Feature Extraction from Distributions of Phase Synchronization Values of EEG Recordings

ABSTRACT Epilepsy is the most common neurological pathology. Despite treatments available to patients, only 58% to 73% will be free of seizures. This uncertainty in treatment outcomes can lead to other psychiatric affectations in cases where treatment success may be in doubt. Seizure prediction models (SPMs) emerged as a measure to help determine when patients may be susceptible to an imminent crisis. These models are based on the continuous monitoring of patient's EEG signals and subsequent continuous analysis to identify features that differentiate ictal from interictal states. This is an ongoing field of research whose aim is to establish a robust set of features to feed the SPM and obtain a high degree of certainty regarding when the next seizure will occur. In this work we propose the analysis of phase differences of EEG as a method to extract features capable of discriminating ictal and preictal states in patients; specifically, the numeric distance between Q1 and Q3 of the distribution of phase differences. We compared this values to other phase synchronization methods and tested our hypothesis getting a p < 0.0009 with our proposed method.

Análisis de fase en estudios Gated-SPECT como predictor de mortalidad en pacientes con enfermedad coronaria y función ventricular izquierda deprimida / Phase analysis in Gated-SPECT studies as a predictor of mortality in patients with coronary diseases and impaired left ventricular function

Resumen Antecedentes: La enfermedad coronaria es una de las principales causas de morbimortalidad en los países occidentales. En etapas avanzadas de la enfermedad, los procesos de remodelación miocárdica pueden conducir a insuficiencia cardíaca progresiva y disfunción ventricular izquierda. El análisis de fase de los estudios de perfusión miocárdica Gated-SPECT muestra parámetros que han sido caracterizados como marcadores válidos de asincronía ventricular. Objetivo: Evaluar los parámetros del análisis de fase en Gated-SPECT como predictores independientes de mortalidad en pacientes con enfermedad coronaria avanzada e insuficiencia ventricular izquierda. Materiales y método: Estudio retrospectivo de cohortes históricas de 185 pacientes consecutivos (140 hombres; edad media=67,6±12,7 años) a los que, entre enero de 2009 y marzo de 2011, se les hizo estudio isotópico de perfusión miocárdica con estimulación farmacológica con resultado positivo para isquemia/necrosis con FEVI ≤ 55%. Adicionalmente, se les realizó seguimiento medio de 32,4±10,5 meses registrándose la aparición de eventos cardíacos mayores (infarto agudo de miocardio no mortal, ingreso hospitalario y revascularización coronaria tardía) y mortalidad total. Resultados: Durante el seguimiento se registraron eventos mayores en 51 pacientes así como 28 fallecimientos, de los cuales, 82,1% mostró valores alterados de los parámetros de fase: media=141,1(±17,6(; desviación estándar=15,8(±10,1(; ancho de banda=59,1(±36( y FEVI=42,4%±10,8%. El análisis de Cox mostró al ancho de banda como un predictor independiente de muerte, disminuyendo significativamente la supervivencia y aumentando el riesgo de muerte (hazard ratio=2,68; p<0,05). Conclusiones: El ancho de banda en el análisis de fase se comporta como un predictor independiente de muerte en pacientes con miocardiopatía conocida y FEVI deprimida.

Abstract Background: Coronary disease is one of the main causes of morbidity and mortality in western countries. In the advanced stages of the disease the myocardial remodelling processes can lead to progressive heart failure and left ventricular impairment. The phase analysis of Gated-SPECT studies of myocardial perfusion show parameters that have been characterised as valid marker of ventricular asynchrony. Objective: To evaluate the phase analysis parameters in Gated SPECT as independent predictors of mortality in patients with advanced coronary disease and left ventricular failure. Materials and method: A retrospective historic cohort study was conducted on 185 consecutive patients (140 males; mean age = 67.6±12.7 years) on whom, between January 2009 and March 2011, an isotope myocardial perfusion study was carried out with pharmacologic stimulation and with a positive result for ischaemia / necrosis, and with a LVEF ≤ 55%. A mean follow-up of 32.4 ±10.5 months was also performed, recording the appearance of major cardiac events (non-fatal acute myocardial infarctions, hospital admission, delayed coronary revascularisation, and total mortality. Results: Major events were recorded in 51 patients during follow-up. There were also 28 deaths, of which 82.1% showed abnormal values of the phase parameters: media=141.1(±17.6(; standard deviation=15.8(±10.1(; bandwidth=59.1(±36(, and LVEF = 42.4%±10.8%. The Cox analysis showed the bandwidth as an independent predictor of death, significantly reducing the survival and increasing the risk of death (hazard ratio=2.68; P<.05). Conclusions: The bandwidth in the phase analysis behaves as an independent predictive factor in patients with known myocardial disease and an impaired LVEF.

Análisis de fase mediante "Gated-SPECT" de perfusión miocárdica para valorar el sincronismo mecánico del ventrículo / Phase analysis to measure left ventricular dyssynchrony by Gated-SPECT myocardial perfusion imaging showed by two different software

Resumen Introducción y objetivos: El análisis de fase mediante Gated-SPECT de perfusión miocárdica (GS-PMI) es una nueva herramienta para medir la asincronía ventricular izquierda con importantes aplicaciones clínicas futuras en resincronización e insuficiencia cardiaca. Se puede medir mediante dos programas (ECTb o QGS C-S). El objetivo es demostrar su factibilidad y verificar si existen diferencias entre ambos. Metodología: Estudio analítico, observacional y retrospectivo en pacientes con GS-PMI normales. Los parámetros obtenidos fueron: la desviación estándar de la fase (DE) y el ancho de banda de histograma (AH). La evaluación de la diferencia entre los grupos se realizó usando pruebas para muestras independientes después de analizar la distribución de datos. Nivel de significación p<0,05. Se utilizó SPSS IBM V.21®. Resultados: Total pacientes: 193 (104 hombres). Edad media: 64 años (24-89).61/193 procesados con QGS C-S y 132/193 con ECTb. Postestrés: la media de la DE fue 6º±3,7º, con mediana de 5º y rango intercuartílico (IR):3.6º. La media de AH fue 22,7º±10º, con mediana de 18º y IR:11.5º. Postreposo: la media de la DE fue 5,76º±4,82º y la mediana 4,5º con IR: 3.1º. La media de AH fue 21.67º± 14.06º y la mediana 18º, IR:12º. Entre ambos programas se encontraron diferencias significativas en la DE en postestrés (p=0,001) y postreposo (p=0,019), sin diferencias en el AH postestrés (p=0,31) y postreposo (p=0,18). Conclusión: Realizar el análisis fase de análisis por GS-PMI es factible. Sin embargo, la DE mostró diferencias significativas entre los dos programas. Aunque los valores mostrados podrían ser utilizados como valores normales, se recomienda que estos se obtengan y utilicen para cada programa por separado.

Abstract Introduction and objectives:Phase analysis by Gated-SPECT myocardial perfusion imaging (G-MPI) is a new tool to measure left ventricular dyssynchrony with important clinical applications in near future (heart failure and resynchronization) and can be measured by two software (ECTb o QGS C-S). The aim is to show its feasibility and verify whether there is difference between the programs. Methodology: Analytical observational and retrospective study in patients with normal G-MPI. The parameters were the phase standard deviation (SD) and the histogram bandwidth (HB) in post-stress and rest tests. Assessment of the difference between groups was performed using tests for independent samples after analyze the distribution of data. The significance level (p) was 0,05 and the software used was SPSS IBM V.21® Results: Total:193 patients (104 men).64 years old ± (24-89).61/193 processed with QGS C-S and 132/193 with ECTb. Post-stress tests: mean of the SD was 6º±3.7º,the median was 5º,interquartile range (IR):3.6º.The mean of HB was 22.7º±10º and the median was 18º IR:11.5º. Post-rest tests: mean of the SD was 5.76º±4.82º and median was 4.5º IR: 3.1º.The overall mean of HB was 21.67º±14.06º and median was 18º IR: 12º. Between the data from both software, significant differences were found in SD in post-stress(p=0.001)and post-rest tests(p=0.019)and no significant differences were found in HB in post-stress(p= 0.31)or post-rest tests(p=0.18). Conclusion: Phase analysis by G-MPI is feasible. However SD showed significant differences between the two groups. Although the values showed could be used as normal values, it is recommended that these have to be obtained and used for each software separately.

The use of the software JST-XRD for identification of crystalline phases in pharmaceutical raw materials and tablets / Uso do software JST-XRD para identifcação de fases cristalinas em insumos farmacêuticos e medicamentos

Study of polymorphism is of great importance for the pharmaceutical industry once polymorphs may display different physicochemical properties, which, in turn, may result in stability differences that can bring problems for the manufacturing stages and the quality of fnal products. Although research on organic polymorphs has greatly increased in the last decades, it still does not cover all needs for the pharmaceutical market. Techniques such as spectroscopy in the infrared region, nuclear magnetic resonance, thermal analysis, X-ray diffraction, etc., can be used to identify polymorphism. The polymorphism is a property of the crystalline solid state, and can be evaluated by X-ray diffraction once each polymorph exhibits one specifc X-ray diffraction pattern. The JST-XRD program is a tool designed to help the identifcation of crystalline phases (including polymorphs) present in pharmaceutical ingredients and tablets by using X-ray diffraction data obtained from scientifc articles and patents. This paper presents new implementations for the JST-XRD and describes its use in the analysis of active pharmaceutical ingredient and marketed tablets of norfloxacin, mebendazole and atorvastatin calcium. By the means of comparison, JSTXRD allowed identifying the crystalline phases in the diffraction patterns of the analyzed drugs, showing the program suitability for polymorphism research, pre-formulation and quality control in pharmaceutical industries. JST-XRD can also be used for educational purposes in undergraduate and graduate programs in order to show the potentiality of X-ray powder diffraction in polymorphism analysis.(AU)

O estudo do polimorfsmo é de grande importância na indústria farmacêutica porque os polimorfos podem apresentar diferentes propriedades físico-químicas, podendo resultar em diferenças na estabilidade e desse modo causar problemas nas etapas de manufatura e no produto fnal. Embora a pesquisa de moléculas orgânicas que apresentam polimorfsmo tenha aumentado bastante nas últimas décadas, ainda não contempla todas as necessidades do mercado farmacêutico. Para a identifcação de polimorfsmo podem ser utilizadas técnicas como espectroscopia na região do infravermelho, ressonância nuclear magnética, análise térmica (DSC), difração de raios X, etc. O polimorfsmo, por ser uma propriedade do estado sólido e cristalino, pode ser avaliado através da difração de raios X, já que cada polimorfo apresenta um padrão de difração de raios X único. O programa JST-XRD é uma ferramenta projetada para auxiliar a identifcação de fases cristalinas, incluindo polimorfos, presentes em insumos farmacêuticos e comprimidos, usando dados de difração de raios X obtidos em artigos científcos e patentes. Esse trabalho apresenta novas implementações no JST-XRD e descreve seu uso na análise de amostras de princípio ativo e comprimidos comerciais de norfloxacino, mebendazol e atorvastatina cálcica. Através das comparações realizadas, JSTXRD permitiu identifcar todas as fases cristalinas dos difratogramas dos fármacos analisados, mostrando que o programa é adequado para pesquisa em polimorfsmo; na pré-formulação e controle de qualidade em indústrias farmacêuticas, assim como para uso didático em cursos de graduação e pós-graduação a fm de mostrar as potencialidades da difração de raios X na análise de polimorfsmo.(AU)

Relationship Between Septal Myocardial Metabolism and Left Ventricular Mechanical Synchronization in Patients With Dilated Cardiomyopathy and Left Bundle Branch Block / 中国循环杂志

Objective: To explore the relationship between septal myocardial metabolism and left ventricular mechanical synchronization in patients with dilated cardiomyopathy (DCM) and left bundle branch block (LBBB) by gated 18F-FDG myocardial metabolic imaging. Methods: A total of 20 consecutive patients diagnosed for DCM with LBBB from 2010-10 to 2013-05 were enrolled, there were 11 male and 9 female at the mean age of (54±11) years. All patients received gated 18F-FDG myocardial metabolic PET imaging. TrueD software was used to determine the maximal standardized 18F-FDG uptake value (S-SUVmax) and the average standardized uptake value (S-SUVavg). QGS software was applied to conduct left ventricular phase analysis and to detect the cardiac function, left ventricular bandwidth (BW), standard deviation of bandwidth (SD), left ventricular end-diastolic volume (LVEDV), LVESV and LVEF. The relationship between 18F-FDG uptake in septal myocardium with the indexes of phase analysis and the indexes of cardiac function was analyzed. Results: S-SUVmax and S-SUVavg were respectively negatively related to BW (r=-0.44, P0.05. Conclusion: In patients of DCM with LBBB, reduced septal myocardial metabolism was closely related to left ventricular mechanical synchronization, gated 18F-FDG myocardial metabolic PET imaging may simultaneously detect both functions, which was important for prognostic evaluation and therapeutic monitoring in clinical practice;phase analysis.

Preparation and in vitro release of lyophilized powder of sorafenib solid lipid nanoparticles / 中国药学杂志

OBJECTIVE: To prepare soraienib solid lipid nanoparticles and investigate its physicochemical properties and in vitro release profile. METHODS: Sorafenib solid lipid nanoparticles were prepared by emulsion evaporation-solidification at low temperature. The morphology was examined by transmission electron microscope. The particle size and Zeta potential were determined by laser granularity equipment. The encapsulation efficiency was detected by Sephadex gel chromatography and HPLC. The in vitro release pro-file of sorafenib solid lipid nanoparticles was studied using dialysis technology. The lyophilized powder of sorafenib solid lipid nanoparticles was prepared by refrigerated air dryer and its material phase was analyzed by DSC. RESULTS: The sorafenib solid lipid nanoparticles assumed spherical shape. The distribution of diameter was even with average particle size of (108.2±7.0) nm. The PDI and Zeta potential were (0.250±0.022) and (-16.4±0.7) mV, respectively. The average encapsulation efficiency was (73.49±1.87)%. The release in vitro accorded with Weibull order model. Equal volume of 15% mannitol was the best protective agent for lyophilized powder of sorafenib solid lipid nanoparticles. The formation of a new material phase was testified by analysis of DSC. CONCLUSION: The method of emulsion evaporation-solidification at low temperature was appropriate for preparation of sorafenib solid lipid nanoparticles. The nanoparticles had stable physical properties and significant sustained-release effect.

Left ventricular regional wall motion assessment in myocardial infarction by phase analysis

BACKGROUND: In patients with myocardial infarction, one needs to know the location, extent and severity of wall motion abnormalities to assess prognosis and guide therapy. Thus more precise quantatative estimates of regional ventricular function are required. Regional wall motion has generally been assessed by displaying the multiple cardiac images of RVG as endless-loop movie, but the cinematic display was not objective. We used the usefulness of the phase analysis in evaluating the global left ventricular function and regional wall motion abnormalities of patients with myocardial infarction. The accuracy of the RVG cinematic display in detecting regional wall motion abnormalities in patients with myocardial infarction was also evaluated. METHODS: Studied cases were 97 patients with myocardial infarction and 20 normals with low likelihood of coronary artery disease. Coronary angiography and contrast left ventriculography were performed in all patients with myocardial infarction. The regional wall myocardial infarction(presence) is defined when the EKG presented the evidence of myocardial infarction, left ventriculogram showed RWMA(regional wall motion abnormality) along with stenosis of 50% or greater of the regional supplying coronary artery. Each patient was imaged in 45 left anterior oblique(LAO) view, anterior(Ant) view and left lateral(Lt Lat) view. We evaluated Left ventricular ejection fraction(LVEF) from time-activity curve. We constructed the histogram for the left ventricle and both ventricle separately to obtain the global and total phase angle(GPA, TPA), standard deviation of phase angle(GSDPh, TSDPh), full width half maximum(GFWHM, TFWHM). The left ventricle was divided into 7 segments. LAO projection ; septal, apical, basal lateral, apical lateral, Ant projection ; anterolateral, Lt Lat projection ; inferior, posterior, Phase angle(RPA) and full width half maximum(RFWHM) from the histogram (regional 7 segments) were examined. On the RVG cinematic display, the standard 4 grading system was used, normal, hypokinesia, akinesia, dyskinesia. The observer evaluated regional wall motion abnormality of the 7 segments for all cases. The sensitivity of the above parameters and RVG cinematic display was evaluated. We analyzed the regional parameters among the patents with regional wall myocardial infarction(presence), those without regional wall myocardial infarction(absence) and control group using the t-test. The statistical analysis was done by one way ANOVA between regional phase analysis and RVG cinematic display. RESULTS: The sensitivity of LVEF was lowest(70.1%) and the GFWHM was highest among the global parameters(89.1%). But RFWHM showed even higher sensitivity(96.9%), thus regional phase analysis was also required. The RVG cinematic display was also sensitive(92.7%), but less sensitive than the RFWHM. On regional phase analysis the RPA of septal, apical, inferior, posterior walls of the left ventricle was able to separate presence group from absence group and also presence group from control group and the RPA of the apical lateral wall could separate presence group from absence group. The RPA of basal lateral and anterolateral wall was inaccurate in diagnosing the regional wall myocardial infarction, because basal lateral wall was overlapped by adjacent vascular structures, and the area of anterolateral wall dose not correlate completely beteen the RVG & the left ventriculogram, also the anterolateral wall can be supplied by the obtuse marginal branch of left circumflex artery. The RFWHM of all regional walls of left ventricle could separate presence group from absence group and presence group from control group. We found good correlation between regional phase analysis & left ventriculogram for detection of regional wall myocardial infartion. On RVG cinematic display, the RPA of the normal group was different from that of dyskinesia, akinesia and hypokinesia groups. The RPA of the dyskinesia group was also different from that of skinesia and hypokinesia groups by oneway ANOVA(p<0.05). The RFWHM of the dskinesia group was different from that of the normal group and hypokinesia group. RVG cinematic display correlated well with regional phase analysis and also quantitation of wall motion. CONCLUSIONS: Thus RVG cinematic display was useful and can not be replaced by phase analysis. But the regional phase analysis was sensitive and objective in diagnosing the wall motion abnormality in myocardial infarction.

Assessment of Ventricular Function and Phase Abnormality by Gated Blood Pool Scan in Dilated Cardiomyopathy

Gated blood pool scan(GBPS) may be used for evaluating patients with dilated cardiomyopathy(DCM) where it can assist in the diagnosis, and evaluation of severity, disease progression or therapeutic efficacy. In addition to the routine parameters that have been available by GBPS, relatively simple mathematical manipulations of the equilibrium time activity curve can derive parameters relating to the degree and sequence of ventricular emptying. This first harmonic phase analysis may enable quantitative and more specific measurements of wall motion abnormalities in DCM and may thus be useful for more accurate assessments in these patients. Thus, in an attempt to evaluate the findings of phase analysis in DCM and to determine their possible usefulness in this entity, we measured parameters of phase analysis from the resting GBPS of 25 DCM patients and 11 normal controls, and compared these with other parameters of ventricular function from GBPS or echocardiography. Parameters of the systolic as well as diastolic function were markedly depressed for both left and right ventricles (all p<0.001), and echocardiographic LV systolic diameter was increased in all patients. Phase analsis showed the mean and standard deviation of phase angle(Mph & SDph) of both ventricles to be singificantly greater, and the mean amplitude smaller in DCM patients compared to controls(p<0.01). SDph appeared to be a sensitive parameter(LV 100%, RV 92%), and LV SDph showed significant correlations with other GBPS parmeters such as LV ejection fraction(LVEF) and LV peak ejection rate(LVPER) (r=-0.85 and 0.75, respectively) (all p<0.001), and with LV systolic diameter (r=0.78, p<0.001). Also, LV mean amplitude correlated well with LVEF (r=0.79, p<0.001). Thus, phase analysis of GBPS was able to show and quantify significant asynchronity in contraction of both ventricles in DCM, and these parameters may by useful in evaluating ventricular performance in these patients.

The Evaluation of Left and Right Ventricular Function by Radionuclide Ventriculography and Echocardiography in Dilated Cardiomyopathy

It has been known that dilated cardiomyopathy(DCM) is characterized by systolic dysfunction of left ventricle(LV), but there were few studies about correlation between LV systolic function, diameter and diastolic function measured by echocardiography and radionuclide ventriculography(RVG) The purpose of this study is to evaluate LV systolic and diastolic function as well as RV function using regional ejection fraction and functional images by RVG in 17 patients with DCM and to compare these variables with echocardiographic data. The results are as follows : 1) DCM showed diffuse systolic and diastolic dysfunction of LV. The systolic impairment is accounted for the diastolic impairment in DCM. 2) The increased standard deviation of phase angle of left ventricle(LVSDph) revealed LV asynchronous contraction in DCM. 3) LVSDph showed significant correlations with other RVG parameters such as LV ejection fraction, and peak ejection rate, peak filling rate and also with LV systolic and diastolic diameter measured by echocardiography. It is concluded that LVSDph may be useful in evaluation of LV systolic and diastolic function in patients with DCM as well as LV asynchronous contraction.