Impact of N-Truncated Aß Peptides on Cu- and Cu(Aß)-Generated ROS: CuI Matters!

In vitro Cu(Aß1-x )-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aß to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aß4-x and Aß11-x ) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2 N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aß1-x peptide. It has further been proposed that the role of Aß4-x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII , CuI coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (CuI and CuII ) complexes of the Aß4-16 and Aß11-16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aß1-16 ), the N-truncated peptides are not able to fully preclude Cu(Aß1-16 )-induced ROS production.

Probabilistic analysis of the specific absorption rate intersubject variability safety factor in parallel transmission MRI.

PURPOSE: Specific absorption rate (SAR) calculations in parallel transmission are commonly performed by using electromagnetic simulations on generic models. In this study, we propose a probabilistic analysis to study the safety factor employed to account for SAR intersubject variability versus risk relationship in head imaging at 7T. METHODS: Thirty-three finite-element electromagnetic simulations were conducted to sample the four-dimensional parameter space consisting of the head length, head breadth, and shifts in Z and Y random variables. Based on the SAR matrices for each configuration, a multivariate second-order polynomial of the SAR versus the different parameters was reconstructed for different types of radiofrequency pulses. A Monte Carlo calculation was then performed to compute the probability of occurrence of a given SAR value. RESULTS: By testing a large number of radiofrequency excitation pulses, the SAR calculated for the average model amplified by a safety margin of 1.5 was found to return a probability of less than 1% to be exceeded across the adult Caucasian population given the investigated parameters. CONCLUSION: The proposed method to study SAR intersubject variability uses a reasonable number of electromagnetic simulations. Look-ahead SAR safety margins can be deduced based on risk/benefit ratio assessments. Magn Reson Med 78:1217-1223, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Nuclear spin noise in NMR revisited.

The theoretical shapes of nuclear spin-noise spectra in NMR are derived by considering a receiver circuit with finite preamplifier input impedance and a transmission line between the preamplifier and the probe. Using this model, it becomes possible to reproduce all observed experimental features: variation of the NMR resonance linewidth as a function of the transmission line phase, nuclear spin-noise signals appearing as a "bump" or as a "dip" superimposed on the average electronic noise level even for a spin system and probe at the same temperature, pure in-phase Lorentzian spin-noise signals exhibiting non-vanishing frequency shifts. Extensive comparisons to experimental measurements validate the model predictions, and define the conditions for obtaining pure in-phase Lorentzian-shape nuclear spin noise with a vanishing frequency shift, in other words, the conditions for simultaneously obtaining the spin-noise and frequency-shift tuning optima.

Generalized double-acquisition imaging for radiofrequency inhomogeneity mitigation in high-field MRI: experimental proof and performance analysis.

Transmit arrays have been developed to compensate for radiofrequency inhomogeneities in high-field MRI using different excitation schemes. They can be classified into static or dynamic shimmings depending on the target: homogenizing the radiofrequency field directly or homogenizing the flip angle distribution using the Bloch equation. We have developed an intermediate solution to compare shimming performances between different transmit arrays. This solution, called generalized double-acquisition imaging, is easier to implement than most dynamic shimming methods and offers more degrees of freedom than static shimmings. It uses two acquisitions so that the second acquisition complements the excitation of the first one to obtain by superposition an image that minimizes radiofrequency artefacts. For validation, the method is demonstrated experimentally for a gradient echo sequence on a spherical homogeneous phantom and by simulation on a human head model.

Local SAR reduction in parallel excitation based on channel-dependent Tikhonov parameters.

PURPOSE: To reduce the local specific absorption rate (SAR) obtained with tailored pulses using parallel transmission while obtaining homogenous flip angle distributions. MATERIALS AND METHODS: Finite-element simulations on a human head model were performed to obtain the individual magnetic and electric field maps for each channel of a parallel transmit array. From those maps, SAR calculations were carried out for "spoke" pulses designed to homogenize the flip angle in an axial slice of a human brain at 7 T. Based on the assumption that the coil element nearest to the maximum local energy deposition is the dominant contributor to the corresponding hot spot, a set of channel-dependent Tikhonov parameters is optimized. Resulting SAR distributions are compared to the ones obtained when using standard pulse design approaches based on a single Tikhonov parameter. RESULTS: In both the small- and large-tip-angle domain, the simulations show local SAR reductions by over a factor of 2 (4) for a well-centered (off-centered) head model at the expense of roughly 1% increment in flip-angle spread over the slice. CONCLUSION: Significant SAR reductions can be obtained by optimizing channel-dependent Tikhonov parameters based on the relation between coil elements and SAR hot spot positions.

Stacked magnetic resonators for MRI RF coils decoupling.

Parallel transmission is a very promising method to tackle B1+ field inhomogeneities at ultrahigh field in magnetic resonant imaging (MRI). This technique is however limited by the mutual coupling between the radiating elements. Here we propose to solve this problem by designing a passive magneto-electric resonator that we here refer to as stacked magnetic resonator (SMR). By combining numerical and experimental methodologies, we prove that this novelty passive solution allows an efficient decoupling of elements of a phased-array coil. We demonstrate the ability of this technique to significantly reduce by more than 10dB the coupling preserving the quality of images compared to ideally isolated linear resonators on a spherical salty agar gel phantom in a 7T MRI scanner.

Homogeneous non-selective and slice-selective parallel-transmit excitations at 7 Tesla with universal pulses: A validation study on two commercial RF coils.

Parallel transmission (pTx) technology, despite its great potential to mitigate the transmit field inhomogeneity problem in magnetic resonance imaging at ultra-high field (UHF), suffers from a cumbersome calibration procedure, thereby making the approach problematic for routine use. The purpose of this work is to demonstrate on two different 7T systems respectively equipped with 8-transmit-channel RF coils from two different suppliers (Rapid-Biomed and Nova Medical), the benefit of so-called universal pulses (UP), optimized to produce uniform excitations in the brain in a population of adults and making unnecessary the calibration procedures mentioned above. Non-selective and slice-selective UPs were designed to return homogeneous excitation profiles throughout the brain simultaneously on a group of ten subjects, which then were subsequently tested on ten additional volunteers in magnetization prepared rapid gradient echo (MPRAGE) and multi-slice gradient echo (2D GRE) protocols. The results were additionally compared experimentally with the standard non-pTx circularly-polarized (CP) mode, and in simulation with subject-specific tailored excitations. For both pulse types and both coils, the UP mode returned a better signal and contrast homogeneity than the CP mode. Retrospective analysis of the flip angle (FA) suggests that the FA deviation from the nominal FA on average over a healthy adult population does not exceed 11% with the calibration-free parallel-transmit pulses whereas it goes beyond 25% with the CP mode. As a result the universal pulses designed in this work confirm their relevance in 3D and 2D protocols with commercially available equipment. Plug-and-play pTx implementations henceforth become accessible to exploit with more flexibility the potential of UHF for brain imaging.

Accelerating parallel transmit array B1 mapping in high field MRI with slice undersampling and interpolation by kriging.

Transmit arrays have been developed to mitigate the RF field inhomogeneity commonly observed in high field magnetic resonance imaging (MRI), typically above 3T. To this end, the knowledge of the RF complex-valued B1 transmit-sensitivities of each independent radiating element has become essential. This paper details a method to speed up a currently available B1-calibration method. The principle relies on slice undersampling, slice and channel interleaving and kriging, an interpolation method developed in geostatistics and applicable in many domains. It has been demonstrated that, under certain conditions, kriging gives the best estimator of a field in a region of interest. The resulting accelerated sequence allows mapping a complete set of eight volumetric field maps of the human head in about 1 min. For validation, the accuracy of kriging is first evaluated against a well-known interpolation technique based on Fourier transform as well as to a B1-maps interpolation method presented in the literature. This analysis is carried out on simulated and decimated experimental B1 maps. Finally, the accelerated sequence is compared to the standard sequence on a phantom and a volunteer. The new sequence provides B1 maps three times faster with a loss of accuracy limited potentially to about 5%.

Exposure system and dosimetry for in vitro studies of biocompatibility of pulse-modulated RF signals of ultrahigh field MRI.

A new setup for exposure of human cells in vitro at 37 °C to pulse-modulated 300 and 500 MHz signals of future magnetic resonance imaging (MRI) systems is designed, built up, and characterized. Two dipole antennas, specifically designed for ultrahigh field MRI, are used as radiating structures. The electromagnetic (EM) field distribution inside the incubator containing the cells is computed, and it is shown to be in a good agreement with measurements. The electric field at the cell level is quantified numerically. Local, 1-g average, and averaged over the culture medium volume SAR are provided along with the standard deviation values for each well. Temperature increments are measured inside the culture medium during the exposure using an optical fiber thermometer. Then, we identify the pulse parameters corresponding to the thermal threshold of 1 °C, usually considered as a threshold for thermally induced biological effects. For these parameters, the induction of heat shock proteins is assessed to biologically verify a potential thermal response of cells. The data demonstrate that, under the considered experimental conditions, exposure to pulse-modulated radiations emulating typical ultrahigh field MRI signals, corresponding to temperature increments below 1 °C, does not trigger any heat shock response in human brain cells.