Interhemispheric connectivity estimated from EEG time-correlation analysis in preterm infants with normal follow-up at age of five.

Brain connectivity is associated with axonal connections between brain structures. Our goal was to quantify the interhemispheric neuronal connectivity in healthy preterm infants by automated quantitative EEG time-correlation analysis. As with advancing postmenstrual age (PMA, gestational age + postnatal age) the neuronal connectivity between left and right hemisphere increases, we expect to observe changes in EEG time-correlation with age. Thirty-six appropriate-for-gestational age preterm infants (PMA between 27-37 weeks) and normal neurodevelopmental follow-up at 5 years of age were included. Of these, 22 infants underwent 3-8 repeated EEG recordings at weekly intervals. The reduced 10-20 EEG electrode system for newborns was used with five sets of bipolar channels: central-temporal, frontal polar-temporal, frontal polar-central, temporal-occipital and central-occipital. We performed EEG time-correlation analysis between homologous channels of the brain hemispheres to identify interhemispheric similarity in EEG signal shape. For each 8 s epoch of the EEG the time-correlation values and the corresponding lag times were calculated for homologous channels on both hemispheres. In all channels, the median correlation value decreased significantly (between -40% and -60% decrease) from 27 to 37 weeks PMA, for gestational maturation. For the postnatal maturation only the central-temporal channel showed a significantly decreasing trend. In contrast, the median lag time showed no uniform change with PMA. The decreasing median correlation values in all homologous channels indicate a decrease in similarity in signal shape with advancing PMA. This finding may reflect greater functional differentiation of cortical areas in the developing preterm brain and may be explained by the increase of complex neural networks with excitatory and inhibitory circuitries.

MRI for diagnosing aortic valve stenosis: a comparison study of MRI and ultrasound.

BACKGROUND: In cases when Doppler ultrasound examinations are not reliable for determining the severity of aortic valve stenosis, patients undergo a catheterisation. Cardiac magnetic resonance imaging (MRI) is a promising tool for the determination of this disease. AIM: We investigated the value of MRI as a substitute for catheterisation in such circumstances, by comparing MRI measurements with Doppler ultrasound measurements. METHODS: Five volunteers and ten patients entered this study, which was approved by the Institutional Ethics Committee. A 1.0T MRI scanner was used for cardiac MRI. On the same day, a Doppler ultrasound examination was performed. The maximum velocity and the orifice area of the aortic valve (called orifice) were compared. RESULTS: A good correlation was observed between the maximum velocity measured with MRI and that measured with ultrasound (r2=0.95) and between the orifice determined by MRI and by ultrasound (r2=0.94); however, the orifice determined by MRI is consistently larger than the orifice determined by ultrasound. CONCLUSION: MRI measurements of velocity and orifice of the aortic valve correlate well with Doppler ultrasound measurement. MRI is a useful diagnostic tool and can be a good substitute for catheterisation, in particular because it allows simultaneous acquisition of anatomical and functional information.

Assessment of aortoiliac obstructive disease by Doppler spectrum analysis of blood flow velocities in the common femoral artery at rest and during reactive hyperemia.

Aortoiliac obstructive disease was assessed by Doppler spectrum analysis of blood flow velocities in the common femoral artery measured both at rest and during reactive hyperemia. The intraarterial femoral artery pressure measured at rest and during reactive hyperemia served as the "gold standard" for the definition of a hemodynamically significant aortoiliac stenosis. Our results, obtained from 93 patients (136 limbs), showed that differences between Doppler spectra obtained from limbs with a hemodynamically significant aortoiliac stenosis and those from limbs without were more pronounced during reactive hyperemia than at rest. The best assessment of aortoiliac obstructive disease could be obtained with a combination of parameters derived from Doppler spectra measured at rest and during reactive hyperemia. With these parameters, obtained by multivariate analysis, 85% of the limbs were diagnosed correctly compared with the gold standard. If angiographic data were added to the gold standard, even 91% of the limbs were diagnosed correctly. We conclude that analysis of Doppler spectra-obtained noninvasively from the common femoral artery at rest and during reactive hyperemia provides an accurate hemodynamic assessment of the aortoiliac segment.

Dealing with the subvoxel vessel position relative to the reconstruction voxel grid in 2D MR quantitative flow measurements.

A method is introduced that quantifies the error in 2D MR Quantitative Flow measurements induced by the position of the vessel relative to the reconstruction voxel grid, called the subvoxel vessel position. In this method, the vessel area and the volume flow rate are determined for all possible subvoxel vessel positions resulting in a mean value with standard deviation. Since the subvoxel vessel position in standard MR image reconstruction is completely arbitrary, the standard deviation can be considered as a measure of its random error contribution. Simulation studies and in vivo measurements show that our method can be used to quantify and subsequently eliminate this random error. It is further quantitatively shown that, for low noise levels, Fourier interpolation to a higher reconstruction matrix also decreases the random error. We conclude that the precision of a 2D MR Quantitative Flow measurement is improved either by using our method or by reconstruction to a higher matrix.

Effect of distal occlusions on the assessment of aorto-iliac pathology by analysis of Doppler spectra.

In patients with multilevel arterial obstructive disease, assessment of the severity and location of the pathology is a difficult diagnostic problem. As reported recently, the intra-arterial pressure in the common femoral artery may become normal, although aorto-iliac obstructive disease is present if the superficial femoral artery is occluded. Aorto-iliac obstructive disease can also be assessed by analysis of Doppler spectra obtained from the common femoral artery. In this study, we evaluate if this assessment of aorto-iliac obstructive disease is also harmfully affected by an occlusion in the superficial femoral artery. The results of this study demonstrate that some Doppler parameters (such as acceleration time, slope of the acceleration phase, and the resistance index), which are essential for the assessment of aorto-iliac obstructive disease, are not significantly affected by an occlusion in the superficial femoral artery. Moreover, the study shows that the status of the superficial femoral artery may also be assessed by analysis of Doppler spectra obtained from the common femoral artery.

Decay Index: a new carotid Doppler waveform measure associated with the Windkessel function of elastic arteries.

The Windkessel function of elastic arteries determines the postpeak contour of the internal carotid artery (ICA) Doppler waveform. To introduce an indicator for the function, the postpeak contour was reproduced by an exponential function, and the exponential coefficient was termed "Decay Index" (DI). DI obtained from 108 stenosis-free ICAs (55.2 +/- 15.8 y) was compared with surrogate measures for the Windkessel function (aortic pulse wave velocity, pulse pressure) and ICA peripheral resistance (resistive index, pulsatility index, systolic-to-diastolic ratio). DI was moderately correlated with the Windkessel and the resistance measures (r ranged 0.44-0.57). To clarify these intercorrelations, principal component analysis revealed two components. The first was loaded by the resistance measures (component load > or = 0.93) although the second was loaded by the Windkessel measures and DI (> or = 0.70), supporting an association between DI and the Windkessel function. Thus, DI is likely to represent an indicator for the Windkessel function.

The uterine artery blood flow velocity waveform in pathological pregnancy.

Uterine artery blood flow velocity waveforms (FVW) were recorded longitudinally in 41 women with undisturbed pregnancy as well as in 32 women with complicated pregnancy at 4-week intervals from a gestational age of 18 weeks onwards. Of these women, four did not complete the study. In a second group of 76 patients at least one FVW was recorded after admission to the obstetrical department because of complicated pregnancy. The Pulsatility-Index (PI) for normal pregnancy was based on the results of the 41 women with undisturbed pregnancy (Mulders et al. (1988) Early Hum. Dev., 17, 55-70). The complete study group (n = 145) was divided in two groups, based on the value of the last measured uterine artery PI before delivery in the abnormal PI group (PI greater than or equal to 1.02 before 32 weeks or PI greater than or equal to 0.91 after 32 weeks, n = 38) hypertension, fetal distress during pregnancy, premature delivery, small for gestational age babies (SGA) and lower placental weight were all significantly increased. In each of the groups of patients with either SGA, fetal distress during pregnancy, pre-existing hypertension with proteinuria and pregnancy-induced hypertension with or without proteinuria the mean PI was significantly increased as compared to the results in normal pregnancy. Sensitivity and specificity of the last uterine artery PI for the detection of SGA and/or fetal distress during pregnancy were 48.8% and 82.7%, respectively. The longitudinally studied women (n = 73) were divided in two groups, based on uterine artery PI before 32 weeks of gestation; in the abnormal PI group (PI greater than or equal to 1.02, n = 12) pregnancy was more complicated by premature delivery and low birth weight. Sensitivity for the early prediction of pathological pregnancies (at least one pathological phenomenon as mentioned above) was 30.4%, whereas specificity was 90.0%.

The uterine artery blood flow velocity waveform: reproducibility and results in normal pregnancy.

Uterine artery blood flow velocity waveforms (FVW) were recorded longitudinally in normal pregnancies (n = 41) at 4-week intervals from a gestational age of 18 weeks onwards. Furthermore, reproducibility of the uterine artery FVWs and the relation with maternal heart rate (MHR) was studied. The uterine artery FVW showed a low resistance flow pattern already from 18 weeks onwards, with high diastolic flow velocity relative to systolic flow velocity. Mean values (+/- S.D.) for the Pulsatility-Index (PI) before and after 32 weeks of normal pregnancy were 0.73 (+/- 0.17) and 0.67 (+/- 0.15) respectively; for the A/B ratio these values were 1.98 (+/- 0.30) and 1.85 (+/- 0.25) respectively. Intra- and interobserver reproducibility could be established for uterine artery FVW analysis. A varying time-period between the FVWs (0-4 min), repositioning of the flow probe and different observers did not cause any systematic effect on the PI, although variation increased in case of a longer time-period between the FVWs. Overall variation of the PI in the reproducibility experiments appeared to be caused more by inter- than intrapatient variance. Inter- and intrapatient variance were in the same range for the results of the longitudinal study. A statistically significant, inverse relationship between uterine artery PI and MHR could be established in a majority of cases. The mean regression coefficient for all patients of the reproducibility study was -0.0061; PI decreases with 0.0061 when maternal heart rate increases 1 beats/min.

The influence of maternal exercise on the uteroplacental vascular bed resistance and the fetal heart rate during normal pregnancy.

The effects of maternal exercise were studied in 20 healthy women with uncomplicated pregnancies. A continuous-wave Doppler ultrasound system was used to record arterial flow velocity waveforms from the ascending vasculature downstream from the uterine artery. The fetal heart rate was monitored with a Doppler ultrasound cardiotocograph. No significant change was found in the uterine blood flow velocity waveform post-exercise, as expressed by the pulsatility index, suggesting absence of change in the uterine vascular bed resistance. The fetal heart rate significantly increased after exercise.

Separation of haemodynamic flow waves measured by MR into forward and backward propagating components.

Physiological information on the action of the heart and on the reflection sites in the arterial system can be derived respectively from the forward and the backward propagating pressure or flow wave components. Earlier work on the separation of these components was exclusively based on invasive measurements of pressure or flow. In this study magnetic resonance (MR), which is a non-invasive imaging technique, was used to measure the blood flow waveform simultaneously at multiple positions along a vessel. Linear one dimensional transmission-line theory was used to separate the flow waves into forward and backward propagating components. First results, obtained from the thoracic aorta of five healthy male volunteers, consistently showed a negative reflection with a delay of about 100 ms between the foot of the forward and the foot of the backward propagating flow wave. Our model, consisting of a single vessel segment with constant diameter and wall properties, was validated by the excellent agreement between the vessel area as calculated from the flow data using the law of mass conservation and as directly measured with a different independent MR technique.

Magnetic resonance angiography used to detect kinking in the iliac arteries in endurance athletes with claudication.

In endurance athletes, leg complaints upon maximal exercise caused by flow limitations in the iliac arteries are frequently encountered. We theorize that functional kinking of the vessels, which occurs especially during hip flexion, may be a cause for such flow limitations. Conventional diagnostic tests cannot demonstrate such kinkings. Using gadolinium-enhanced magnetic resonance angiography, a 3D dataset of the aorto-iliac arteries could be obtained with the hips flexed. An image processing procedure was developed using a new segmentation algorithm to be able to use standard surface rendering techniques to visualize the arteries with an improved 3D appearance. These techniques were applied in the current study in 42 endurance athletes with documented flow limitations in the iliac arteries. As a control group 16 national level competitive cyclists without flow limitations in the iliac arteries were studied. Forty-six affected legs were examined in 42 patients. In all patients and reference persons image quality was adequate and the segmentation algorithm could be applied. In 22 affected legs (48%) a kinking in the common iliac artery could be demonstrated, compared with one leg (3%) in the control group. In 13 affected legs (28%) a kinking in the external iliac artery could be demonstrated, compared with three legs (9%) in the control group. It can be concluded that flow limitations in the iliac arteries in endurance athletes are associated with kinkings in the common and/or the external iliac arteries. Magnetic resonance angiography with the hips flexed followed by this newly developed segmentation algorithm is effective to visualize and score these kinkings.

Customized spectral band analysis compared with conventional Fourier analysis of heart rate variability in neonates.

A customized filtering technique is introduced and compared with fast Fourier transformation (FFT) for analyzing heart rate variability (HRV) in neonates from short-term recordings. FFT is classically the most commonly used spectral technique to investigate cardiovascular fluctuations. FFT requires stability of the physiological signal within a 300 s time window that is usually analyzed in adults. Preterm infants, however, show characteristics of rapidly fluctuating heart rate and blood pressure due to an immature autonomic regulation, resulting in non-stationarity of these signals. Therefore neonatal studies use (half-overlapping or moving) windows of 64 s length within a recording time of 2-5 min. The proposed filtering technique performs a filtering operation in the frequency range of interest before calculating the spectrum, which allows it to perform an analysis of shorter periods of only 42 s. The frequency bands of interest are 0.04-0.15 Hz (low frequency, LF) and 0.4-1.5 Hz (high frequency, HF). Although conventional FFT analysis as well as the proposed alternative technique result in errors in the estimation of LF power, due to spectral leakage from the very low frequencies, FFT analysis is more sensitive to this effect. The response times show comparable behavior for both the techniques. Applying both the methods to heart rate data obtained from a neonate before and after atropine administration (inducing a wide range of HRV), shows a very significant correlation between the two methods in estimating LF and HF power. We conclude that a customized filtering technique might be beneficial for analyzing HRV in neonates because it reduces the necessary time window for signal stability.

The effectiveness of ketanserin in patients with primary Raynaud's phenomenon. A randomized, double blind, placebo controlled study.

In 41 patients with Primary Raynaud's Phenomenon (PRP) the effectiveness of the serotonin receptor blocker ketanserin has been studied in a double blind cross-over study. Subjective assessments included: frequency and duration of the attacks (both per se and combined to a severity score), cold sensation, numbness, paresthesia, pain, cold water and cold weather provocation and the appearance of spontaneous attacks. The objective measurements comprised Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar arteries. All measurements were performed both at room temperature and after instant cold provocation. The severity score, the occurrence of numbness and paresthesia and cold weather provocation improved significantly on ketanserin treatment. All objective measurements with the exception of the end-diastolic blood flow velocity of DOSA did not show significant improvements. Neither blood chemistry nor systemic blood pressure showed any significant change during ketanserin treatment. However, in the 6 (15%) patients with hypertension both systolic and diastolic blood pressure normalized. Although in objective measurements hardly any significant effects of ketanserin could be demonstrated, the results of the study suggest that orally administered ketanserin is effective for minimizing subjective complaints in patients with PRP. Ketanserin did not show any side effects.

The effectiveness of isoxsuprine in patients with intermittent claudication.

Sixty male patients with intermittent claudication were investigated in a randomized, double-blind, placebo-controlled study in order to determine the effectiveness of Isoxsuprine. The analysis of the results was made on the basis of subjective assessment of symptoms by the patients themselves and also on the results of segmental blood-pressure measurements and ankle/arm indices at rest and after standardised exercise. Significant differences were demonstrated between the active and placebo groups as regards pain-free walking distance although arterial pressure measurements did not show statistically significant differences between the two groups. Isoxsuprine appears to be significantly beneficial only for patients with obstructions at the femoro-popliteal level.

Digital blood pressure and flow measurements in patients with primary Raynaud's phenomenon.

The value of digital systolic blood pressure (DBP) and flow (DBF) measurements for a quantitative diagnosis of Primary Raynaud's Phenomenon (PRP) was evaluated by comparing the results obtained in 10 patients and 20 normals. Digital skin temperature (DST), DBP and brachial systolic blood pressure (BBP) and DBF were measured at room temperature, at maximal vasodilatation and during cold provocation. At room temperature DST discriminates between normals and patients with an accuracy of 77%. On maximum vasodilatation no significant differences can be found in DBP and DBF between normals and patients. However, DBF was significantly different between male and females both in normals and in patients. During gradual cooling a decrease in DBF (a closing phenomenon) was observed both in normals and patients. In contrast DBP did not show a substantial pressure drop. Calculating digit to brachial systolic pressure indexes (DBI) a slight significant increase can be found during cold provocation both in normals and in patients. Only the DBI of digit IV during cold provocation showed a significant difference between normals and patients which resulted in an accuracy of 83%.

Noninvasive hemodynamic assessment of vasospasm in patients with primary Raynaud's phenomenon.

In order to assess vasospastic ischemic disease objectively 41 patients with primary Raynaud's phenomenon and 21 normal volunteers were investigated noninvasively by digital systolic blood pressure and digital skin temperature measurements before and after instant cold provocation. Much care had been taken to be certain that all patients had primary Raynaud's phenomenon. The results of digital pressure measurements appeared to be affected by interindividual variations in systemic systolic blood pressure. By introducing a digit-to-brachial systolic blood pressure index (DBI), such variations could be eliminated. Instant cold provocation did not change DBI significantly. No pressure drop due to a closing phenomenon could be observed. Both digital skin temperature and DBI differed significantly between healthy males and females. In the patient group males and females did not show significant differences. The results in healthy females were hardly different from the results in patients. Healthy males could be well discriminated from patients with both techniques. Sex differentiation appeared to be essential for the objective assessment of primary Raynaud's phenomenon.

Functional connectivity in preterm infants derived from EEG coherence analysis.

OBJECTIVE: To quantify the neuronal connectivity in preterm infants between homologous channels of both hemispheres. METHODS: EEG coherence analysis was performed on serial EEG recordings collected from preterm infants with normal neurological follow-up. The coherence spectrum was divided in frequency bands: δnewborn(0-2 Hz), θnewborn(2-6 Hz), αnewborn(6-13 Hz), ßnewborn(13-30 Hz). Coherence values were evaluated as a function of gestational age (GA) and postnatal maturation. RESULTS: All spectra show two clear peaks in the δnewborn and θnewborn-band, corresponding to the delta and theta EEG waves observed in preterm infants. In the δnewborn-band the peak magnitude coherence decreases with GA and postnatal maturation for all channels. In the θnewborn-band, the peak magnitude coherence decreases with GA for all channels, but increases with postnatal maturation for the frontal polar channels. In the ßnewborn-band a modest magnitude coherence peak was observed in the occipital channels, which decreases with GA. CONCLUSIONS: Interhemispherical connectivity develops analogously with electrocortical maturation: signal intensities at low frequencies decrease with GA and postnatal maturation, but increase at high frequencies with postnatal maturation. In addition, peak magnitude coherence is a clear trend indicator for brain maturation. SIGNIFICANCE: Coherence analysis can aid in the clinical assessment of the functional connectivity of the infant brain with maturation.

QRS classification and spatial combination for robust heart rate detection in low-quality fetal ECG recordings.

Non-invasive fetal electrocardiography (ECG) can be used for prolonged monitoring of the fetal heart rate (FHR). However, the signal-to-noise-ratio (SNR) of non-invasive ECG recordings is often insufficient for reliable detection of the FHR. To overcome this problem, source separation techniques can be used to enhance the fetal ECG. This study uses a physiology-based source separation (PBSS) technique that has already been demonstrated to outperform widely used blind source separation techniques. Despite the relatively good performance of PBSS in enhancing the fetal ECG, PBSS is still susceptible to artifacts. In this study an augmented PBSS technique is developed to reduce the influence of artifacts. The performance of the developed method is compared to PBSS on multi-channel non-invasive fetal ECG recordings. Based on this comparison, the developed method is shown to outperform PBSS for the enhancement of the fetal ECG.

Treatment options for active removal of renal stones.

This study provides an update on the technological aspects of the methods for active removal of renal stones. Currently, extracorporeal shock wave lithotripsy (ESWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are the available options. Findings are based upon recent literature from the PubMed database and the European Association of Urology (EAU) guidelines. ESWL remains the option of choice for stones with diameter ≤ 20 mm due to its low invasive character, whereas PCNL is the standard for stones with diameter > 20 mm because of its high stone-free rates. Although ESWL treatment has become more patient friendly, its efficacy has not improved. On the other hand, URS has gained renewed interest due to new technological developments and improved treatment methods.

Beat-to-beat heart rate detection in multi-lead abdominal fetal ECG recordings.

Reliable monitoring of fetal condition often requires more information than is provided by cardiotocography, the standard technique for fetal monitoring. Abdominal recording of the fetal electrocardiogram may offer valuable additional information, but unfortunately is troubled by poor signal-to-noise ratios during certain parts of pregnancy. To increase the usability of abdominal fetal ECG recordings, an algorithm was developed that enhances fetal QRS complexes in these recordings and thereby provides a promising method for detecting the beat-to-beat fetal heart rate in recordings with poor signal-to-noise ratios. The method was evaluated on generated recordings with controlled signal-to-noise ratios and on actual recordings that were performed in clinical practice and were annotated by two independent experts. The evaluation on the generated signals demonstrated excellent results (sensitivity of 0.98 for SNR≥1.5). Only for SNR<2, the inaccuracy of the fetal heart rate detection exceeded 2 ms, which may still suffice for cardiotocography but is unacceptable for analysis of the beat-to-beat fetal heart rate variability. The sensitivity and positive predictive value of the method in actual recordings were reduced to approximately 90% for SNR≤2.4, but were excellent for higher signal-to-noise ratios.