental factors that are predictors for PD onset in the Cypriot population. Methods: A case-control study was conducted with a total of 235 PD patients and 464 healthy controls of Greek-Cypriot ethnicity. Demographic and lifestyle characteristics, exposure to PD risk factors and clinical data were collected. Moreover, 13 previously GWAS-identified PD risk variants were genotyped. Univariate and multivariate regression analyses examined the association between a number of environmental and genetic factors and PD. Results: Multivariable regression analysis revealed that exposure to both pesticides and other toxic substances (P = 0.03), severe head injury accompanied with fainting (P = 0.001), nuts consumption (P = 0.004), red meat consumption (P = 0.02), and soft drinks consumption (P = 0.008) were increasing the risk for PD, whereas cumulative smoking (P = 0.02), and fish consumption (P = 0.02) were decreasing the risk for PD. Five out of the 13 tested SNPs (rs12185268, rs6599389, rs356220, rs13312, and rs17649553) were confirmed to be nominally significantly associated (P < 0.05) with PD risk in the Cypriot population. Conclusions: Collectively, this case-control study has shed some light on the nature of PD epidemiology in Cyprus, by demonstrating a number of genetic and environmental determinants of PD in the Cypriot population.

An integrated system for the segmentation of atherosclerotic carotid plaque.

In this paper, we propose and evaluate an integrated system for the segmentation of atherosclerotic plaque in ultrasound imaging of the carotid artery based on normalization, speckle reduction filtering, and four different snakes segmentation methods. These methods are the Williams and Shah, Balloon, Lai and Chin, and the gradient vector flow (GVF) snake. The performance of the four different plaque snakes segmentation methods was tested on 80 longitudinal ultrasound images of the carotid artery using receiver operating characteristic (ROC) analysis and the manual delineations of an expert. All four methods were very satisfactory and similar in all measures evaluated, with no significant differences between them; however, the Lai and Chin snakes segmentation method gave slightly better results. Concluding, it is proposed that the integrated system investigated in this study could be used successfully for the automated segmentation of the carotid plaque.

Texture Feature Variability in Ultrasound Video of the Atherosclerotic Carotid Plaque.

The objective of this paper was to investigate texture feature variability in ultrasound video of the carotid artery during the cardiac cycle in an attempt to define new discriminatory biomarkers of the vulnerable plaque. More specifically, in this paper, 120 longitudinal ultrasound videos, acquired from 40 normal (N) subjects from the common carotid artery and 40 asymptomatic (A) and 40 symptomatic (S) subjects from the proximal internal carotid artery were investigated. The videos were intensity normalized and despeckled, and the intima-media complex (IMC) (from the N subjects) and the atherosclerotic carotid plaques (from the A and S subjects) were segmented from each video, in order to extract the M-mode image, and the texture features associated with cardiac states of systole and diastole. The main results of this paper can be summarized as follows: 1) texture features varied significantly throughout the cardiac cycle with significant differences identified between the cardiac systolic and cardiac diastolic states; 2) gray scale median was significantly higher at cardiac systole versus diastole for the N, A, and S groups investigated; 3) plaque texture features extracted during the cardiac cycle at the systolic and diastolic states were statistically significantly different between A and S subjects (and can thus be used to discriminate between A and S subjects successfully). The combination of systolic and diastolic features yields better performance than those alone. It is anticipated that the proposed system may aid the physician in clinical practice in classifying between N, A, and S subjects using texture features extracted from ultrasound videos of IMC and carotid artery plaque. However, further evaluation has to be carried out with more videos and additional features.

Comparative evaluation of despeckle filtering in ultrasound imaging of the carotid artery.

It is well-known that speckle is a multiplicative noise that degrades the visual evaluation in ultrasound imaging. The recent advancements in ultrasound instrumentation and portable ultrasound devices necessitate the need of more robust despeckling techniques for enhanced ultrasound medical imaging for both routine clinical practice and teleconsultation. The objective of this work was to carry out a comparative evaluation of despeckle filtering based on texture analysis, image quality evaluation metrics, and visual evaluation by medical experts in the assessment of 440 (220 asymptomatic and 220 symptomatic) ultrasound images of the carotid artery bifurcation. In this paper a total of 10 despeckle filters were evaluated based on local statistics, median filtering, pixel homogeneity, geometric filtering, homomorphic filtering, anisotropic diffusion, nonlinear coherence diffusion, and wavelet filtering. The results of this study suggest that the first order statistics filter lsmv, gave the best performance, followed by the geometric filter gf4d, and the homogeneous mask area filter lsminsc. These filters improved the class separation between the asymptomatic and the symptomatic classes based on the statistics of the extracted texture features, gave only a marginal improvement in the classification success rate, and improved the visual assessment carried out by the two experts. More specifically, filters lsmv or gf4d can be used for despeckling asymptomatic images in which the expert is interested mainly in the plaque composition and texture analysis; and filters lsmv, gf4d, or lsminsc can be used for the despeckling of symptomatic images in which the expert is interested in identifying the degree of stenosis and the plaque borders. The proper selection of a despeckle filter is very important in the enhancement of ultrasonic imaging of the carotid artery. Further work is needed to evaluate at a larger scale and in clinical practice the performance of the proposed despeckle filters in the automated segmentation, texture analysis, and classification of carotid ultrasound imaging.

An effective ultrasound video communication system using despeckle filtering and HEVC.

The recent emergence of the high-efficiency video coding (HEVC) standard promises to deliver significant bitrate savings over current and prior video compression standards, while also supporting higher resolutions that can meet the clinical acquisition spatiotemporal settings. The effective application of HEVC to medical ultrasound necessitates a careful evaluation of strict clinical criteria that guarantee that clinical quality will not be sacrificed in the compression process. Furthermore, the potential use of despeckle filtering prior to compression provides for the possibility of significant additional bitrate savings that have not been previously considered. This paper provides a thorough comparison of the use of MPEG-2, H.263, MPEG-4, H.264/AVC, and HEVC for compressing atherosclerotic plaque ultrasound videos. For the comparisons, we use both subjective and objective criteria based on plaque structure and motion. For comparable clinical video quality, experimental evaluation on ten videos demonstrates that HEVC reduces bitrate requirements by as much as 33.2% compared to H.264/AVC and up to 71% compared to MPEG-2. The use of despeckle filtering prior to compression is also investigated as a method that can reduce bitrate requirements through the removal of higher frequency components without sacrificing clinical quality. Based on the use of three despeckle filtering methods with both H.264/AVC and HEVC, we find that prior filtering can yield additional significant bitrate savings. The best performing despeckle filter (DsFlsmv) achieves bitrate savings of 43.6% and 39.2% compared to standard nonfiltered HEVC and H.264/AVC encoding, respectively.

An integrated system for the segmentation of atherosclerotic carotid plaque ultrasound video.

The robust border identification of atherosclerotic carotid plaque, the corresponding degree of stenosis of the common carotid artery (CCA), and also the characteristics of the arterial wall, including plaque size, composition, and elasticity, have significant clinical relevance for the assessment of future cardiovascular events. To facilitate the follow-up and analysis of the carotid stenosis in serial clinical investigations, we propose and evaluate an integrated system for the segmentation of atherosclerotic carotid plaque in ultrasound videos of the CCA based on video frame normalization, speckle reduction filtering, M-mode state-based identification, parametric active contours, and snake segmentation. Initially, the cardiac cycle in each video is identified and the video M-mode is generated, thus identifying systolic and diastolic states. The video is then segmented for a time period of at least one full cardiac cycle. The algorithm is initialized in the first video frame of the cardiac cycle, with human assistance if needed, and the moving atherosclerotic plaque borders are tracked and segmented in the subsequent frames. Two different initialization methods are investigated in which initial contours are estimated every 20 video frames. In the first initialization method, the initial snake contour is estimated using morphology operators; in the second initialization method, the Chan-Vese active contour model is used. The performance of the algorithm is evaluated on 43 real CCA digitized videos from B-mode longitudinal ultrasound segments and is compared with the manual segmentations of an expert, available every 20 frames in a time span of 3 to 5 s, covering, in general, 2 cardiac cycles. The segmentation results were very satisfactory, according to the expert objective evaluation, for the two different methods investigated, with true-negative fractions (TNF-specificity) of 83.7 ± 7.6% and 84.3 ± 7.5%; true-positive fractions (TPF-sensitivity) of 85.42 ± 8.1% and 86.1 ± 8.0%; and between the ground truth and the proposed segmentation method, kappa indices (KI) of 84.6% and 85.3% and overlap indices of 74.7% and 75.4%. The segmentation contours were also used to compute the cardiac state identification and radial, longitudinal, and shear strain indices for the CCA wall and plaque between the asymptomatic and symptomatic groups were investigated. The results of this study show that the integrated system investigated in this study can be successfully used for the automated video segmentation of the CCA plaque in ultrasound videos.

Despeckle filtering software toolbox for ultrasound imaging of the common carotid artery.

Ultrasound imaging of the common carotid artery (CCA) is a non-invasive tool used in medicine to assess the severity of atherosclerosis and monitor its progression through time. It is also used in border detection and texture characterization of the atherosclerotic carotid plaque in the CCA, the identification and measurement of the intima-media thickness (IMT) and the lumen diameter that all are very important in the assessment of cardiovascular disease (CVD). Visual perception, however, is hindered by speckle, a multiplicative noise, that degrades the quality of ultrasound B-mode imaging. Noise reduction is therefore essential for improving the visual observation quality or as a pre-processing step for further automated analysis, such as image segmentation of the IMT and the atherosclerotic carotid plaque in ultrasound images. In order to facilitate this preprocessing step, we have developed in MATLAB(®) a unified toolbox that integrates image despeckle filtering (IDF), texture analysis and image quality evaluation techniques to automate the pre-processing and complement the disease evaluation in ultrasound CCA images. The proposed software, is based on a graphical user interface (GUI) and incorporates image normalization, 10 different despeckle filtering techniques (DsFlsmv, DsFwiener, DsFlsminsc, DsFkuwahara, DsFgf, DsFmedian, DsFhmedian, DsFad, DsFnldif, DsFsrad), image intensity normalization, 65 texture features, 15 quantitative image quality metrics and objective image quality evaluation. The software is publicly available in an executable form, which can be downloaded from http://www.cs.ucy.ac.cy/medinfo/. It was validated on 100 ultrasound images of the CCA, by comparing its results with quantitative visual analysis performed by a medical expert. It was observed that the despeckle filters DsFlsmv, and DsFhmedian improved image quality perception (based on the expert's assessment and the image texture and quality metrics). It is anticipated that the system could help the physician in the assessment of cardiovascular image analysis.

Manual and automated intima-media thickness and diameter measurements of the common carotid artery in patients with renal failure disease.

The objective of this study was to investigate differences in intima-media thickness (IMT) and diameter (D) measurements of the common carotid artery (CCA) in ultrasound imaging in normal subjects and renal failure disease (RFD) patients. Manual measurements by two experts and automated segmentation measurements (based on snakes and active contour models (ACM)) were carried out on 73 normal subjects, and 80 RFD patients. Statistical analysis was carried out using the Wilcoxon rank-sum test at p<0.05. Results demonstrated that the mean IMT and D measurements were significantly higher for the RFD group versus the normal group. Moreover, there was no significant difference between the manual and automated measurements. The ACM segmentation was slightly more accurate than segmentation based on snakes. Further work is needed to validate these findings on a larger group of subjects.

Segmentation of the common carotid intima-media complex in ultrasound images using active contours.

The segmentation of the intima-media complex (IMC) of the common carotid artery (CCA) wall is important for the evaluation of the intima media thickness (IMT) on B-mode ultrasound (US) images. The IMT is considered an important marker in the evaluation of the risk for the development of atherosclerosis. The fully automated segmentation algorithm presented in this article is based on active contours and active contours without edges and incorporates anatomical information to achieve accurate segmentation. The level set formulation by Chan and Vese using random initialization provides a segmentation of the CCA US images into different distinct regions, one of which corresponds to the carotid wall region below the lumen and includes the far wall IMC. The segmented regions are used to automatically achieve image normalization, which is followed by speckle removal. The resulting smoothed lumen-intima boundary combined with anatomical information provide an excellent initialization for parametric active contours that provide the final IMC segmentation. The algorithm is extensively evaluated on 100 different cases with ground truth (GT) segmentation available from two expert clinicians. The GT mean IMT value is 0.6679 mm +/ - 0.1350 mm and the corresponding automatically segmented (AS) mean IMT value is 0.6054 mm +/ - 0.1464 mm. The mean absolute difference between the GT IMT and the IMT evaluated from from the AS region is 0.095 mm +/ - 0.0615 mm. The polyline distance is 0.096 mm +/ - 0.034 mm while the Hausdorff distance is 0.176 mm +/ - 0.047 mm. The algorithm compares favorably to both automatic and semiautomatic methods presented in the literature.

A fully automated method using active contours for the evaluation of the intima-media thickness in carotid US images.

The thickness of the intima-media complex (IMC) of the common carotid artery (CCA) wall is important in the evaluation of the risk for the development of atherosclerosis. This paper presents a fully automated algorithm for the segmentation of the IMC. The segmentation of the IMC of the CCA wall is important for the evaluation of the intima media thickness (IMT) on B-mode ultrasound images. The presented algorithm is based on active contours and active contours without edges. It begins with image normalization, followed by speckle removal. The level set formulation of Chan and Vese using random initialization provides a segmentation of the CCA ultrasound (US) images into different distinct regions, one of which corresponds to the carotid wall region above the lumen whilst another corresponds to the carotid wall region below the lumen and includes the IMC. The results of the corresponding segmentation combined with anatomical information provide a very accurate outline of the lumen-intima boundary. This outline serves as an excellent initialization for segmentation of the IMC using parametric active contours. The method lends itself to the development of a fully automated method for the delineation of the IMC. The mean and standard deviation of the thickness of the automatically segmented regions are 0.65 mm +/-0.17 mm and the corresponding values for the ground truth IMT are 0.66 mm +/-0.18 mm. The Wilcoxon rank sum test shows no significant difference.

Manual and automated media and intima thickness measurements of the common carotid artery.

The intima-media thickness (IMT) of the common carotid artery (CCA) is widely used as an early indicator of the development of cardiovascular disease (CVD). It was proposed but not thoroughly investigated that the media layer (ML) thickness (MLT), its composition, and its texture may be indicative of cardiovascular risk and for differentiating between patients with high and low risk. In this study, we investigate an automated method for segmenting the ML and the intima layer (IL) and measurement of the MLT and the intima layer thickness (ILT) in ultrasound images of the CCA. The snakes segmentation method was used and was evaluated on 100 longitudinal ultrasound images acquired from asymptomatic subjects, against manual segmentation performed by a neurovascular expert. The mean +/- standard deviation (sd) for the first and second sets of manual and the automated IMT, MLT, and ILT measurements were 0.71 +/- 0.17 mm, 0.72 +/- 0.17 mm, 0.67 +/- 0.12 mm; 0.25 +/- 0.12 mm, 0.27 +/- 0.14 mm, 0.25 +/- 0.11 mm; and 0.43 +/- 0.10 mm, 0.44 +/- 0.13 mm, and 0.42 +/- 0.10 mm, respectively. There was overall no significant difference between the manual and the automated IMC, ML, and IL segmentation measurements. Therefore, the automated segmentation method proposed in this study may be used successfully in the measurement of the MLT and ILT complementing the manual measurements. MLT was also shown to increase with age (for both the manual and the automated measurements). Future research will incorporate the extraction of texture features from the segmented ML and IL bands, which may indicate the risk of future cardiovascular events. However, more work is needed for validating the proposed technique in a larger sample of subjects.