Soft sensors for a sensing-actuation system with high bladder voiding efficiency.

Sensing-actuation systems can assist a bladder with lost sensation and weak muscle control. Here, we advance the relevant technology by integrating a soft and thin capacitive sensor with a shape memory alloy-based actuator to achieve a high-performance closed-loop configuration. In our design, sensors capable of continuous bladder volume detection and actuators with strong emptying force have been used. This integration has previously hindered performance due to large bladder volume changes. Our solution integrates sensing-actuation elements that are bladder compatible but do not interfere with one another, achieving real-time bladder management. The system attains a highly desirable voiding target of 71 to 100% of a rat's bladder with a volume sensitivity of 0.7 µF/liter. Our system represents an efficient voiding solution that avoids overfilling and represents a technological solution to bladder impairment treatment, serving as a model for similar soft sensor-actuator integration with other organs.

Spinal cord integrity monitoring by adaptive coherence measurement.

OBJECTIVE: Injury during routine spinal cord procedures could result in devastating consequences for the surgical patient. Spinal cord monitoring through somatosensory evoked potentials (SEPs) remains a viable method for prevention of serious injury. METHODS: The adaptive coherence estimation (ACE) is a method to iteratively calculate signal match quality through successive filter entrainment. Here we compare the speed of detection with ACE to conventional amplitude measurements. Both absolute magnitude of ACE and amplitude as well as slope change detector algorithm (Farley-Hinich) was run as well to determine the earliest time when a significant change occurred. RESULTS: The standard error for the ACE algorithm is close to one tenth of the amplitude measure, Since the ACE algorithm achieved low variance during baseline measurement, we were able to achieve rapid detection of injury. For absolute magnitude detection ACE was faster than amplitude for the 20 g injury weight class. It took an average of 10 epochs to detect the injury with adaptive coherence and nearly 19 with standard amplitude metrics using absolute magnitude changes. Abrupt change detection methods using slope change show that ACE provides more favorable detection capabilities comparable to amplitude. Additionally, there was a significant increase in the ROC curve between ACE and amplitude alone (p<0.05). CONCLUSIONS: Because of its excellent detection capabilities, the adaptive coherence method provides an excellent supplement to traditional amplitude for capturing injury-related changes in SEPs. SIGNIFICANCE: Adaptive coherence remains a viable method for rapidly and accurately detecting spinal injury.

Monitoring of global cerebral ischemia using instantaneous phase variation plots.

In this paper, the derivative of the instantaneous phase of electroencephalographic (EEG) signals is used as a basis for monitoring of global cerebral ischemia. Visual and quantitative results were obtained from six rodents that were subject to 3, 5 and 7 minutes of global ischemic brain injury by asphyxic cardiac arrest. Results show that the variations in the instantaneous phase are capable of amplifying the variations during the various stages of the recovery process and may serve as a novel analytical approach to grade and classify brain rhythms during global ischemic brain injury and recovery.

VLSI Potentiostat Array With Oversampling Gain Modulation for Wide-Range Neurotransmitter Sensing.

A 16-channel current-measuring very large-scale integration (VLSI) sensor array system for highly sensitive electrochemical detection of electroactive neurotransmiters like dopamine and nitric-oxide is presented. Each channel embeds a current integrating potentiostat within a switched-capacitor first-order single-bit delta-sigma modulator implementing an incremental analog-to-digital converter. The duty-cycle modulation of current feedback in the delta-sigma loop together with variable oversampling ratio provide a programmable digital range selection of the input current spanning over six orders of magnitude from picoamperes to microamperes. The array offers 100-fA input current sensitivity at 3.4-muW power consumption per channel. The operation of the 3 mm times3 mm chip fabricated in 0.5-mum CMOS technology is demonstrated with real-time multichannel acquisition of neurotransmitter concentration.

Monitoring of global cerebral ischemia using wavelet entropy rate of change.

In this paper, the subband wavelet entropy (SWE) and its time difference are proposed as two quantitative measures for analyzing and segmenting the electroencephalographic (EEG) signals. SWE for EEG subbands, namely Delta, Theta, Alpha, Beta, and Gamma, is calculated and segmented using wavelet analysis. In addition, a time difference entropy measure was calculated because it does not require a baseline and equals to zero in all clinical bands as the initial condition. Visual and quantitative results were obtained from 11 rodents that were subjected to 3, 5, and 7 min of global ischemic brain injury by asphyxic cardiac arrest. We found that the time difference of SWE is capable of amplifying the variations between clinical bands during the various stages of the recovery process and may serve as a novel analytical approach to grade and classify brain rhythms during global ischemic brain injury and recovery.

MEMSurgery: an integrated test-bed for vascular surgery.

Many surgical procedures require skillful manipulations of blood vessels, especially in conventional invasive or minimally invasive surgical procedures. Current surgical methods do not allow the surgeon to receive any real time feedback of the tissue properties when operating on the vessel. As a result, the unintentional application of excessive force may damage the blood vessel. To minimize such trauma, and to study the interaction of surgical instruments with the vessel structure, we have developed an integrated surgical testbed called MEMSurgery (Microelectromechanical Sensory augmented Surgery). The test-bed integrates four elements: a) force sensors mounted on surgical appliances, b) a feedback control mechanism utilizing the intrinsic mechanical properties of the blood vessel, c) feedback of the force applied on the tissue back to the surgeon through a haptic feedback device, and d) visual feedback by a graphical computer model of the vessel. Finally, we evaluate the performance of MEMSurgery by testing the hypothesis that the combination of haptic feedback, feedback control based on vascular mechanical properties, and real-time visual representation of the vessel will help the surgeon decrease the probability of applying excess force while occluding the blood vessel. To this end, we designed a rodent experimental model to obtain the ideal minimum occlusion force (MOF). After a series of human performance studies, and subsequent comparison to direct application of force on the forceps (without feedback), the results show that the probability of applying reasonable MOF increases from 35.5% to 80%. After a brief training period, the probability increases to 90%.

Vulnerability of the thalamic somatosensory pathway after prolonged global hypoxic-ischemic injury.

The aim of this study was to test the hypothesis that under prolonged global ischemic injury, the somatosensory thalamus and the cortex would manifest differential susceptibility leading to varying degrees of thalamo-cortical dissociation. The thalamic electrical responses displayed increasing suppression with longer durations of ischemia leading to a significant thalamo-cortical electrical dissociation. The data also point to a selective vulnerability of the network oscillations involving the thalamic relay and reticular thalamic neurons. An adult rat model of asphyxial cardiac arrest involving three cohorts with 3 min (G1, n=5), 5 min (G2, n=5) and 7 min (G3, n=5) of asphyxia respectively was used. The cortical evoked response, as quantified by the peak amplitude at 20 ms in the cortical evoked potential, recovers to more than 60% of baseline in all the cases. The multi-unit responses to the somatosensory stimuli recorded from the thalamic ventral posterior lateral (VPL) nuclei consists typically of three components: (1). the ON response (<30 ms after stimulus), (2). the OFF response (period of inhibition, from 30 ms to 100 ms after stimulus) and (3). rhythmic spindles (beyond 100 ms after stimulus). Asphyxia has a significant effect on the VPL ON response at 30 min (P<0.025), 60 min (P<0.05) and 90 min (P<0.05) after asphyxia. Only animals in G3 show a significant suppression (P<0.05) of the VPL ON response when compared to the sham group at 30 min, 60 min and 90 min after asphyxia. There was no significant reduction in somatosensory cortical N20 (negative peak in the cortical response at 20 ms after stimulus) amplitude in any of the three groups with asphyxia indicating a thalamo-cortical dissociation in G3. Further, rhythmic spindle oscillations in the thalamic VPL nuclei that normally accompany the ON response recover either slowly after the recovery of ON response (in the case of G1 and G2) or do not recover at all (in the case of G3).We conclude that there is strong evidence for selective vulnerability of thalamic relay neurons and its network interactions with the inhibitory interneurons in the somatosensory pathway leading to a thalamo-cortical dissociation after prolonged durations of global ischemia.

Detection of asphyxia using heart rate variability.

The long-term aims of this study are to find a parameter derived from the ECG that has a high sensitivity and specificity to asphyxia and, once we know or suspect that asphyxia occurred, to estimate how severe it was. We carried out a pilot study in which 24 adult Wistar rats were anaesthetised and subjected to controlled asphyxia for specified durations. We measured the pH, 'neurological score' and the ECG, extracting from this heart rate and heart rate variability (HRV). We have developed a technique capable of detecting asphyxia in less than 1 min, based on monitoring the ECG and estimating HRV by measuring the standard deviation of normal RR intervals (the RR interval is the time interval between two consecutive R-points of the QRS complex). In all cases the heart rate decreased and HRV increased, by an average of 46 +/- 33 ms in relation to the baseline, at the onset of asphyxia. The comparison of the base level of HRV after and before asphyxia shows promise for the estimation of the severity of the episode; however, the limitations of this study should be noted as they include the small size of the cohort and the methods of analysis.

A short-time multifractal approach for arrhythmia detection based on fuzzy neural network.

We have proposed the notion of short-time multifractality and used it to develop a novel approach for arrhythmia detection. Cardiac rhythms are characterized by short-time generalized dimensions (STGDs), and different kinds of arrhythmias are discriminated using a neural network. To advance the accuracy of classification, a new fuzzy Kohonen network, which overcomes the shortcomings of the classical algorithm, is presented. In our paper, the potential of our method for clinical uses and real-time detection was examined using 180 electrocardiogram records [60 atrial fibrillation, 60 ventricular fibrillation, and 60 ventricular tachycardia]. The proposed algorithm has achieved high accuracy (more than 97%) and is computationally fast in detection.

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics.

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VT rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.

Detection of non-linearity in the EEG of schizophrenic patients.

OBJECTIVE: The aim of this study is to detect non-linearity in the EEG of schizophrenia with a modified method of surrogate data. We also want to identify if dimension complexity (correlation dimension using spatial embedding) could be used as a discriminating statistic to demonstrate non-linearity in the EEG. The difference between the attractor dimension of healthy subjects and schizophrenic subjects is expected to be interpreted as reflecting some mechanisms underlying brain wave by views of non-linear dynamics analysis may reflect mechanistic differences. METHODS: EEGs were recorded with 14 electrodes in 18 healthy male subjects (average age: 26.3; range: 20--35) and 18 male schizophrenic patients (average age: 30.6; range: 24--40) during a resting eye-closed state. Neither of two groups was taking medicines. All artificial epochs in the EEG records were rejected by an experienced doctor's visual inspection. RESULTS: Testing non-linearity with modified surrogate data, we showed that correlation dimension of EEG data of schizophrenia does refuse the null hypothesis that the data were resulted from a linear dynamic system. A decrease of dimension complexity was found in the EEG of schizophrenia compared with controls. We interpreted it as the result of the psychopath's dysfunction overall brain. The surrogating procedure results in a significant increase in D(s). CONCLUSIONS: Non-linearity of the EEG in schizophrenia was proven in our study. We think the correlation dimension with spatial embedding as a good discriminating statistic for testing such non-linearity. Moreover, schizophrenic patients' EEGs were compared with controls and a lower dimension complexity was found. The results of our study indicate the possibility of using the methods of non-linear time series analysis to identify the EEGs of schizophrenic patients.

Transcranial magnetic stimulation in the rat.

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7+/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS, 1 and MEPTMS, 2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS, 2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS, 1 followed a sigmoid course, no supramaximal response was reached for MEPTMS, 2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.29+/-0.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS.

The nonlinear dynamical analysis of the EEG in schizophrenia with temporal and spatial embedding dimension.

We applied nonlinear dynamics theory to EEG analysis of schizophrenic patients and estimated the correlation dimension with both temporal embedding and spatial embedding. A higher D2 was found when using a time-delay embedding method. Especially at F7 and Fp1, a significant increase showed. We concluded that more complex activity occurred in certain lobes of schizophrenic patients. Using the spatial embedding method, a relative lower global correlation dimension was obtained. This shows that there might be a diffuse slow wave activity through a schizophrene's global cerebrum. Finally, we discuss the study from three angles of clinical semiology, spectrum analysis and neuropsychology and draw some conclusions about the relationship between the nonlinear analysis of schizophrenia EEG and clinical research. It seems that the theory of a nonlinear dynamics system is a powerful tool for EEG research and may prove useful in complementing visual analysis of EEG accompanied with other study means for brain electrical activity.

Optical scatter imaging: subcellular morphometry in situ with Fourier filtering.

We demonstrate a quantitative optical scatter imaging (OSI) technique, based on Fourier filtering, for detecting alterations in the size of particles with wavelength-scale dimensions. We generate our scatter image by taking the ratio of images collected at high and low numerical aperture in central dark-field microscopy. Such an image spatially encodes the ratio of wide to narrow angle scatter and hence provides a measure of local particle size. We validated OSI on sphere suspensions and live cells. In live cells, OSI revealed biochemically induced morphological changes that were not apparent in unprocessed differential interference contrast images. Unlike high-resolution imaging methods, OSI can provide size information for particles smaller than the camera's spatial resolution.

Coherence-weighted Wiener filtering of somatosensory evoked potentials.

In this paper, we present a Wiener filtering (WF) approach for extraction of somatosensory evoked potentials (SEPs) from the background electroencephalogram (EEG), with sweep-to-sweep variations in its signal power. To account for the EEG power variations, WF is modified by iteratively weighting the power spectrum using the coherence function. Coherence-weighted Wiener filtering (CWWF) is able to extract SEP waveforms, which have a greater level of detail as compared with conventional time-domain averaging (TDA). Using CWWF, the components of the SEP show significantly less variability. As such, CWWF should be useful as an important diagnostic tool able to detect minimal changes in the SEP. In an experimental study of cerebral hypoxia, CWWF is shown to be more responsive to detection of injury than WF or TDA.

A novel quantitative EEG injury measure of global cerebral ischemia.

OBJECTIVE: To develop a novel quantitative EEG (qEEG) based analysis method, cepstral distance (CD) and compare it to spectral distance (SD) in detecting EEG changes related to global ischemia in rats. METHODS: Adult Wistar rats were subjected to asphyxic-cardiac arrest for sham, 1, 3, 5 and 7 min (n=5 per group). The EEG signal was processed and fitted into an autoregressive (AR) model. A pre-injury baseline EEG was compared to selected data segments during asphyxia and recovery. The dissimilarities in the EEG segments were measured using CD and SD. A segment measured was considered abnormal when it exceeded 30% of baseline and its duration was used as the index of injury. A comprehensive Neurodeficit Score (NDS) at 24 h was used to assess outcome and was correlated with CD and SD measures. RESULTS: A higher correlation was found with CD and asphyxia time (r=0.81, P<0.001) compared to SD and asphyxia time (r=0.69, P<0.001). Correlation with cardiac arrest time (MAP<10 mmHg) showed that CD was superior (r=0.71, P<0.001) to SD (r=0.52, P=0.002). CD obtained during global ischemia and 90 min into recovery correlated significantly with NDS at 24 h after injury (Spearman coefficient=-0.83, P<0.005), and was more robust than the traditional SD (Spearman coefficient=-0.63, P<0.005). CONCLUSION: The novel qEEG-based injury index from CD was superior to SD in quantifying early cerebral dysfunction after cardiac arrest and in providing neurological prognosis at 24 h after global ischemia in adult rats. Studying early qEEG changes after asphyxic-cardiac arrest may provide new insights into the injury and recovery process, and present opportunities for therapy.

Effects of anodal vs. cathodal pacing on the mechanical performance of the isolated rabbit heart.

Previous studies have suggested that anodal pacing enhances electrical conduction in the heart near the pacing site. It was hypothesized that enhanced conduction by anodal pacing would also enhance ventricular pressure in the heart. Left ventricular pressure measurements were made in isolated, Langendorff-perfused rabbit hearts by means of a Millar pressure transducer with the use of a balloon catheter fixed in the left ventricle. The pressure wave was analyzed for maximum pressure (Pmax) generated in the left ventricle and the work done by the left ventricle (Parea). Eight hearts were paced with monophasic square-wave pulses of varying amplitudes (2, 4, 6, and 8 V) with 100 pulses of each waveform delivered to the epicardium. Anodal stimulation pulses showed statistically significant improvement in mechanical response at 2, 4, and 8 V. Relative to unipolar cathodal pacing, unipolar anodal pacing improved Pmax by 4.4 +/- 2.3 (SD), 5.3 +/- 3.1, 3.5 +/- 4.9, and 4.8 +/- 1.9% at 2, 4, 6, and 8 V, respectively. Unipolar anodal stimulation also improved Parea by 9.0 +/- 3.0, 12.0 +/- 6.0, 10.1 +/- 7.7, and 11.9 +/- 6.0% at 2, 4, 6, and 8 V, respectively. Improvements in Pmax and Parea indicate that an anodally paced heart has a stronger mechanical response than does a cathodally paced heart. Anodal pacing might be useful as a novel therapeutic technology to treat mechanically impaired or failed hearts.

Optical light scatter imaging of cellular and sub-cellular morphology changes in stressed rat hippocampal slices.

Optical imaging, such as transmission imaging, is used to study brain tissue injury. Transmission imaging detects cellular swelling via an increase in light transmitted by tissue slices due to a decrease in scattering particle concentration. Transmission imaging cannot distinguish sub-cellular particle size changes from cellular swelling or shrinkage. We present an optical imaging method, based on Mie scatter theory, to detect changes in sub-cellular particle size and concentration. The system uses a modified inverted microscope and a 16-bit cooled CCD camera to image tissue light scatter at two angles. Dual-angle scatter ratio imaging successfully discriminated latex microsphere suspensions of differing sizes (0.6, 0.8, 1 and 2 microm) and concentrations. We applied scatter imaging to hippocampal slices treated with 100 microM N-methyl-D-aspartate (NMDA) to model excitotoxic injury or -40 mOsm hypotonic perfusion solution to cause edema injury. We detected light scatter decreases similar to transmission imaging in the CA1 region of the hippocampus for both treatments. Using our system, we could distinguish between NMDA and hypotonic treatments on the basis of statistically significant (P<0.0003) differences in the scatter ratio measured in CA1. Scatter imaging should be useful in studying tissue injuries or activity resulting in brain tissue swelling as well as morphological changes in sub-cellular organelles such as mitochondrial swelling.

Wavelet analysis and time-frequency distributions of the body surface ECG before and after angioplasty.

In a pilot study, electrocardiographic (ECG) recordings of patients with left and right coronary stenosis taken before and after angioplasty were analyzed using the continuous wavelet transform. Time-frequency distributions were obtained for different leads in order to examine the dynamics of the QRS-spectrum and establish features specific of ischemia in the time-frequency domain. We found relevant changes in the mid-frequency range, reflecting the ECG's response to percutaneous transluminal coronary angioplasty (PTCA). The changes appeared in ECG leads close to ischemic zones of the myocardium. Time-frequency distributions of the ECG during the QRS may thus become another electrocardiographic indicator of ischemia, alternative to ST-level in standard ECG or body surface mapping. The paper demonstrates the ability of the continuous wavelet transform to detect short lasting events of low amplitude superimposed on large signal deflections.