Changes in High-Frequency Intracardiac Electrogram Indicate Cardiac Ischemia.

High-frequency QRS (HFQRS) analysis of surface ECG is a reliable marker of cardiac ischemia (CI). This study aimed to assess the response of HFQRS signals from standard intracardiac electrodes (iHFQRS) to CI in swine and compare them with conventional ST-segment deviations. Devices with three intracardiac leads were implanted in three swine in a controlled environment. CI was induced by inflating a balloon in epicardial coronary arteries. A designated signal-processing algorithm was applied to quantify the iHFQRS content before, during, and after each occlusion. iHFQRS time responses were compared to conventional ST-segment deviations. Thirty-three over thirty-nine (85%) of the occlusions presented significant reduction in the iHFQRS signal, preceding ST-segment change, being the only indicator of CI in brief occlusions. iHFQRS was found to be an early indicator for the onset of CI and demonstrated superior sensitivity to conventional ST-segment deviations during brief ischemic episodes.

High-frequency QRS analysis in the evaluation of chest pain in the emergency department.

OBJECTIVES: High frequency QRS (HFQRS) analysis has been shown to be an accurate marker for myocardial ischemia. Our objective was to test the use of HFQRS in diagnosing ACS in the emergency department. METHODS: 324 patients presenting to the ED with chest pain were enrolled. Resting ECG was recorded and later analyzed by an HFQRS algorithm. Results were compared to the conventional ECG diagnosis by 3 independent interpretations: treating physician, expert cardiologist and an automated computer program. RESULTS: The HFQRS analysis demonstrated improved sensitivity (67.5%) for the NSTE-ACS group compared to the human interpreters (59.7% and 53.2% for the treating physician and cardiologist respectively) with similar specificity. The automatic program had significantly lower sensitivity (31%) with a higher specificity (77%). CONCLUSIONS: HFQRS which has shown great promise in diagnosing stable CAD may also be helpful in the ED for diagnosing ACS.

Quantifying QRS changes during myocardial ischemia: Insights from high frequency electrocardiography.

Over four decades of high frequency electrocardiography research have provided a body of knowledge about QRS changes during myocardial ischemia, and the techniques to measure and quantify them. High-frequency QRS (HFQRS) components, being closely related to the pattern of ventricular depolarization, carry valuable clinical information. Changes in HFQRS amplitude and morphology have been shown to be sensitive diagnostic markers of myocardial ischemia, often superior to measures of ST-T segment changes. Clinical studies in patients undergoing exercise testing have consistently demonstrated the incremental diagnostic value of HFQRS analysis in detection of demand ischemia. In 6 studies that evaluated the HyperQ™ technology, the average sensitivity and specificity of HFQRS analysis were 75%±6% and 80%±6%, respectively, compared to average sensitivity 48%±16% and average specificity 70%±15% of ST segment analysis. In patients with acute supply ischemia, recent studies characterized and quantified the ischemic HFQRS patterns. HFQRS morphology index was found to be higher in patients with acute coronary syndrome (ACS), compared to non-ischemic, with good sensitivity in patients without ST elevation. These research findings may be translated into commercially-available ECG systems and be used in clinical practice for improved diagnosis and monitoring of myocardial ischemia.

In vivo imaging of irreversible electroporation by means of electrical impedance tomography.

Electroporation, the increased permeability of cell membranes due to a large transmembrane voltage, is an important clinical tool. Both reversible and irreversible in vivo electroporation are used for clinical applications such as gene therapy and solid malignant tumor ablation, respectively. The primary advantage of in vivo electroporation is the ability to treat tissue in a local and minimally invasive fashion. The drawback is the current lack of control over the process. This paper is the first report of a new method for real-time three-dimensional imaging of an in vivo electroporation process. Using two needle electrodes for irreversible electroporation and a set of electrodes for reconstructing electrical impedance tomography (EIT) images of the treated tissue, we were able to demonstrate electroporation imaging in rodent livers. Histology analysis shows good correlation between the extent of tissue damage caused by irreversible electroporation and the EIT images. This new method may lead the way to real-time control over genetic treatment of diseases in tissue and tissue ablation.

A new concept for medical imaging centered on cellular phone technology.

According to World Health Organization reports, some three quarters of the world population does not have access to medical imaging. In addition, in developing countries over 50% of medical equipment that is available is not being used because it is too sophisticated or in disrepair or because the health personnel are not trained to use it. The goal of this study is to introduce and demonstrate the feasibility of a new concept in medical imaging that is centered on cellular phone technology and which may provide a solution to medical imaging in underserved areas. The new system replaces the conventional stand-alone medical imaging device with a new medical imaging system made of two independent components connected through cellular phone technology. The independent units are: a) a data acquisition device (DAD) at a remote patient site that is simple, with limited controls and no image display capability and b) an advanced image reconstruction and hardware control multiserver unit at a central site. The cellular phone technology transmits unprocessed raw data from the patient site DAD and receives and displays the processed image from the central site. (This is different from conventional telemedicine where the image reconstruction and control is at the patient site and telecommunication is used to transmit processed images from the patient site). The primary goal of this study is to demonstrate that the cellular phone technology can function in the proposed mode. The feasibility of the concept is demonstrated using a new frequency division multiplexing electrical impedance tomography system, which we have developed for dynamic medical imaging, as the medical imaging modality. The system is used to image through a cellular phone a simulation of breast cancer tumors in a medical imaging diagnostic mode and to image minimally invasive tissue ablation with irreversible electroporation in a medical imaging interventional mode.

Mass Transfer Model for Drug Delivery in Tissue Cells with Reversible Electroporation.

Reversible electroporation is the temporary permeabilization of the cell membrane through the formation of nano-scale pores that are transient defects in the membrane. These pores are caused by short electrical pulses, typically on the order of a few to several hundred microseconds that are delivered by electroporation electrodes inserted around the treated tissue. Reversible electroporation has become an important technique in molecular medicine. It is used to introduce macromolecules such as genes or anti-cancer drugs, to which the cell membrane is normally not permeable, into the cytosol. For optimal application of molecular medicine, it is important to be able to predict precisely the mass transfer in tissue during reversible electroporation. In this study, we introduce a first attempt at developing a macroscopic mathematical model for analyzing the mass transfer into cells during reversible electroporation of tissue. The model combines a macroscopic model of the electrical fields around electroporation electrodes with a new cells-scale model of electroporation-driven mass transfer and with a macroscopic mass transfer model in tissue. The model is illustrated for a situation typical to that in electrochemotherapy in which cancer is treated with reversible electroporation and a non-cell membrane permeant drug such as bleomycin.

Methods of optimization of electrical impedance tomography for imaging tissue electroporation.

Tissue electroporation is a medical technique in which electrical pulses of microsecond to millisecond length are applied to a tissue in order to permeabilize the membrane of targeted cells, either temporarily or permanently, for the purpose of drug delivery and gene therapy or tissue ablation, respectively. Electrical impedance tomography (EIT) has been suggested as an effective means of imaging the treated area and thereby providing control of electroporation. In this simulation based study we introduce methods for optimizing the use of EIT under the special conditions of electroporation. First, we address the issue of the rapid changes in tissue conductivity, during and after the application of pulses. We propose a solution through a method of simultaneously collecting data from all the electrodes, essentially capturing the state of the tissue at a single instant. This method, which employs several distinct frequencies, one for each electrode, allows a speedy and continuous collection of data, a vital part of real-time electroporation monitoring. The second issue is taking advantage of the presence of electroporation electrodes for the EIT process. We show how the electroporation electrodes that are normally found inside the tissue may help improve the reconstruction compared to data collected only from the body's boundary. This mathematical study employs recently collected in vivo data of rat liver electroporation to obtain a model which represents, as closely as possible, the reality of electroporation procedures.

Frequency-division multiplexing for electrical impedance tomography in biomedical applications.

Electrical impedance tomography (EIT) produces an image of the electrical impedance distribution of tissues in the body, using electrodes that are placed on the periphery of the imaged area. These electrodes inject currents and measure voltages and from these data, the impedance can be computed. Traditional EIT systems usually inject current patterns in a serial manner which means that the impedance is computed from data collected at slightly different times. It is usually also a time-consuming process. In this paper, we propose a method for collecting data concurrently from all of the current patterns in biomedical applications of EIT. This is achieved by injecting current through all of the current injecting electrodes simultaneously, and measuring all of the resulting voltages at once. The signals from various current injecting electrodes are separated by injecting different frequencies through each electrode. This is called frequency-division multiplexing (FDM). At the voltage measurement electrodes, the voltage related to each current injecting electrode is isolated by using Fourier decomposition. In biomedical applications, using different frequencies has important implications due to dispersions as the tissue's electrical properties change with frequency. Another significant issue arises when we are recording data in a dynamic environment where the properties change very fast. This method allows simultaneous measurements of all the current patterns, which may be important in applications where the tissue changes occur in the same time scale as the measurement. We discuss the FDM EIT method from the biomedical point of view and show results obtained with a simple experimental system.