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Biomedical subjects

Kim H Parker

Publications and source records attributed to Kim H Parker.

At least 19 recordsLinked to original sources

Segmentation of blood vessels from red-free and fluorescein retinal images.

The morphology of the retinal blood vessels can be an important indicator for diseases like diabetes, hypertension and retinopathy of prematurity (ROP). Thus, the measurement of changes in morphology of arterioles and venules can be of diagnostic value. Here we present a method to automatically segment retinal blood vessels based upon multiscale feature extraction. This method overcomes the problem of variations in contrast inherent in these images by using the first and second spatial derivatives of the intensity image that gives information about vessel topology. This approach also enables the detection of blood vessels of different widths, lengths and orientations. The local maxima over scales of the magnitude of the gradient and the maximum principal curvature of the Hessian tensor are used in a multiple pass region growing procedure. The growth progressively segments the blood vessels using feature information together with spatial information. The algorithm is tested on red-free and fluorescein retinal images, taken from two local and two public databases. Comparison with first public database yields values of 75.05% true positive rate (TPR) and 4.38% false positive rate (FPR). Second database values are of 72.46% TPR and 3.45% FPR. Our results on both public databases were comparable in performance with other authors. However, we conclude that these values are not sensitive enough so as to evaluate the performance of vessel geometry detection. Therefore we propose a new approach that uses measurements of vessel diameters and branching angles as a validation criterion to compare our segmented images with those hand segmented from public databases. Comparisons made between both hand segmented images from public databases showed a large inter-subject variability on geometric values. A last evaluation was made comparing vessel geometric values obtained from our segmented images between red-free and fluorescein paired images with the latter as the "ground truth". Our results demonstrated that borders found by our method are less biased and follow more consistently the border of the vessel and therefore they yield more confident geometric values.

Algorithms↗

Detection of nitric oxide release from single neurons in the pond snail, Lymnaea stagnalis.

Multiple film-coated nitric oxide sensors have been fabricated using Nafion and electropolymerized polyeugenol or o-phenylenediamine on 30-microm carbon fiber disk electrodes. This is a rare study that utilizes disk electrodes rather than the widely used protruding tip microelectrodes in order to measure from a biological environment. These electrodes have been used to evaluate the differences in nitric oxide release between two different identified neurons in the pond snail, Lymnaea stagnalis. These results show the first direct measurements of nitric oxide release from individual neurons. The electrodes are very sensitive to nitric oxide with a detection limit of 2.8 nM and a sensitivity of 9.46 nA microM-1. The sensor was very selective against a variety of neurochemical interferences such as ascorbic acid, uric acid, and catecholamines and secondary oxidation products such as nitrite. Nitric oxide release was measured from the cell bodies of two neurons, the cerebral giant cell (CGC) and the B2 buccal motor neuron, in the intact but isolated CNS. A high-Ca2+/high-K+ stimulus was capable of evoking reproducible release. For a given stimulus, the B2 neuron released more nitric oxide than the CGC neuron; however, both cells were equally suppressed by the NOS inhibitor l-NAME.

Animals↗

Subsecond voltammetric separation between dopamine and serotonin in the presence of ascorbate.

Although voltammetry has proved an important tool for unraveling the dynamics of specific neurotransmitter molecules during the past decade, it has been very difficult to monitor more than one neurotransmitter simultaneously. In this work, we present a voltammetric methodology that allows discrimination between dopamine and serotonin, two important neurotransmitter molecules with very similar electrochemical properties, in the presence of high concentrations of ascorbate. We combined the application of a novel large-amplitude/high-frequency voltage excitation with signal processing techniques valid for the analysis of nonstationary and nonlinear phenomena. This allows us to minimize the contribution from capacitance and preserve the faradaic features of the voltammetric response providing us with excellent voltammetric detail. Using appropriate voltage excitation parameters and defining specific regions in the voltage space, so-called voltage windows, we can measure the concentrations of dopamine and serotonin separately or independently in mixed solutions even in the presence of high concentrations of ascorbate. Because of the enhanced voltammetric detail of this new technique, it is also possible to explore effects attributed to interfacial phenomena such as adsorption/desorption and electrode fouling.

Ascorbic Acid↗

Microwave induced jet boiling investigated via voltammetry at ring-disk microelectrodes.

High intensity microwave radiation is (self-)focused at metal electrodes immersed in aqueous electrolyte solutions to generate highly localized superheating and convection effects. It is shown that, for an electrode pointing downward, low intensity microwave radiation causes density driven convective flow (upward), which at the onset of boiling abruptly switches to a fast jet of liquid moving away from the electrode surface (downward). This "jet-boiling" phenomenon allows extremely high rates of mass transport and mixing to be realized at the electrode surface. Cyclic voltammograms obtained at electrodes placed into a microwave field show very strong mass transport enhancement effects. Cyclic voltammograms recorded at a Pt/Pt ring-disk electrode system (r(1) = 25 microm, r(2) = 32 microm, r(3) = 32.4 microm) in the presence of microwave radiation are employed to further explore mass transport effects under microwave conditions. Mass transport coefficients, collection efficiencies, and temperatures are determined as a function of microwave intensity.

Chemistry, Physical↗

Characterization of ac voltammetric reaction-diffusion dynamics: from patterns to physical parameters.

Despite the widespread use of electrochemical sensing techniques, the determination of the physical parameters from the current response of rapid voltammetric measurements has been difficult for two reasons: large capacitance contributions overwhelm the current response of transient measurements and the reaction dynamics are inherently nonlinear and nonstationary. In this work, we present a signal processing methodology that in combination with a large-amplitude/high-frequency voltage waveform method, ac voltammetry, is able to determine the underlying physical parameters in heterogeneous electrochemical reaction-diffusion processes. Through a large number of numerical calculations, we explore the effect of kinetic, thermodynamic, and mass transport parameters on two components of the current response, the even and the odd. We study the even component directly whereas for the odd component, which is considerably influenced by capacitance, we use the Hilbert transform, which is suitable for the analysis of nonstationary and nonlinear data sets, to minimize the capacitance contribution. The theoretical analysis is applied to measurements of well-characterized electrochemical reactions, Ru(NH3)6(2+/3+) and Fe(CN)6(4-/3-), using two different electrode materials, glassy carbon and platinum, and the physical parameters deduced are in excellent agreement with published results.

Diffusion↗

Metal-metal oxide pH sensors for physiological application.

Metal-metal oxide electrodes provide robust and miniaturised pH sensors. Iridium oxide electrodes prepared by thermal oxidation and by anodisation are described and their relative merits discussed. The effects of chloride and protein adsorption on sensor performance are investigated using cyclic voltammetry and the mechanism by which Nafion membranes can stabilise sensor response is identified. Applications in cultured intervertebral disc are reported.

Biosensing Techniques↗

Evidence of a dominant backward-propagating "suction" wave responsible for diastolic coronary filling in humans, attenuated in left ventricular hypertrophy.

BACKGROUND: Coronary blood flow peaks in diastole when aortic blood pressure has fallen. Current models fail to completely explain this phenomenon. We present a new approach-using wave intensity analysis-to explain this phenomenon in normal subjects and to evaluate the effects of left ventricular hypertrophy (LVH). METHOD AND RESULTS: We measured simultaneous pressure and Doppler velocity with intracoronary wires in the left main stem, left anterior descending, and circumflex arteries of 20 subjects after a normal coronary arteriogram. Wave intensity analysis was used to identify and quantify individual pressure and velocity waves within the coronary artery circulation. A consistent pattern of 6 predominating waves was identified. Ninety-four percent of wave energy, accelerating blood forward along the coronary artery, came from 2 waves: first a pushing wave caused by left ventricular ejection-the dominant forward-traveling pushing wave; and later a suction wave caused by relief of myocardial microcirculatory compression-the dominant backward-traveling suction wave. The dominant backward-traveling suction wave (18.2+/-13.7 x 10(3) W m(-2)s(-1), 30%) was larger than the dominant forward-traveling pushing wave (14.3+/-17.6 x 10(3) W m(-2) s(-1), 22.3%, P =0.001) and was associated with a substantially larger increment in coronary blood flow velocity (0.51 versus 0.14 m/s, P <0.001). In LVH, the dominant backward-traveling suction wave percentage was significantly decreased (33.1% versus 26.9%, P =0.01) and inversely correlated with left ventricular septal wall thickness (r =-0.52, P <0.02). CONCLUSIONS: Six waves predominantly drive human coronary blood flow. Coronary flow peaks in diastole because of the dominance of a "suction" wave generated by myocardial microcirculatory decompression. This is significantly reduced in LVH.

Adult↗

Quantification of topological changes in retinal vascular architecture in essential and malignant hypertension.

OBJECTIVE: Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation. METHODS: The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees. RESULTS: EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects. CONCLUSIONS: Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.

Adult↗

Use of simultaneous pressure and velocity measurements to estimate arterial wave speed at a single site in humans.

It has not been possible to measure wave speed in the human coronary artery, because the vessel is too short for the conventional two-point measurement technique used in the aorta. We present a new method derived from wave intensity analysis, which allows derivation of wave speed at a single point. We apply this method in the aorta and then use it to derive wave speed in the human coronary artery for the first time. We measured simultaneous pressure and Doppler velocity with intracoronary wires at the left main stem, left anterior descending and circumflex arteries, and aorta in 14 subjects after a normal coronary arteriogram. Then, in 10 subjects, serial measurements were made along the aorta before and after intracoronary isosorbide dinitrate. Wave speed was derived by two methods in the aorta: 1) the two-site distance/time method (foot-to-foot delay of pressure waveforms) and 2) a new single-point method using simultaneous pressure and velocity measurements. Coronary wave speed was derived by the single-point method. Wave speed derived by the two methods correlated well (r = 0.72, P < 0.05). Coronary wave speed correlated with aortic wave speed (r = 0.72, P = 0.002). After nitrate administration, coronary wave speed fell by 43%: from 16.4 m/s (95% confidence interval 12.6-20.1) to 9.3 m/s (95% confidence interval 6.5-12.0, P < 0.001). This single-point method allows determination of wave speed in the human coronary artery. Aortic wave speed is correlated to coronary wave speed. Finally, this technique detects the prompt fall in coronary artery wave speed with isosorbide dinitrate.

Aorta↗

Systemic venous circulation. Waves propagating on a windkessel: relation of arterial and venous windkessels to systemic vascular resistance.

Compared with arterial hemodynamics, there has been relatively little study of venous hemodynamics. We propose that the venous system behaves just like the arterial system: waves propagate on a time-varying reservoir, the windkessel, which functions as the reverse of the arterial windkessel. During later diastole, pressure increases exponentially to approach an asymptotic value as inflow continues in the absence of outflow. Our study in eight open-chest dogs showed that windkessel-related arterial resistance was approximately 62% of total systemic vascular resistance, whereas windkessel-related venous resistance was only approximately 7%. Total venous compliance was found to be 21 times larger than arterial compliance (n = 3). Inferior vena caval compliance (0.32 +/- 0.015 ml x mmHg(-1) x kg(-1); mean +/- SE) was approximately 14 times the aortic compliance (0.023 +/- 0.002 ml x mmHg(-1) x kg(-1); n = 8). Despite greater venous compliance, the variation in venous windkessel volume (i.e., compliance x windkessel pulse pressure; 7.8 +/- 1.1 ml) was only approximately 32% of the variation in aortic windkessel volume (24.3 +/- 2.9 ml) because of the larger arterial pressure variation. In addition, and contrary to previous understanding, waves generated by the right heart propagated upstream as far as the femoral vein, but excellent proportionality between the excess pressure and venous outflow suggests that no reflected waves returned to the right atrium. Thus the venous windkessel model not only successfully accounts for variations in the venous pressure and flow waveforms but also, in combination with the arterial windkessel, provides a coherent view of the systemic circulation.

Animals↗

Thermal fluctuations of red blood cell membrane via a constant-area particle-dynamics model.

We describe a model of the mechanical properties of the cell plasma membrane using a finite-temperature particle-dynamics simulation of the whole cell, in which a two-dimensional network of virtual particles embedded in a three-dimensional closed surface represents the membrane. The particles interact via harmonic potential and dihedral angle potential and are subject to a constant area constraint. The evolution of the positions of the particles yields the equilibrium state of the membrane and allows determination of the membrane thermal fluctuations and the elastic moduli. We show that time-averaging of the cell-model configurations allows quantitative comparison with experimental data on membrane fluctuations and elastic moduli of the red blood cell.

Cell Polarity↗

Determination of kinetic and thermodynamic parameters of surface confined species through ac voltammetry and a nonstationary signal processing technique: the Hilbert transform.

Data analysis of voltammetric responses has usually been done through application of the fast Fourier transform although it is widely accepted that electrochemical signals are intrinsically nonlinear and nonstationary. In this work, we present a time-series analysis based on the Hilbert transform (HT), a nonstationary signal processing technique, as an alternative tool that can overcome many of the difficulties associated with Fourier techniques. We use the HT to study the behavior of thin-film processes when the excitation perturbation is ac voltammetry. From the analysis of simulated data, we propose simple relations that enable species-specific kinetic and thermodynamic parameters to be estimated, without prior utilization of baseline subtraction even when double layer capacitance significantly influences the current response. We also propose a method to determine whether the characteristics of the applied voltage perturbation are adequate for the accurate estimation of these parameters. The methodology developed here will be applied to previously published experimental time series data (Guo, S. X.; Zhang, J.; Elton, D. M.; Bond, A. M. Anal. Chem. 2004, 76, 166-177.) obtained with ac voltammetry to show how a number of physical parameters can be directly extracted from the processed data.

Algorithms↗

Simple and rapid determination of serotonin and catecholamines in biological tissue using high-performance liquid chromatography with electrochemical detection.

Using the CNS of Lymnaea stagnalis a method is described for the rapid analysis of neurotransmitters and their metabolites using high performance liquid chromatography coupled with electrochemical detection. Tissue samples were homogenised in ice-cold 0.1 M perchloric acid and centrifuged. Using a C(18) microbore column the mobile phase was maintained at a flow rate of 100 microl/min and consisted of sodium citrate buffer (pH 3.2)-acetonitrile (82.5:17.5, v/v) with 2 mM decane-sulfonic acid sodium salt. The potential was set at +750 mV versus Ag|AgCl reference electrode at a sensitivity of 50 nA full scale deflection. The detection limit for serotonin was 11.86 ng ml(-1) for a 5 microl injection. Preparation of tissue samples in mobile phase reduced the response to dopamine and serotonin compared with perchloric acid. In addition it was found that the storage of tissue samples at -20 degrees C caused losses of dopamine and serotonin. As a result of optimising the sample preparation and mobile phase the total time of analysis was substantially reduced resulting in a sample preparation and assay time of 15-20 min.

Animals↗

Intra-aortic balloon pumping: does posture matter?

BACKGROUND: The effect of the posture of semirecumbent patients on the hemodynamics and performance of intra-aortic balloon (IAB) were studied in vivo and in vitro. METHODS: An IAB was inserted into a glass tube filled with saline, fully inflated and deflated using an intra-aortic balloon pump (IABP). Three successive cycles were filmed at 125 frames/s with the tube positioned at various angles between 0 degrees (horizontal) and 90 degrees (vertical). Pressure and flow were measured distal to both ends of the balloon. In parallel, coronary left anterior descending (LAD) flow velocity and aortic pressure were recorded in 6 patients using IABP, postcardiac surgery in the intensive care unit. Recordings were made when the patient was lying horizontally (recumbent) and when the patient's torso was inclined at 30 degrees to the horizontal (semirecumbent). RESULTS: With the tube horizontal, the inflation was effectively uniform along the length of the balloon. At all other angles, the higher end of the balloon inflated first, and mean pressure and flow measured distal to the higher end of the balloon were less than those measured at 0 degrees . Mean aortic pressure and LAD flow decreased by 10 +/- 2% (P = 0.001) and 15 +/- 3% (P = 0.001), respectively, when the patient was semirecumbent compared to when the patient was recumbent. CONCLUSION: The decreased mean aortic pressure and LAD flow velocity suggests that unless patients using IABP are required to be semirecumbent, it may be best to position them horizontally to gain the full benefits of balloon counter pulsation to the coronary circulation.

Aged↗

Assessment of left ventricular diastolic suction in dogs using wave-intensity analysis.

Two apparently different types of mechanisms have emerged to explain diastolic suction (DS), that property of the left ventricle (LV) that tends to cause it to refill itself during early diastole independent of any force from the left atrium (LA). By means of the first mechanism, DS depends on decreased elastance [e.g., the relaxation time constant (tau)] and, by the second, end-systolic volume (V(LVES)). We used wave-intensity analysis (WIA) to measure the total energy transported by the backward expansion wave (I(W-)) during LV relaxation in an attempt to reconcile these mechanisms. In six anesthetized, open-chest dogs, we measured aortic, LV (P(LV)), LA (P(LA)), and pericardial pressures and LV volume by orthogonal ultrasonic crystals. Mitral velocity was measured by Doppler echocardiography, and aortic velocity was measured by an ultrasonic flow probe. Heart rate was controlled by pacing, V(LVES) by volume loading, and tau by isoproterenol or esmolol administration. I(W-) was found to be inversely related to tau and V(LVES). Our measure of DS, the energy remaining after mitral valve opening, I(W-DS), was also found to be inversely related to tau and V(LVES) and was approximately 10% of the total "aspirating" energy generated by LV relaxation (i.e., I(W-)). The size of the Doppler (early filling) E wave depended on I(W-DS) in addition to I(W+), the energy associated with LA decompression. We conclude that the energy of the backward-going wave generated by the LV during relaxation depends on both the rate at which elastance decreases (i.e., tau) and V(LVES). WIA provides a new approach for assessing DS and reconciles those two previously proposed mechanisms. The E wave depends on DS in addition to LA decompression.

Animals↗

Effects of left ventricular contractility and coronary vascular resistance on coronary dynamics.

Wave-intensity analysis, which separates upstream from downstream events and defines their interaction, has been used to study the effects of changes in left ventricular (LV) contractility (E(max)) and left circumflex coronary artery resistance (R(LCx)) on the coronary systolic flow impediment (CSFI). In 10 anesthetized, open-chest dogs, we measured coronary, aortic, and LV pressures, coronary velocity (Flowire), and flow. E(max) was increased by paired pacing and R(LCx) was modulated by intracoronary infusions of vasodilators (adenosine and nitroglycerin) and a vasoconstrictor (phenylephrine). When both E(max) and R(LCx) were varied, CSFI and the energy of the backward-going compression wave (I(W-)) were greatest at the highest levels of E(max) and the lowest levels of R(LCx). I(W-) was proportional to the CSFI. We conclude that contractility and coronary resistance change CSFI by modulating the backward-going compression wave.

Algorithms↗

Direct and series transmission of left atrial pressure perturbations to the pulmonary artery: a study using wave-intensity analysis.

Pressure waves are thought to travel from the left atrium (LA) to the pulmonary artery (PA) only retrogradely, via the vasculature. In seven anesthetized open-chest dogs, a balloon was placed in the LA, which was rapidly inflated and deflated during diastole, early systole, and late systole. High-fidelity pressures were measured within and around the heart. Measurements were made at low volume [LoV; left ventricular end-diastolic pressure (LVEDP) = 5-9 mmHg], high volume (HiV; LVEDP = 16-19 mmHg), and HiV with the pericardium removed. Wave-intensity analysis demonstrated that, except during late systole, balloon inflation created forward-going PA compression waves that were transmitted directly through the heart without measurable delay; backward PA compression waves were transmitted in-series through the pulmonary vasculature and arrived after delays of 90 +/- 3 ms (HiV) and 103 +/- 5 ms (LoV; P < 0.05). Direct transmission was greater during diastole, and both direct and series transmission increased with volume loading. Pressure waves from the LA arrive in the PA by two distinct routes: rapidly and directly through the heart and delayed and in-series through the pulmonary vasculature.

Animals↗

Intra-aortic balloon pumping: effects on left ventricular diastolic function.

OBJECTIVE: The intra-aortic balloon pump is the most widely used form of temporary cardiac assist and often utilised in patients before and after cardiac surgery. Several effects of balloon counter-pulsation have been reported previously, but its effect on left ventricular diastolic function has not been thoroughly investigated. The aim of this study is to examine the effect of the intra-aortic balloon pump on left ventricular wall motion and transmitral flow. METHODS: We studied 20 patients in the intensive care unit, less than 36 h following cardiac surgery. We recorded left anterior descending coronary artery and transmitral E-wave flow velocities using transesophageal echocardiography pulsed Doppler. We also recorded left ventricular long axis free-wall movement using M-mode. The intra-aortic balloon pump was set to full augmentation and recordings were made at pumping cycles 1:1, 1:2, 1:3, and when the pump was on stand-by, leaving a minimum of 5 min between the pumping modes to allow the return to control conditions. In order to eliminate time effects, the sequence of recording was varied between patients using a 4 by 4 Latin-square. RESULTS: The peak diastolic left anterior descending coronary artery and transmitral E-wave flow velocities, and left ventricular free-wall early diastolic lengthening velocity increased significantly with intra-aortic balloon pumping cycles 1:1, 1:2 and 1:3 compared to their value with the pump on stand-by, all P < 0.001. The increase in peak transmitral E-wave flow velocity correlated with the increase in peak left anterior descending coronary artery diastolic flow velocity (r = 0.74, P = 0.02), and with the increase in left ventricular free-wall early diastolic lengthening velocity (r = 0.80, P < 0.001). CONCLUSION: Using the intra-aortic balloon pump post-cardiac surgery significantly increases peak diastolic left anterior descending coronary artery flow velocities and left ventricular free-wall early diastolic lengthening velocity, whose increase explains the increase in peak transmitral E-wave velocity. Although coronary flow is epicardial and mitral flow is intracardial, their close relationship suggests an improvement in left ventricular diastolic function with intra-aortic balloon pump.

Aged↗