A Novel Application of Multiscale Entropy in Electroencephalography to Predict the Efficacy of Acetylcholinesterase Inhibitor in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia. According to one hypothesis, AD is caused by the reduced synthesis of the neurotransmitter acetylcholine. Therefore, acetylcholinesterase (AChE) inhibitors are considered to be an effective therapy. For clinicians, however, AChE inhibitors are not a predictable treatment for individual patients. We aimed to disclose the difference by biosignal processing. In this study, we used multiscale entropy (MSE) analysis, which can disclose the embedded information in different time scales, in electroencephalography (EEG), in an attempt to predict the efficacy of AChE inhibitors. Seventeen newly diagnosed AD patients were enrolled, with an initial minimental state examination (MMSE) score of 18.8 ± 4.5. After 12 months of AChE inhibitor therapy, 7 patients were responsive and 10 patients were nonresponsive. The major difference between these two groups is Slope 2 (MSE6 to 20). The area below the receiver operating characteristic (ROC) curve of Slope 2 is 0.871 (95% CI = 0.69-1). The sensitivity is 85.7% and the specificity is 60%, whereas the cut-off value of Slope 2 is -0.024. Therefore, MSE analysis of EEG signals, especially Slope 2, provides a potential tool for predicting the efficacy of AChE inhibitors prior to therapy.

A new method to derive fetal heart rate from maternal abdominal electrocardiogram: monitoring fetal heart rate during cesarean section.

BACKGROUND: Monitoring of fetal heart rate (FHR) is important during labor since it is a sensitive marker to obtain significant information about fetal condition. To take immediate response during cesarean section (CS), we noninvasively derive FHR from maternal abdominal ECG. METHODS: We recruited 17 pregnant women delivered by elective cesarean section, with abdominal ECG obtained before and during the entire CS. First, a QRS-template is created by averaging all the maternal ECG heart beats. Then, Hilbert transform was applied to QRS-template to generate the other basis which is orthogonal to the QRS-template. Second, maternal QRS, P and T waves were adaptively subtracted from the composited ECG. Third, Gabor transformation was applied to obtain time-frequency spectrogram of FHR. Heart rate variability (HRV) parameters including standard deviation of normal-to-normal intervals (SDNN), 0V, 1V, 2V derived from symbolic dynamics of HRV and SD1, SD2 derived from Poincareé plot. Three emphasized stages includes: (1) before anesthesia, (2) 5 minutes after anesthesia and (3) 5 minutes before CS delivery. RESULTS: FHRs were successfully derived from all maternal abdominal ECGs. FHR increased 5 minutes after anesthesia and 5 minutes before delivery. As for HRV parameters, SDNN increased both 5 minutes after anesthesia and 5 minutes before delivery (21.30±9.05 vs. 13.01±6.89, P < 0.001 and 22.88±12.01 vs. 13.01±6.89, P < 0.05). SD1 did not change during anesthesia, while SD2 increased significantly 5 minutes after anesthesia (27.92±12.28 vs. 16.18±10.01, P < 0.001) and both SD2 and 0V percentage increased significantly 5 minutes before delivery (30.54±15.88 vs. 16.18±10.01, P < 0.05; 0.39±0.14 vs. 0.30±0.13, P < 0.05). CONCLUSIONS: We developed a novel method to automatically derive FHR from maternal abdominal ECGs and proved that it is feasible during CS.

Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing.

Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.

Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1-58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.

Empirical mode decomposition based detrended sample entropy in electroencephalography for Alzheimer's disease.

Quantitative electroencephalographs (qEEG) provide a potential method to objectively quantify the cortical activations in Alzheimer's disease (AD), but they are too insensitive to probe the alteration of EEG in the early AD. The sample entropy (SaEn) attempts to quantify the complex information embedded in EEG non-linearly, which fits in that EEG originates from non-linear interactions. However, a technical issue which has been ignored by most researchers is that the signal should be stationary. In order to resolve the non-stationarity of SaEn in EEG to improve the sensitivity, an empirical mode decomposition (EMD) was applied for detrending in this study. Twenty-seven AD patients (9M/18F; mean age 74.0±1.5 years) were included. Their initial Minimal Mental Status Examination was 19.3±0.7. They received the first resting-awake 30-mine EEG before the therapy. Five of them received a follow-up examination within 6 months after the therapy. The 30-s EEG data without artifacts were selected and analyzed with a new proposed method, "EMD-based detrended-SaEn" to attenuate the influence of intrinsic non-stationarity. The correlation factors in 27 AD patients showed a moderate correlation (0.361-0.523, p<0.05) between MMSE and EMD-based detrended SaEn in Fp1, Fp2, F4 and T3. There was a high correlation (Correlation coefficient=0.975, p<0.05) between the changes of MMSE and the changes of EMD-based detrended-SaEn in F7 in 5 follow-up patients. The dynamic complexity of EEG fluctuations is degraded by pathological degeneration, and EMD-based detrended SaEn provides an objective, non-invasive and non-expensive tool for evaluating and following AD patients.

A consistent tissue attenuation coefficient estimator using bubble harmonic echoes.

The ultrasonic property of soft tissue can be quantified by its attenuation coefficient α. Traditionally the backscattering signal of tissue is used to estimate α. To improve precision, a large number of spatially independent samples of tissue echoes are required for averaging. In this paper, we propose a new estimation method, which makes use of microbubbles to provide temporally independent samples for averaging. It is easier for temporal sampling to maintain ergodicity and provide a large number of independent samples for statistical averaging. A stochastic model for the harmonic signals of an ideal bubble attenuated by tissue is derived based on Kuc's and Miller's works. An estimator of α is then presented. This estimator is consistent and could be biased because of the unknown squarelaw relation between the second and fundamental harmonics for non-ideal bubble oscillation. In experimental works, we design a simplified phantom for demonstrating the performance of the proposed estimator. It is shown that both first and second harmonics can estimate α consistently. However, the interference of the tissue backscattering signal may cause additional estimation error using the first harmonic.

Dosage prediction via estimation of shell thickness and concentration of drug carrier with microbubbles.

For drug delivery applications, dosage prediction before release and estimation after release are required functions. In this study, we attempted to establish a method to evaluate liposome concentrations and liposome shell thickness for dosage prediction. We use the Trilling model with parameter of phospholipids bilayers to simulate the frequency responses under the different acoustic pressure and establish an experimental protocol to evaluate the liposome concentrations and the liposome shell thickness. Our results illustrate the changes on the signal strength for different concentrations and show that it is relatively stable to estimate the concentrations when the cycles are lower (15 cycles). Besides, it is verified that the second harmonic signal is more sensitive in analyzing different concentrations. On the other hand, it is proved that the liposome shell thickness affect signal strength and thinner thickness will increase the second harmonic response. Therefore, in accordance with the theoretical and experimental results, we would be able to estimate the concentration and the shell thickness of the liposomes. By numerical analysis methods, dosage prediction would be built.

Ultrasonic renal-stone tracking with mesh regularization.

The efficacy of Extracorporeal Shock Wave Lithotripsy (ESWL) depends greatly on the capability to focus shock waves on renal stone. To achieve automatic focusing on moving target, the target must be under tracking. A mesh-based block matching algorithm is proposed for renal stone tracking using ultrasound image sequence. Since multiple targets are tracked together, the mesh-based tracking algorithm can provide a function of contextual regularization for solving the target missing and image degradation problems in renal stone tracking. Recorded ultrasound images of kidney during ESWL treatment are modified for demonstrating the capability of this algorithm.

The effects of sampling rate on the texture separability of ultrasound images.

Ultrasound machine has been a useful diagnosis tool for several decades, and many researches tried to use computerized algorithms to help physicians diagnose diseases according to the ultrasound texture patterns. However, the effects of sampling format and the sampling rate on the texture feature were not treated properly. In this paper, the authors try to evaluate the effects of the scan conversion done at imaging stage and the sampling rate used at the texture feature extraction stage. They demonstrate the indispensability of considering sampling format and sampling rate according to the feature used, and their proposed method would improve the separability of texture feature for coarse and homogeneous ultrasound images.

An ultrasonic microbubble semi-intermodulated imaging technique.

The performance of contrast imaging technique is critically influenced by some factors, such as spatial resolution, agent-to-tissue ratio, lifetime of contrast agents and attenuation effect. By using a transducer with higher frequency and higher bandwidth of transmitted signals, the spatial resolution can be improved. Similarly, a better signal-to-interference ratio (SIR) can improve the agent-to-tissue ratio, a lower transmission pressure can prolong the lifetime of contrast agents and a lower center frequency can diminish the attenuation effect. We extend the two-frequency analytic solutions of to approximate the short-pulse responses of microbubbles in a low-amplitude field. Based on their results, there is an expected component near 0 Hz in the spectrum of bubble echoes excited by a short pulse of ultrasound. Here, this component is called the low-frequency response; and it is shown to have a special bandwidth-dependent property and to have potential applications in imaging. We have established the procedure of semi-intermodulated (low-frequency) imaging and the effects of the attenuation effect on imaging resolution, SIR, and signal-to-noise ratio are also analyzed. The obtained experimental images demonstrate that the SIR in semi-intermodulated imaging is better than that in fundamental imaging under various attenuation conditions.

Ultrasonic renal-stone detection and identification for extracorporeal lithotripsy.

The efficacy of extracorporeal shock wave lithotripsy (ESWL) depends greatly on the capability to focus shock waves on renal stone in real time. To achieve automatic focusing on moving targets, target detection, identification and tracking are required functions. An algorithm for renal stone detection and identification based on ultrasound images is proposed. Two types of image features (contrast and target shape) are selected for stone detection and identification. A feature extraction algorithm is proposed and tested. Statistical characteristics of these features are studied based on the images of kidney recorded during ESWL treatment. The results demonstrate the feasibility of automatic detection and identification of renal stone based on ultrasound images.

The effect of back-scan conversion on the texture features of ultrasound image.

Ultrasound is an important way of physical examination nowadays. Many literatures tried to find a quantified standard for diagnosing ultrasonic images; however, they neglected the effect of scan-conversion on image textures. This paper provides a preprocessing method, which practically conforms to the ultrasound image formats, and then compares the effect of the preprocessing method. Several images of sponges were used to evaluate the effect of the preprocessing because of their nearly homogeneous texture. It was found that the spread of standard deviations of the extracted features got narrower, at best 4 times, with preprocessing than that without preprocessing. The back-scan conversion is indispensable for the analysis of ultrasound images using features sensitive to depth and orientation.

Aperture size effect on ultrasonic wavefront distortion correction.

The influences of aperture size on wavefront distortion correction are investigated both theoretically and numerically. A multilayer, phase-screen model is assumed to be the underlying, distorting medium. Numerical simulations were performed using three wavefront distortion correction methods: time-shift compensation (TSC), backpropagation followed by time-shift compensation (BP+TSC), and the previously proposed, multilayer, phase-screen compensation (MPSC) method. The distorted wavefronts were generated by propagating a planar wavefront through a multilayer, phase-screen model constructed with a two-dimensional (2-D) scanned map of a real abdominal slice. Performances were evaluated by L2 errors between the corrected wavefronts and the undistorted planar wavefront. Point spread functions also were calculated to evaluate the relative image quality. Theoretical analysis shows L2 error will decrease as aperture size grows when exact phase compensation (EPC) is applied, although finite errors will always exist along the edges of the corrected wavefront. Three different aperture sizes, 14.24 mm (64 elements), 28.48 mm (128 elements), and 56.96 mm (256 elements) are considered in this study. Numerical results show that the quality of wavefront with EPC is essentially limited by the aperture size, and the correction methods considered are relatively robust against the aperture size. It also shows that, for low aberration, results with MPSC and EPC are comparable. However, for high aberration, MPSC significantly outperforms EPC in suppression of L2 error and sidelobes. This study suggests that, for most medical ultrasound imaging systems, the exact structure of the distorting medium may not be necessary to be known a priori for optimal distortion correction because of the limitation imposed by finite aperture size.

Factor analysis in both spatial and temporal domains of color blooming artifacts in ultrasound investigations utilizing contrast agents.

Color blooming artifacts can cause misinterpretations of normal and pathological structures during color Doppler flow imaging with ultrasound contrast agents (USCAs). These artifacts are characterized in both the spatial and temporal domains: in the spatial domain, artifacts result from wave propagation and the ultrasound system; and in the temporal domain, the color blooming time (CBT) is used to denote the duration of artifacts. In our experiments, CBT decreased from 86.7 to 46.8 s when the transmitting pressure was decreased from 370 to 180 kPa. From this, we conclude that an adaptive mechanical index can significantly shorten the CBT, which may in turn prolong the optimal viewing time during in vivo ultrasound investigations utilizing USCAs.

The ultrasonic weak short-pulse responses of microbubbles based on a two-frequency approximation.

The ultrasonic short-pulse responses of microbubbles are of interest in cavitation, transient responses, and contrast imaging. We extend the two-frequency analytic solutions of Newhouse and Shankar [J. Acoust. Soc. Am. 75, 1473-1477 (1984)] to approximate the short-pulse responses of microbubbles in a low-amplitude field. Based on their results, there is an expected component near dc in the spectrum of bubble echoes excited by a short pulse. Here this component is named the low-frequency response, and its theoretical properties are verified experimentally. Including the fundamental and second-harmonic components, the weak short-pulse responses of microbubbles include three types of response. Our work has determined the constraint conditions under which this approximated solution can be used to analyze these short-pulse responses. This paper also provides the amplitude and spectral properties of these responses. The low-frequency response has a special bandwidth-dependent property and has potential applications in imaging and bubble sizing.

Volume scattering of distributed microbubbles and its influence on blood flow estimation.

In recent years, microbubble contrast agents have become a potential adjunct in Doppler ultrasound diagnosis. In this paper, we show that volume scattering makes the effective band in Doppler spectrum shift downward after injection of microbubbles. Because the insonified volume comprises a collection of distributed microbubbles, the statistical properties such as the autocorrelation function and ensemble average power spectrum of the echoes from a collection of distributed microbubbles were derived first. It can be observed that, beyond a critical frequency, the theoretical volume backscattering cross section derived from the ensemble average power spectrum of microbubbles decreases with frequency. On the contrary, the volume backscattering cross section of red cells increases with frequency. Using two-dimensional (2-D) Fourier transform, the variation in Doppler spectrum caused by different volume backscattering cross section can be demonstrated, and the consequential downward shifts of the estimated Doppler parameters (e.g., the mean and maximum Doppler shifts, and the variance of Doppler power spectrum) after microbubble injection are shown. In addition, it can be observed that the variation gets larger as the transmitted bandwidth increases. And, the variations in Doppler parameters estimated with experimental data are presented to verify the theoretical deviations.

Analysis and correction of ultrasonic wavefront distortion based on a multilayer phase-screen model.

A model is introduced that incorporates the cumulative wavefront distortion effects caused by spatial heterogeneities along the path of propagation, and a corresponding model-based wavefront distortion-correction method is presented. In the proposed model, a distributed heterogeneous medium is lumped into a series of parallel phase screens. The distortion effects can be compensated--without a priori knowledge of the distorting structure--by backpropagation of received wavefronts through hypothetical multiple phase screens located between the imaging system and targets, while each pointwise time shift is adjusted iteratively to maximize a specified image quality factor at the final layer. Theoretical analyses indicate that the mean speckle brightness decreases monotonically with the root-mean-square value of distributed phase distortions; therefore, the speckle brightness can be used as an image quality factor. Experimental one-dimensional (1-D) array data with simulated distortion effects based on a real 2-D abdominal-tissue map were used to evaluate the performance of the proposed method and existing aberration-correction techniques. The simulated characteristics of wavefront distortion and relative performance of existing correction techniques were similar to reports based on abdominal-wall data and breast data. This investigation shows that the proposed method provides better compensation for wavefront distortion.