Evidence of piezoelectric resonance in isolated outer hair cells

Our results demonstrate high-frequency electrical resonances in outer hair cells (OHCs) exhibiting features analogous to classical piezoelectric transducers. The fundamental (first) resonance frequency averaged f(n) approximately 13 kHz (Q approximately 1.7). Higher-order resonances were also observed. To obtain these results, OHCs were positioned in a custom microchamber and subjected to stimulating electric fields along the axis of the cell (1-100 kHz, 4-16 mV/80 microm). Electrodes embedded in the side walls of the microchamber were used in a voltage-divider configuration to estimate the electrical admittance of the top portion of the cell-loaded chamber (containing the electromotile lateral wall) relative to the lower portion (containing the basal plasma membrane). This ratio exhibited resonance-like electrical tuning. Resonance was also detected independently using a secondary 1-MHz radio-frequency interrogation signal applied transversely across the cell diameter. The radio-frequency interrogation revealed changes in the transverse electric impedance modulated by the axial stimulus. Modulation of the transverse electric impedance was particularly pronounced near the resonant frequencies. OHCs used in our study were isolated from the apical region of the guinea pig cochlea, a region that responds exclusively to low-frequency acoustic stimuli. In this sense, electrical resonances we observed in vitro were at least an order of magnitude higher (ultrasonic) than the best physiological frequency of the same OHCs under acoustic stimuli in vivo. These resonance data further support the piezoelectric theory of OHC function, and implicate piezoelectricity in the broad-band electromechanical behavior of OHCs underlying mammalian cochlear function.     

Preliminary Investigation of a 64-element Capacitive Micromachined Ultrasound Transducer (CMUT) Annular Array Designed for High Intensity Focused Ultrasound (HIFU)

Background

Treatment of prostate cancer using endocavitary High Intensity Focused Ultrasound (HIFU) has become more commonplace since the first treatments in the 1990s. The gold standard HIFU strategy to treat prostate cancer is the complete thermal ablation of the entire prostate gland under real-time ultrasound (US) image guidance. A more desirable treatment and the current trend, however, is towards a focal treatment but more accurate and finely tunable thermal lesions are needed along with improved US imaging guidance. In this study, Capacitive Micromachined Ultrasound Transducer (CMUT) technology is being investigated, as they have shown recent promise for US imaging and potential to be used for HIFU therapy. They offer potential advantages over current piezoelectric designs in the context of ultrasound-guided HIFU (USgHIFU) focal therapies.

High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke

It is estimated that only 2-6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (～70%) animals tested. Histological analysis confirmed thatthe sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments.     

Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm²), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction.     

Magnetic Resonance Imaging Assessment of Effective Ablated Volume following High Intensity Focused Ultrasound

Under magnetic resonance (MR) guidance, high intensity focused ultrasound (HIFU) is capable of precise and accurate delivery of thermal dose to tissues. Given the excellent soft tissue imaging capabilities of MRI, but the lack of data on the correlation of MRI findings to histology following HIFU, we sought to examine tumor response to HIFU ablation to determine whether there was a correlation between histological findings and common MR imaging protocols in the assessment of the extent of thermal damage. Female FVB mice (n = 34), bearing bilateral neu deletion tumors, were unilaterally insonated under MR guidance, with the contralateral tumor as a control. Between one and five spots (focal size 0.5 × 0.5 × 2.5 mm³) were insonated per tumor with each spot receiving approximately 74.2 J of acoustic energy over a period of 7 seconds. Animals were then imaged on a 7T MR scanner with several protocols. T1 weighted images (with and without gadolinium contrast) were collected in addition to a series of T2 weighted and diffusion weighted images (for later reconstruction into T2 and apparent diffusion coefficient maps), immediately following ablation and at 6, 24, and 48 hours post treatment. Animals were sacrificed at each time point and both insonated/treated and contralateral tumors removed and stained for NADH-diaphorase, caspase 3, or with hematoxylin and eosin (H&E). We found the area of non-enhancement on contrast enhanced T1 weighted imaging immediately post ablation correlated with the region of tissue receiving a thermal dose CEM43 ≥ 240 min. Moreover, while both tumor T2 and apparent diffusion coefficient values changed from pre-ablation values, contrast enhanced T1 weighted images appeared to be more senstive to changes in tissue viability following HIFU ablation.     

High-Intensity Focused Ultrasound in Functional Neurosurgery

Stereotactic functional neurosurgical interventions for basal ganglia are an important method for treating pain, obsessive–compulsive, movement and depressive disorders. These interventions include destructive surgeries and deep brain stimulation through implanted electrodes. Destructive surgeries have a number of serious limitations, since they are associated with a higher risk of complications, especially in case of bilateral interventions. High-intensity focused ultrasound (HIFU) is a novel noninvasive approach proposed for destruction of a certain target point in the brain. We discuss the technical foundations of HIFU, thoroughly analyze the advantages and drawbacks of the method compared to other methods of modern functional neurosurgery, and summarize the first results of using HIFU in the world’s leading clinics. Further accumulation of experience is needed to perform a well-considered analysis of the potential of HIFU and to assess the long-term effects of the interventions performed and the role of this procedure in the algorithms for treating various nervous system diseases.     

高强度聚焦超声可治疗区域的仿真研究

数值仿真不同治疗参数条件下高强度聚焦超声(high intensity focused ultrasound,HIFU)可治疗区域的变化,对HIFU治疗剂量的确定具有重要的指导意义。本文采用Westervelt方程的近似式,结合Pennes生物热传导方程,以离体猪肝组织为例,在考虑组织声学特性对HIFU焦域温度场影响的条件下,通过时域有限差分法(finite difference time domain,FDTD)对HIFU焦域温度场进行仿真研究。研究结果表明,照射时间越长,组织声学特性的影响就越明显;焦点处的最高温升相同时,可治疗区域的大小差异较小;声强越大,形成可治疗区域所需的时间也越短;当声强一定时,随着照射时间的增加,可治疗区域的长、短轴长度均呈非线性增加;在相同可治疗区域的长轴或短轴长度一定时,输入声强和照射时间呈负相关。     

Simultaneous positioning of cells into two-dimensional arrays using ultrasound

Contactless simultaneous positioning of micrometer-sized particles in suspension (e.g., copolymer beads, living cells, silicon microparts) can be performed using ultrasound. Current devices are capable of collecting particles into planes or lines by exciting a resonance in the fluid by means of a piezoelectric transducer located beneath the fluidic cavity and are designed such that a one-dimensional pressure field is created. The focus of this work is to collect cells in distinct point locations for potential drug screening array applications. A device to create two-dimensional arrays of cells within a micromachined chamber is described. The chamber is etched into a silicon wafer and sealed with glass; on the underside of the silicon layer a piezoelectric actuator is attached. A signal is applied to each of two orthogonally aligned strips electrodes defined on the surface of the piezoelectric plate. These two strip electrodes create independently addressable approximately one-dimensional pressure fields. It is shown that by applying the same signal to each electrode a diagonally aligned grid of cells can be produced. However, the independence of the two electrodes allows the application of two signals with slightly different frequencies to be applied which creates a grid of circular cell clumps highly suitable for the identified application. (c)     

Intercellular power transmission along trichomes of cyanobacteria

An attempt at demonstrating lateral power transmission over millimeter distances along a coupling membrane has been undertaken. Trichomes of the multicellular filamentous cyanobacteria Phormidium uncinatum were illuminated with a very narrow light beam forming a light spot that covered only 4–5% of a 1–2 mm long cyanobacterial trichome. Such illumination was found to support motility (gliding along agar surface) of the trichome under conditions when the light was the only energy source. It was also shown that illumination with the light spot caused rotation of rings of slime (accompanying the operation of the ‘motors’ responsible for the motility of cyanobacteria) not only in the illuminated, but also in the distal, nonilluminated part of the trichome. Electric potential transmission along trichomes was revealed by means of the extracellular electrode technique. The light spot was found to induce generation of an electric potential difference between two electrodes in the dark region of the trichomes, which were placed at different distances from the illuminated end. Cutting the trichomes between the light spot and the closest ‘dark’ electrode abolished this effect. Valinomycin + K⁺ and carbonyl cyanide p-trifluoromethoxyphenylhydrazone affected the potential difference formation between two ‘dark’ electrodes much stronger than that between a light and a dark electrode. All the light spot-induced effects develop in the seconds time scale. Both the amplitudes and the kinetics of the potential difference measured with four electrodes placed along the trichome prove to be in good agreement with the theoretical curves computed on the basis of the electric cable equation. It is concluded that transcellular power transmission in the form of Δψ takes place along trichomes of cyanobacteria. This confirms the hypothesis about the biological function of Δψ as a transportable form of energy.     

The properties of bird feathers as converse piezoelectric transducers and as receptors of microwave radiation. I. Bird feathers as converse piezoelectric transducers.

An investigation was made of the properties of bird feathers as piezoelectric transducers in the audiofrequency range and as dielectric receptors of electromagnetic radiation in the microwave region. In the first case, cartridges of the ceramic and magnetic type and an electromagnetic transducer probe were used as detecting devices. Results show piezoelectric resonances in the 1 to 20-kHz region for the calami of feathers.     

Modeling Analysis on Germination and Seedling Growth Using Ultrasound Seed Pretreatment in Switchgrass

Switchgrass is a perennial C4 plant with great potential as a bioenergy source and, thus, a high demand for establishment from seed. This research investigated the effects of ultrasound treatment on germination and seedling growth in switchgrass. Using an orthogonal matrix design, conditions for the ultrasound pretreatment in switchgrass seed, including sonication time (factor A), sonication temperature (factor B) and ultrasound output power (factor C), were optimized for germinating and stimulating seedling growth (indicated as plumular and radicular lengths) through modeling analysis. The results indicate that sonication temperature (B) was the most effective factor for germination, whereas output power (C) had the largest effect on seedling growth when ultrasound treatment was used. Combined with the analyses of range, variance and models, the final optimal ultrasonic treatment conditions were sonication for 22.5 min at 39.7°C and at an output power of 348 W, which provided the greatest germination percentage and best seedling growth. For this study, the orthogonal matrix design was an efficient method for optimizing the conditions of ultrasound seed treatment on switchgrass. The electrical conductivity of seed leachates in three experimental groups (control, soaked in water only, and ultrasound treatment) was determined to investigate the effects of ultrasound on seeds and eliminate the effect of water in the ultrasound treatments. The results showed that the electrical conductivity of seed leachates during either ultrasound treatment or water bath treatment was significantly higher than that of the control, and that the ultrasound treatment had positive effects on switchgrass seeds.     

Measurement of discrete vertical in-shoe stress with piezoelectric transducers

The purpose of this investigation was to design and validate a system suitable for non-invasive measurement of discrete in-shoe vertical plantar stress during dynamic activities. Eight transducers were constructed, with small piezoelectric ceramic squares (4.83 × 4.83 × 1.3 mm) used to generate a charge output proportional to vertical plantar stress. The mechanical properties of the transducers included 2.3% linearity and 3.7% hysteresis for stresses up to 2000 kPa and loading times up to 200 ms. System design efficacy was analysed by means of a multiple day, multiple trial data collection. With the transducers placed beneath plantar landmarks, the footstrike of one subject was recorded ten times on each of five days while running at 3.58 m/s on a treadmill. Within-day and between-day proportional error (PE) was used to estimate the error contained in the mean peak stress during foot contact. Within-day PE focused on trial to trial variability associated with the subject and equipment, and averaged 3.1% (range 2.5–4.0%) across transducer location. Between-day PE provided a cumulative estimate of subject, transducer placement, and random equipment variability, but excluded trial to trial variability. It ranged from 4.9 to 15.8%, with a mean of 9.9%. Peak stress, impulse, and sequence of loading data were examined to identify discrete foot function patterns and highlight the value of discrete stress analysis.     

Confinement and manipulation of actin filaments by electric fields

When an AC electric field was applied across a small gap between two metal electrodes elevated above a surface, rhodamine-phalloidin-labeled actin filaments were attracted to the gap and became suspended between the two electrodes. The variance of each filament's horizontal, lateral displacement was measured as a function of electric field intensity and position along the filament. markedly decreased as the electric field intensity increased. Hypothesizing that the electric field induces tension in the filament, we estimated the tension using a linear, Brownian dynamic model. Our experimental method provides a novel means for trapping and manipulating biological filaments and for probing the surface conductance and mechanical properties of single polymers.     

The Value of Proton Magnetic Resonance Spectroscopy in High-Intensity Focused Ultrasound Treatment of Experimental Liver Cancer

High-intensity focused ultrasound (HIFU) is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS) on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho) and choline/lipid (Cho/Lip) ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05), but the Cho/Lip ratio was decreased (P < .05). Cho in liver VX2 tumor was much higher than that in normal liver (P < .001). Cho and Cho/Lip ratio were significantly decreased in tumor after complete HIFU ablation and partial HIFU ablation, and the Cho value in complete HIFU tumor ablation did not show any difference from that in normal liver after HIFU (P > .05); however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001). The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.     

Ultrahigh frequency lensless ultrasonic transducers for acoustic tweezers application

Similar to optical tweezers, a tightly focused ultrasound microbeam is needed to manipulate microparticles in acoustic tweezers. The development of highly sensitive ultrahigh frequency ultrasonic transducers is crucial for trapping particles or cells with a size of a few microns. As an extra lens would cause excessive attenuation at ultrahigh frequencies, two types of 200‐MHz lensless transducer design were developed as an ultrasound microbeam device for acoustic tweezers application. Lithium niobate single crystal press‐focused (PF) transducer and zinc oxide self‐focused transducer were designed, fabricated and characterized. Tightly focused acoustic beams produced by these transducers were shown to be capable of manipulating single microspheres as small as 5 µm two‐dimensionally within a range of hundreds of micrometers in distilled water. The size of the trapped microspheres is the smallest ever reported in the literature of acoustic PF devices. These results suggest that these lensless ultrahigh frequency ultrasonic transducers are capable of manipulating particles at the cellular level and that acoustic tweezers may be a useful tool to manipulate a single cell or molecule for a wide range of biomedical applications. Biotechnol. Bioeng. 2013; 110: 881–886. © 2012 Wiley Periodicals, Inc.     

Numerical study of the effect of ultrasound frequency on temperature distribution in layered tissue

The high intensity focused ultrasound (HIFU) technology can produce therapeutic benefits in deep-seated tissues of interest, selectively and noninvasively. In order to control the treatment process, it is important to recognize the heat generation in biological tissue and the parameters that have an effect on temperature rising. This study investigates the influence of frequency and source intensity on temperature distribution during high-intensity focused ultrasound (HIFU). A nonlinear full wave equation model is simulated to compute the pressure field. Additionally, the absorbed coefficient of tissue is added to the nonlinear equations to simulate accurately the wave propagation in tissue with high absorbed coefficient. In addition, temperature distribution was solved by the Pennes bio-heat equation. Conclusively, frequencies in the range of 1–1.5 MHz are prescribed to have maximum heat absorption in the focal region.     

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

Purpose

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system.

Methods

Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining.

Results

All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation.

Conclusion

Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.     

Interferometric optical fiber sensor for optoacoustic endomicroscopy

Optical fiber sensors can offer robust and miniaturized detection of wideband ultrasound, yielding high sensitivity and immunity to electromagnetic interference. However, the lack of cost-effective manufacturing methods prevents the disseminated use of these sensors in biomedical applications. In this study, we developed and optimized a simple method to create optical cavities with high-quality mirrors for acoustic sensing based on micro-manipulation of UV-curable optical adhesives and electroless chemical silver deposition. This approach enables the manufacturing of ultrasound sensors based on Fabry-Pérot interferometers on optical fiber tips with minimal production costs. Characterization and high-resolution optoacoustic imaging experiments show that the manufacturing process yielded a fiber sensor with a small NEP () over a broad detection bandwidth (25 MHz), generally outperforming conventional piezoelectric based transducers. We discuss how the new manufacturing process leads to a high-performance acoustic detector that, due to low cost, can be used as a disposable sensor.     

Optimisation of the transmit beam parameters for generation of subharmonic signals in native and altered populations of a commercial microbubble contrast agent SonoVue®

The aim of this work was to establish the optimum acoustic characterisation approach and insonation transmit beam parameters for subharmonic signal generation with ‘native’ and ‘altered’ populations of a commonly-used microbubble contrast agent. Dynamic contrast-enhanced (DCE) ultrasound is a non-invasive method of imaging the microvasculature, typically implemented using harmonic imaging. Subharmonic imaging, in which echoes at half the fundamental frequency are detected, detects signals which are generated by the ultrasound contrast agents (UCAs) but not by tissue. However, optimal transmission parameters and furthermore, the optimum acoustic characterisation method have not been established. The subharmonic response of ‘native’ and ‘altered’ UCA, altered through decantation, was investigated at transmit centre frequencies 1.8–5 MHz and pulse lengths 1–8 cycles. The ‘altered’ UCA had reduced polydispersity (1–4 µm: 82% bubble volume), compared to ‘native’ (4–10 µm: 57% bubble volume). A custom-built narrow-band acoustic characterisation system was found to be more appropriate for acoustic characterisation compared to the commonly used broadband pulse-echo approach. Both UCA generated the highest subharmonic signal at pulse length of 3-cycles. The maximum ‘native’ subharmonic signal was generated at a transmit centre frequency of 1.9 MHz, corresponding to a subharmonic at 0.95 MHz. This optimal frequency increased in the ‘altered’ population to 2.3–2.5 MHz, bringing the subharmonic above 1 MHz and hence into a range amenable to clinical abdominal imaging transducers. The use of subharmonic signal detection coupled with a modified UCA size distribution has potential to significantly improve the quantification sensitivity and accuracy of DCE ultrasound imaging.     

Spatial Analysis of Slowly Oscillating Electric Activity in the Gut of Mice Using Low Impedance Arrayed Microelectrodes

Smooth and elaborate gut motility is based on cellular cooperation, including smooth muscle, enteric neurons and special interstitial cells acting as pacemaker cells. Therefore, spatial characterization of electric activity in tissues containing these electric excitable cells is required for a precise understanding of gut motility. Furthermore, tools to evaluate spatial electric activity in a small area would be useful for the investigation of model animals. We thus employed a microelectrode array (MEA) system to simultaneously measure a set of 8×8 field potentials in a square area of ∼1 mm². The size of each recording electrode was 50×50 µm², however the surface area was increased by fixing platinum black particles. The impedance of microelectrode was sufficiently low to apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto-correlation and cross-correlation parameters characterized the spatial properties of spontaneous electric activity in the ileum of wild-type (WT) and W/W^v mice, the latter serving as a model of impaired network of pacemaking interstitial cells. Namely, electric activities measured varied in both size and cooperativity in W/W^v mice, despite the small area. In the ileum of WT mice, procedures suppressing the excitability of smooth muscle and neurons altered the propagation of spontaneous electric activity, but had little change in the period of oscillations. In conclusion, MEA with low impedance electrodes enables to measure slowly oscillating electric activity, and is useful to evaluate both histological and functional changes in the spatio-temporal property of gut electric activity.