Assessment of the brain ischemia during orthostatic stress and lower body negative pressure in air force pilots by near-infrared spectroscopy.

A methodology for the assessment of the cerebral hemodynamic reaction to normotensive hypovolemia, reduction in cerebral perfusion and orthostatic stress leading to ischemic hypoxia and reduced muscular tension is presented. Most frequently, the pilots of highly maneuverable aircraft are exposed to these phenomena. Studies were carried out using the system consisting of a chamber that generates low pressure around the lower part of the body - LBNP (lower body negative pressure) placed on the tilt table. An in-house developed 6-channel NIRS system operating at 735 and 850 nm was used in order to assess the oxygenation of the cerebral cortex, based on measurements of diffusely reflected light in reflectance geometry. The measurements were carried out on a group of 12 active pilots and cadets of the Polish Air Force Academy and 12 healthy volunteers. The dynamics of changes in cerebral oxygenation was evaluated as a response to LBNP stimuli with a simultaneous rapid change of the tilt table angle. Parameters based on calculated changes of total hemoglobin concentration were proposed allowing to evaluate differences in reactions observed in control subjects and pilots/cadets. The results of orthogonal partial least squares-discriminant analysis based on these parameters show that the subjects can be classified into their groups with 100% accuracy.

Optimal ECG Lead System for Exercise Assessment of Ischemic Heart Disease.

The diagnostic value of an ECG exercise test in diagnosis of ischemic heart disease (IHD) is limited. We investigated whether it is possible to develop a method for diagnosis of IHD which uses a low number of optimal ECG leads and has a higher diagnostic efficiency than conventional exercise ECG. This study was carried out on 43 patients. The 67-lead high-resolution ECG was recorded at rest and during exercise. The diagnostic value of ST segment depression (ΔST60) and T-wave morphology change (δT) determined in optimized ECG lead configurations was higher than for the standard 12-lead ECG. The best results were obtained for δT determined from 6 ECG electrode locations where sensitivity and specificity were 70% and 69% whereas for the standard exercise ECG were 63% and 62%, respectively. The small number of ECG leads used allows for easy hardware implementation of the methods for use in clinical settings.

Influence of intra-abdominal pressure on the amplitude of fluctuations of cerebral hemoglobin concentration in the respiratory band.

An intra-abdominal pressure (IAP) is correlated with cerebral perfusion, in a mechanism of reducing venous outflow. The elevated intra-abdominal pressure leads to an increase in the intracranial pressure and a decrease in the cerebral perfusion pressure. We studied the relationship between the IAP and the cerebral oxygenation with the use of the near infrared spectroscopy technique during a gynecological surgery. The changes in hemoglobin concentrations were analyzed in the time-frequency domain in the frequency band related to respiration. The measurements were carried out in 15 subjects who underwent laparoscopic surgery. During the laparoscopy, the intra-abdominal cavity was insufflated with CO2, which caused a controlled increase in the IAP. It was observed that the amplitudes of respiration-related waves present in hemoglobin concentration signals show an increase of 1.5 to 8.5 times during elevation of the IAP by 15 mmHg.

High-Resolution Body Surface Potential Mapping in Exercise Assessment of Ischemic Heart Disease.

Standard 12-lead ECG exercise testing is commonly used for screening of ischemic heart disease (IHD). We studied if high-resolution body surface potential mapping (HR-BSPM) during exercise offers advantages over current standards in noninvasive evaluation of IHD. This study was carried out on 90 IHD patients and 33 healthy controls. The 67-lead HR-BSPM was recorded at rest and during exercise. Twenty-one ECG parameters including classical ST criteria were compared. The effectiveness of methods was verified based on the results of SPECT and coronary angiography. The most effective parameters in the diagnosis of IHD were: amplitude parameter ΔST60 and δT parameter showing T-wave morphology changes during exercise. The sensitivities/specificities of ΔST60 and δT parameters for the HR-BSPM were 70/69 and 59/62%, while for the standard 12-lead ECG system they were: 63/62 and 59/56%. These results demonstrate the usefulness of HR-BSPM measurements during exercise. HR-BSPM resulted in higher sensitivities and specificities compared to the standard 12-lead exercise test. The advantage was partially associated with observed ischemic changes outside standard precordial leads position that were not visible when using the standard 12-lead exercise test. This justifies research into the optimization of the number and position of ECG leads in exercise testing.

Confirmation of brain death using optical methods based on tracking of an optical contrast agent: assessment of diagnostic feasibility.

We aimed to determine whether optical methods based on bolus tracking of an optical contrast agent are useful for the confirmation of cerebral circulation cessation in patients being evaluated for brain death. Different stages of cerebral perfusion disturbance were compared in three groups of subjects: controls, patients with posttraumatic cerebral edema, and patients with brain death. We used a time-resolved near-infrared spectroscopy setup and indocyanine green (ICG) as an intravascular flow tracer. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was carried out to build statistical models allowing for group separation. Thirty of 37 subjects (81.1%) were classified correctly (8 of 9 control subjects, 88.9%; 13 of 15 patients with edema, 86.7%; and 9 of 13 patients with brain death, 69.2%; p < 0.0001). Depending on the combination of variables used in the OPLS-DA model, sensitivity, specificity, and accuracy were 66.7-92.9%, 81.8-92.9%, and 77.3-89.3%, respectively. The method was feasible and promising in the demanding intensive care unit environment. However, its accuracy did not reach the level required for brain death confirmation. The potential usefulness of the method may be improved by increasing the depth of light penetration, confirming its accuracy against other methods evaluating cerebral flow cessation, and developing absolute parameters for cerebral perfusion.

Application of optical methods in the monitoring of traumatic brain injury: A review.

We present an overview of the wide range of potential applications of optical methods for monitoring traumatic brain injury. The MEDLINE database was electronically searched with the following search terms: "traumatic brain injury," "head injury," or "head trauma," and "optical methods," "NIRS," "near-infrared spectroscopy," "cerebral oxygenation," or "cerebral oximetry." Original reports concerning human subjects published from January 1980 to June 2015 in English were analyzed. Fifty-four studies met our inclusion criteria. Optical methods have been tested for detection of intracranial lesions, monitoring brain oxygenation, assessment of brain perfusion, and evaluation of cerebral autoregulation or intracellular metabolic processes in the brain. Some studies have also examined the applicability of optical methods during the recovery phase of traumatic brain injury . The limitations of currently available optical methods and promising directions of future development are described in this review. Considering the outstanding technical challenges, the limited number of patients studied, and the mixed results and opinions gathered from other reviews on this subject, we believe that optical methods must remain primarily research tools for the present. More studies are needed to gain confidence in the use of these techniques for neuromonitoring of traumatic brain injury patients.

Evaluation of T-wave alternans in high-resolution ECG maps recorded during the stress test in patients after myocardial infarction.

INTRODUCTION: Recent studies point to analysis of T-wave alternans as a promising indicator of an increased risk of life-threatening ventricular arrhythmias. In this study the occurrence of T-wave alternans in the high-resolution ECGs recorded during the exercise stress test and scintigraphic tests (SPECT) in patients with ischemic heart disease was examined. MATERIAL AND METHODS: The study group consisted of 33 patients after myocardial infarction. In the group of patients after myocardial infarction and with low left ventricular ejection fraction correlations of 70% between the test results of T-wave alternans and SPECT and 60% between the test results of T-wave alternans and stress test were found. RESULTS: In the group of patients after myocardial infarction but with high left ventricular ejection fraction correlations were respectively 39% and 48%. The analysis of the electrocardiographic maps showed a strong dependence of this correlation on the T-wave alternans amplitude and location of the ECG measuring electrode on the chest. The results might suggest that in patients after myocardial infarction and at increased risk for sudden cardiac death T-wave alternans may also provide information about cardiac electrical instability associated with ischemia. CONCLUSIONS: It can also be assumed that the position of the electrode where the highest level of the T-wave alternans was detected can indicate the location of the ischemic region of the heart.

Prolonged postocclusive hyperemia response in patients with normal-tension glaucoma.

BACKGROUND: It is believed that endothelial dysfunction may be a link between systemic and ocular dysregulation in glaucoma. The aim of this study was to evaluate peripheral vascular reactive hyperemia in response to occlusion test and to correlate peripheral vascular findings with retrobulbar hemodynamics parameters in patients with normal-tension glaucoma. MATERIAL AND METHODS: Forty-eight patients with normal-tension glaucoma (mean age 58.1 years, 38 women) and 40 control subjects (mean age 54.1 years, 36 women) were subjected to a brachial arterial occlusion test and color Doppler imaging (LOGIQ 9, GE Medical Systems) of the retrobulbar arteries. Finger hyperemia was assessed by using a 2-channel laser Doppler flowmeter (MBF-3D, Moor Instruments, Ltd.). Time parameters (time to peak flow, half-time of hyperemia, time of recovery) and amplitude parameters (maximum hyperemia response, biological zero) of the post-occlusive reactive hyperemia signal pattern as well as velocities and resistance index of the ophthalmic, central retinal, and short posterior ciliary arteries were evaluated and compared between study groups. RESULTS: In glaucoma patients, time to peak flow and half-time of hyperemia were significantly longer (21.4 vs. 12.0 s, p=0.02 and 74.1 vs. 44.2 s, p=0.03, respectively) and biological zero was significantly lower (2.4 vs. 3.2, p=0.01) comparing with healthy subjects. In glaucoma patients, peak-systolic and end-diastolic velocities of central retinal artery were significantly lower (12.8 vs.14.1, p=0.03 and 3.9 vs. 4.7, p=0.01, respectively) and resistance index of this artery was significantly higher (0.69 vs. 0.67, p=0.03) compared to controls. In the glaucoma group, maximum hyperemic response was negatively correlated with the resistance index of temporal short posterior ciliary arteries (r=-0.4, p=0.01), whereas in the control group half-time of hyperemia was negatively correlated with end-diastolic velocity of the central retinal artery (r=-0.3, p=0.03). CONCLUSIONS: Arterial occlusion test elicited a prolonged systemic hyperemia response in patients with glaucoma as compared with healthy subjects. Retrobulbar blood flow alterations in glaucoma patients may be related to systemic vascular dysregulation.

Performance assessment of time-domain optical brain imagers, part 2: nEUROPt protocol.

The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.

An analysis of the U-wave and its relation to the T-wave in body surface potential maps for healthy subjects and MI patients.

BACKGROUND: The aim of this study was to analyze the U-wave morphology and its relation to the T-wave in one group of healthy subjects and in two groups of myocardial infarction (MI) patients-with and without ventricular tachycardia (VT) episodes. The context of the U-wave origin was also discussed and the U-wave as a potential marker of VT was investigated. METHODS: The study was carried out on three groups of subjects: 20 healthy subjects, 14 MI patients not at risk of VT, and 22 MI patients at risk of VT. The morphology of the repolarization phase was examined in the high-resolution body surface potential maps recorded from 64 surface ECG leads. The temporal and spatial distributions of several ECG parameters were studied. RESULTS: The U-wave was present in almost all the studied subjects. The spatial heterogeneity and smooth change in both the T- and U-wave shapes on the entire torso were observed in all the studied groups. The statistical significance of discrimination between the MI patients without VT and MI patients with VT was observed for QRS interval, QT interval, U-wave integral, and normalized U-wave integral. CONCLUSIONS: High-resolution measurement of body surface potentials and an advanced data analysis allow for a detailed description of U-wave morphology and its relation to the T-wave. This might be of value in discriminating intracardiac repolarization effects, mechano-electrical feedback, and arrhythmia risk stratification.

The effect of precordial lead displacement on ECG morphology.

Inaccurate electrode placement and differences in inter-individual human anatomies can lead to misinterpretation of ECG examination. The aim of the study was to investigate the effect of precordial electrodes displacement on morphology of the ECG signal in a group of 60 patients with diagnosed cardiac disease. Shapes of ECG signals recorded from precordial leads were compared with signals interpolated at the points located at a distance up to 5 cm from lead location. Shape differences of the QRS and ST-T-U complexes were quantified using the distribution function method, correlation coefficient, root-mean-square error (RMSE), and normalized RMSE. The relative variability (RV) index was calculated to quantify inter-individual variability. ECG morphology changes were prominent in all shape parameters beyond 2 cm distance to precordial leads. Lead V2 was the most sensitive to displacement errors, followed by leads V3, V1, and V4, for which the direction of electrodes displacement plays a key role. No visible changes in ECG morphology were observed in leads V5 and V6, only scaling effect of signal amplitude. The RV ranged from 0.639 to 0.989. Distortions in ECG tracings increase with the distance from precordial lead, which are specific to chosen electrode, direction of displacement, and for ECG segment selected for calculations.

ST-segment changes in high-resolution body surface potential maps measured during exercise to assess myocardial ischemia: a pilot study.

INTRODUCTION: The aim of the study was to assess myocardial ischemia by analysis of ST-segment changes in high-resolution body surface potential maps (HR-BSPM) measured at rest and during an exercise stress test. MATERIAL AND METHODS: The study was carried out on a group of 28 patients with stable coronary artery disease and 15 healthy volunteers. The HR-BSPM were measured at rest and during the exercise stress test on a supine ergometer. The workload was increased in stages by 25 W every 2 min, beginning at 50 W. The maps of ST-segment depression (ST60) were calculated from time averaged recordings at rest and at maximal workload. RESULTS: The efficiency in detection of myocardial ischemia was higher for HR-BSPM than for standard 12-lead electrocardiography (ECG) when both methods were evaluated by outcomes of coronarography. The sensitivity of HR-BSPM was 82.4% while for the standard 12-lead ECG exercise stress test it was 58.8%. For some patients significant changes in the ST segment were observed at stress HR-BSPM but were not visible in standard 12-lead ECG recorded under the same conditions. CONCLUSIONS: Obtained high values of sensitivity and specificity in myocardial ischemia detection suggest that maps of ST60 calculated from HR-BSPM can improve detection of patients with ischemic heart disease in comparison to the standard electrocardiographic exercise stress test examinations.

Fluorescence-based method for assessment of blood-brain barrier disruption.

We report on a fluorescence-based optical method for assessment of blood-brain barrier in humans. The technique is based on monitoring of fluorescence light excited in the dye circulating in the brain. Measurements were carried out in healthy volunteers and in patients with disruption of the blood-brain barrier with the use of time-resolved method during inflow and washout of indocyanine green after its intravenous injection. We show large differences in the fluorescence signals - in healthy subjects a fast washout of the dye can be observed whereas in patients the washout is significantly prolonged. We conclude that the monitoring of the fluorescence signals during injection of exogenous optical contrast agent can be used for the assessment of the condition of blood-brain barrier at the bedside. The technique may be of benefit for diagnosis of the patients suffering from damage of the blood-brain barrier and in monitoring of therapies used in such patients.

Multiwavelength time-resolved detection of fluorescence during the inflow of indocyanine green into the adult's brain.

Optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for clinical assessment of brain perfusion in adults at the bedside. Methodology of multiwavelength and time-resolved detection of fluorescence light excited in the ICG is presented and advantages of measurements at multiple wavelengths are discussed. Measurements were carried out: 1. on a physical homogeneous phantom to study the concentration dependence of the fluorescence signal, 2. on the phantom to simulate the dynamic inflow of ICG at different depths, and 3. in vivo on surface of the human head. Pattern of inflow and washout of ICG in the head of healthy volunteers after intravenous injection of the dye was observed for the first time with time-resolved instrumentation at multiple emission wavelengths. The multiwavelength detection of fluorescence signal confirms that at longer emission wavelengths, probability of reabsorption of the fluorescence light by the dye itself is reduced. Considering different light penetration depths at different wavelengths, and the pronounced reabsorption at longer wavelengths, the time-resolved multiwavelength technique may be useful in signal decomposition, leading to evaluation of extra- and intracerebral components of the measured signals.

Time-resolved detection of fluorescent light during inflow of ICG to the brain-a methodological study.

It was reported that time-resolved reflectance measurements carried out during inflow and washout of an optical contrast agent may provide information on the blood supply to the brain cortex of human adults. It was also shown that a measurement of fluorescence excited in the dye circulating in the brain is feasible. Unfortunately, patterns of time-resolved fluorescence signals observed during in vivo measurements are difficult to interpret. The aim of this study was to analyze the influence of several factors on the fluorescence signals measured during in vivo experiments. A laboratory instrument for recording the distributions of arrival of fluorescence photons was constructed and optimized for measurements on humans. Monte Carlo simulations and laboratory measurements on liquid phantoms as well as in vivo measurements on healthy volunteers were carried out. An influence of source-detector separation, position of the source-detector pair on the head, as well as a dose of the injected indocyanine green (ICG) on the fluorescence signals were studied in detail. It was shown that even for a small dose of ICG (0.025 mg kg(-1)) the time-resolved signals can be successfully detected on the surface of the head. Strong influence of the studied factors on the fluorescence signals was observed. It was also noted that the changes in moments of distributions of arrival times of fluorescence photons depend on the anatomical structure of the tissues located between the source and the detector.

Application of a time-resolved optical brain imager for monitoring cerebral oxygenation during carotid surgery.

Recent studies have shown that time-resolved optical measurements of the head can estimate changes in the absorption coefficient with depth discrimination. Thus, changes in tissue oxygenation, which are specific to intracranial tissues, can be assessed using this advanced technique, and this method allows us to avoid the influence of changes to extracerebral tissue oxygenation on the measured signals. We report the results of time-resolved optical imaging that was carried out during carotid endarterectomy. This surgery remains the "gold standard" treatment for carotid stenosis, and intraoperative brain oxygenation monitoring may improve the safety of this procedure. A time-resolved optical imager was utilized within the operating theater. This instrument allows for the simultaneous acquisition of 32 distributions of the time-of-flight of photons at two wavelengths on both hemispheres. Analysis of the statistical moments of the measured distributions of the time-of-flight of photons was applied for estimating changes in the absorption coefficient as a function of depth. Time courses of changes in oxy- and deoxyhemoglobin of the extra- and intracerebral compartments during cross-clamping of the carotid arteries were obtained. A decrease in the oxyhemoglobin concentration and an increase in the deoxyhemoglobin concentrations were observed in a large area of the head. Large changes were observed in the hemisphere ipsilateral to the site of clamped carotid arteries. Smaller amplitude changes were noted at the contralateral site. We also found that changes in the hemoglobin signals, as estimated from intracerebral tissue, are very sensitive to clamping of the internal carotid artery, whereas its sensitivity to clamping of the external carotid artery is limited. We concluded that intraoperative multichannel measurements allow for imaging of brain tissue hemodynamics. However, when monitoring the brain during carotid surgery, a single-channel measurement may be sufficient.

Influence of individual torso geometry on inverse solution to 2 dipoles.

BACKGROUND: The purpose of this study was to observe the influence of variety in individual torso geometries on the results of inverse solution to 2 dipoles. METHODS: The inverse solution to 2 dipoles was computed from the measured data on 8 patients using either standard torso with various shapes and sizes of the heart and lungs in it or using various outer torso geometries with the same inhomogeneities. The vertical position of the heart relative to the fourth intercostal level was kept constant in all models. The results were compared with the reference solution computed in standard torso. RESULTS: The inverse solution was influenced in 4 of 8 cases by changes of torso geometry and only in 1 of 8 cases by changes of internal inhomogeneities. CONCLUSIONS: The use of individual torso geometry with the knowledge of the true heart position is very important for correct inverse results.

Assessment of inflow and washout of indocyanine green in the adult human brain by monitoring of diffuse reflectance at large source-detector separation.

Recently, it was shown in measurements carried out on humans that time-resolved near-infrared reflectometry and fluorescence spectroscopy may allow for discrimination of information originating directly from the brain avoiding influence of contaminating signals related to the perfusion of extracerebral tissues. We report on continuation of these studies, showing that the near-infrared light can be detected noninvasively on the surface of the tissue at large interoptode distance. A multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The instrument was applied during intravenous injection of indocyanine green and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye in the tissue. Time courses of the statistical moments of distributions of times of flight of photons are presented and compared to the results obtained simultaneously at shorter source-detector separations (3, 4, and 5 cm). We show in a series of experiments carried out on physical phantom and healthy volunteers that the time-resolved data acquisition in combination with very large source-detector separation may allow one to improve depth selectivity of perfusion assessment in the brain.

Risk assessment of ventricular arrhythmia using new parameters based on high resolution body surface potential mapping.

BACKGROUND: The effective screening of myocardial infarction (MI) patients threatened by ventricular tachycardia (VT) is an important issue in clinical practice, especially in the process of implantable cardioverter-defibrillator (ICD) therapy recommendation. This study proposes new parameters describing depolarization and repolarization inhomogeneity in high resolution body surface potential maps (HR BSPM) to identify MI patients threatened by VT. MATERIAL/METHODS: High resolution ECGs were recorded from 64 surface leads. Time-averaged HR BSPMs were used. Several parameters for arrhythmia risk assessment were calculated in 2 groups of MI patients: those with and without documented VT. Additionally, a control group of healthy subjects was studied. To assess the risk of VT, the following parameters were proposed: correlation coefficient between STT and QRST integral maps (STT_QRST_CORR), departure index of absolute value of STT integral map (STT_DI), and departure index of absolute value of T-wave shape index (TSI_DI). These new parameters were compared to known parameters: QRS width, QT interval, QT dispersion, Tpeak-Tend interval, total cosines between QRS complex and T wave, and non-dipolar content of QRST integral maps. RESULTS: STT_DI, TSI_DI, STT_QRST_CORR, QRS width, and QT interval parameters were statistically significant (p ≤ 0.05) in arrhythmia risk assessment. The highest sensitivity was found for the STT_DI parameter (0.77) and the highest specificity for TSI_DI (0.79). CONCLUSIONS: Arrhythmia risk is demonstrated by both abnormal spatial distribution of the repolarization phase and changed relationship between depolarization and repolarization phases, as well as their prolongation. The proposed new parameters might be applied for risk stratification of cardiac arrhythmia.

Time-resolved diffuse reflectance measurement carried out on the head of an adult at large source-detector separation.

Multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The system is based on femtosecond TiSa laser and sensitive photomultiplier tube detector. The laser light of 300mW of power was delivered to the surface of the head with the use of an optical fiber. A beam expander was applied in order to distribute the laser light on a large spot which allowed to avoid energetic stimulation of the tissue. The photomultiplier tube detector was positioned directly on the surface of the medium at the distance of 9cm from the center of the source position. In this paper we report results of an in-vivo experiment carried out on the head of an adult healthy volunteer. The time-resolved system was applied during intravenous injection of an optical contrast agent (indocyanine green - ICG) and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye to the tissue. Time-courses of the moments of distributions of times of flight of photons are presented and compared with the results obtained simultaneously at shorter source-detector separations (3 cm, 4 cm and 5 cm).