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.

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.

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.

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.

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.

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.

Estimation of speed distribution of particles moving in an optically turbid medium using decomposition of a laser-Doppler spectrum.

In this paper we present validation of laser-Doppler spectrum decomposition procedure in estimation of speed distribution of particles. Decomposition method is based on assumption that measured laser-Doppler spectrum can be approximated by linear combination of Doppler shift probability distributions calculated for different speeds of particles and anisotropy of light scattering in the medium. The Doppler shift probability distributions were calculated using Monte-Carlo simulations for Henyey-Greenstein scattering phase function. This decomposition method allows to obtain distribution of speeds of moving particles in the medium, not only average speed as it was possible in laser-Doppler perfusion monitors. Recently we reported that the method was positively verified on spectra generated for different speed distributions using Monte Carlo simulations. In this study we present results of application of the decomposition procedure in analysis of laser-Doppler spectra obtained in physical phantom experiments. A diluted solution of milk was pumped through a tube with different speeds. The dependence of the obtained distributions of speed of moving particles on the speed of flow was observed. Laser-Doppler spectra obtained during in-vivo experiment were also successfully decomposed. A healthy volunteer was investigated and the spectra of laser-Doppler signal during postocclusive hyperemia test were recorded and analyzed. We conclude that the spectrum decomposition procedure can be successfully applied in analysis of the measured laser-Doppler spectra and the amount of information provided by laser-Doppler technique can be significantly increased.

Time-resolved optical imager for assessment of cerebral oxygenation.

A time-resolved optical instrument allowing for noninvasive assessment of cerebral oxygenation is presented. The instrument is equipped with picosecond diode lasers, fast photodetectors, and time-correlated single photon counting electronics. This technology enables depth-resolved estimation of changes in absorption and, in consequence, assessment of changes in hemoglobin concentrations in the brain cortex. Changes in oxyhemoglobin (HbO(2)) and deoxyhemoglobin (Hb) can be evaluated selectively in extra- and intracerebral tissue compartments using the moments of distributions of times of flight of photons measured at two wavelengths in the near-infrared region. The combination of the data acquired from multiple sources and detectors located on the surface of the head with the depth-resolved analysis, based on the moments, enables imaging of cortex oxygenation. Results of the tests on physical phantoms as well as in vivo validation of the instrument during the motor stimulation experiment are presented.

Optimization of the Monte Carlo code for modeling of photon migration in tissue.

The Monte Carlo method is frequently used to simulate light transport in turbid media because of its simplicity and flexibility, allowing to analyze complicated geometrical structures. Monte Carlo simulations are, however, time consuming because of the necessity to track the paths of individual photons. The time consuming computation is mainly associated with the calculation of the logarithmic and trigonometric functions as well as the generation of pseudo-random numbers. In this paper, the Monte Carlo algorithm was developed and optimized, by approximation of the logarithmic and trigonometric functions. The approximations were based on polynomial and rational functions, and the errors of these approximations are less than 1% of the values of the original functions. The proposed algorithm was verified by simulations of the time-resolved reflectance at several source-detector separations. The results of the calculation using the approximated algorithm were compared with those of the Monte Carlo simulations obtained with an exact computation of the logarithm and trigonometric functions as well as with the solution of the diffusion equation. The errors of the moments of the simulated distributions of times of flight of photons (total number of photons, mean time of flight and variance) are less than 2% for a range of optical properties, typical of living tissues. The proposed approximated algorithm allows to speed up the Monte Carlo simulations by a factor of 4. The developed code can be used on parallel machines, allowing for further acceleration.