Assessing effects of PEEP and global expiratory lung volume on regional electrical impedance tomography.

OBJECTIVE: This study was performed to assess the value of electrical impedance tomography (EIT) as an indicator of tidal (V(T)) and end expiratory lung volume (EELV). METHODS: EIT measurements were performed in seven healthy piglets during constant tidal volume ventilation at incremental and decremental positive end-expiratory pressure (PEEP) levels. Tidal impedance changes were calibrated to volume using V(T) calculated from flow at the airway opening. Simultaneously, calibrated respiratory inductive plethysmography was used to measure EELV changes, and used as a reference standard. RESULTS: EIT systematically underestimated both V(T) and EELV changes when EELV deviated from the level at which it was calibrated. Calculated over the entire pressure-volume curve, EIT systematically underestimated V(T) by 28 ml, with a precision from -16 to 72 ml. EELV was systemically underestimated by 406 ml, with a precision of -38 to 849 ml. Nonlinear recruitment in the ventral regions of the lungs was the main cause of this underestimation. CONCLUSIONS: Tidal and end-expiratory changes in pulmonary impedance reflect corresponding changes in lung volume, but the increasing underestimation with increasing lung volume should be taken into account in the analysis of EIT data.

Interactions between different EEG frequency bands and their effect on alpha-fMRI correlations.

In EEG/fMRI correlation studies it is common to consider the fMRI BOLD as filtered version of the EEG alpha power. Here the question is addressed whether other EEG frequency components may affect the correlation between alpha and BOLD. This was done comparing the statistical parametric maps (SPMs) of three different filter models wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. EEG and fMRI were co-registered in a 30 min resting state condition in 15 healthy young subjects. Power variations in the delta, theta, alpha, beta and gamma bands were extracted from the EEG and used as regressors in a general linear model. Statistical parametric maps (SPMs) were computed using three different filter models, wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. Results show that the SPMs of different EEG frequency bands, when significant, are very similar to that of the alpha rhythm. This is true in particular for the beta band, despite the fact that the alpha harmonics were discarded. It is shown that inclusion of EEG frequency bands as confounder in the fMRI-alpha correlation model has a large effect on the resulting SPM, in particular when for each frequency band the HRF is extracted from the data. We conclude that power fluctuations of different EEG frequency bands are mutually highly correlated, and that a multi frequency model is required to extract the SPM of the frequency of interest from EEG/fMRI data. When no constraints are put on the shapes of the HRFs of the nuisance frequencies, the correlation model looses so much statistical power that no correlations can be detected.

A study of the brain's resting state based on alpha band power, heart rate and fMRI.

Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during non-specific general tasks, is a hemodynamic effect caused by heart rate variations. Of fifteen healthy controls ECG, EEG and fMRI were co-registered. Slice time dependent heart rate regressors were derived from the ECG data and correlated to fMRI using a linear correlation analysis where the impulse response is estimated from the data. It was found that in most subjects substantial correlations between heart rate variations and fMRI exist, both within the brain and at the ventricles. The brain areas with high correlation to heart rate are different from the "default network" and the response functions deviate from the canonical hemodynamic response function. Furthermore, a general negative correlation was found between heart beat intervals (reverse of heart rate) and alpha power. We interpret this finding by assuming that subject's state varies between drowsiness and wakefulness. Finally, given this large correlation, we re-examined the contribution of heart rate variations to earlier reported fMRI/alpha band correlations, by adding heart rate regressors as confounders. It was found that inclusion of these confounders most often had a negligible effect. From its strong correlation to alpha power, we conclude that the heart rate variations contain important physiological information about subject's resting state. However, it does not provide a full explanation of the behaviour of the "default network". Its application as confounder in fMRI experiments is a relatively small computational effort, but may have a substantial impact in paradigms where heart rate is controlled by the stimulus.

Change in the accommodative force on the lens of the human eye with age.

The aim of the study was to determine the age-dependence of the accommodative force on the lens in order to make it clear whether the causes of presbyopia are due to lenticular or extralenticular changes. A finite element model of the lens of an 11-, 29- and 45-year-old human eye was constructed to represent the fully accommodated state. Subsequently, the force that was needed to mould the lens into its unaccommodated state was calculated. The force on the lens appeared to be preserved with age, with only a slight increase to a value of approximately 0.06N. In conclusion, the preservation of the net force delivered by the extralenticular ciliary body indicates that the causes of presbyopia must be ascribed to lenticular changes.

Artifact removal in co-registered EEG/fMRI by selective average subtraction.

OBJECTIVE: Co-registration of EEG (electroencephalogram) and fMRI (functional magnetic resonance imaging) remains a challenge due to the large artifacts induced on the EEG by the MR (magnetic resonance) sequence magnetic fields. Thus, we present an algorithm, based on the average-subtraction method, which is able to correct EEG data for gradient and pulse artifacts. METHODS: MR sequence timing parameters are estimated from the EEG data and both slice and volume artifact templates are subtracted from the data. A clustering algorithm is proposed to account for the variability of the pulse artifact. RESULTS: The algorithm is able to keep the spontaneous EEG as well as visual evoked potentials (VEPs), while removing gradient and pulse artifacts with only a subtraction of selectively averaged data. In the frequency domain, the artifact frequencies are strongly attenuated. Estimated MR sequence time parameters showed that the correction is extremely sensitive to the slice time value. Pulse artifact clustering showed that most of the variability is due to the time jitter of the pulse artifact markers. CONCLUSIONS: Selective subtraction of averages in combination with proper time alignment is enough to remove most of the MR-induced artifacts. SIGNIFICANCE: Clean EEG can be obtained from raw signals that are corrupted by MR-induced artifacts during simultaneous EEG-fMRI scanning without using dedicated hardware to synchronize EEG and fMRI clocks.

Haemodynamic changes in the second half of pregnancy: a longitudinal, noninvasive study with thoracic electrical bioimpedance.

OBJECTIVE: Maternal cardiovascular adaptations to pregnancy are necessary for an adequate fetomaternal circulation. However, the time course of physiological haemodynamic changes during the second half of pregnancy remains unclear. Various methods, invasive and noninvasive, are described to measure these changes. The thoracic electrical bioimpedance (TEB) technique is a method which is especially suitable to measure haemodynamic changes over time. The aim of the study was to determine both individual and group trends of haemodynamic changes in healthy pregnant women during the second half of pregnancy by means of TEB. Outcome variables are heart rate (HR), stroke volume (SV), cardiac output (CO) and blood pressure. DESIGN: Longitudinal study. SETTING: Outpatient antenatal care clinic of university hospital. POPULATION: A total of 22 healthy nonsmoking women with an uncomplicated singleton pregnancy and without pre-existing vascular disorders were invited. METHODS: TEB and blood pressure measurements were performed at each regular visit from about 24 weeks of gestation through term age. MAIN OUTCOME MEASURES: Trends were calculated with the random effects model. RESULTS: Data obtained from 19 women were analysed, with a median of eight (range 3-11) measurements. HR showed a linear increase (P < 0.0005) and a quadratic trend (P < 0.0005). SV decreased linearly (P = 0.046), without a quadratic course. CO remained stable over time. CONCLUSION: During the second half of physiological pregnancy, significant trends could be determined. An increase in HR, a decrease in SV, a stable CO and an increase in systolic and diastolic blood pressures were found.

The hemodynamic response of the alpha rhythm: an EEG/fMRI study.

EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier studies, no a priori assumptions were made on the expected shape of the alpha band response function (ARF). The ARF of different brain regions and subjects were explored and compared. It was found that: (1) the ARF of the thalamus is mainly positive. (2) The ARFs at the occipital and left and right parietal points are similar in amplitude and timing. (3) The peak time of the thalamus is a few seconds earlier than that of occipital and parietal cortex. (4) No systematic BOLD activity was found preceding the alpha band activity, although in the two subjects with the strongest alpha band power such correlation was present. (5) There is a strong and immediate positive correlation at the eyeball, and a strong negative correlation at the back of the eye. Furthermore, it was found that in one subject the cortical ARF was positive, contrary to the other subjects. Finally, a cluster analysis of the observed ARF, in combination with a Modulated Sine Model (MSM) fit to the estimated ARF, revealed that within the cortex the ARF peak time shows a spatial pattern that may be interpreted as a traveling wave. The spatial pattern of alpha band response function represents the combined effect of local differences in electrical alpha band activity and local differences in the hemodynamic response function (HRF) onto these electrical activities. To disentangle the contributions of both factors, more advanced integration of EEG inverse modeling and hemodynamic response modeling is required in future studies.

Estimating the external force acting on the human eye lens during accommodation by finite element modelling.

Using new geometric information on the shape of the lens that has recently become available, a finite element model has been developed in order to estimate the forces that act on the lens during accommodation for a typical 29-year-old human eye. To investigate the influence of the anterior, posterior and central zonular fibres insertion regions, three models with different configurations were built. All three configurations appeared to be capable of inducing the required accommodative changes in the lens. Based on material properties from the literature, the estimated summed net force for each of the three models was approximately 0.08 N.

Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject variability.

Simultaneous recording of electroencephalogram/functional magnetic resonance images (EEG/fMRI) was applied to identify blood oxygenation level-dependent (BOLD) changes associated with spontaneous variations of the alpha rhythm, which is considered the hallmark of the brain resting state. The analysis was focused on inter-subject variability associated with the resting state. Data from 7 normal subjects are presented. Confirming earlier findings, three subjects showed a negative correlation between the BOLD signal and the average power time series within the alpha band (8--12 Hz) in extensive areas of the occipital, parietal and frontal lobes. In small thalamic areas, the BOLD signal was positively correlated with the alpha power. For subjects 3 and 4, who displayed two different states during the data acquisition time, it was shown that the corresponding correlation patterns were different, thus demonstrating the state dependency of the results. In subject 5, the changes in BOLD were observed mainly in the frontal and temporal lobes. Subject 6 only showed positive correlations, thus contradicting the negative BOLD alpha power cortical correlations that were found in most subjects. Results suggest that the resting state varies over subjects and, sometimes, even within one subject. As the resting state plays an important role in many fMRI experiments, the inter-subject variability of this state should be addressed when comparing fMRI results from different subjects.

Regional timing of myocardial shortening is related to prestretch from atrial contraction: assessment by high temporal resolution MRI tagging in humans.

Earlier studies have shown substantial nonuniformity in normal left ventricular (LV) myocardial function concerning both the degree of shortening and timing of shortening. We hypothesized that nonuniform LV function may be related to nonuniform prestretch induced by atrial contraction. Eleven healthy human subjects were studied using MRI myocardial tagging and strain analysis. The amount of circumferential prestretch was assessed in 30 LV segments. Prestretch was defined as the difference in strain between end diastole (at ECG R wave) and diastasis. Furthermore, both the degree of shortening (quantified as peak circumferential shortening, peak systolic shortening rate, and amount of postsystolic shortening) and timing of shortening (quantified as the onset time of shortening and time to peak shortening) were assessed. LV prestretch was found to be nonuniform, with the highest values in the lateral wall. The amount of segmental prestretch correlated significantly with peak shortening (r = 0.79), peak shortening rate (r = 0.50), amount of postsystolic shortening (r = 0.67), onset time of shortening (r = -0.57), and time to peak shortening (r = 0.71) (P < 0.001 for each of these relations). These relations may be explained by regional differences in wall stress or by a regional Frank-Starling effect. The correlation between timing of shortening and prestretch demonstrates that mechanical timing is not determined by electrical phenomena alone. In conclusion, regional variation in LV function correlates with the nonuniform prestretch from atrial contraction.

A maximum-likelihood estimator for trial-to-trial variations in noisy MEG/EEG data sets.

The standard procedure to determine the brain response from a multitrial evoked magnetoencephalography (MEG) or electroencephalography (EEG) data set is to average the individual trials of these data, time locked to the stimulus onset. When the brain responses vary from trial-to-trial this approach is false. In this paper, a maximum-likelihood estimator is derived for the case that the recorded data contain amplitude variations. The estimator accounts for spatially and temporally correlated background noise that is superimposed on the brain response. The model is applied to a series of 17 MEG data sets of normal subjects, obtained during median nerve stimulation. It appears that the amplitude of late component (30-120 ms) shows a systematic negative trend indicating a weakening response during stimulation time. For the early components (20-35 ms) no such a systematic effect was found. The model is furthermore applied on a MEG data set consisting of epileptic spikes of constant spatial distribution but varying polarity. For these data, the advantage of applying the model is that positive and negative spikes can be processed with a single model, thereby reducing the number of degrees of freedom and increasing the signal-to-noise ratio.

On the flow dependency of the electrical conductivity of blood.

Experiments presented in the literature show that the electrical conductivity of flowing blood depends on flow velocity. The aim of this study is to extend the Maxwell-Fricke theory, developed for a dilute suspension of ellipsoidal particles in an electrolyte, to explain this flow dependency of the conductivity of blood for stationary laminar flow in a rigid cylindrical tube. Furthermore, these theoretical results are compared to earlier published measurement results. To develop the theory, we assumed that blood is a Newtonian fluid and that red blood cells can be represented by oblate ellipsoids. If blood flows through a cylindrical tube, shear stresses will deform and align the red blood cells with one of their long axes aligned parallel to the stream lines. The pathway of a low-frequency (< 1 MHz) alternating electrical current will be altered by this orientation and deformation of the red blood cells. Consequently, the electrical conductivity in the flow direction of blood increases. The theoretically predicted flow dependency of the conductivity of blood corresponds well with experimental results. This theoretical study shows that red blood cell orientation and deformation can explain quantitatively the flow dependency of blood conductivity.

Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI tagging: early onset and late peak of shortening in lateral wall.

Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge of cardiac contraction timing in healthy persons is scarce. In this work, timing of cardiac contraction was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI myocardial tagging and strain analysis. Both the onset time of circumferential shortening (T(onset)) in early systole and the time of peak circumferential shortening (T(peak)) at end systole were determined. The onset of shortening width (time needed for 20-90% of the left ventricle to start shortening) was small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with earliest onset in the lateral wall and latest onset in the septum (P = 0.001). Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an opposite spatial pattern, with peak shortening occurring earlier in the septum than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments, mainly in the lateral and basal segments. Shortening in these segments continued 58 +/- 14 ms after aortic valve closure, during which circumferential shortening increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction in normal subjects may serve as a reference in detecting mechanical asynchrony due to intraventricular conduction defects or ischemia.

The influence of brain tumor treatment on pathological delta activity in MEG.

The goal of the MEG study was to investigate the influence of tumor treatment on pathological delta activity (1-4 Hz). The treatment consisted of neurosurgery, and in some of the patients, additional radiotherapy. MEG and MR recordings were made both before and after the treatment in 17 patients. The signal power in the delta frequency band was determined for each recording. The malignant tumors were associated with large tumor volumes. Furthermore, both malignant tumors and tumor volume were associated with high signal powers in the delta band, indicating a correlation of delta power with the severity of the lesions. In all patients with high grade tumors, the delta power was lower after the treatment. The sources underlying the delta signals were estimated with an automatic single dipole analysis method. Estimated sources were projected onto MR scans. Preoperatively 14 clusters of equivalent sources describing focal activity were found in 12 out of 17 patients. Thirteen of these clusters were located near the tumor, and one cluster near an edema border. The locations near tumors are plausible and suggest that in general the source estimation was reliable. After the operation, 13 such clusters were found in 12 patients. Eleven clusters were located near the lesion border and one cluster near the edema border. Furthermore a cluster contralateral to the lesion in the other hemisphere indicated that brain lesions can affect the functioning of more distant brain areas than just the peritumoral brain tissue. Of the 12 patients who had preoperatively peritumoral clusters, 11 patients had postoperatively perilesional sources. In these cases the shift in source locations was in general considerably smaller than the dimension of the preoperative tumors. This finding indicates that similar areas generate the pre- and postoperative delta activity. Furthermore, focal delta sources were found in a case without tumor recurrence, and also in cases that most tumor tissue was removed. These findings suggest that the pathology underlying the slow waves is not the presence of the tumor bulk but the structural damage done by the tumors on the surrounding white/gray matter.

In vivo measurement of the brain and skull resistivities using an EIT-based method and the combined analysis of SEF/SEP data.

Results of "in vivo" measurements of the skull and brain resistivities are presented for six subjects. Results are obtained using two different methods, based on spherical head models. The first method uses the principles of electrical impedance tomography (EIT) to estimate the equivalent electrical resistivities of brain (rhobrain), skull (rhoskull) and skin (rhoskin) according to. The second one estimates the same parameters through a combined analysis of the evoked somatosensory cortical response, recorded simultaneously using magnetoencephalography (MEG) and electroencephalography (EEG). The EIT results, obtained with the same relative skull thickness (0.05) for all subjects, show a wide variation of the ratio rhoskull/rhobrain among subjects (average = 72, SD = 48%). However, the rhoskull/rhobrain ratios of the individual subjects are well reproduced by combined analysis of somatosensory evoked fields (SEF) and somatosensory evoked potentials (SEP). These preliminary results suggest that the rhoskull/rhobrain variations over subjects cannot be disregarded in the EEG inverse problem (IP) when a spherical model is used. The agreement between EIT and SEF/SEP points to the fact that whatever the source of variability, the proposed EIT-based method

Measures of cardiovascular autonomic nervous function: agreement, reproducibility, and reference values in middle age and elderly subjects.

AIMS/HYPOTHESIS: Currently, three categories of cardiovascular autonomic nervous function measures are used: classic Ewing-test measures, measures of heart-rate variability (HRV), and measures of baroreflex sensitivity (BRS). Little is known about the agreement between these measures, and reference and reproducibility values for these measures have not been reported within the same group. METHODS: As part of the Hoorn Study, 631 subjects aged 50 to 75 participated in a study of autonomic nervous function. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during spontaneous breathing, during six deep breaths over 1 min, and during an active change in position from lying to standing. From these readings, ten measures of autonomic function were assessed (mean heart rate, three Ewing test measures, five HRV measures and one BRS measure). RESULTS: Regression analysis in a healthy subgroup (n=191) showed sex differences for two of the ten measures and seven measures decreased with age. Therefore, appropriate age-specific and sex-specific reference values were calculated. Reproducibility (n=39) of most measures was moderate, with a reliability coefficient of around 50%. Agreement between the measures of autonomic nervous function varied greatly, between 0% and 87%. The HRV-power ratio measure and the blood pressure changes in the lying-to-standing test showed the lowest agreement with all other measures. CONCLUSION/INTERPRETATION: This study provides age-specific and sex-specific reference values for a wide range of different autonomic function measures in an elderly population. Agreement among the different measures varied widely and reproducibility was only moderate.

Imaging of thoracic blood volume changes during the heart cycle with electrical impedance using a linear spot-electrode array.

Electrical impedance (EI) measurements conducted on the thorax contain useful information about the changes in blood volume that occur in the thorax during the heart cycle. The aim of this paper is to present a new (tomographic-like) method to obtain this relevant information with electrical impedance measurements, using a linear electrode array. This method is tested on three subjects and the results are compared with results, obtained from magnetic resonance cine-images showing the cross-sectional surface area changes of the aorta, the vena cava, the carotid arteries, and the heart. This paper shows that the different sources of the thoracic EI waveform may be separated in time and location on the thoracic surface and that aortic volume changes may be estimated accurately.

Comparing spot electrode arrangements for electric impedance cardiography.

This study investigates whether an arrangement with nine spot electrodes, for thoracic bio-impedance cardiography, can be replaced by an arrangement with five spot electrodes. The study was conducted on 15 healthy subjects, six females and nine males, in supine rest. The variables obtained from the measurements were the mean of the impedance of the thorax segment between the recording electrodes, the maximum negative deflection of the first derivative of the thoracic impedance, the left ventricular ejection time and an estimate of left ventricular stroke volume. An analysis of variance for a randomized complete block design was used to determine whether significant differences exist in the group means of the observed variables between six different electrode arrangements. If no statistically significant differences were found in these group means between pairs of arrangements, Bland and Altman analyses were used to determine the differences in the observed variables between pairs of arrangements for individual subjects. This study concludes that reducing the number of spot electrodes from nine to five, does not yield significant differences in the group means of the observed variables, but it could result in large differences in the values of these variables for individual subjects.

Characteristics of the parallel-plate flow chamber for mechanical stimulation of bone cells under microgravity.

We show the use of a dimensionless parameter alpha h, in properly downscaling a parallel-plate flow chamber system for flow stimulation of bone cells under microgravity. The proper experimental regime for exposing cells to predictable levels of dynamic fluid shear stress requires: 1) alpha h < 2, based on the consequent quasi-parabolic form of the velocity profile in this regime, and 2) fo m

Improved harmonic phase myocardial strain maps.

Magnetic resonance tagging has proven a valuable tool in the quantification of myocardial deformation. However, time-consuming postprocessing has discouraged the use of this technique in clinical routine. Recently, the harmonic phase (HARP) technique was introduced for automatic calculation of myocardial strain maps from tagged images. In this study, a comparison was made between HARP instantaneous strain maps calculated from single tagged images (SPAMM) and those calculated from subtracted tagged images (CSPAMM). The performance was quantified using simulated images of an incompressible cylinder in the 'end-systolic' state with realistic image contrast and noise. The error in the second principal stretch ratio was 0.009 +/- 0.032 (mean +/- SD) for the SPAMM acquisition, and 0.007 +/- 0.016 for CSPAMM at identical contrast-to-noise ratio. Furthermore, differences between the methods were illustrated with in vivo strain maps. Those calculated from CSPAMM images showed fewer artifacts and were less sensitive to the choice of cut-off frequencies in the HARP band-pass filter. A prerequisite for the method to become practical is that the CSPAMM images should be acquired in a single breathhold.