Tamar Manor

Cortical spreading depression recorded from the human brain using a multiparametric monitoring system.

The number of parameters (i.e., EEG or ICP-intracranial pressure) routinely monitored under clinical situations is limited. The brain function analyzer described in this paper enables simultaneous, continuous on-line monitoring of cerebral blood flow (CBF) and volume (CBV), intramitochondrial NADH redox state, extracellular K+ concentrations, DC potential, electrocorticography and ICP from the cerebral cortex. Brain function of 14 patients with severe head injury (GCS < or = 8), who were hospitalized in the neurosurgical or general intensive care unit was monitored using this analyzer. Leao cortical spreading depression (SD) has been reported in many experimental animals but not in the human cerebral cortex. In one of the patients monitored, spreading depression was observed. This is the first time that spontaneous repetitive cortical SD cycles have been recorded from the cerebral cortex of a patient suffering from severe head injury. Typical SD cycles appeared 4-5 h after the beginning of monitoring this patient. During the first 3-4 cycles the responses of this patient were very similar to the responses to SD recorded in normoxic experimental animals. Electrocorticography was depressed whereas extracellular K+ levels increased. The metabolic response to spreading depression was characterized by oxidation of intramitochondrial NADH concomitant to a large increase in CBF. During brain death, an ischemic depolarization, characterized by decrease in CBF and an irreversible increase in extracellular K+, was recorded.

Optical Monitoring of Nadh Redox State and Blood Flow as Indicators of Brain Energy Balance

Real-time evaluation of brain vitality in situ could be done by monitoring different parameters, which are complementary to each other. During the last 40 years the following four minimally invasive techniques were developed and applied to monitor the brain in situ: (1) Cerebral Blood Flow (CBF) using laser Doppler flowmetry (Stern et al., 1977; Dirnagl et al., 1989). (2) Hemoglobin oxygenation or saturation (HbO2) by dual wavelength reflectometry (Rampil et al., 1992) or spectral analysis (Frank et al., 1989). (3) Brain average oxygenation using oxygen electrodes (Mayevsky et al., 1980). (4) Mitochondrial redox state by monitoring of NADH fluorescence using surface fluorometry (Chance et al., 1962; Jobsis et al., 1971b; Mayevsky and Chance, 1982).

Metabolic and Hemodynamic Oscillations Monitored Optically in the Brain Exposed to Various Pathological States

Slow (<1 Hz) oscillations of cerebral blood flow (CBF) and oxidative metabolism have been previously reported in several animal species under different physiological/pathological conditions (Vern et al., 1998, Mayevsky and Ziv 1991, Hudetz et al., 1992, Deyoe et al., 1995). Spontaneous oscillations in cerebral circulation have been demonstrated as periodic variations of blood volume, oxygen availability, NAD+NADH oxidative state (Dora and Kovach 1981), cytochrome aa3 redox state (Jobsis 1978), ischemia and anesthesia.

Effects of Fluid Percussion Injury on Rat Brain Hemodynamics, Ionic, Electrical Activity, and Energy Metabolism in Vivo

The most commonly used evaluation method for severity of brain injury in patients is the level of consciousness, which is measured by the Glasgow Coma Scale (GCS). The majority of cases admitted to hospitals alive are classified as “mild” (GCS 13-15), 10% as moderate (GCS 9-12) and 10% are classified as severe (GCS<_8)

Real-time optical monitoring of tissue vitality in vivo

Evaluation of tissue O2 balance (Supply/Demand) could be done by monitoring in real-time 2 out of the 3 components of the tissue O2 balance equation. In our previous publication (Mayevsky et al, SPIE Vol. 4255:33-39, 2001) we had shown the use of the multiparametric monitoring approach in the neurosurgical operating room, using a device combined of laser Doppler flowmeter (LDF) and surface fluorometer reflectometer. The two instruments having two different light sources, were connected to the tissue via a combined bundle of optical fibers. In order to improve the correlation between tissue blood flow and mitochondrial NADH redox state, the new Tissue Spectroscope (TiSpec) that was designed has a single light source and a single bundle of optical fibers. Preliminary results show very clear correlation between TBF and NADH redox state. In addition, the reflected light at the excitation wavelength could be used as an indication for blood volume changes. The results obtained by the TiSpec enabled us to compare tissue O2 delivery (TBF) with O2 balance (NADH redox state) in the brain of gerbils and rats exposed to ischemia, anoxia and spreading depression. Real-time monitoring of the metabolic state of the tissue has immense potential during surgical procedures.

Optical monitoring of tissue viability using reflected spectroscopy in vivo

Only few techniques that could provide real-time continuous multiparametric physiological data have been developed. Therefore, experimental and clinical monitoring devices for organ and tissue viability evaluation are still lacking. In this study, we present the new concept of tissue vitality defined as a product of a few parameters monitored in real- time by a combined measurement of tissue blood flow and volume as well as the oxidation reduction state of the mitochondria. The hypothesis behind the new approach is that in order to evaluate in real-time tissue vitality, it is necessary to monitor both microcirculatory blood flow and volume as well as the intracellular O2 balance as reflected in the mitochondrial redox state.

Multiparametric monitoring of tissue vitality in clinical situations

The monitoring of various tissues physiological and biochemical parameters is one of the tools used by the clinicians to improve diagnosis capacity. As of today, the very few devices developed for real time clinical monitoring of tissue vitality are based on a single parameter measurement. Tissue energy balance could be defined as the ratio between oxygen or energy supply and demand. In order to determine the vitality of the brain, for example, it is necessary to measure at least the following 3 parameters: Energy Demand--potassium ion homeostasis; Energy Supply-- cerebral blood flow; Energy Balance--mitochondrial NADH redox state. For other tissues one can measure various energy demand processes specific to the tested organ. We have developed a unique multiparametric monitoring system tested in various experimental and clinical applications. The multiprobe assembly (MPA) consists of a fiber optic probe for measurement of tissue blood flow and mitochondrial NADH redox state, ion selective electrodes (K+, Ca2+, H+), electrodes for electrical activities (ECoG or ECG and DC potential), temperature probe and for monitoring the brain - Intra Cranial Pressure probe (ICP). The computerized monitoring system was used in the neurological intensive care unit to monitor comatose patients for a period of 24-48 hours. Also, a simplified MPA was used in the neurosurgical operating room or during organ transplantation procedure. It was found that the MPA could be used in clinical situations and that the data collected has a significant diagnosis value for the medical team.

Multiparametric monitoring of rat brain retraction

Neurosurgical procedures often involve the use of brain retractors (BR) although the risk of dysfunction is well appreciated. There is no efficient tool for continuous monitoring of the effects of the retraction on the tissue, which may alert the surgeon in real time. This study aims to use the Multiprobe Assembly (MPA) in real-time, in order to monitor the brain underneath theMPA, exposed to local pressure. The MPA, which combines Laser Doppler Flowmetery, NADH redox state fluorometry, EEG, Extracellular K+ measurement and an ICP sensor, was positioned on exposed cortex of rats, and controlled pressure was applied by a micromanipulator. The experimental BR state (pressure application at three levels) was monitored for 30 minutes, then recovery was monitored for 2 hours. Many animals exhibited damage, seen as an increase in CBF after the initial drop, and swelling of the tissue around the probe. Most animals exhibited EEG depression, transient increase of Extracellular K+, changes in NADH levels and DC potential, as well as development of one or more Spreading Depression waves. The study clearly observes impairment of normal brain tissue metabolism and function, due to the retraction pressure and emphasizes the need for real-time assessment of retraction effects during neurosurgical procedures.

Responses to Cortical Spreading Depression During Normoxia and Ischemia: Multiparametric Monitoring Study in Animals and the Human Brain

Ischemia and spreading depression (SD) are interconnected, and understanding the basic mechanisms of brain responses to those two situations in experimental animals and the human brain are of great significance. Massive depolarization, which is part of both ischemia and SD, is followed by large changes in ionic homeostasis and tissue energy metabolism. The multiparametric monitoring assembly used in this study provided the following real-time continuous parameters: cerebral blood flow and volume, intramitochondrial NADH redox state, extracellular ions concentration (K+, Ca2+, H+), direct current potential, and spontaneous electrical activity. The results of our experimental and clinical studies (severe brain injury patients) suggest that the responses to cortical depolarization, developed under both ischemia and SD, are dependent on the energy state of the tissue. During ischemia depolarization developed owing to limited energy availability and therefore inhibition of active transport processes. With SD, where depolarization is the initial event, the energy metabolism is not limited but, rather, stimulated; and therefore the time to recovery of the normal state is rapid. Inhibition of NO synthase by L-NAME led to a different response to SD. When SD was developed under partial ischemia (similar to the penumbra zone), recovery of the tissue depended solely on the limited mitochondrial activity and the possibility of restoring normal ionic homeostasis.