Quantification and classification of potassium and calcium disorders with the electrocardiogram: What do clinical studies, modeling, and reconstruction tell us?

Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this need and becomes an established diagnostic tool allowing home monitoring of the electrolyte concentration also by wearable devices. In this review, we present the current state of potassium and calcium concentration monitoring using the ECG and summarize results from previous work. Selected clinical studies are presented, supporting or questioning the use of the ECG for the monitoring of electrolyte concentration imbalances. Differences in the findings from automatic monitoring studies are discussed, and current studies utilizing machine learning are presented demonstrating the potential of the deep learning approach. Furthermore, we demonstrate the potential of computational modeling approaches to gain insight into the mechanisms of relevant clinical findings and as a tool to obtain synthetic data for methodical improvements in monitoring approaches.

Ultimate Limit in the Spectral Resolution of Extreme Ultraviolet Frequency Combs.

We present the results of direct interferometric measurements on the pulse-to-pulse phase jitter of a metrological, fiber-based, infrared (IR) frequency comb. We show that the short-time evolution of such phase fluctuations, which cannot be actively controlled by any feedback system, imposes a stringent limit on the tooth linewidth of extreme ultraviolet (XUV) combs produced by high-order harmonic conversion, thus explaining the difference of 9 orders of magnitude between the coherence times of state-of-the-art IR and XUV frequency combs.

An ultrastable Michelson interferometer for high-resolution spectroscopy in the XUV.

We developed an ultra-stable and accurately-controllable Michelson interferometer to be used in a deeply unbalanced arm configuration for split-pulse XUV Ramsey-type spectroscopy with high-order laser harmonics. The implemented active and passive stabilization systems allow one to reach instabilities in the nanometer range over meters of relative optical path differences. Producing precisely delayed pairs of pump pulses will generate XUV harmonic pulses that may significantly improve the achievable spectral resolution and the precision of absolute frequency measurements in the XUV.

Fully automated assessment of left ventricular volumes and mass from cardiac magnetic resonance images.

Quantification of left ventricular (LV) size and function from cardiac magnetic resonance (CMR) images requires manual tracing of LV borders on multiple 2D slices, which is subjective, tedious and time-consuming experience. This paper presents a fully automated method for endocardial and epicardial boundaries detection for the assessment of LV volumes, ejection fraction (EF) and mass from CMR images. The segmentation procedure is based on a combined level set approach initialized by an automatically detected point inside the LV cavity. To validate the proposed technique, myocardial boundaries were manually traced on end-diastolic (ED) and end-systolic (ES) frames by an experienced cardiologist. Bland-Altman analysis and linear regression were used to validate LV volumes, EF and mass and similarity metrics were applied to assess the agreement between manually and automatically detected contours. We found minimal biases and narrow limits of agreement for LV volumes, EF and mass; Dice coefficient, Jaccard index and Hausdorff distance evaluated for 2D ED and ES endocardial and epicardial boundaries showed adequate overlapping. The proposed technique allows fast and accurate assessment of LV volumes, EF and mass as a basis for accurate quantification of LV size and function, and myocardial scar from CMR images.

Method for high-resolution frequency measurements in the extreme ultraviolet regime: random-sampling Ramsey spectroscopy.

Ramsey-like schemes have been recently introduced in combination with high-order laser harmonic sources for high-resolution spectroscopic studies in the extreme ultraviolet (XUV). Here we demonstrate a novel method, combining measurements only in a limited subset of randomly chosen time-sampling intervals, which lead us to perform the first high-resolution XUV spectroscopy of atomic argon with a simple split-pulse setup. Providing an experimentally simple and convenient solution to the problem of performing high-resolution absolute frequency measurements in the XUV, our approach will help paving new roads into this challenging spectral territory.

Split-pulse spectrometer for absolute XUV frequency measurements.

A split-pulse spectrometer based on pairs of time-delayed femtosecond pulses can give access to accurate frequency measurements in the extreme ultraviolet (XUV) spectral domain. We demonstrate this approach by measuring the absolute frequency of a single-XUV-photon transition to a bound state of atomic argon excited with the ninth harmonic of an amplified Ti:sapphire laser.

Left ventricular modelling: a quantitative functional assessment tool based on cardiac magnetic resonance imaging.

We present the development and testing of a semi-automated tool to support the diagnosis of left ventricle (LV) dysfunctions from cardiac magnetic resonance (CMR). CMR short-axis images of the LVs were obtained in 15 patients and processed to detect endocardial and epicardial contours and compute volume, mass and regional wall motion (WM). Results were compared with those obtained from manual tracing by an expert cardiologist. Nearest neighbour tracking and finite-element theory were merged to calculate local myocardial strains and torsion. The method was tested on a virtual phantom, on a healthy LV and on two ischaemic LVs with different severity of the pathology. Automated analysis of CMR data was feasible in 13/15 patients: computed LV volumes and wall mass correlated well with manually extracted data. The detection of regional WM abnormalities showed good sensitivity (77.8%), specificity (85.1%) and accuracy (82%). On the virtual phantom, computed local strains differed by less than 14 per cent from the results of commercial finite-element solver. Strain calculation on the healthy LV showed uniform and synchronized circumferential strains, with peak shortening of about 20 per cent at end systole, progressively higher systolic wall thickening going from base to apex, and a 10° torsion. In the two pathological LVs, synchronicity and homogeneity were partially lost, anomalies being more evident for the more severely injured LV. Moreover, LV torsion was dramatically reduced. Preliminary testing confirmed the validity of our approach, which allowed for the fast analysis of LV function, even though future improvements are possible.

Ramsey spectroscopy of bound atomic states with extreme-ultraviolet laser harmonics.

We report the experimental measurement of Ramsey interference fringes in the single-photon excitation to a high-lying bound state of atomic argon by pairs of phase-locked, time-delayed, extreme UV high-order-harmonic pulses at 87 nm. High-visibility Ramsey fringes are observed for delays larger than 100 ps, thus demonstrating a potential resolving power >10(5) at this wavelength.

The ejection of triatomic molecular hydrogen ions H(3) (+) produced by the interaction of benzene molecules with ultrafast laser pulses.

The ejection process of triatomic molecular hydrogen ions produced by the interaction of benzene with ultrafast laser pulses of moderate strong intensity ( approximately 10(14) W/cm(2)) is studied by means of TOF mass spectrometry. The H(3) (+) formation can only take place through the rupture of two C-H bonds and the migration of hydrogen atoms within the molecular structure. The H(3) (+) fragments are released with high kinetic energy (typically 2-8 eV) and at laser intensities >or=10(14) W/cm(2), well above that required for the double ionization of benzene, suggesting that its formation is taking place within multiply charged parent ions. The relative ejection efficiency of H(3) (+) molecular hydrogen ions with respect to the atomic ones is found to be strongly decreasing as a function of the laser intensity and pulse duration (67-25 fs). It is concluded that the H(3) (+) formation is only feasible within parent molecular precursors of relatively low charged states and before significant elongation of their structure takes place, while the higher multiply charged molecular ions preferentially dissociate into H(+) ions. The ejection of H(2) (+) ions is also discussed in comparison to the production of H(3) (+) and H(+) ions. Finally, by recording the mass spectra of two deuterium label isotopes of benzene (1,2-C(6)H(4)D(2), 1,4-C(6)H(4)D(2)) it is verified that the ejection efficiency of some molecular fragments, such as D(2)H(+), DH(+), is dependent on the specific position of hydrogen atoms in the molecular skeleton prior dissociation.

Vogt-Koyanagi-Harada disease after head trauma.

PURPOSE: To report two cases of Vogt-Koyanagi-Harada disease after closed head trauma. METHODS: Case report. RESULTS: Two patients, one male and one female, developed headache, dysacusis, vertigo, tinnitus, and hair hypersensitivity shortly after a closed head trauma and, 10 and 18 days later, a bilateral uveitis with papillitis and exudative retinal detachment in one and a bilateral mild uveitis with macular exudative detachment in the other. The ocular lesions resolved with intravenous high-dose steroid therapy, but recurred after reduction of the dosages, requiring further steroid therapy. The course of the disease in both patients, with the appearance of fundus depigmentation and pigment clumping, and the occurrence of a concomitant ocular and auditory relapse in one, were typical of Vogt-Koyanagi-Harada disease. CONCLUSIONS: Vogt-Koyanagi-Harada disease may appear after a closed head trauma suggesting that even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response within the eye.

Evaluation of alterations on mitral annulus velocities, strain, and strain rates due to abrupt changes in preload elicited by parabolic flight.

We tested the hypothesis that in normal subjects, cardiac tissue velocities, strain, and strain rates (SR), measured by Doppler tissue echocardiography (DTE), are preload dependent. To accomplish it, immediately preceding image acquisition, reversible, repeatable, acute nonpharmacological changes in preload were induced by parabolic flight. DTE has been proposed as a new approach to assess left ventricular regional myocardial function by computing tissue velocities, strain, and SR. However, preload dependence of these parameters in normal subjects still remains controversial. DTE images (Philips) were obtained in 10 normal subjects in standing upright position at normogravity (1 Gz), hypergravity (1.8 Gz), and microgravity (0 Gz) with and without -50 mmHg lower body negative pressure (LBNP). Myocardial velocity curves in the basal interventricular septum were reconstituted offline from DTE images, from which peak systolic (S'), early (E') and late (A') diastolic velocities, SR, and peak systolic strain (PSepsilon) were measured and averaged over four beats. At 1.8 Gz (reduced venous return), S', E', and A' decreased by 21%, 21%, and 26%, respectively, compared with 1-Gz values, while at 0 Gz (augmented venous return), E', A', and PSepsilon increased by 57%, 53%, and 49%, respectively. LBNP reduced E' and PSepsilon. In conclusion, our results were in agreement with those obtained in animal models, in which preload was changed in a controlled, acute, and reversible manner, and image acquisition was performed immediately following preload modifications. The hypothesis of preload dependence was confirmed for S', E', A', and PSepsilon, while SR appeared to be preload independent, probably reflecting intrinsic myocardial properties.

Gene expression analysis of early and advanced gastric cancers.

Gastric carcinoma is one of the major causes of cancer mortality worldwide. Early detection results in excellent prognosis for patients with early cancer (EGC), whereas the prognosis of advanced cancer (AGC) patients remains poor. It is not clear whether EGC and AGC are molecularly distinct, and whether they represent progressive stages of the same tumor or different entities ab initio. Gene expression profiles of EGC and AGC were determined by Affymetrix technology and quantitative polymerase chain reaction. Representative regulated genes were further analysed by in situ hybridization (ISH) on tissue microarrays. Expression analysis allowed the identification of a signature that differentiates AGC from EGC. In addition, comparison with normal gastric mucosa indicated that the majority of alterations associated with EGC are retained in AGC, and that further expression changes mark the transition from EGC to AGC. Finally, ISH analysis showed that representative genes, differentially expressed in the invasive areas of EGC and AGC, are not differentially expressed in the non-invasive areas of the same tumors. Our data are more directly compatible with a progression model of gastric carcinogenesis, whereby EGC and AGC may represent different molecular stages of the same tumor. Finally, the identification of an AGC-specific signature might help devising novel therapeutic strategies for advanced gastric cancer.

Changing patterns of ocular manifestations in HIV seropositive patients treated with HAART.

PURPOSE: To report the changing patterns of ocular manifestations in human immunodeficiency virus (HIV) seropositive patients treated with highly active antiretroviral therapy (HAART). METHODS: The clinical charts of HIV seropositive patients, 735 examined from 1997 to 2003 and treated with HAART for at least 2 months (Group 1), and 838 untreated examined from 1988 to 1995 (Group 2), were reviewed to assess the frequency of ocular manifestations. RESULTS: HIV-related retinal microangiopathy and opportunistic retinal infections (cytomegalovirus retinitis and toxoplasmic retinochoroiditis) were significantly higher in Group 2 than 1 (p<0.0001), while in patients treated with HAART a statistically significant increase in the frequency of chalazion (p<0.0001), diabetic and hypertensive retinopathy (p<0.0001), lipid arc of the cornea (p<0.0001), cataract and glaucoma (p<0.0001), and uveitis (p=0.026) was observed. CONCLUSIONS: HAART therapy has induced a dramatic decrease in the incidence of HIV-related microangiopathy and opportunistic retinal infection and the occurrence of new lesions related both to the metabolic alterations induced by HAART and to immune reconstitution, such as uveitis.

Tracking of left ventricular long axis from real-time three-dimensional echocardiography using optical flow techniques.

Two-dimensional echocardiography (2DE) is routinely used in clinical practice to measure left ventricular (LV) mass, dimensions, and function. The reliability of these measurements is highly dependent on the ability to obtain nonforeshortened long axis (LA) images of the left ventricle from transthoracic apical acoustic windows. Real time three-dimensional echocardiography (RT3DE) is a novel imaging technique that allows the acquisition of dynamic pyramidal data structures encompassing the entire ventricle and could potentially overcome the effects of LA foreshortening. Accordingly, the aim of this paper was to develop a nearly automated method based on optical flow techniques for the measurement of the left ventricular (LV) LA throughout the cardiac cycle from RT3DE data. The LV LA measurements obtained with the automated technique has been compared with LA measurements derived from manual selection of the LA from a volumetric display of RT3DE data. High correlation (r = .99, SEE = 1.8%, y = .94x + 5.3), no significant bias (-0.18 mm), and narrow limits of agreement (SD: 1.91 mm) were found. The comparison between the LA length derived from 2DE and RT3DE data showed significant underestimation of the 2DE based measurements. In conclusion, this study proves that RT3DE data overcome the effects of foreshortening and indicates that the method we propose allows fast and accurate quantification of LA length throughout the cardiac cycle.

Improved quantification of left ventricular mass based on endocardial and epicardial surface detection with real time three dimensional echocardiography.

OBJECTIVE: To develop a technique for volumetric analysis of real time three dimensional echocardiography (RT3DE) data aimed at quantifying left ventricular (LV) mass and to validate the technique against magnetic resonance (MR) assumed as the reference standard. DESIGN: RT3DE, which has recently become widely available, provides dynamic pyramidal data structures that encompass the entire heart and allows four dimensional assessment of cardiac anatomy and function. However, analysis techniques for the quantification of LV mass from RT3DE data are fundamentally two dimensional, rely on geometric modelling, and do not fully exploit the volumetric information contained in RT3DE datasets. Twenty one patients underwent two dimensional echocardiography (2DE), RT3DE, and cardiac MR. LV mass was measured from 2DE and MR images by conventional techniques. RT3DE data were analysed to semiautomatically detect endocardial and epicardial LV surfaces by the level set approach. From the detected surfaces, LV mass was computed directly in the three dimensional space as voxel counts. RESULTS: RT3DE measurement was feasible in 19 of 21 patients and resulted in higher correlation with MR (r = 0.96) than did 2DE (r = 0.79). RT3DE measurements also had a significantly smaller bias (-2.1 g) and tighter limits of agreement (2SD = +/-23 g) with MR than did the 2DE values (bias (2SD) -34.9 (50) g). Additionally, interobserver variability of RT3DE (12.5%) was significantly lower than that of 2DE (24.1%). CONCLUSIONS: Direct three dimensional model independent LV mass measurement from RT3DE images is feasible in the clinical setting and provides fast and accurate assessment of LV mass, superior to the two dimensional analysis techniques.

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Changes in left ventricular size during parabolic flights by two-dimensional echocardiography and level set method.

This study aims to evaluate changes on cardiac chambers size, induced by gravitational stresses. During parabolic flight, seven subjects underwent 2-D transthoracic echocardiography at three different gravity phases (1 Gz, 1.8 Gz, and 0 Gz). LV endocardial borders were detected applying a semi-automatic segmentation procedure based on level set methods. LV cavity area was computed frame-by-frame for a whole cardiac cycle during each gravity phase. Expected modifications in LV area with different gravity were found: at 1.8 Gz, end-diastolic (ED) and end-systolic (ES) areas were significantly (p<0.05) reduced of 10.7 +/- 5.4% and 21.6 +/- 11.1% respectively, compared to 1 Gz values, while they were increased of 11.2 +/- 5.4% and 11.1 +/- 6% during 0 Gz. Fractional area change was augmented of 20.9 +/- 29.1% at 1.8 Gz, while it remained unchanged at 0 Gz, compared with 1 Gz values. Furthermore, LV filling due to atrial contraction was increased at 0 Gz of 39 +/- 35.6%.

Fast interactive real-time volume rendering of real-time three-dimensional echocardiography: an implementation for low-end computers.

Real-time three-dimensional echocardiography (RT3DE) is an innovative cardiac imaging modality. However, partly due to lack of user-friendly software, RT3DE has not been widely accepted as a clinical tool. The object of this study was to develop and implement a fast and interactive volume renderer of RT3DE datasets designed for a clinical environment where speed and simplicity are not secondary to accuracy. Thirty-six patients (20 regurgitation, 8 normal, 8 cardiomyopathy) were imaged using RT3DE. Using our newly developed software, all 3D data sets were rendered in real-time throughout the cardiac cycle and assessment of cardiac function and pathology was performed for each case. The real-time interactive volume visualization system is user friendly and instantly provides consistent and reliable 3D images without expensive workstations or dedicated hardware. We believe that this novel tool can be used clinically for dynamic visualization of cardiac anatomy.

Adenosine extracellular brain concentrations and role of A2A receptors in ischemia.

Various experimental approaches have been used to determine the concentration of adenosine in extracellular brain fluid. The cortical cup technique or the microdialysis technique, when adenosine concentrations are evaluated 24 hours after implantation of the microdialysis probe, are able to measure adenosine in the nM range under normoxic conditions and in the microM range under ischemia. In vitro estimation of adenosine show that it can reach 30 microM at the receptor level during ischemia, a concentration able to stimulate all adenosine receptor subtypes so far identified. Although the protective role of A1 receptors in ischemia seems consistent, the protective role of A2A receptors appears to be controversial. Both A2A agonists and antagonists have been shown to be neuroprotective in various in vivo ischemia models. Although A2A agonists may be protective, mainly through peripherally mediated effects, A2A antagonists may be protective through local brain mediated effects. It is possible that A2A receptors are tonically activated following a prolonged increase of adenosine concentration, such as occurs during ischemia. A2A receptor activation desensitizes A1 receptors and reduces A1 mediated effects. Under these conditions A2A receptor antagonists may be protective by potentiating all the neuroprotective A1 mediated effects, including decreased neurotoxicity due to reduced ischemia induced glutamate outflow.