Cavity-enhanced biosensing utilizing plasmon resonance modes.

Traditionally, surface plasmon resonance (SPR) biosensors utilize absorption of light radiation incident upon noble metal films above the total internal reflection angles. Herein we extend the SPR phenomenon to incorporate cavity plasmon resonance (CPR) excitation of metallic films at incidence angles below the critical angle. While SPR occurs for TM polarized light only and requires very specific excitation conditions, which could be disadvantageous in some practical designs, CPR does not require complicated evanescent field excitation above the critical total internal reflection angle and can be implemented for both transverse electric (TE) and transverse magnetic (TM) fields even under normal incidence (TEM). These and other unique features of CPR enable a more flexible design of highly efficient and sensitive biosensing devices.

Optimized microbolometers with higher sensitivity for visible and infrared imaging.

Optimal absorption method for improving the sensitivity of bolometric detection is explored. We show that, in addition to its role in conventional conducting-film detection, the application of plasmon resonance absorption offers highly promising characteristics for efficient far-field thermal detection and imaging. These characteristics include good frequency sensitivity, intrinsic spatial (angle) selectivity without focusing lenses, wide tunability over both infrared and visible light domains, high responsivity and miniaturization capabilities. In this context, we examine the well-known surface plasmon resonance (SPR) regime, but also report on a new type of plasmon resonance excitation, the cavity plasmon resonance (CPR), which offers more flexibility over wide ranges of wavelengths, bandwidths, and device dimensions. Both CPR and SPR occur in metallic films, which are characterized by high thermal diffusivity essential for fast bolometric response.

Broadband absorption spectroscopy via excitation of lossy resonance modes in thin films.

It is shown that broadband absorption spectroscopy utilizing thin lossy film configurations can be optimally facilitated when applied to metallic and insulating materials. For metallic films, the zero-order highly lossy resonance mode, characterized by ultra wideband absorption behavior under normal incidence, can be shifted, under parallel-polarization oblique incidence, toward a narrow band light-wavelength surface plasmon resonance condition. Higher order low-loss modes, however, occur in thin insulating films, exhibiting Debye relaxation behavior, typical for many aqueous solutions and biological substances. They can be excited in a highly scalable and sensitive manner in various frequency bands, between light and radio frequencies.

Optimal dispersion relations for enhanced electromagnetic power deposition in dissipative slabs.

Broadband analysis of a prototype model associated with electromagnetic waves absorption in a lossy dielectric slab renders a closed-form theoretical prediction of an infinite number of optimal absorption paths in the complex refractive index domain. While for thin slabs (in terms of incident wavelength range) each path corresponds to a lossy Fabry-Perot-type resonance modes of order m=0,1,2,... and provides at least 50% absorption of the incident wave power even for ultrathin slabs, for optimal thick slabs, the fraction of absorbed power, asymptotically estimated via Lambert W function, increases up to 100% for consecutive continuation of the m=1 normal mode only.

Increased acoustic and electromagnetic energy deposition in a layered tissue model.

By analyzing and optimizing acoustic and electromagnetic waves absorption in a simplified layered model of hyperthermic configuration, it is shown that the commonly used attenuation metrics are not always proper means for determining the generally optimal parameters of typical thermal therapy problem with finite extent target The conditions, parameters and bounds for optimal (maximal) incident power absorption for the layered model have been found analytically and explicitly and are presented in terms of basic wave propagation characteristics, thus, also providing the necessary data for optimal synthesis of absorbing tissues and materials.

Mechanism of Ca++ release from the sarcoplasmic reticulum: a computer model.

The proposed model describes myocyte calcium (Ca++) cycling, emphasizing the kinetics of sarcoplasmic reticulum (SR) Ca++ release channels. The suggested SR channel regulating mechanism includes two types of Ca++ binding sites: (1) low affinity sites with high binding rates, regulating the opening of Ca++ channels and (2) high affinity sites with low binding rates, which regulate their closing. The amount of Ca++ released from the SR and the peak value of Ca++ ion concentration [Ca++] in the cytoplasm were found to depend on the rate of the increase of [Ca++], similar to Ca++ induced Ca++ release experiments. The model describes spontaneous release of Ca++ from overloaded SR. The dependence of the control mechanism on the activating and inactivating sites is substantiated by simulations of ryanodine intervention, providing results similar to experimental results. Simulations under conditions of isolated SR vesicles produced Ca++ release results similar to measured data. Consequently, it is suggested that the recovery of Ca++ release channels represents the rate limiting factor in the process of mechanical restitution.

Vascular imaging by ultrasound: 3D reconstruction of flow velocity fields for endothelial shear stress calculation.

A new method for quantitative reconstruction of a three dimensional (3D) velocity field from ultrasound color doppler mapping (USCDM) images is used here to calculate the shear stress distribution on the endothelial layer of an artery. Measurements of a few spatially unrestricted USCDM transverse cross sectional images of the artery, and of several echo-ultrasound B-mode images of the same area, are required for reconstructing the geometry of the vessel's endothelial surface. The calculation is based on assuming a physical model of flow, and solving the Continuity and the Navier-Stokes equations numerically for a steady flow of an incompressible Newtonian fluid at constant temperature within a non-flexible tube. The correct choice of the penalty parameter in the finite element method (FEM) algorithm provides proper convergence of the reconstruction. The endothelial shear stress is calculated from the gradient of the velocity field at each point of the vessel's inner surface.

Cardiovascular flow velocity measurements by 2D Doppler imaging for assessment of vascular function.

Clinical two-dimensional (2D) Doppler ultrasound flow velocity measurement is important for determination of arterial wall shear stress, blood-tissue exchange, myocardial and valvular function. Such 2D Doppler flow velocity images are usually displayed in color, superimposed on the gray-scale, cross-section structural images of the tissue. There are several limitations to this technique of flow measurement, some due to the instrumentation and some to the way the measurement is made. In this report we concentrate on the latter, identifying the main causes of errors and distortion, and outlining the methodology for minimizing them. The suggested method takes into account the spatial location and orientation of both the ultrasound transducer and the blood vessel. It allows quantification of vascular flow patterns, thus enhancing the usefulness of this important non-invasive diagnostic tool.

Propagation of depolarization and repolarization processes in the myocardium--an anisotropic model.

A three-dimensional finite-elements model of the left and right ventricles has been developed to study the process of myocardial electrical activation. The experimentally measured velocity is known to depend on membrane processes, the cellular shape, fiber orientation, and the interaction with neighboring cells. The simulated process is, therefore, governed by the geometry and by the directional conduction velocity at each point in the myocardial volume. The geometry of the ventricles is described by ellipsoidal shape, and divided to layers and sections, each filled with "cells" of preassigned properties. It allows for taking into account the local orientation of the myocardial fibers and their distributed velocities and refractory periods. The values are Gaussly distributed around the mean, and the mean and variance differ at each section. A conduction network of Purkinje "cells" is included on the endocardial surface. The anisotropic properties are demonstrated during simulation of an abnormal cardiac cycle, when propagating is initiated at an ectopic ventricular site. Ischemia is simulated by low conduction velocities in the ischemic zone and wide dispersion of values in nearby locations; automaticity is described by restimulating "cells" in the injured area; the dangerous effects of a premature beat leading to reentry are simulated by reduction of propagation velocity in "cells" that are reactivated while they repolarize. The different activation patterns are calculated throughout the myocardium and on its surface. The generated surface activation maps are not sensitive to minute changes in location of the foci of activation within the normal conduction system. The maps show sensitivity to pathological velocities, ischemic areas, and the existence of ectopic foci.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative characterization and sorting of three-dimensional geometries: application to left ventricles in vivo.

A procedure for automatic sorting of three-dimensional (3-D) shapes is proposed. The procedure is applied to sort into normal and abnormal categories, human left ventricles (LV) using in vivo data from 19 subjects (ten normal and nine abnormal LV's) studied by ultrafast tomography (Cine-CT). The procedure starts by utilizing a vector in a helical coordinate system to describe the spatial geometry of each individual LV cavity. This individual vector is then anatomically aligned and normalized to eliminate effects due to size, yielding a dimensionless vector, denoted as "geometrical cardiogram" (GCG). The GCG characterizes the instantaneous 3-D geometrical information of the individual LV. For the group of healthy subjects, the Karhunen-Loeve Transform (KLT) is then applied to compress the geometric information contained in their individuals' GCG vectors, at end diastole (ED) and end systole (ES), and yield a unique set of basis vectors. The "normal shape domain" is next defined as a truncated set of the KLT basis vectors from which a normal GCG can be reconstructed with a mean squared error (MSE) smaller than a defined threshold. The calculated MSE of any individual GCG reconstructed in this domain is then used as a criterion for sorting the 3-D shapes. Hearts which yield MSE greater than the threshold are considered abnormal. When applied to the study group of 19 subjects a significant difference (p less than 0.0001) between the MSE values obtained for the normal LV's, and those obtained for the abnormal LV's was detected, thus leading to a successful sorting of all the studied LV's. Finally, the KLT is applied to yield a compact representation of the 3-D geometry of any LV (normal or abnormal).

Gastric inhibitory polypeptide (GIP) responses after oral glucose ingestion in hyperthyroidism.

Gastric inhibitory polypeptide (GIP) is a gastrointestinal hormone stimulated after oral nutrient ingestion, but not after intravenous nutrient administration. GIP stimulates insulin release in the presence of hyperglycemia and as such is considered a major enteroinsular hormone. Since elevated glucose and insulin levels are found in hyperthyroidism, we compared the GIP responses to oral glucose ingestion in 12 hyperthyroid patients and 10 age-matched controls. Seventy-five grams of oral glucose was ingested after overnight fasting and samples were obtained at 0, 30, 60, 90, 120, and 180 min for serum glucose and immunoreactive insulin (IRI) and GIP (IRGIP). The mean serum glucose levels in hyperthyroid subjects were significantly higher (P less than or equal to 0.05) at every time studied except at 180 min. At 60 min, peak mean glucose was 171 +/- 14 mg/dl versus 128 +/- 7 mg/dl in controls (P less than 0.02). Except for fasting, mean IRI levels were significantly higher (P less than 0.001) in hyperthyroid subjects than in controls at all times studied. At 60 min, IRI rose to a peak of 125 +/- 11 microU/ml in hyperthyroid subjects versus 50 +/- 9 microU/ml in controls (P less than 0.001). Mean fasting, stimulated, and incremental IRGIP levels were slightly higher but not statistically different in the hyperthyroid subjects versus controls. Glucose and IRI responses are exaggerated in hyperthyroidism after oral glucose ingestion. Even though GIP has insulinotropic action, its role in the hyperinsulinism found in hyperthyroid subjects appears to be minimal.

Significance of spontaneous ketonuria and serum C-peptide levels in obese type II diabetic patients.

Patients with type II diabetes mellitus (type II DM patients) are characteristically obese, hyperinsulinemic, and non-ketosis prone. Recently, we have encountered several obese type II DM patients with either diabetic ketoacidosis or significant ketonuria after insulin withdrawal. There was no evidence of infection, stress, or starvation to explain their ketonuria. Therefore, we assessed serum connecting peptide (C-peptide) response to oral glucose in 14 obese, insulin-treated type II DM patients: 6 with and 8 without episodes of spontaneous ketonuria. The group presenting with ketonuria had low to absent basal and stimulated serum C-peptide responses. The nonketonuric group had higher basal C-peptide (P less than 0.01) concentrations that increased significantly (P less than 0.001) after oral glucose compared with those of the ketonuric group. Clinical characteristics and biochemical control were similar in both groups. Our findings confirm that obese type II diabetes mellitus is a heterogeneous disease with variable fasting and stimulated C-peptide responses. Spontaneous ketonuria could be a feature in the clinical presentation of the patients especially in the presence of both low fasting and stimulated C-peptide levels. The significance of these findings is unclear but suggests individualization in the management of type II DM patients and cautious withdrawal of insulin therapy in such patients. Furthermore, serum C-peptide levels alone cannot be recommended to classify patients into either type I or type II diabetes mellitus.

Decreased serum C-peptide/insulin molar ratios after oral glucose ingestion in hyperthyroid patients.

Since C-peptide/immunoreactive insulin (IRI) molar ratios may reflect hepatic extraction of insulin, we measured simultaneous serum glucose, IRI, and C-peptide levels during fasting and 30, 60, 90, 120, and 180 min after 75 g of oral glucose in 10 hyperthyroid patients and 10 age- and weight-matched controls. Mean fasting serum glucose and IRI levels were significantly higher in the hyperthyroid versus control subjects (glucose: 4.9 +/- 0.3 mmol/L versus 4.36 +/- 0.11 mmol/L, P less than 0.01; IRI: 0.10 +/- 0.02 pmol/ml versus 0.05 +/- 0.01 pmol/ml; P less than 0.025). After glucose, mean serum glucose levels were significantly higher in the hyperthyroid versus control subjects at all times studied except for 180 min (P less than 0.01). Mean IRI levels were significantly higher at all times studied including 180 min (P less than 0.01). Mean fasting C-peptide levels were significantly greater in the hyperthyroid patients compared with the controls (1.2 +/- 0.25 pmol/ml versus 0.62 +/- 0.09 pmol/ml; P less than 0.025). After oral glucose, mean C-peptide levels were significantly higher (P less than 0.025) in the hyperthyroid compared with control subjects at 30-60 min but not at 90-180 min. Molar ratios of C-peptide/IRI were significantly lower (P less than 0.05) in the hyperthyroid versus control subjects at all times studied except fasting. In summary, glucose intolerance and hyperinsulinism occur in hyperthyroidism. In addition, C-peptide/IRI molar ratios are reduced after oral glucose ingestion.

Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation.

Susceptibility of the ventricles to fibrillation has been related to the degree of spatial inhomogeneity in the repolarization process. We studied the pattern of beat-to-beat fluctuations in ventricular repolarization processes in order to determine whether a relationship also exists between the temporal variability of ventricular repolarization and susceptibility to ventricular fibrillation. We used the morphology of the T-wave recorded in surface and epicardial leads as a measure of the ventricular repolarization process. The Ventricular Fibrillation Threshold (VFT) was used as the standard measure of cardiac susceptibility to fibrillation. In dog experiments, T-wave morphologic indices were computed on 1,024 sequential beats. Histogram, autocorrelation and power spectrum analyses were performed on the sequence of T-wave morphologic indices. A series of 27 experiments were performed on 20 dogs in which VFT was reduced by several different interventions--hypothermia, tachycardia and coronary artery ligation. For all three interventions we observed the same characteristic change in the pattern of T-wave morphology fluctuations. In particular, we found that as the VFT was reduced, a pattern of T-wave alternans developed. This pattern was generally not detectable by visual inspection of the ECG. It was, on the other hand, easily quantified in terms of a T-wave alternans index (TWAI) which we computed from the power spectrum of the T-wave fluctuations. In 26 of the 27 experiments, measured VFT decreased (p less than .001); in 20 of these experiments the TWAI computed from the surface ECG increased (decreased) when VFT decreased (increased) (p less than .01). In 17 experiments epicardial electrograms were recorded. In 16 of these experiments VFT decreased (p less than .001). In 16 of these 17 experiments TWAI computed from the epicardial ECG increased (decreased) when the VFT decreased (increased) (p less than .001). We conclude that statistical analysis of fluctuations in ECG complex morphology may provide a sensitive probe of ventricular vulnerability to fibrillation.

Period multupling-evidence for nonlinear behaviour of the canine heart.

Although there has recently been considerable interest in applying the theory of nonlinear dynamics to the analysis of complex systems, as yet applications of the theory to biological systems in vivo have been very limited. We report here evidence of nonlinear behaviour in the electrocardiogram and arterial blood pressure traces of the noradrenaline-treated dog. Noradrenaline produces variations in these traces that repeat themselves with regular periods of integral numbers of heart-beats (period multupling), an effect that resembles the 'period-doubling' and other 'bifurcative' behaviour observed when the driving frequency of a nonlinear oscillator is increased above a critical value. The simplest type of periodic variation that we report is the so-called 'electrical alternans', which has long been known as one response of cardiac electrical activity to certain stresses and disease states.