Fast cerebral functional signal in the 100-ms range detected in the visual cortex by frequency-domain near-infrared spectrophotometry

Brain activity is associated with physiological changes, which alter the optical properties of the tissue in the near-infrared part of the spectrum. Two major types of optical signals following functional brain activation can be distinguished: a slow signal due to hemodynamic changes and a fast signal, which is directly related to neuronal activity. The fast signal is small and therefore difficult to detect. We used a specially noise-optimized frequency-domain near-infrared spectrometer with a pi-sensor, which was expected to be particularly sensitive to deeper tissue layers, to investigate the human visual cortex during visual stimulation generated by a checkerboard. We were able to detect significant fast signals in single light bundles, but not in pi-signals. The fast signals were mostly collocated with strong slow hemodynamic signals, but showed a higher degree of localization than the latter. The latencies of 40 +/- 16 ms of the fast signals were similar between locations. Our results also indicate that the brain responds differently to a single and double (forth and back) reversal of the checkerboard, with a stronger reaction upon the double reversal.     

一种桡动脉脉搏信号的自动检波算法

现有的基于桡动脉脉搏波的心血管功能参数检测仪能够无创地检测心血管参数,但要求使用者具备一定的医学知识,需人工判断用于检测心血管功能参数的脉搏波波形,从而降低了仪器的普适性.本文利用小波变换对脉搏波进行分析,实现了一种新的基于连续小波变换的桡动脉脉搏波检波算法.实验结果表明:该算法准确性好,能有效提高心血管功能参数检测的智能化程度,降低操作难度,有利于心血管功能检测仪在家庭医疗保健中的推广使用.     

基于Blackfin DSP的便携式妊娠高血压综合征监测仪的研制

目的 为实现应用血流动力学参数动态预测妊娠高血压综合征（pregnancy-induced hypertension,PIH）,并提高预测的准确率,研制了一种便携式妊娠高血压综合征监测系统.方法 根据血流动力学预测妊娠高血压综合征的原理,结合脉搏波法检测血流动力学参数的关键技术要求,以ADSP-BF531处理器为控制核心,利用压力传感器提取孕妇脉搏波信号,通过对波形的分析,提取有关的血流动力学参数.结果 实现了对孕妇血流参数的实时检测与显示,为妊娠高血压综合征的及时诊断提供有效信息.结论 该系统体积小,无创,操作简单方便,不仅适用于临床,更适合社区及家庭使用.     

Development of artificial neural network-based algorithms for the classification of bileaflet mechanical heart valve sounds

Objectives: As is true for all mechanical prostheses, bileaflet heart valves are prone to thrombus formation; reduced hemodynamic performance and embolic events can occur as a result. Prosthetic valve thrombosis affects the power spectra calculated from the phonocardiographic signals corresponding to prosthetic closing events. Artificial neural network-based classifiers are proposed for automatically and noninvasively assessing valve functionality and detecting thrombotic formations. Further studies will be directed toward an enlarging data set, extending the investigated frequency range, and applying the presented approach to other bileaflet mechanical valves. Methods: Data were acquired for the normofunctioning St. Jude Regent valve mounted in the aortic position of a Sheffield Pulse Duplicator. Different pulsatile flow conditions were reproduced, changing heart rate and stroke volume. The case of a thrombus completely blocking 1 leaflet was also investigated. Power spectra were calculated from the phonocardiographic signals and used to train artificial neural networks of different topologies; neural networks were then tested with the spectra acquired in vivo from 33 patients, all recipients of the St. Jude Regent valve in the aortic position. Results: The proposed classifier showed 100% correct classification in vitro and 97% when applied to in vivo data: 31 spectra were assigned to the right class, 1 received a false positive classification, and 1 was "not classifiable." Conclusion: Early malfunction detection is necessary to prevent thrombotic events in bileaflet mechanical heart valves. Following further clinical validation with an extended patient database, artificial neural network-based classifiers could be embedded in a portable device able to detect valvular thrombosis at early stages of formation: this would help clinicians make valvular dysfunction diagnoses before the appearance of critical symptoms.     

Inflammatory reaction and infection in severe burns

Major burn injury is a lesion where the inflammatory reaction is exported to the whole body. After a short time of hemodynamic changes, this inflammation is kept by necrotic tissues, persistence of an opened wound, and by the pulmonary and gut reactions. When infection starts, it becomes difficult to distinguish its symptoms among the inflammatory signals. The main point of the care of burn patient consists in trying to control this reaction and the immuno-depression it leads to: early excision and grafts, early enteral nutrition, perfect nursing care. There is no specific medical treatment of this state. The antibiotic use must be well weighed up. Infection is often the trigger of the multiple organ dysfunction which is the way the burn patient dies but is not mandatory.     

Current and developing technologies for monitoring agents of bioterrorism and biowarfare

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents.     

SUTIL: Intelligent ischemia monitoring system

SUTIL is an intelligent monitoring system for intensive and exhaustive follow up of patients in coronary care units. This system processes electrocardiographic and hemodynamic signals in real time, with the main objective of detecting ischemic episodes. In this paper, we describe the tasks included in SUTIL. In addition to basic tasks, those at higher levels will also be presented. Some of these latter tasks attempt to mimic, to some extent, the way in which the human expert operates.     

基于嵌入式CPU模块的血流参数检测系统的设计

设计了一个脉搏波心血管血流参数检测系统.该系统基于嵌入式CPU模块,采用简洁的旋转编码开关作为输入控制接口,集成了血压测量、检测结果快速打印的功能,同时可以保存检测结果以便于跟踪检测和动态分析.系统体积小、便于携带、操作简单、检测方便、无创,不仅可应用于临床,更适合在家庭及社区中使用.     

Multisensory enhancement: gains in choice and in simple response times

Human observers can detect combinations of multisensory signals faster than each of the corresponding signals presented separately. In simple detection tasks, this facilitation in response times may reflect an enhancement in the perceptual processing stage or/and in the motor response stage. The current study compared the multisensory enhancements obtained in simple and choice response times (SRT and CRT, respectively) in bi- and tri-sensory (audio–visual–haptic) signal combinations using an identical experimental setup that differed only in the tasks—detecting the signals (SRT) or reporting the signals’ location (CRT). Our measurements show that RTs were faster in the multisensory combinations conditions compared to the single stimulus conditions and that the absolute multisensory gains were larger in CRT than in SRT. These results can be interpreted in two ways. According to a serial stages model, the larger multisensory gains in CRT may suggest that when combinations of multisensory signals are presented, an additional enhancement occurs in the cognitive processing stages engaged in the CRT, beyond the enhancement in the perceptual and motor stages common to both SRT and CRT. Alternatively, the results suggest that multisensory enhancement reflect task-dependent interactions within and between multiple processing levels rather than facilitated processing modules. Thus, the larger absolute multisensory gains in CRT may reflect the inverse effectiveness principle, and Bayesian statistics, in that the maximal multisensory enhancements occur in the more difficult (less precise) uni-sensory conditions, i.e., in the CRT.     

Diffuse optical imaging of the whole head

Near-Infrared Spectroscopy (NIRS) and diffuse optical imaging (DOI) are increasingly used to detect hemodynamic changes in the cerebral cortex induced by brain activity. Until recently, the small number of optodes in NIRS instruments has hampered measurement of optical signals from diverse brain regions. Our new DOI system has 32 detectors and 32 sources; by arranging them in a specific pattern, we can cover most of the adult head. With the increased number of optodes, we can collect optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously. We describe the system and report system characterization measurements on phantoms as well as on human subjects at rest and during visual, motor, and cognitive stimulation. Taking advantage of the system's larger number of sources and detectors, we explored the spatiotemporal patterns of physiological signals during rest. These physiological signals, arising from cardiac, respiratory, and blood-pressure modulations, interfere with measurement of the hemodynamic response to brain stimulation. Whole-head optical measurements, in addition to providing maps of multiple brain regions' responses to brain activation, will enable better understandings of the physiological signals, ultimately leading to better signal processing algorithms to distinguish physiological signal clutter from brain activation signals.     

Functional connectivity in the prefrontal cortex measured by near-infrared spectroscopy during ultrarapid object recognition

Near-infrared spectroscopy (NIRS) is a developing technology for low-cost noninvasive functional brain imaging. With multichannel optical instruments, it becomes possible to measure not only local changes in hemoglobin concentrations but also temporal correlations of those changes in different brain regions which gives an optical analog of functional connectivity traditionally measured by fMRI. We recorded hemodynamic activity during the Go-NoGo task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Subjects were detecting animals as targets in natural scenes pressing a mouse button. Data were low-pass filtered<1 Hz and cardiac∕respiration∕superficial layers artifacts were removed using Independent Component Analysis. Fisher's transformed correlations of poststimulus responses (30 s) were averaged over groups of channels unilaterally in each hemisphere (intrahemispheric connectivity) and the corresponding channels between hemispheres (interhemispheric connectivity). The hemodynamic response showed task-related activation (an increase∕decrease in oxygenated∕deoxygenated hemoglobin, respectively) greater in the right versus left hemisphere. Intra- and interhemispheric functional connectivity was also significantly stronger during the task compared to baseline. Functional connectivity between the inferior and the middle frontal regions was significantly stronger in the right hemisphere. Our results demonstrate that optical methods can be used to detect transient changes in functional connectivity during rapid cognitive processes.     

Multiple signal integration by decision tree induction to detect artifacts in the neonatal intensive care unit

The high incidence of false alarms in the intensive care unit (ICU) necessitates the development of improved alarming techniques. This study aimed to detect artifact patterns across multiple physiologic data signals from a neonatal ICU using decision tree induction. Approximately 200 h of bedside data were analyzed. Artifacts in the data streams were visually located and annotated retrospectively by an experienced clinician. Derived values were calculated for successively overlapping time intervals of raw values, and then used as feature attributes for the induction of models trying to classify 'artifact' versus 'not artifact' cases. The results are very promising, indicating that integration of multiple signals by applying a classification system to sets of values derived from physiologic data streams may be a viable approach to detecting artifacts in neonatal ICU data.     

Hemodynamic Changes Associated with Interictal Spikes Induced by Acute Models of Focal Epilepsy in Rats: A Simultaneous Electrocorticography and Near-Infrared Spectroscopy Study

Interictal spikes can be generated by blocking GABA_A receptor-mediated inhibition. The nature of the hemodynamic activities associated with interictal spikes in acute models of focal epilepsy based on GABA deactivation has not been determined. We analyzed systemic changes in hemodynamic signals associated with interictal spikes generated by acute models of focal epilepsy. Simultaneous ElectroCorticoGraphy (ECoG) and Near-InfraRed Spectroscopy (NIRS) recordings were obtained in vivo from adult Sprague–Dawley rat brain during semi-periodic focal interictal spikes induced by local cortical application of low doses of Penicillin G (PG) and Bicuculline Methiodide (BM) as GABA deactivation agents. The Finite Impulse Response deconvolution technique was used to estimate the profile of hemodynamic changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) concentrations associated with interictal ECoG spikes in each rat. Our results show that, in both acute models of focal epilepsy, the hemodynamic changes associated with interictal spikes were characterized by pre-spike and post-spike primary NIRS responses, and recovery periods with slight differences in amplitude and latency. The pre-spike period starting at least 2 s prior to the onset of ECoG spikes was characterized by a significant decrease in HbO concomitant with an increase in HbR with respect to baseline. The post-spike primary NIRS response exhibited the expected changes described according to the classical view of neurovascular coupling, i.e., a significant increase in HbO and a significant decrease in HbR in response to interictal spikes. The recovery period was characterized by a decreased HbO signal and an increased HbR signal, followed by a return to baseline. Compared to the BM epilepsy model, the PG model was more stable and showed lower variability in the shape, amplitude and latency of the components of spike-related hemodynamic changes. Our findings support a prominent role for pre-spike hemodynamic changes in the initiation of interictal spikes. The mechanism of interactions between neuronal and vascular networks during the pre-spike period constitutes a complex process, resulting in increased sensitivity of the epileptogenic focus to induce neuronal spiking.     

Acoustic emission technology can warn of impending iatrogenic femur fracture during femoral canal preparation for uncemented hip replacement. A cadaveric animal bone study

During uncemented hip arthroplasty the femoral prosthesis can be fitted too tightly into the femoral canal, causing a hoop-stress fracture of the proximal femur. The research undertaken evaluated Acoustic Emission (AE) technology as a potential method of detecting a fracture forming in this manner, in an attempt to assess whether this technology may be used as a means of early warning of impending fracture during surgery. Deer femora were prepared in a manner similar to surgery and uncemented hip arthroplasty broaches were inserted until fracture occurred. AE sensors were mounted on the femoral cortex and also on the broach. Five femora were fractured manually by hammering the broaches in a manner similar to surgery. Four femora were fractured using a hydraulic loading machine to insert the broach. Stepwise increases in the AE signals coincided with stepwise increases in surface strain of the femoral cortex, crack mouth growth and fracture. Both sensors recorded similar signal profiles. The sensor on the femur registered greater magnitude signals than the sensor on the broach, suggesting that there is signal impedance across the bone-broach interface. AE signals from sensors mounted on the femur and on the broach can detect damage processes happening within the femur during insertion of the broach in the time period of approximately 100 s prior to fracture. These damage processes may represent micro cracking, and ultimately fracture. This supports the possibility of the use of AE signals as a means to monitor internal damage within the femur and possibly predict impending fracture. It is clear that AE signals change significantly prior to fracture however in order to attempt to develop a warning system, further understanding of the significance of the signals and limitations of these methods must be gained.     

Fisher information and Shannon entropy for on-line detection of transient signal high-values in laser Doppler flowmetry signals of healthy subjects

Laser Doppler flowmetry (LDF) is an easy-to-use method for the assessment of microcirculatory blood flow in tissues. However, LDF recordings very often present TRAnsient Signal High-values (TRASH), generally of a few seconds. These TRASH can come from tissue motions, optical fibre movements, movements of the probe head relative to the tissue, etc. They often lead to difficulties in signal global interpretations. In order to test the possibility of detecting automatically these TRASH for their removal, we process noisy and noiseless LDF signals with two indices from information theory, namely Fisher information and Shannon entropy. For this purpose, LDF signals from 13 healthy subjects are recorded at rest, during vascular occlusion of 3 min, and during post-occlusive hyperaemia. Computation of Fisher information and Shannon entropy values shows that, when calibrated, these two indices can be complementary to detect TRASH and be insensitive to the rapid increases of blood flow induced by post-occlusive hyperaemia. Moreover, the real-time algorithm has the advantage of being easy to implement and does not require any frequency analysis. This study opens new fields of application for Fisher information and Shannon entropy: LDF 'denoising'.     

Random mutagenesis-PCR to introduce alterations into defined DNA sequences for validation of SNP and mutation detection methods

Sensitive and high throughput techniques are required for the detection of DNA sequence variants such as single nucleotide polymorphisms (SNPs) and mutations. One problem, common to all methods of SNP and mutation detection, is that experimental conditions required for detection of DNA sequence variants depend on the specific DNA sequence to be analyzed. Although algorithms and other calculations have been developed to predict the experimental conditions required to detect DNA sequence variation in a specific DNA sequence, these algorithms do not always provide reliable information and experimental conditions for SNP and mutation detection must be devised empirically. Determination of experimental conditions for detection of DNA sequence variation is difficult when samples containing only wild type sequence are available. When patient derived positive controls are used, increasingly there are valid concerns about commercial ownership and patient privacy. This report presents a rapid and efficient method, employing random mutagenesis-PCR (RM-PCR) using low fidelity DNA polymerase, to randomly introduce single and multiple base substitutions and deletions into DNA sequences of interest. Clones with sequence changes were used to validate denaturing HPLC (DHPLC) algorithm predictions, optimize conditions for mutation detection in exon 15 of the tyrosine kinase domain of the MET proto-oncogene, and to confirm the association between specific DNA sequence changes and unique DHPLC chromatographic profiles (signatures). Finally, DNA from 33 papillary renal carcinoma (PRC) patients was screened for mutations in exon 15 of MET using "validated" DHPLC conditions as a proof of principle application of RM-PCR. Use of RM-PCR for DHPLC and other SNP/mutation detection methods is discussed along with challenges associated with detecting sequence alterations in mixed tumor/normal tissue, pooled samples, and from regions of the genome that have been amplified during tumorigenesis or duplicated during evolution. Hum Mutat 17:210-219, 2001. Published 2001 Wiley-Liss, Inc.     

Wavelet-Crosscorrelation Analysis: Non-Stationary Analysis of Neurophysiological Signals

Summary:Objective: Wavelet-crosscorrelation analysis is a new application of wavelet analysis used to show the propagation of epileptiform discharges and to localize the corresponding lesions. We have shown previously that this analysis can help predict brain conditions statistically (Mizuno-Matsumoto et al. 2002). Our objective was to assess whether wavelet-crosscorrelation analysis reveals the initiation and propagation of epileptiform activity in human patients.Methods: The data obtained from three patients with simple partial seizures (SPS) using whole-head magnetoencephalography (MEG) were analyzed by the wavelet-crosscorrelation method. Wavelet-crosscorrelation coefficients (WCC), the coherent structure of each possible pair of signals from 64 MEG channels for various periods, and the time lag (TL) in two related signals, were ascertained.Results: We clearly demonstrated both localization of the irritative zone and propagation of the epileptiform discharges.Conclusions: Wavelet-crosscorrelation analysis can help reveal and visualize the dynamic changes of brain conditions. The method of this analysis can compensate for other existing methods for the analysis of MEG, electroencephalography (EEG) or Elecotrocorticography (ECoG).Significance: Our proposed method suggests that revealing and visualizing the dynamic changes of brain conditions can help clinicians and even patients themselves better understand such conditions.     

Development and preliminary clinical tests of an impedance sensing VDD recording pacemaker for diagnosis and research

Episodes of serious but infrequently occurring cardiac arrhythmias can be difficult to detect and analyse, even with modern Holter monitoring. A previous diagnostic pacemaker developed by this group provided VVI pacing therapy and recorded intracardiac ECG signals but had no atrial sensing or impedance measuring capability. A new external diagnostic pacemaker system is described that has been developed to assist in diagnosing intermittent arrhythmias by selectively recording intracardiac signals. Unlike other ambulatory monitors, in addition to recording ECG, the device combines VDD pacing therapy with the capability of monitoring and recording intracardiac impedance and pressure waveforms through a temporary intracardiac lead. A PCMCIA memory card allows storage of 48 arrhythmic events of 21 seconds each. Twelve seconds of waveform are retained before the event occurs and nine seconds after. Data retrieval and processing is performed with a PC which reconstructs each waveform for display. The ECG provides data on cardiac rhythm while cardiac function is inferred from the haemodynamic signals. During simulated trials, 14 event types were presented to the system. All events were successfully detected and recorded. During in vivo clinical tests 83 waveform recordings were made. Impedance fluctuations with typical peak-to-peak values of 64 ohms were successfully recorded.     

血流的导管测量方法及其装置

血流测量有稀释法、电磁血流钳、核磁共振、超声Doppler等，这些方法对血流动力学研究都有一定的局限性。本文提出一种操作简单、性能可靠、价格低廉的血流测量技术，以满足血流动力学研究的需要。当流体流过导管时，在导管顶端和侧端会产生与流速平方成比例的差压。导管既可以测量血压或输药，又可以测量血流。经过临床脑血流测量表明这种血流测量方法可以记录动态血流图，是血流动力学研究的一种有效测量手段。     

Development and preliminary clinical tests of an impedance sensing VDD recording pacemaker for diagnosis and research

Episodes of serious but infrequently occurring cardiac arrhythmias can be difficult to detect and analyse, even with modern Holter monitoring. A previous diagnostic pacemaker developed by this group provided VVI pacing therapy and recorded intracardiac ECG signals but had no atrial sensing or impedance measuring capability. A new external diagnostic pacemaker system is described that has been developed to assist in diagnosing intermittent arrhythmias by selectively recording intracardiac signals. Unlike other ambulatory monitors, in addition to recording ECG, the device combines VDD pacing therapy with the capability of monitoring and recording intracardiac impedance and pressure waveforms through a temporary intracardiac lead. A PCMCIA memory card allows storage of 48 arrhythmic events of 21 seconds each. Twelve seconds of waveform are retained before the event occurs and nine seconds after. Data retrieval and processing is performed with a PC which reconstructs each waveform for display. The ECG provides data on cardiac rhythm while cardiac function is inferred from the haemodynamic signals. During simulated trials, 14 event types were presented to the system. All events were successfully detected and recorded. During in vivo clinical tests 83 waveform recordings were made. Impedance fluctuations with typical peak-to-peak values of 64 ohms were successfully recorded.