Electro-Thermal Bioinstrumentation Laboratory

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Selected Research Papers

Admittance for Detecting the Progression of Heart Failure
Admittance measured using chronically implanted RV and Bi-V AICD leads can monitor increases in cardiac size with the onset of acute decompensated HF. Admittance can not only detect heart dilation but can also track heart function as the heart dilates and systolic dysfunction develops. Thus admittance measurements with ICD leads could potentially serve as an effective tool for detecting the progression of HF. Heart Rhythm Society May 2015

Stroke Volume Detection Using Existing RV Shocking Leads
Modern ICDs monitor intracardiac electrograms (EGM) and respond to detected arrhythmias through observation, anti-tachycardia pacing or shock delivery. However, inappropriate shocks are delivered to many patients within the first year. Coupling EGMs with a hemodynamic assessment of RV Stroke Volume (SV) may help to discriminate between malignant and benign arrhythmias. We propose the use of admittance measured using a single existing RV lead, as a new method to monitor right sided hemodynamics. Heart Rhythm Society May 2014

Analysis of the Spatial Sensitivity of Conductance / Admittance Catheter Ventricular Volume Estimation
Conductance catheters are known to have a nonuniform spatial sensitivity due to the distribution of the electric field. The Geselowitz relation is applied to murine and multi-segment conductance catheters using finite element models to determine the spatial sensitivity in a uniform medium and simplified left ventricle models. A new formulation is proposed that allows determination of the spatial sensitivity to admittance.
Analysis of FEM numerical modeling results using the Geselowitz relation provides a true measure of parallel conductance in simplified left ventricle models for assessment of the admittance method and hypertonic saline techniques. The spatial sensitivity of blood conductance (Gb) is determined throughout the cardiac cycle. Gb is converted to volume using Wei’s equation to determine if the presence of myocardium alters the nonlinear relationship through changes to the electric field. Results show that muscle conductance (Gm) from the admittance method matches results from the Geselowitz relation, and that the relationship between Gb and volume is accurately fit using Wei’s equation. Single segment admittance measurements in large animals result in a more evenly distributed sensitivity to the LV blood pool. The hypertonic saline method overestimates parallel conductance throughout the cardiac cycle in both murine and multi-segment conductance catheters. IEEE Transactions on Biomedical Engineering, TBME-01930-2012.R1, Volume: 60 Issue: 8, pp1-9, August 2013

Embedded Medical Devices: Pressure Volume Loops in Rodents
A medical device, implanted in conscious, ambulatory rodents, measures cyclic left ventricle blood volume and pressure. The volume sensing component of the catheter consists of electrodes in a tetrapolar configuration. The same catheter has a high fidelity micro pressure sensor centered in the electrode array. In addition to the two sensors, the embedded device requires a microcontroller, analog electronics, wireless communication and a battery. For optimal ergonomics, the miniaturized implant package is located subcutaneously between the rat’s shoulder blades. The device samples dynamic pressure and volume using an energy conserving duty cycle scheme, and transmits the raw data to a base station. The base station converts the raw data to calibrated pressure and blood volume units. The calibrated signals are plotted in XY format as pressure-vs-volume loops. The pressure-volume data provided by the embedded device provides academic and pharmaceutical researchers with a broad index of established cardiovascular parameters that are used for assessing heart performance and advancing the field of cardiology. IEEE Potentials, November/December 2012

A bio-telemetric device for measurement of left ventricular pressure–volume loops using the admittance technique in conscious, ambulatory rats
This paper presents the design, construction and testing of a device to measure pressure–volume loops in the left ventricle of conscious, ambulatory rats. Pressure is measured with a standard sensor, but volume is derived from data collected from a tetrapolar electrode catheter using a novel admittance technique. There are two main advantages of the admittance technique to measure volume. First, the contribution from the adjacent muscle can be instantaneously removed. Second, the admittance technique incorporates the nonlinear relationship between the electric field generated by the catheter and the blood volume. A low power instrument weighing 27 g was designed, which takes pressure–volume loops every 2 min and runs for 24 h. Pressure–volume data are transmitted wirelessly to a base station. The device was first validated on 13 rats with an acute preparation with 2D echocardiography used tomeasure true volume. From an accuracy standpoint, the admittance technique is superior to both the conductance technique calibrated with hypertonic saline injections, and calibrated with cuvettes. The device was then tested on six rats with 24 h chronic preparation. Stability of animal preparation and careful calibration are important factors affecting the success of the device. Physiol. Meas. 32 (2011) 701–715

Left ventricular epicardial admittance measurement for detection of acute LV dilation
There are two implanted heart failure warning systems incorporated into biventricular pacemakers/automatic implantable cardiac defibrillators and tested in clinical trials: right heart pressures, and lung conductance measurements. However, both warning systems postdate measures of the earliest indicator of impending heart failure: left ventricular (LV) volume. There are currently no proposed implanted technologies that can perform LV blood volume measurements in humans. We propose to solve this problem by incorporating an admittance measurement system onto currently deployed biventricular and automatic implantable cardiac defibrillator leads. This study will demonstrate that an admittance measurement system can detect LV blood conductance from the epicardial position, despite the current generating and sensing electrodes being in constant motion with the heart, and with dynamic removal of the myocardial component of the returning voltage signal. Specifically, in 11 pigs, it will be demonstrated that 1) a physiological LV blood conductance signal can be derived; 2) LV dilation in response to dose-response intravenous neosynephrine can be detected by blood conductance in a similar fashion to the standard of endocardial crystals when admittance is used, but not when only traditional conductance is used; 3) the physiological impact of acute left anterior descending coronary artery occlusion and resultant LV dilation can be detected by blood conductance, before the anticipated secondary rise in right ventricular systolic pressure; and 4) a pleural effusion simulated by placing saline outside the pericardium does not serve as a source of artifact for blood conductance measurements. Journal of Applied Physiology (JAPPL-01047-2010R1, 2010) Volume 110: 799–806, 2011.

Kahn Process Networks Applied to Distributed Heterogeneous HW/SW Cosimulation

Heterogeneous, distributed hardware/software cosimulation techniques using the backplane method encounter complex interface protocols for simulator communication and synchronization, limiting their adoption or abstraction. We simplify the dynamics of backplane cosimulation to the properties of a Kahn Process Network (KPN), such that tokens of the KPN are interpolated events. This simplifies the backplane API and reduces the coordination problem to a parameterization of token update rates. The performance of this method is reported on a timed ISS model for Freescale HC12 microcontrollers (TExaS) coordinated with a Spice (Ngspice) circuit simulation. 2011 Electronic System Level Synthesis Conference, ECSI. 5-6 June 2011.

Dynamic Correction for Parallel Conductance, GP, and Gain Factor, α, in Invasive Murine Left Ventricular Volume Measurements  
 The conductance catheter technique could be improved by determining instantaneous parallel conductance (GP) which is known to be time-varying, and by including a time-varying calibration factor in Baan’s equation (α(t)). We have recently proposed solutions to the problems of both time-varying GP and time varying α, which we term “admittance” and “Wei’s equation”, respectively. We validate both our solutions in mice, compared to the currently accepted methods, hypertonic saline (HS) to determine GP and Baan’s equation calibrated with both stroke volume (SV) and cuvette. New theory and method for instantaneous GP removal, as well as application of Wei’s equation, are presented and validated in vivo in mice. We conclude that for closed-chest mice, admittance (dynamic GP) and Wei’s equation (dynamic α) provide more accurate volumes than traditional conductance, are more sensitive to inotropic changes, eliminate the need for hypertonic saline, and can be accurately extended to aortic banded mice. J Appl Physiol (August 20, 2009). doi:10.1152.

Electrical conductivity and permittivity of murine myocardium IEEE TBME-00330-2008
Abstract— A classic problem in traditional conductance measurement of left ventricular (LV) volume is the separation of the contributions of myocardium from blood. Measurement of both the magnitude and the phase of admittance allow estimation of the time-varying myocardial contribution, which provides a substantial improvement by eliminating the need for hypertonic saline injection. We present in vivo epicardial surface probe measurements of electrical properties in murine myocardium using two different techniques (a digital and an analog approach). These methods exploit the capacitive properties of the myocardium, and both methods yield similar results. The relative permittivity varies from approximately 100,000 at 2 kHz to approximately 5,000 at 50 kHz. The electrical conductivity is approximately constant at 0.16 S/m over the same frequency range. These values can be used to estimate and eliminate the time-varying myocardial contribution from the combined signal obtained in LV conductance catheter measurements, thus, yielding the blood contribution alone. To study the effects of albumin on the blood conductivity, we also present electrical conductivity estimates of murine blood with and without typical administrations of albumin during the experiment. The blood conductivity is significantly altered (p<0.0001) by administering albumin (0.941 S/m with albumin, 0.478 S/m without albumin). IEEE Transactions On Biomedical Engineering, 2008

Volume Catheter Parallel Conductance Varies Between End-systole and End-diastole
The conductance catheter system provides a method to determine instantaneous cardiac blood volume; but it is necessary to determine and remove the contribution from parallel myocardial tissue. In previous studies, the myocardium has been treated as either purely resistive or purely capacitive when developing methods to estimate myocardial contribution. We propose that both the capacitive and the resistive properties of the myocardium are substantial and neither should be ignored. Hence, the measured result should be labeled admittance rather than conductance. We measure the admittance (magnitude and phase angle) of the Left Ventricle in the mouse, and show that it is measurable and increases with frequency. Further, the more accurate technique suggests that the myocardial contribution to measured admittance varies between end-systole and end-diastole, contrary to previous literature. We test these hypotheses both with numerical finite element models for a mouse left ventricle constructed from MRI images, and with in vivo admittance measurements in the murine LV. Finally, we propose a new method to determine the instantaneous myocardial contribution to the measured left ventricular admittance that does not require saline injection or other intervention to calibrate. IEEE Transactions On Biomedical Engineering, 2006

 Nonlinear Conductance-Volume Relationship for Murine Conductance Catheter Measurement System
The conductance catheter system is a tool to determine instantaneous left ventricular volume in vivo by converting measured conductance to volume. The currently adopted conductance-to-volume conversion equation was proposed by Baan, and the accuracy of this equation is limited by the assumption of a linear conductance-volume relationship. The electric field generated by a conductance catheter is nonuniform, which results in a nonlinear relationship between conductance and volume. This paper investigates this nonlinear relationship and proposes a new nonlinear conductance-to-volume conversion equation. The proposed nonlinear equation uses a single empirically determined calibration coefficient, derived from independently measured stroke volume. In vitro experiments and numerical model simulations were performed to verify and validate the proposed equation. IEEE Transactions On Biomedical Engineering, Vol. 52, No. 10, October 2005

 Evidence of Time-Varying Myocardial Contribution by In Vivo Magnitude and Phase Measurement in Mice
Cardiac volume can be estimated by a conductance catheter system. Both blood and myocardium are conductive, but only the blood conductance is desired. Therefore, the parallel myocardium contribution should be removed from the total measured conductance. Several methods have been developed to estimate the contribution from myocardium, and they only determine a single steady state value for the parallel contribution. Besides, myocardium was treated as purely resistive or mainly capacitive when estimating the myocardial contribution. We question these assumptions and propose that the myocardium is both resistive and capacitive, and its contribution changes during a single cardiac cycle. In vivo magnitude and phase experiments were performed in mice to confirm this hypothesis.  Proc. of IEEE-Engr. In Med. And Biol. Soc., 26th Annual International Conference, vol. 2, pp. 3674 – 3677, Sep. 2004.

Skin Burns: Numerical Model Study of Radio Frequency Current Sources
Skin burns from radio frequency (RF) current remain an important clinical consideration. The classical studies on the kinetics of skin burns in the 1940s and 1950s continue to be the most often cited and utilized framework for their prediction and analysis. The objective of this study was to apply numerical models to more thoroughly analyze previously-described experimental skin burns created by RF current under disk electrodes. Proceedings of the ASME 2009 Summer Bioengineering Conference (SBC2009), June 17-21, Lake Tahoe, CA, SBC2009-206161

Effect of Formalin Fixation on Thermal Conductivity of the Biological Tissue
Effect of formalin fixation on thermal conductivity of the biological tissues is presented. A self-heated thermistor probe was used to measure the tissue thermal conductivity. The thermal conductivity of porcine aorta, fat, heart, and liver was measured before the formalin fixation and then 1 day, 4 days, and 11 days after formalin fixation. The results indicate that the formalin fixation does not cause a significant change in the tissue thermal conductivity of the tissues studied. In the clinical setting, tissues removed surgically are often fixed in formalin for subsequent pathological analysis. These results suggest that, in terms of thermal properties, it is equally appropriate to perform in vitro studies in either fresh tissue or formalin-fixed tissue. Journal of Biomechanical Engineering. 2009.

Pulse-power integrated-decay technique for the measurement of thermal conductivity
A pulse-power integrated-decay technique for the measurement of thermal conductivity of biological tissues is presented. A self-heated thermistor probe is used to deliver heat and also to measure the temperature response. Three-dimensional finite element analyses are used in this paper to design and optimize the technique. The thermal conductivity measurements from
the computer simulations were in close accordance with the experimental data. An empirical calibration process, performed in glycerol and agar-gelled water, provides accurate thermal conductivity measurements. An accuracy analysis evaluated multiple experimental protocols using three solutions of known thermal properties. The results indicate that the thermal decay
technique protocol had better accuracy than the constant temperature heating techniques. In vitro measurements demonstrate the variability of tissue thermal conductivity, and the need to perform direct measurements for tissues of interest. The factors that may introduce error in the experimental data are (i) poor thermal/physical contact between the thermistor probe and
tissue sample, (ii) water loss from tissue during the course of experimentation and (iii) temperature stability. Meas. Sci. Technol. 19 (2008)

Effects of the time response of the temperature sensor on thermodilution measurements
Thermodilution is widely used to measure cardiac output, ejection fraction and end diastolic volume. Even though the method is based on dynamic temperature measurements, little attention has been paid to the characterization of the dynamic behavior of the temperature sensor and to its influence on the accuracy of the method. This paper presents several theoretical and empirical results related to the thermodilution method. The results show that, at flow velocities above 0.2 m s−1, the response of temperature sensors embedded in Swan–Ganz catheters can be accurately described by a convolution operation between the true temperature of the blood and the impulse response of the sensor. The model developed is used to assess the influence of the probe response on the measurement of cardiac output, and this study leads us to the conclusion that the probe response can cause errors in the cardiac output measurement, but this error is usually small (2% in cases with a high degree of arrhythmia). The results show that these small errors appear during arrhythmias that affect the R–R interval and when the real temperature distribution at the pulmonary artery does not possess a shape with perfect temperature plateau. Physiol. Meas. 26 (2005) 885–901.

Bioheat Transfer
Bioheat transfer is the study of the transport of thermal energy in living systems. Because biochemical processes are temperature dependent, heat transfer plays a major role in living systems. Also, because the mass transport of blood through tissue causes a consequent thermal energy transfer, bioheat transfer methods are applicable for diagnostic and therapeutic applications involving either mass or heat transfer. This article presents the characteristics of bioheat transfer that distinguish it from nonliving systems, including the effects of blood perfusion on temperature distribution, coupling with biochemical processes, therapeutic and injury processes, and thermoregulation. Wiley Encyclopedia of Medical Devices, 2005

 Thermal Conductivity and Diffusivity of Biomaterials Measured with Self-Heated Thermistors
Thermal Properties measured with self-heat thermistors, and includes theory, instrumentation, calibration, and results measured from 3 to 45 C. International Journal of Thermophysics, 6 (3), 301-311, 1985.

A Small Artery Heat Transfer Model for Self-Heated Thermistor Measurements of Perfusion in the Kidney Cortex
A small artery model (SAM) for self-heated thermistor measurements of perfusion in the canine kidney is developed based on the anatomy of the cortex vasculature. In this model interlobular arteries and veins play a dominant role in the heat transfer due to blood flow. Effective thermal conductivity, kss , is calculated from steady state thermistor measurements of heat transfer in the kidney cortex. This small artery and vein model of perfusion correctly indicates the shape of the measured kss versus perfusion curve. It also correctly predicts that the sinusoidal response of the thermistor can be used to measure intrinsic tissue conductivity, km , in perfused tissue. Although this model is specific for the canine kidney cortex, the modeling approach is applicable for a wide variety of biologic tissues.  Journal of Biomechanical Engineering. 116, 71-78, Feb. 1994.

Bioheat Properties of Biomaterials
The transport of thermal energy in living tissue is a complex process involving multiple phenomenological mechanisms including conduction, convection, radiation, metabolism, evaporation, and phase change. The equilibrium thermal properties presented in this chapter were measured after temperature stability had been achieved.

2-D Finite Difference Modeling of Microwave Heating in the Prostate
Accurate prediction of temperatures in the prostate undergoing thermally-based treatments is crucial to assessing efficacy and safety. A two-dimensional transient finite difference model for predicting temperatures in prostate undergoing microwave heating via a transurethral fluid-cooled catheter is presented. Unconditional stability and good accuracy are achieved by using the alternating direction implicit method. A transverse section of the prostate centered at the urethra is modeled in cylindrical coordinates. The model geometry consists of a hollow silicone cylinder, representing the catheter, surrounded by multiple regions of tissue. Cold fluid flowing through the catheter minimizes the temperature in the periurethral tissue. This flow is modeled as a convective boundary condition at the surface between the catheter lumen and wall. The outer surface of the tissue is assumed to remain at baseline temperature. Microwave heating has both a radial and angular dependence. In order to maximize the heat to the target tissue, the microwave field emitted from the transurethral catheter focuses heat away from the rectum. Different perfusion situations within the prostate are simulated. Pennes' perfusion term is assumed to model the effect of perfusion on heat transfer. Results of the numerical model are compared to phantom experiment results. The model parameters which provided the best fit for the phantom was extended to model canine prostate.

Treatment of Benign Prostatic Hyperplasia
The treatment of benign prostatic hyperplasia (BPH) has implications which affect the majority of the adult male population. Although benign compared to prostate cancer, clinical symptoms can dramatically alter the quality of life. The hyperplastic tissue can cause constriction of the urethra and thus affect voiding of urine. Factors to consider for thermally-based treatments of the prostate include minimization of thermal injury to the urethra and rectum, and maximal delivery of thermal energy to target tissue. Minimizing temperature rise in the urethra allows for minimal or no anesthesia, and has been shown to reduce post-operative complications. Protection of the rectal wall is imperative since injury can lead to clinical complications as severe as a rectal fistula. Due to its location immediately dorsal to the prostate, the ventral aspect of the rectal wall is susceptible to overheating when a uniform radiating microwave heat source is applied transurethrally to treat the prostate.

Interactive 6811 Simulator for Microcontroller Software Interfacing
This paper presents a microcontroller hardware/software simulator which is used in a laboratory setting to educate undergraduate electrical engineering students. The specific objectives of the course include microcomputer architecture, assembly language programming, data structures, modular programming techniques, debugging strategies, hardware/software interfaces and embedded microcontroller applications. In this paper, I present both basic concepts and specific implementations which create an effective learning environment for my students. In particular, I wrote a DOS-based interactive simulator for the Motorola 6811. The application runs on a standard IBM-PC compatible with minimal requirements: Intel 386DX, 640K RAM, VGA color monitor, and 2 Megabytes of hard drive space. The student develops Motorola 6811 software which is cross-assembled and simulated. The major features of this interactive programming environment include user-configurable interactive external I/O devices, multiple display windows, extensive information available describing the activity both inside and outside the processor, elaborate protection against and explanation of programming errors, effective mechanisms for setting breakpoints, and user-defined “scan points” which allow the user program to interact with the graphics display.

Analysis of the Weinbaum-Jiji Model of Blood Flow in the Canine Kidney Cortex for Self-Heated Thermistors
The Weinbaum-Jiji equation can be applied to situations where: 1) the vascular anatomy is known; 2) the blood velocities are known; 3) the effective modeling volume includes many vessels; and 4) the vessel equilibration length is small compared to the actual length of the vessel. These criteria are satisfied in the situation where steady-state heated thermistors are placed in the kidney cortex. In this paper, the Weinbaum-Jiji bioheat equation is used to analyze the steady state response of four different sized self-heated thermistors in the canine kidney. This heat transfer model is developed based on actual physical measurements of the vasculature of the canine kidney cortex. In this model, parallel-structured interlobular arterioles and venules with a 60 µm diameter play the dominant role in the heat transfer due to blood flow. Continuous power is applied to the thermistor, and the instrument measures the resulting steady state temperature rise. If an accurate thermal model is available, perfusion can be calculated from these steady-state measurements. The finite element simulations correlate well in shape and amplitude with experimental results in the canine kidney. In addition, this paper shows that the Weinbaum-Jiji equation can not be used to model the transient response of the thermistor because the modeling volume does not include enough vessels and the vessel equilibration length is not small compared to the actual length of the vessel. Journal of Biomechanical Engineering, 116, 201-207, May 1994.

Modeling of Temperature Probes in Convective Media
This paper discusses the dynamic behavior of probes embedded in convective media during temperature measurements. In certain conditions the temperature measured by a probe can be written as the convolution of the true temperature with the impulse response of the probe. We present a general method to find the natural response of any kind of probe, and then we present results for a more realistic 1-D model for the thermistor probe in a thermodilution catheter. The results of these analyzes can be applied to enhance the dynamic response of temperature measurements made by probes in convective media. 17th Southern Biomedical Engineering Conference, Feb. 7, 1998.

Measurement of the Dynamic Response of a Contact Probe Thermosensor in Conductive Media
This paper describes a method for characterizing the step response of a thermistor probe embedded in a low-conductivity solid. We define the “step response” as the dynamic response of a finite-size thermosensor instantaneously plunged into an infinite homogeneous conductive solid. The final goal of this research is to evaluate and enhance the time-dependent response of contact-type thermosensors. We will use the step response as the parameter for optimizing the probe time-dependent behavior. Although our research focuses on thermistors, the results could be applied to other contact-type sensors like thermocouples and RTD’s.

Methodology for Modeling the Response of Temperature Probes in Convective Media
This paper discusses the dynamic behavior of probes embedded in convective media during temperature measurements. It will be shown that in certain conditions the temperature measured by a probe can be written as the convolution of the true temperature with the impulse response of the probe. We present a general method to find the natural response of any kind of probe, and then we present results for a more realistic 1-D model for the thermistor probe in a thermodilution catheter. The results of these analyzes can be applied to enhance the dynamic response of temperature measurements made by probes in convective media.

Thermal Properties by Kenneth Holmes
The following physiological properties were compiled by Professor Kenneth R. Holmes <krholmes@ux1.cso.uiuc.edu> and were published in part previously. The tabulation includes values for both the native thermal conductivity of biomaterials (Appendix A) and the blood perfusion rates for specific tissues and organs (Appendix B). Original sources are documented in the dedicated list of references at the end of each appendix. Knowledge of the perfusion behavior of tissues is important in that the flow of blood can have a direct quantitative effect on the temperature distribution within living tissue.

Real Time Data Acquisition and Control
This paper presents a laboratory environment for the development of real time data acquisition and control on the IBM-PC platform. The laboratory station involves the integration of low-cost computer technology with powerful software components which empower the student to efficiently and effectively construct real time systems. The software base integrates an editor, a spreadsheet, and a real time programming environment built around Druma FORTH. We have written multiple FORTH libraries to assist the student in the translation of engineering concept into creation. Real time events are managed using a rich set of FORTH software routines which guarantee that time-critical software is executed on schedule. The real time color-VGA graphic library includes many types of windows. We have developed an extendible debugging tool called PROSYM (PROfiler and SYMbolic debugger.) PROSYM provides a simple set of primitives with a high expressive power that may be used singly or may be combined to construct customized debugging tools. In addition to providing basic debugging functions, PROSYM supports an event-action model of debugging. We have evaluated this development system on the full range of PC platforms from the original PC-XT to the newest 486 systems. The environment has been used for two years by Biomedical and Electrical Engineering graduate students performing both teaching and research projects. Gulf-Southwest Section of the American Society of Engineering Education, Austin, pp. 597-604, 1993.



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Last updated January 27, 2013 Send comments to: Jonathan W. Valvano .