Transient global brain ischemia in young and aged rats: differences in severity and progression, but not localisation, of lesions evaluated by magnetic resonance imaging

A model of transient global brain ischemia consisting of bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O₂−85% N₂) for 20 min was studied by means of MRI in young and aged Fischer 344 rats (3–4 and 24–26 months, respectively). Ischemia was assessed by full suppression of spontaneous EEG activity, which reappeared and normalized similarly in the two age-groups. The survival of young with respect to aged rats was considerably higher both at 24 h (20/20, i.e. 100% vs 12/16, i.e. 75%) and at 48 h (16/20, i.e. 80% vs 6/16, i.e. 38%). The localisation of brain lesions, their severity and progression were evaluated by a diffusion-weighted MRI (DWI) sequence at 24 and 48 h post-ischemia. There were no DWI-detectable lesions in eight out of 20 young and two out of 12 aged rats. The localisation of DWI-detected lesions was rather similar in rats of the two age-groups. In fact, the cerebral cortex, mainly parietal, occipital and temporal lobes were damaged in 83% of young and 90% of aged rats. The respective percentages for the thalamus were 83 and 60%, for the striatum 58 and 50%, and for the hippocampus 25 and 30%. The lesions present in the cerebral cortex and the thalamus were considerably more severe in aged than in young rats. In conclusion, in spite of similar localisation of ischemic lesions in the two age-groups, their incidence was higher, appearance more rapid and severity more pronounced in aged with respect to young rats. This resulted in a considerably higher mortality of the former. The overall data indicate that the age issue is very important in experimental ischemia research.     

Cerebral blood flow response to a hypoxic-ischemic insult differs in neonatal and juvenile rats

To compare the cerebral blood flow (CBF) response to a transient episode of hypoxia–ischemia producing damage in neonatal and juvenile rats. One- and four-week-old rats were subjected to unilateral carotid artery occlusion plus hypoxia (8% oxygen). Perfusion MR images were acquired either in sham controls or in hypoxic–ischemic rats before, during, 1 h and 24 h after hypoxia–ischemia. At 24 h post hypoxia–ischemia, T₂ maps and histology were used to assess damage. In sham controls, CBF increased twofold between the age of one and four weeks. Reductions in CBF ipsilateral to the occlusion occurred during hypoxia–ischemia followed by a substantial recovery at 1 h post in both age groups. However, contralaterally, hyperemia occurred during hypoxia–ischemia in four-week but not one-week-old rats. Similarly, hyperemia occurred ipsilaterally at 24 h post hypoxia–ischemia in four-week but not one-week-olds, corresponding to the distribution of elevations in T_2. Despite CBF differences, extensive cell death occurred ipsilaterally in both age groups. The CBF responses to hypoxia–ischemia and reperfusion differ depending on postnatal age, with hyperemia occurring in juvenile but not neonatal rats. The results suggest a greater CBF responsiveness and differential relationship between post-ischemic vascular perfusion and tissue injury in older compared with immature animals.     

Early changes in apparent diffusion coefficient of rat brain following total circulatory arrest

The apparent diffusion coefficient (ADC) of rat brain was determined for the cortex [(771±23)×10^–6 m²/s] and caudate-putamen (CP) [(601±25)×10^–6 m²/s]. Using the ultrafast imaging technique U-FLARE changes in ADC were followed with a 2.4-min temporal resolution after the induction of total circulatory arrest by intravenous KC1 injection. For both tissue types, a biphasic decrease of ADC was observed. The initial fast phase led to an ADC decrease by (27±4)% (cortex) and (29±3)% (CP) within 5 min, whereas the slow continuous decrease of the second phase resulted in (68±3)% (cortex) and (66±3)% (CP) of control after 18 min. The similar relative reduction in ADC for the cortex and the CP meant that an effective distinction between both tissue types persisted after the cessation of systemic and cerebral blood flow.Address for correspondence: Max-Planck Institut für neurologische Forschung, Gleuelerstrasse 50, D-50931 Köln, Germany. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Venn Plaza, New York, NY 10119.     

Complete elimination of the hepatobiliary mr contrast agent Gd-EOB-DTPA in hepatic dysfunction: An experimental study using transport-deficient,mutant rats

Mutant Wistar rats (TR^– rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR^/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25µmol kg^–1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250µmolkg^–1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR^– rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25µmol kg^–1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.     

Quantitative assessment of regional myocardial function in a rat model of myocardial infarction using tagged MRI

We characterized global and regional left ventricular (LV) function during post myocardium infarction (MI) remodeling in rats, which has been incompletely described by previous MRI studies. To assess regional wall motion, four groups of infarcted animals corresponding to 1–2, 3–4, 6–8 and 9–12 weeks post-MI respectively were imaged using a fast gradient echo sequence with a 2D spatial modulation of magnetization (SPAMM) tagging preparation. An additional group was serially imaged (1–2 and 6–7 weeks post-MI) to assess the global function. Regional and global functional parameters of infarcted rats were compared to non-infarcted normal rats. Compared to normal rats, a decrease in ejection fraction (70 ±7 vs. 40 ± 8%, p<0.05) was observed in rats with MI. Maximal and minimal principal stretches (₁, ₂) and strains (E₁, E₂), principal angle () and displacement varied regionally in normal rats but deviated significantly from the normal values in rats with MI particularly in the infarcted and adjacent zones. Not only was strain magnitude reduced segmentally post-MI, but strain direction became more circumferentially oriented, particularly in rats with larger infarctions. We report the first regional myocardial strain values in normal and infarcted rats. These results parallel findings in humans, and provide a unique tool to examine regional mechanical influences on the remodeling process.     

Defect Chemical Modeling of (La, Sr)(Co, Fe)O3 − δ

Different defect chemical models for calculation of ionic and electronic defect concentrations are discussed regarding their applicability to transition metal perovskite-type oxides (ABO_{3 –} ) with large ranges of oxygen non-stoichiometry. A point defect model, which allows simultaneous consideration of three different B-site species concentrations as a function of the oxygen partial pressure is compared to a simple point defect model, considering only two different B-site species. Additionally, a model assuming electrons/holes as negative resp. positive electronic charge carriers is presented. Further, models involving association of point defects in different complexes are discussed. Examples are given for fits of experimental data of La_{1 – x}Sr_xBO_{3 –} (x = 0.6, B = Fe, Co) to selected models in the temperature range 700–900_C and oxygen partial pressures 10^{– 5} < pO₂/atm < 1.     

Rat cerebral ischemia induced with photochemical occlusion of proximal middle cerebral artery: a stroke model for MR imaging research

A stroke model in rats with photochemically induced thrombosis (PIT) of proximal cerebral middle artery (MCA) is introduced for magnetic resonance imaging (MRI) study. Thirty-seven rats subjected to surgical and optical procedures for inducing the PIT models were scanned using a 1.5-T scanner with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced perfusion-weighted imaging (PWI) at 1 h and 24 h after MCA occlusion. The penumbra evolution and PWI-derived parameters including relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were monitored; and the relative lesion size (RLS) was compared with the final RLS on the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. The results showed that the focal cerebral ischemic lesions were detectable in all rats with different MR approaches. The lesion on PWI at 1 h and on all MR images at 24 h was matched well with that seen on TTC staining; the peri-infarct area decreased from 6.2 ± 7.2% of the brain volume at 1 h to 0.3 ± 5.6% at 24 h. Compared to that in the contralateral hemisphere, rCBV in ischemic region was 52.6 ± 21.4 and 40.0 ± 15.8% (p > 0.05), and rCBF was 64.6 ± 11.2 and 47.3 ± 11.1% (p < 0.05) at 1 h and 24 h respectively. The present PIT model in rats has been successfully adopted for MRI research, which might be feasible for certain stroke studies and should be beneficial for the evaluation on effects of potential diagnostic and therapeutic approaches.     

Comparison of Three Quantum Correction Models for the Charge Density in MOS Inversion Layers

In order to obtain high density integration for MOS devices, it is necessary to reduce the gate oxide thickness and increase the substrate doping concentration. This results in a narrow and deep potential well in which electrons are confined at the semiconductor-insulator interface and it becomes necessary to take quantum mechanical (QM) effects into consideration. In this study, we compare three well established quantum correction models, i.e., the Hänsch model (Hänsch W. et al. 1989. Solid State Electronics 32(10): 839–849), the modified local density approximation (MLDA) model (Paasch G. and Ubensee H. 1982. Phys. Stat. Sol. (b) 113: 165–178), and the density-gradient (D-G) model (Ancona M.G. and Tiersten H.F. 1987. Physical Review B 35(15): 7959–7965; Ancona M.G. 1997. JTCAD 97–100) in terms of accuracy for predicting the inversion layer charge distribution.     

An adaptive continuous-time incremental Σ∆ ADC for neural recording implants

In this paper, an analog-to-digital converter (ADC) with adaptive resolution is presented for wireless neural recording implants. The resolution of the ADC is changed according to the neural signal content, and for this purpose, a continuous-time (CT) incremental sigma-delta (IΣ∆) modulator is employed. The ADC digitizes the action potential (AP) and background noise (B-noise) with 8-bit and 3-bit resolutions, respectively. An automatic AP detector is used to separate the APs from the B-noise in order to select one of the two proportional resolutions. The power dissipation and output data rate of the ADC are reduced by using this technique. Analytical calculations and behavioral simulation results are provided to evaluate the performance of the proposed ADC. To further confirm its efficiency, the circuit-level implementation of the CT IΣ∆ ADC is presented in Taiwan Semiconductor Manufacturing Company (TSMC) 90-nm complementary metal-oxide semiconductor (CMOS) process. According to the simulation results, the proposed ADC achieves 8-bit or 3-bit resolution adaptively with 10 kHz bandwidth while the average power consumption is less than 1.89 μW from a single 1-V power supply.     

Fast adaptive comparator offset calibration in pipeline ADC with self-repairing thermometer to binary encoder

This paper presents a fast background calibration method for comparator offsets in pipeline ADCs and analyzes the practical considerations in a 1.8 V 0.18 μm 100Msps pipeline ADC with 15-bit resolution (74 dB-Signal-to-noise plus Distortion Ratio [SNDR]). A self-repairing (SR) thermometer-to-binary encoder is developed to deal with malfunctioning in presence of high comparator offsets greater than one-half least-significant bit (LSB). In this situation, the effective thresholds between two adjacent comparators could be inverted leading to a faulty behavior with conventional architectures. The proposed solution allows a dynamic assignment of the calibration code associated to each comparator improving convergence speed. As demonstrator, its application to a 15-bit pipeline ADC using a novel calibrated dynamic-latch comparator (DLC) with internal threshold reference generation and no preamplifier is presented, showing a reduction on the total power consumption of 22% with respect to a design without calibration targeting the same specifications.     

1H magnetic resonance spectroscopy of the brains of normal infants and after perinatal hypoxia-ischemia

The aims of this study were to define proton (¹H) metabolite peak-area ratios in the brains of normal infants and to investigate abnormalities after perinatal hypoxia-ischemia. Point-resolved spectroscopy (PRESS) data were collected at 2.4 T with an echo time (TE) of 270 ms from 8-ml voxels located in the thalamus or occipito-parietal region. Fourteen normal and 9 asphyxiated infants were studied. The gestational plus postnatal ages (GPA) of these two groups were 31–41 (median 36) and 27–41 (37) weeks, respectively, and the asphyxiated infants were studied aged 0–10 (2) days. Peak-area ratios were determined in the normal infants for choline-containing compounds (Cho), creatine plus phosphocreatine (Cr),N-acetylaspartate (NAA) and lactate (Lac). Lactate was detected in all the normal infants and Lac/NAA was higher in the occipito-parietal region than in the thalamus (p<0.005). Lac/NAA decreased with increasing GPA in both the thalamus (p=0.014) and the occipito-parietal region (p=0.033). In six of the nine asphyxiated infants, Lac/NAA was above 95% confidence intervals for either the thalamus and/or the occipito-parietal region. Of these six infants, two died and three were neurologically abnormal aged 2 months, indicating that elevated Lac/NAA after perinatal hypoxia-ischemia may convey a poor prognosis. Propan-l,2-diol (the phenobarbitone injection medium) was detected at 1.1 ppm in three infants.     

Evolution of beta-amyloid induced neuropathology: magnetic resonance imaging and anatomical comparisons in the rodent hippocampus

Alzheimer’s disease (AD) is characterized by the anatomical appearance of β-amyloid (βA) plaques and neurofibrillary tangles. These changes are also associated with cyclical inflammation, oxidative damage and, as inferred from the autopsied brains of patients, progressive injury to neurons. Here, we report the short-term effects of an intrahippocampal injection of the toxic βA peptide fragment 25–35 in rats using quantitative magnetic resonance imaging (MRI) methods. Physiological changes within the cornu ammonis 1 (CA1) region of the hippocampus were monitored using a 1.5 T scanner at time points of 0.25, 1 and 24 h, and 7 and 14 days post injection. Spin echo T2-weighted (T2W) and diffusion weighted (DW) images were sequentially acquired. Apparent diffusion coefficients (ADC) were calculated and compared with histological alterations. A significant elevation in mean ADC values (17%) was observed in the ipsilateral CA1 at 14 days. The ADC changes were associated with disrupted pyramidal cells and nuclear lysis observed in histological sections. The contralateral CA1 exhibited a significant decrease in mean ADC of 15% at 14 days post treatment. Histological changes in the contralateral hippocampus suggested decreased neuronal density. T2W maps revealed no significant differences between the active βA 25–35 fragment and its non-active analog, βA 35–25. In conclusion, these results, based on changes in hippocampal ADC, demonstrate that the βA 25–35 treatment induced pathology consistent with edema and cellular necrosis. This is the first report describing the evolution of AD-like pathology in an animal model using DW imaging.     

Water diffusion in rat brain in vivo as detected at very largeb values is multicompartmental

The diffusion-weighted signal attenuation of water in rat brain was measured with pulsed-field gradient nuclear magnetic resonance methods in a single voxel under in vivo and global ischemic conditions. The diffusion-attenuated water signal was observed in vivo atb values of 300 ms/μm² (strength of diffusion weighting) and diffusion times up to 400 ms. A series of constant diffusion time (CT) experiments with varied gradient directions and diffusion times revealed a multiexponential decay with apparent diffusion coefficients (ADC) covering two orders of magnitude from 1 to 0.01 μm²/ms. In a four-exponential fit, the observed changes during global ischemia could be fully explained by changes in the relative volume fractions only with unchanged ADCs. An anisotropy of the ADC, detected at smallb values, was not observed for the ADC at largeb values, but for the concomitant volume fractions. An inverse Laplace Transform of the CT curves, performed with CONTIN, resulted in continuously distributed diffusion coefficients, for which the term ‘diffusogram’ is proposed. This approach was more appropriate than a discrete exponential model with four to six components, being related to the morphology of brain tissue and its cell size distribution. On the basis of an analytical, quantitative model, it is suggested that the measured ADC at smallb values reflects mainly properties of the restricting boundaries, i.e. the relative volume fractions and the extracellular tortuosity, while the intrinsic intracellular diffusion constant and the exchange time are predicted to have minor influence.     

Hepatic pseudo-anisotropy: a specific artifact in hepatic diffusion-weighted images obtained with respiratory triggering

Purpose: Hepatic pseudo-anisotropy is an artifact observed in hepatic diffusion-weighted imaging under respiratory triggering (RT-DWI). To determine the clinical significance of this phenomenon, hepatic RT-DW images were reviewed. Methods: One hundred and five MR examinations, including RT-DWI, were assessed. The patient group included 62 non-cirrhotic and 43 cirrhotic individuals. All images were evaluated by mutual agreement of two radiologists from the viewpoints of incidence of pseudo-anisotropy and correlation between pseudo-anisotropy and the quality of trace images. The ADC of normal hepatic parenchyma of non-cirrhotic livers were measured in both areas with and without pseudo-anisotropy. Results: Pseudo-anisotropy was observed in 60% of non-cirrhotic (37/62) and 30% of cirrhotic (13/43) images. The difference between the two groups was statistically significant (P < 0.001). The quality of trace images showed a tendency to worsen as pseudo-anisotropy became significant. However, the quality of trace images was generally satisfactory, with only two patients whose trace images were difficult to interpret due to pseudo-anisotropy. The areas with pseudo-anisotropy showed higher ADC than those without pseudo-anisotropy (P < 0.001). Conclusion: Pseudo-anisotropy is a type of artifact that originates from respiratory movement. Even though respiratory triggering is employed, ADC measurement of the liver is inaccurate because of pseudo-anisotropy, especially in non-cirrhotic patients.     

<Superscript>1</Superscript>H NMR relaxation times of skeletal muscle metabolites at 3 T

This study reports proton relaxation times of water and metabolites in soleus and tibialis anterior muscles of young healthy volunteers at 3 T. The results are in agreement with data reported for 1.5 and 4 T, showing a steady increase of spin-lattice relaxation times of water, creatine and lipids with B₀ and no effect of B₀ on spin–spin relaxation. Comparison between muscles revealed a longer spin–spin relaxation time of water in soleus than in tibialis anterior muscle (31±1 ms vs. 28±1 ms, p<0.05). These data can be applied to relaxation correction for the absolute quantification of skeletal muscle metabolite concentrations and further sequence optimization.     

Design considerations for low power time‐mode SAR ADC

This paper describes circuit design considerations for realization of low power dissipation successive approximation register (SAR) analog‐to‐digital converter (ADC) with a time‐mode comparator. A number of design issues related to time‐mode SAR ADC are discussed. Also, noise and offset models describing the impact of the noise and offset on the timing error of time‐domain comparator are presented. The results are verified by comparison to simulations. The design considerations mentioned in this paper are useful for the initial design and the improvements of time‐mode SAR ADC. Then, a number of practical design aspects are illustrated with discussion of an experimental 12‐bit SAR ADC that incorporates a highly dynamic voltage‐to‐time converter and a symmetrical input time‐to‐digital converter. Prototyped in a 0.18‐µm six‐metal one‐polysilicon Complementary Metal‐Oxide‐Semiconductor (CMOS) process, the ADC, at 12 bit, 500 kS/s, achieves a Nyquist signal‐to‐noise‐and‐distortion ratio of 53.24 dB (8.55 effective number of bits) and a spurious‐free dynamic range of 70.73 dB, while dissipating 27.17 μW from a 1.3‐V supply, giving a figure of merit of 145 fJ/conversion‐step. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis, Physicochemical Characterization and Ionic Conductivity of LaGa0.4Mg0.2M0.4O3−δ (M = Cr, Mn, Fe, Co)

Partial electronic and ionic conductivities, crystal structure, thermal expansion and infrared absorption spectra of the perovskite-type series, LaGa_0.40Mg_0.20M_0.40O_3– (M = Cr, Mn, Fe, and Co), have been studied. The rhombohedral distortion of the perovskite lattice decreases and the unit cell volume increases in the sequence Co < Cr < Mn < Fe. The p-type electronic conduction increases with atomic number of the transition metal cation; the activation energy varies in air from 15.9 to 32.1 kJ/mol. The oxygen ionic conductivity of the M-doped phases at temperatures below 1200 K is significantly lower than that of LaGa(Mg)O₃. The highest ionic conductivity was found for the Fe- and Co-containing phases. The ion transference numbers of La(Ga,Mg,M)O_3– at 970–1270 K were determined to vary in a wide range, from 2 × 10^–5 to 3 × 10^–2. Thermal expansion coefficients, calculated from the dilatometric data collected in the temperature range 300–1100 K, lie in the range (7.2–15.5) × 10^–6 K^–1.     

Characterization and detection of experimental rat gliomas using magnetic resonance imaging

Two different experimental rat brain tumours (F98 glioma and 9L glioma) were characterized using T1 and T2, apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Even though both tumours appeared homogenous at the early stage of growth, significant differences were measured for all parametric images between tumours and normal brain tissue. Irrespective of the sequence used, tumour lesion/normal parenchyma contrast for the non-infiltrative 9L was twice that of the infiltrative F98 glioma. The use of spin preparation via an inversion pulse in a fast spin echo sequence increases contrast by a factor of 20–30.     

Näherungen für die elliptische Integral-Funktion K/K' und Rekursionen zur beliebigen Verbesserung ihrer Genauigkeit,insbesondere zur Wellenwiderstandsberechnung

Übersicht Für die FunktionK/K' und ihre Umkehrfunktion [K/K']^–1 können Näherungen aufgestellt werden, deren Genauigkeit mit Hilfe von Rekursionen beliebig gesteigert werden kann. Die Näherungen erfassen den gesamten Definitionsbereich. Drei Beispiele werden explizit angegeben für einen maximalen relativen Fehler <2,4·10^–3 in (30), sowie für einen maximalen relativen Fehler <2,·10^–6 in (32) und einen solchen von <4·10^–12 in (33). Da die Näherungen nur elementare Funktionen enthalten, eignen sie sich sowohl für weitergehende allgemeine Berechnungen als auch für die praktische Anwendung, in denen die hier mitgeteilten Beispiele fast immer ausreichen dürften. Die Algorithmen sind in (31), (34) und (35) so geschrieben worden, daß sie sich als vollständige Rechenanweisungen für die Ermittlung beliebig guter Funktionen mit Hilfe von Rechenmaschinen eignen.

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Contents Recursion formulae starting with approximations are derived for the functionK/K' and the converse function [K/K]^–1. The recursion converges very rapidly and comprises the whole range of definition. The first three approximations are given explicitly. The first one has only a maximal relative error smaller than 2.4·10^–3, the second one smaller than 2.3·10^–6 and the third one smaller than 4·10^–12. As the recursion formulae contain only elementary functions and no integrals, they are adapted for further general calculations as well as for practical use. The basic algorithms finally derived in (31, 34) and (35) are given in such a form, that they are well suited for practical computations with digital computers.

     

Study of the Electrical Properties of Pb(Mg,Ni)1/3Nb2/3O3-PbTiO3 System Across the Morphotropic Phase Boundary

Phase transitional behavior and electrical properties of (1 – x)Pb(Mg,Ni)_1/3Nb_2/3O₃-xPbTiO₃ ceramics (PMNN-PT with Mg/Ni = 1:1, x = 0.20–0.40) across the morphotropic phase boundary (MPB) were examined. X-ray diffraction and dielectric measurement reveal that two phases, pseudocubic and tetragonal phases, coexist in the composition range x = 0.30–0.36. The maximum d ₃₃ (about 570 pC/N) was observed at the composition x = 0.32–0.34. Dielectric and ferroelectric properties exhibit abnormal high near the MPB. An unusual peak shoulder occurred in the dielectric measurement upon thermal cycling for poled samples. This phenomenon was considered to be associated with the macro to micro domain transition and depolarization.