Measuring Intra/Extracellular Volume and Hemodynamics

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DESCRIPTION (provided by applicant): A device capable of noninvasive real-time measurement of intravascular and extravascular fluid volumes and blood flows does not currently exist. Such a device would provide vital information in the treatment of diverse pathophysiologic fluid volume and hemodynamic states including, for example, the management of increased intracranial pressure following trauma, the treatment of disequilibrium and hypotension during renal dialysis, the monitoring of hydrational state of premature infants, and the investigation and diagnosis of orthostatic intolerance associated with dysautonomia and space flight. Currently employed methods are either invasive, such as tracer dilution techniques, or bulky and expensive such as MRI technologies, and often do not yield easily used real-time data during physiologic stress. The central objective of this proposal is to perfect and test a bioelectric impedance device capable of measuring blood flows by impedance plethysmography (IPG) and of measuring compartmental fluid volumes by electrical impedance spectrography (EIS). Fixed frequency bioimpedance by IPG has been reliably used to estimate blood flow and intravascular volume shifts. Swept frequency bioimpedance by EIS has been used to estimate intravascular, interstitial and intracellular fluid volumes. We will base the IPG module of the device on the fixed frequency Tetrapolar High Resolution Impedance Monitor (THRIM Model 2994-D) digital impedance plethysmograph that was developed by UFi, Inc. This employs a fixed frequency of 50 KHz and has been extensively benchmarked in animal and human blood flow studies. For EIS operation, 40 different frequencies will be provided, at log intervals, between 3 and 300 KHz. EIS will use a constant current transformer coupled excitation stage in conjunction with a digital demodulation stage to supply both resistive and reactive impedance components. This will be controlled by a microprocessor system connected via an RS-232 serial interface to PC analysis software. The microprocessor control system will store impedance parameters and signal waveform segments prior to supplying the data to the host for on-line real time analysis and display. Host software will use a deconvolution algorithm to obtain parameters for an R-C equivalent circuit used to model the intravascular, interstitial and intracellular fluid spaces. In this first stage of development we will test the device against a Whitney strain gauge system using occlusion cuffs to 1) measure forearm and calf blood flows in order to validate the IPG module; 2) produce controlled increases in interstitial and intravascular volumes by stepwise venous occlusion to validate the EIS module. It is hoped that the instrument may be further validated during statistically significant clinical trials during a Phase II NIH SBIR grant.