Investigation of blood-brain barrier permeability to magnetite-dextran nanoparticles (MD3) after osmotic disruption in rats

The permeability of experimentally disrupted blood-brain barrier (BBB) to superparamagnetic nanoparticles (MD3) was studied in rats. BBB opening was induced by intracarotid injection of mannitol. One hundred eighty rats were used for the study. Rats were examined at two time points, 30 minutes and 12 hours after intracarotid mannitol injection. Different preparations intravenously injected 30 minutes before rat sacrifice were used for characterization of BBB disruption. BBB integrity was determined with^99mTc-diethylenetriamine pentaacetic acid (DTPA) and^99mTc-albumin. Iron oxide-glucose particles (12-nm mean diameter),^99mTc-labeled lecithin-cholesterol liposomes of three different sizes (50, 100, and 200 nm), and polyethylene glycol (PEG)-coated^99mTc liposomes (50 nm) were used for investigations of the dependence of BBB permeability on particle system size or surface. Magnetite-dextran nanoparticles (MD3) were evaluated as superparamagnetic contrast agent to monitor with magnetic resonance imaging (MRI) the BBB breakdown.In vitro T₁ and T₂ relaxation times of the brain tissue were measured at 40 MHz and 37°C, and T₂-weighted MR images were acquired at 0.5 T. After intracarotid mannitol infusion, as expected, the BBB breakdown was immediate and temporary as judged by soluble molecule diffusion. MD3 nanoparticles crossed the BBB 12 hours after intravenous mannitol injection, at a time when brain permeability for molecules or small particles returns to normal. Magnetite crystals were found in cytoplasmic vesicles of glial cells. On MRI, signal intensity decreased after injection of MD3, even 12 hours after mannitol injection. This particularity could be useful in the study of focal pathological lesions accompanied by BBB permeability modifications. In such conditions, superparamagnetic particle contrast agents could be caught by the BBB, allowing the observation of impaired BBB areas without detectable cellular lesions. V. Rousseau was supported by a grant from the city of Angers.     

Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI

In an experimental study MRI was used to compare the pathophysiological changes of brain tissue after lateral fluid percussion injury (FPI) versus cold injury (CI) as models of traumatic brain injury (TBI). Two groups of Sprague-Dawley rats (n = 23) were subjected to mild FPI, respectively, CI localized over the right parietal cortex. MRI was performed at different time points including Tlw, T2w and Tlw-CE (Gd-DTPA 0.2 mmol/kg BW) sequences as well as perfusion-weighted imaging with calculation of regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF). T2w and Tlw-CE images showed hyperintense areas in the traumatised cortex demonstrating brain edema and blood-brain barrier (BBB)-breakdown increasing up to 12 h. Perfusion-weighted imaging demonstrated a significant decrease of rCBV and rCBF in the ipsilateral cortex of CI animals compared with the contralateral hemisphere. In contrast, rats of the FPI group showed only slight differences in rCBF and rCBV comparing the left and right cortex. The results of our study confirm that both mild FPI and CI produced focal brain edema with concomitant breakdown of the BBB as a model of TBI. Since differences regarding perfusion are much more pronounced in CI our results suggest that, this model more likely seems to reflect pathophysiological changes of brain ischemia, whereas FPI seems to be better suited to model the pathophysiological characteristics of TBI.     

Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO

The aim of this study was to detect late radiation effects in the rat spinal cord using MR imaging with ultra-small particles of iron oxide (USPIO) contrast agent to better understand the development of late radiation damage with emphasis on the period preceding neurological signs. Additionally, the role of an inflammatory reaction was assessed by measuring macrophages that internalized USPIO. T₂-weighted spin echo MR measurements were performed at 7T in six rats before paresis was expected (130–150 days post-irradiation, early group), and in six paretic rats (150–190 days post-irradiation, late group). Measurements were performed before, directly after and, only in the early group, 40 h after USPIO administration and compared with histology. In the early group, MR images showed focal regions in grey matter (GM) and white matter (WM) with signal intensity reduction after USPIO injection. Larger lesions with contrast enhancement were located in and around edematous GM of three animals of the early group and five of the late group. Forty hours after injection, additional lesions in WM, GM and nerve roots appeared in animals with GM edema. In the late paretic group, MR imaging showed WM necrosis adjacent to areas with large contrast enhancement. In conclusion, detection of early focal lesions was improved by contrast administration. In the animals with extended radiation damage, large hypo-intense regions appeared due to USPIO, which might be attributed to blood spinal cord barrier breakdown, but the involvement of blood-derived iron-loaded macrophages could not be excluded.     

GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Objective

Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein.

Materials and methods

Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T.

Results

In high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor.

Conclusion

First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

     

The EMF to BBB connection

The author considers the effects of electromagnetic energy on the blood-brain barrier (BBB). The integrity of the BBB is necessary for proper function of the brain in mammals. Minor leakage of the BBB can lead to neural dysfunction and major leakage is associated with brain swelling, which can lead to death. Thus, any change in the BBB of humans by EM fields could cause significant adverse effects. It is well established that RF heating of the brain by several degrees will cause gross and easily detectable disruption of the BBB. Such exposure is far above recommended safety limits and would be clearly hazardous to a person for other reasons as well. This level of exposure is unlikely to occur from environmental or occupational exposures to microwaves, low frequency fields, or from MRI scanners. It may be a factor in hyperthermia treatment of brain cancer. It is far less clear that EM fields have any effect on the BBB, apart from those resulting from gross brain heating. Roughly an equal number of studies using low-level (nonheating) exposures to either RF or low frequency fields have reported effects as have found no effects. In retrospect, it is clear that any effect from such exposure is small. To measure reliably a small breakdown of the BBB in the face of biological and experimental variability requires quantitative techniques tailored for measurement of small changes in transcapillary transport. Such a study has never been carried out     

MRI correlates of disease course and activity in multiple sclerosis

We have carried out a comparative cross-sectional study of patients with relapsing and remitting MS (multiple sclerosis) (RRMS) (n=9), primary progressive MS (PPMS) (n=7), and secondary progressive MS (SPMS) (n=10) using image analysis techniques to determine the number and volume of Gd-DTPA-enhancing lesions. RRMS patients had more lesions than either PPMS or SPMS (ns), and the mean volume of the lesions (p=0.006) and the total volume of enhancing lesions (p<0.03) were significantly larger in patients with RRMS compared with PPMS. The prevalence of blood-brain barrier (BBB) breakdown appears to be similar in PPMS and SPMS, with the higher rate in RRMS suggesting a suppressive effect of disease duration (and/or age). Similarly, the volume of the lesion load overall was negatively correlated with disease duration (p –0.56,p<0.003). Differences between PPMS and RRMS/SPMS patients in the volume of the enhancing lesions may reflect differences in the ability of these patients to suppress the immune-mediated damage to axons which may follow episodic BBB breakdown and which is not visualized on conventional magnetic resonance imaging.     

Mr imaging of avascular femoral head necrosis: pre- and postoperative studies

Forty-six patients with suspected avascular necrosis of the femoral head were examined by T2- and T1-weighted sequences before and after intravenous infusion of Gd-DTPA. Both sides were involved in 12 cases. The classification was done according to Ficat [1]. In early stages and in postoperative studies a correlation of signal intensity increase after infusion of Gd-DTPA and clinical symptoms was found. Contrast enhancement of the plain low signal intensity area or of the implanted graft on T1-weighted images was assumed vascularized or vital components in seven cases of Ficat I and in 13 postoperative studies. Contrawise, in seven patients with severe postoperative symptoms we found no contrast enhancement indicating avascular regions.     

Electrical characterization of benzocyclobutene polymers for electric micromachines

An approach using interdigitated capacitors for electrical characterization of CYCLOTENE, a spin-on low-k benzocyclobutene (BCB)-based polymer is introduced and the effect of moisture uptake is investigated. The dielectric constant of CYCLOTENE is extracted from capacitance measurements with a systematic error less than 0.1%, giving an average value of 2.49 with a standard deviation of 1.5%. The dielectric constant increases by 1.2% after a humidity stress of 85% RH at 85/spl deg/C. The I-V characteristics of CYCLOTENE show a dependency of breakdown strength and leakage current on the geometrical dimensions of the device under test. A breakdown strength of 225V//spl mu/m and 320 V//spl mu/m for 2-/spl mu/m and 3-/spl mu/m finger spacing, respectively, and a leakage current of a few to tens of pA are measured. The I-V characteristics degrade drastically after the humidity stress, showing a breakdown strength of 100 V//spl mu/m and 180 V//spl mu/m for 2-/spl mu/m and 3-/spl mu/m finger spacing, respectively, and a maximum increase in the leakage current as large as one order of magnitude. The maximum performance and long-term reliability of an electric micromachine are adversely affected by the degradation of the breakdown voltage and the leakage current after moisture absorption. It is expected, however, that the electrical efficiency is improved using BCB-based polymers with negligible dependency on moisture absorption.     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution 201Thallium (201Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between 201Tl uptake and MRI signal intensity, i.e. infarcted tissue (low 201Tl uptake) had increased MR signal intensity. Segments were separated into normal (201Tl uptake > 90%) and infarcted (< 601%). lnfarcted MRI segments had greater signal intensity than normal segments (179 +/- 50 vs. 102 +/- 14%; P < 0.0001). WTI in normal segments increased by 18 +/- 8.5% (P < 0.0001) from baseline to 10 microg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8 +/- 7.2% (P = 0.17). Thus regions of myocardium that were infarcted as defined by reduced 201Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.     

Off-state breakdown of GaAs PHEMTs: review and new data

This paper reviews the literature dealing with off-state gate-drain breakdown in MESFET and HEMT structures, with particular emphasis on GaAs PHEMTs, in terms of: 1) the physics of the breakdown phenomenon; 2) the breakdown walkout effect; 3) the impact of design and process choices on the breakdown behavior; and 4) the experimental techniques used for breakdown characterization. A thorough temperature-dependent breakdown characterization of commercial PHEMTs is also shown and discussed. It is found that different physical mechanisms may dominate the gate-drain leakage depending on the reverse bias and temperature range considered, and the particular PHEMT technology. The main results shown here tell us the following. 1) The breakdown voltages are decreasing functions of temperature between room temperature and 160/spl deg/C. 2) Between room temperature and 90-100/spl deg/C, thermionic-field emission seems be dominant, with low activation energies below 0.15 eV; as a consequence, the temperature dependence of the breakdown voltage is weak. 3) Between 110/spl deg/C and 160/spl deg/C, higher activation energy mechanisms (possibly trap-assisted tunneling and thermionic emission over a field-dependent barrier) tend to dominate, and the temperature dependence of the breakdown voltages is stronger.     

介质阻挡放电检测塑料容器的密封性能

利用介质阻挡放电检测在食品和医疗行业中广泛使用的塑料容器密封性能是一种可检测微小渗漏的非接触式新型检漏方法,而高压放电电源是该技术的关键。为了解高压放电电源性能和参数变化的规律,建立了高频高压电源和负载的等效电路模型并进行了仿真和放电实验研究。研究结果表明,当置于2个高压电极中的塑料容器出现密封不良时,在2个电极之间产生比较强的介质阻挡放电,使高频高压电源的谐振电路偏离其谐振点,高压电压和谐振电流都会减小,放电电流会增大。因此,监测介质阻挡放电电源的谐振回路中的相关电路参数的变化情况,能够可靠地实现塑料容器的密封性能的检测。     

NMR investigation of experimental chemical induced brain tumors in rats, potential of a superparamagnetic contrast agent (MD3) to improve diagnosis

The different steps of development of chemically induced brain tumors were investigated in rats by MRI using a superparamagnetic contrast agent, magnetite-dextran nanoparticles (MD3). Sprague-Dawley strain pregnant female rats were injected intravenously with ethynitrosourea solution at the end of pregnancy. Offspring whelped by the inoculated mother were followed. MRI examinations were performed at 0.5 T. MD3 nanoparticles were injected intravenously at a dose of 5 mg Fe kg^-1 body weight 30 min before rat sacrifice. After sacrifice, histological slices were stained with hematoxylin-eosin. Relaxation times were measured at 40 MHz and 37°. MD3 nanoparticles act differently according to the step of the tumor development. Before tumor appearance, at a step characterized by the presence of abnormal cell clusters, relaxation time T2 increased significantly. The T2-weighted image showed a small increase in signal intensity in the lesion. Image contrast was improved by MD3 nanoparticles injection because of the decrease in healthy tissue signal intensity. The Tl-weighted image did not provide any additional information. In presence of a minute tumor, relaxation times decreased in tumor but increased in surrounding tissue. The Tl-weighted image showed a hypersignal on the border of an hyposignal. T2-weighted image showed a hypersignal in the same area. Signal intensity was not modified after MD3 nanoparticles injection. When new vascular capillaries developed in the tumor, MD3 nanoparticles cross into the cerebral parenchyma. Transmission electron microscopy showed magnetite crystals in this specific area on cytoplasm vesicles of glial cells and in tumor-specific membrane arrangements. On T2-weighted image, the hypersignal consisted of a well defined part and a second more fuzzy part, its signal being extinguished after MD3 nanoparticles injection. Necrotic areas and edema can be discriminated. The use of such a superparamagnetic contrast agent would be helpful in early detection of tumor development and in improving distinction of tumor mass from its vascular environment in patients. © 1998 Elsevier Science B.V. All rights reserved.     

Gadolinium-containing copolymeric chelates—a new potential MR contrast agent

Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents.Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers.Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. Ther ₁ (1/T1, mM⁻¹ s⁻¹) for Gd-DTPA=4.1. Ther ₁ values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowestr ₁ for the polymer prepared with the lowest-molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd-DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement—a reflection of distribution into extravascular fluid space—was observed.Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd-DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase inr ₁ relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd-copolymers are promising agents that merit additional study.     

环境因素对避雷器泄漏电流影响研究

避雷器泄漏电流幅值会受环境气象条件影响,建立泄漏电流幅值模型对于避雷器健康状况判断具有重要意义。通过分析避雷器周围的环境因素,建立基于多元线性回归的避雷器泄漏电流数学模型。首先,收集影响泄漏电流幅值主要因素的数据,包括温度、湿度、大气压强与光照强度;然后,基于散点图与趋势线对这些因素进行分析,借助MATLAB软件对收集到的数据建模,获得基于最小二乘法的多元线性回归模型,并通过基于方差膨胀因子的共线性进行诊断;最后,运用所获得的模型对未来10 d泄漏电流进行了预测。预测结果表明,所提模型精度较高,可满足工程实用要求。     

Partial and complete electrical breakdown in simulated hightemperature superconducting coils

The partial breakdown (PBD) and complete breakdown (BD) phenomena in a composite insulation system of glass fiber reinforced plastic (GFRP) and liquid nitrogen are investigated to find the PBD and BD characteristics in high temperature superconducting (HTS) coils at quench. The electrode system used is made from a coaxial spiral coil-to-cylindrical electrode with an insulation barrier and spacers, and is immersed in liquid nitrogen. A heater is mounted inside the coil electrode to generate boiling which occurs on quenched superconducting coils. The experimental results show that (1) the polarity of PBD initiation under 60 Hz ac applied voltage depends on the width l_c of the cooling channel, (2) PBD appears through a gas bubble locked between the coil and concentric insulation barrier due to the electrical gradient and the spacer, (3) breakdown voltages are affected severely by the risetime of the applied voltage and the current amplitude associated with PBD, (4) two kinds of BD mechanisms are found depending on the shape of the spacer, length of cooling channel and heater power     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution²⁰¹Thallium (²⁰¹Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between²⁰¹Tl uptake and MRI signal intensity, i.e. infarcted tissue (low²⁰¹Tl uptake) had increased MR signal intensity. Segments were separated into normal (²⁰¹Tl uptake >90%) and infarcted (<60%). Infarcted MRI segments had greater signal intensity than normal segments (179±50 vs. 102±14%;P<0.0001). WTI in normal segments increased by 18±8.5% (P<0.0001) from baseline to 10 μg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8±7.2% (P=0.17). Thus regions of myocardium that were infarcted as defined by reduced²⁰¹Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.     

Nano-enabled metal oxide varistors

Zinc oxide based metal oxide varistors (MOV) are widely used electrical surge protection components. The design of modern high power, high-density electronic systems necessitate the need for smaller footprint, higher current density and higher nonlinearity MOVs. Such requirements can no longer be satisfied by commercially available MOVs due to their limited voltage capability, high leakage current and mechanical cracking related reliability issues, most of which are associated with the presence of defects and coarse granularity and lack of uniformity in their microstructures. New formulations and processes have been developed to overcome such limitations. This work has developed nano-enabled MOV compositions that can be sintered at relatively lower temperatures than typical commercial MOVs, but with largely improved I-V characteristics due to refined and uniform sub-micron structures. These nano-enabled MOVs show not only high breakdown strength (1.5 kV/mm) with low leakage current, but also a large nonlinear alpha coefficient > 50 at high fields, a measure of the speed of the transition from the insulating to conducting state and the effectiveness of over-voltage protection. A > 10x increase in breakdown strength compared to commercial MOVs, along with much higher nonlinearity, will enable MOV miniaturization, high voltage surge protection, and open up new areas of application.     

Y电容引起的手机充电器漏电研究

手机充电器的安全问题受到越来越多的关注,Y电容是引起手机充电器漏电的一个原因。基于目前市场上应用最为广泛的一款5 V/2 A手机充电器,研究了Y电容引起的手机充电器漏电问题,论述了市电电源结构、USB电缆线结构以及手机充电器结构,详细分析了Y电容正常和Y电容短路击穿两种情况下的漏电回路、等效电路以及漏电回路中关键元件的电压、电流波形,总结了漏电流与Y电容的关系,得到了Y电容短路击穿以及Y电容容值过大是造成人被电击的原因之一,最后通过仿真和实验,验证了理论分析的正确性。     

Microwave radiation and leakage of albumin from blood to brain

The blood-brain barrier (BBB) is a cell layer in the blood vessels of the brain. The BBB partitions the circulating blood from the brain tissue proper and regulates the passage of vital substances and nutrients into brain tissues and carbon dioxide and metabolic waste products out of it. The selective passage prohibits harmful toxins from infiltrating the brain, and also excludes many drugs and therapeutic agents from reaching brain tissues. Many investigators have published studies on the effect of microwave radiation on the BBB of experimental animals with varied results. Studies showing, and not showing, a microwave-induced increase in rat BBB permeability changes had used both high and low levels of microwave exposure. However, a series of reports showing disruption of BBB at various times following microwave exposure has caught the attention of many in the field.     

Imaging breakdown spots in SiO/sub 2/ films and MOS devices with a conductive atomic force microscope

Conductive atomic force microscopy (C-AFM) was used to study the dielectric breakdown of SiO/sub 2/ layers at a nanometric scale. First, bare oxide regions were stressed and broken down using the tip as the metal electrode of a MOS structure. The results show that the initial breakdown is electrically propagated to neighbor regions, affecting their dielectric strength. Moreover, the area affected by the initial breakdown depends on the breakdown hardness. In particular, it is shown that this area is smaller when the current through the structure is limited during the experiments. The effect of the current limitation is analyzed in detail. Based on the results, a qualitative picture of the breakdown process is presented, which accounts for this effect. Finally, for the first time, the breakdown spots in standard MOS devices (with poly-Si gate) are electrically imaged with C-AFM. The areas of the observed spots are in agreement with those obtained on bare oxides.