Short echo time proton spectroscopy of the brain in healthy volunteers using an insert gradient head coil

An insert gradient head coil with built-in X, Y, and Z gradients was used for localized proton spectroscopy in the brain of healthy volunteers, using short echo time stimulated echo acquisition mode (STEAM) sequences. Volume of interest size was 3.4 ml, repetition time was 6.0 s, and echo times were 10 and 20 ms, respectively. Good quality proton spectra with practically no eddy current artefacts were acquired allowing observation of strongly coupled compounds, and compounds with short T₂ relaxation times. The gradient head coil thus permits further studies of compounds such as glutamine/glutamate and myo-inositols. These compounds were more prominent within grey matter than within white matter. Rough estimations of metabolite concentrations using water as an internal standard were in good agreement with previous reports.     

N-Acetylaspartate concentrations in the thalami of neuropathic pain patients and healthy comparison subjects measured with (1)H-MRS

We investigated the absolute concentration of N-acetylaspartate (NAA) in the thalami of neuropathic pain patients and healthy comparison subjects by single-voxel proton magnetic resonance spectroscopy ((1)H-MRS). (1)H-MRS was performed with a 1.5-T MR system on a voxel in the thalamus bilaterally in 9 neuropathic pain patients and 14 healthy control subjects. We measured the absolute concentration of NAA using a linear combination model. The NAA concentration in the thalamus decreased significantly on the contralateral side in seven patients and on the ipsilateral side in two patients, as compared with the mean NAA concentration of the healthy control subjects. The NAA concentrations in two patients who did not respond to standard pain treatments were extremely decreased. Our results using (1)H-MRS suggest that neuropathic pain seems to be associated with an abnormal balance of the neural activity in the thalamus. The NAA concentration of the thalamus may be related to the efficacy of therapy. (1)H-MRS may serve as a useful noninvasive tool for evaluating thalamic neural activity in neuropathic pain patients.     

Diffusion-weighted imaging of the brain at 7 T with echo-planar and turbo spin echo sequences: preliminary results

Ultra-high-field clinical MRI scanners (e.g., 7 T and above) are becoming increasingly prevalent and can potentially enhance diagnostic ability through higher contrast, resolution and/or sensitivity. Diffusion-weighted MRI is a highly valued component in today's radiological exam and may benefit from the enhanced signal-to-noise ratio provided by high field with the appropriate imaging strategy. The most common diffusion pulse sequence readout (echo-planar imaging (EPI)) has been widely employed for in vivo human 7 T diffusion tensor imaging (DTI). In this article, we present results of brain DTI at 7 T with two diffusion-weighted imaging pulse sequence readouts: echo-planar imaging (EPI-DTI) and turbo spin echo (TSE-DTI). Results indicate that analogous coverage, quality and resolution typical of lower field (2 mm) can be obtained by properly processed EPI-DTI at 7 T, and, with some reduction in efficiency and sharpness, TSE-DTI at 7 T. Furthermore, 7 T TSE-DTI shows promise in obtaining higher-resolution results in targeted acquisitions of specific brain areas.     

Magnetic resonance T21 measurements of the normal human lung in vivo with ultra-short echo times

The objective of this study was to measure T₂1 values of the normal human lung in vivo during breathhold using a rapid gradient-echo sequence with ultra-short echo times (TE). A sagittal slice of the right lung was imaged in six volunteers with various TE ranging from 0.5 ms to 5 ms using a clinical 1.5 Tesla MR scanner. T₂1 values were calculated in a region of interest in the dependent and non-dependent lung. In the dependent lung, T₂1 values of 1.1 ms ± 0.15 ms were measured, and in the non-dependent lung, 0.86 ms ± 0.11 (p < 0.01). T₂1 measurements of the normal human lung during breathhold are feasible with a clinical MR unit. The short T₂1 values require the use of very short TE times (<2.5 ms) in gradient-echo sequences to obtain adequate signal intensity from lung tissue.     

In vivo quantitative 1H MRS of cerebellum and evaluation of quantitation reproducibility by simulation of different levels of noise and spectral resolution

A quantitative analysis of cerebellar metabolites in normal subjects has been performed by proton MR spectroscopy (MRS) with relaxation time correction. Quantitation was carried out in seven healthy human subjects with the well-established LCModel program. The prior knowledge utilized for quantitation was obtained from solutions containing the major brain metabolites and MRS investigated under the same experimental conditions. The tissue water signal was used as an internal standard for the in vivo studies. Both in vitro (for the prior knowledge template) and in vivo data were acquired separately at 1.5 T by PRESS sequence (TR, 1500 ms; TE, 30 ms). The absolute concentration of main cerebellar metabolites was corrected for relaxation time effects. Different noise and line broadening conditions were considered and simulated in the spectral processing in order to evaluate the effect of spectral quality on the concentration estimates.     

Sensitivity of single-voxel 1H-MRS in investigating the metabolism of the activated human visual cortex at 7 T

Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to noninvasively assess the temporal changes of lactate in the activated human brain. However, the results have not been consistent. The aim of the present study was to test the sensitivity of 1H-MRS during functional experiments at the highest magnetic field currently available for human studies (7 T). Stability and reproducibility of the measurements were evaluated from LCModel analysis of time series of spectra measured during a visual stimulation paradigm and by examination of the difference between spectra obtained at rest and during activation. The sensitivity threshold to detect concentration changes was 0.2 micromol/g for most of the quantified metabolites. The possible variations of metabolite concentrations during visual stimulation were within the same range (+/-0.2 micromol/g). In addition, the influence of a small line-narrowing effect due to the blood oxygenation level-dependent (BOLD) T2* changes on the estimated concentrations was simulated. Quantification of metabolites was, in general, not affected beyond 1% by line-width changes within 0.5 Hz.     

In vivo evaluation of the reproducibility of T1 and T2 measured in the brain of patients with multiple sclerosis.

The precision (reproducibility) of relaxation times derived from magnetic resonance images of patients with multiple sclerosis (MS) were investigated. Measurements of 10 MS patients were performed at 1.5 T on two occasions within 1 wk. T1 and T2 was measured using a partial saturation inversion recovery sequence (6 points) and a Carr-Purcell-Meiboom-Gill phase alternating-phase shift multiple spin-echo sequence with 32 echoes. Regions of interest (ROI) were placed both in apparently normal white matter and plaques. The precision (+/- 1.96 SD) and the confidence intervals for T1 and T2 for white matter and plaques were calculated. The precision of T1 for white matter and plaques was respectively +/- 94 msec and +/- 208 msec. The precision of T2 for white matter and plaques was respectively +/- 18 msec and +/- 26 msec. For all measurements the coefficient of variation was about 9%. Judging from our own study and others as well, a precision better than 10% for T1 and T2 would seem unrealistic at present.     

1H-MRS of the macaque monkey primary visual cortex at 7 T: strategies and pitfalls of shimming at the brain surface

Magnetic resonance spectroscopy (MRS) is ideally suited for physiology-neurochemistry experiments with the living brain and particularly for studies on the primary visual cortex (striate cortex or area V1). Yet, the highly convoluted form of the human V1 has thus far prevented the performance of MRS investigations that are spatially confined within the gray matter of this area. Typically, these studies are compromised by partial volume contaminations originating from white matter tissue, cerebrospinal fluid and other cortical areas. In this study, was exploited the relative flatness of V1 in macaques to enable single-voxel 1H-MRS from a small volume (5 x 1.6 x 5 mm3, 40 microl) that was entirely confined within the V1 gray matter of anesthetized monkeys. Linewidths of 13.5+/-1.9 Hz and 13.0+/-1.3 Hz for water and creatine, respectively, were achieved with a two-step shimming strategy for voxels at the brain surface. The quality of the obtained results paves the way for further neuroscientific research, including studies on the cortical microcircuits and the dynamic longitudinal changes occurring during cortical reorganization and plasticity.     

Short- and midterm repeatability of magnetic resonance elastography in healthy volunteers at 3.0 T

The purpose of this study was to evaluate the short- and midterm repeatability of liver stiffness measurements with magnetic resonance elastography (MRE) in healthy subjects at 3.0 T. Twenty-two healthy volunteers were enrolled in this prospective study. The stiffness measurements were obtained from three slices with three repeated acquisitions for each slice (session 1) by two independent raters. After a mean period of 7 ± 2 days (session 2) and 195 ± 15 days (session 3), each subject was scanned again using the same protocol and MR system. The liver stiffness differences were calculated between sessions or raters. The intraclass correlation coefficient (ICC) was calculated to assess interrater agreement and intersession agreement. The stiffness differences over the short- and midterm intervals was (− 0.004 ± 0.086) kPa for sessions 1–2, lower than (− 0.055 ± 0.150) kPa for sessions 1–3 and (− 0.051 ± 0.173) kPa for sessions 2–3. The liver stiffness was more repeatable for the short-term interval with the mean overall ICC of 0.96 (sessions 1–2) (95% confidence interval [CI]: 0.90–0.98) compared with 0.91 (sessions 1–3) (95% CI: 0.78–0.96) and 0.87 (sessions 2–3) (95% CI: 0.69–0.95) for the midterm intervals. The overall ICC of interrater agreement was excellent at 0.987 (95% CI: 0.983 to 0.990). These results confirm that MRE is a reproducible technique for liver stiffness quantification over short- and midterm intervals up to 6 months in a healthy population at 3.0 T.     

An integrated approach for the systematic evaluation of polymeric nanoparticles in healthy and diseased organisms

Innovative strategies that utilize nanoparticles (NPs) for a better delivery of drugs and to improve their therapeutic efficacy have been widely studied in many clinical fields, including oncology. To develop safe and reliable devices able to reach their therapeutic target, a hierarchical characterization of NP interactions with biological fluids, cells, and whole organisms is fundamental. Unfortunately, this aspect is often neglected and the development of standardized characterization methods would be of fundamental help to better elucidate the potentials of nanomaterials, even before the loading of the drugs. Here, we propose a multimodal in vitro/in vivo/ex vivo platform aimed at evaluating these interactions for the selection of the most promising NPs among a wide series of materials. To set the system, we used non-degradable fluorescent poly(methyl-methacrylate) NPs of different sizes (50, 100, and 200 nm) and surface charges (positive and negative). First we studied NP stability in biological fluids. Then, we evaluated NP interaction with two cell lines of triple-negative breast cancer (TNBC), 4T1, and MDA-MB231.1833, respectively. We found that NPs internalize in TNBC cells depending on their physico-chemical properties without toxic effects. Finally, we studied NP biodistribution in terms of tissue migration and progressive clearance in breast-cancer bearing mice. The use of highly stable poly(methyl-methacrylate) NPs enabled us to track them for a long time in cells and animals. The application of this platform to other nanomaterials could provide innovative suggestions for the development of a systematic method of characterization to select the most reliable nanodrug candidates for biomedical applications.     

Straightforward relative quantitation and age-related human standards of N-acetylaspartate at the centrum semiovale level by CSI (1)H-MRS

1H-MRS was aimed to monitor metabolite concentrations in homogeneous interaxial slices of cerebral matter at the centrum semiovale level in healthy volunteers. NAA (N-acetylaspartate + N-acetylglutamate), Cr (creatine + phosphocreatine), and Cho (choline + acetylcholine) were evaluated by resonance integrations. Using Cr as an internal standard, NAA/Cr ratio was considered as a relative measure of concentration. CSI sequence explored volunteer's interaxial slices of white and gray matter by means of 8 x 8 matrices of (1)H-NMR spectra. NAA/Cr integral ratios were averaged over the whole spectral matrix to obtain the Index of NAA at Centrum Semiovale (INACS) of each individual. Indexes of the sixty-eight healthy volunteers, divided into three groups by age, showed good intraindividual reproducibility, and were virtually unaffected by small shifts or bendings of the interaxial slice analyzed. The INACSs were used to estimate Age-Sectorial INACS Ranges (ASIR), the intervals that, on the basis of a normal statistical distribution, should comprise 95% of the age-matched healthy population. Individual INACSs, compared to accurately defined ASIRs taken as standards, could early detect subtle, diffuse neuronal or axonal damage within centrum semiovale interaxial slices. Periodic inspection of INACS could also allow monitoring of progressive neuronal or axonal degeneration.     

Spin echo MRI in the evaluation of hearts with a double outlet right ventricle: usefulness and limitations

The surgical approach to a double outlet right ventricle (DORV) is dependent on the spatial relationship of the semilunar valves, outflow tracts and ventricular septal defect (VSD). The purpose of the study was to assess the value of MRI for the evaluation of cardiovascular anatomy in patients before and after surgery for DORV. Spin echo MRI was performed in 12 patients with DORV (eight preoperative and four postoperative patients). Thin-section MRI was performed in three orthogonal planes and selected angulated views were obtained. Conventional imaging by color Doppler echocardiography and cine-angiocardiography and surgical findings, when present, served as the reference standards. The results found that the spatial relationship between semilunar valves and VSD was accurately assessed by MRI in eight out of eight preoperative patients. In the four postoperative cases MRI depicted the morphology of both outflow tracts and provided adequate information on their patency. Of the eight preoperative patients, five have undergone corrective surgery and the MRI findings were confirmed. MRI provided additional information to conventional imaging preoperatively in three cases in which the VSD opened into the outlet portion of the DORV, without there being a direct relation to a semilunar valve. In two preoperative cases in which the VSD was directly committed to the aorta, conventional imaging was conclusive. MRI was unable to depict aberrant chordae tendineae in four out of four cases. We conclude that MRI provides accurate additional anatomic information in patients with DORV, which is helpful in presurgical planning as well as during follow-up. Spin echo MRI does not visualize aberrant chordae tendineae.     

广泛性焦虑大鼠前额叶皮质和海马磁共振波谱的研究

以广泛性焦虑大鼠为研究载体,探讨其前额叶皮质和海马组织质子磁共振波谱(1H-MRS)的变化及意义.大鼠分为正常组和模型组各8只,采用慢性情绪应激的方法建立广泛性焦虑大鼠模型,以国际公认的高架十字迷宫试验对其进行评价,在活体状态下,通过pharmascan70/16超导磁共振仪(7.0T)检测双侧海马及前额叶皮质N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、谷氨酸(Glu)、肌酸(Cr)等代谢物水平,分别计算NAA、Cho和Glu与Cr的比值,进而对脑组织代谢进行定性及定量分析.正常组与广泛性焦虑组双侧海马及左侧前额叶皮质代谢物无明显差异(P0.05),广泛性焦虑大鼠右侧前额叶皮质NAA、Cho相对浓度较正常组显著降低(P0.05),Glu相对浓度则明显升高(P0.05).慢性焦虑情绪的产生可能与右侧前额叶皮质兴奋性神经递质谷氨酸的浓度升高、神经元的损伤或数量减少及细胞内信号转导的异常有关.     

14N Pulsed nuclear quadrupole resonance. 4. Two-pulse sequences for the determination of T1 and T2 relaxation times

A general theory, based on density matrix calculations, has been developed for the special case of a two-pulse sequence applied to spin 1 (¹⁴N) nuclear quadrupole resonance (NQR) of a powder sample. It is shown that the homolog of the NMR inversion-recovery experiment leads easily to the spin-lattice relaxation time T ₁ (associated with the diagonal elements of the density matrix) provided that an appropriate phase cycling is used. Conversely, in spite of two-step phase cycling schemes adapted to spin-spin relaxation measurements, the homolog of the NMR Hahn spin-echo sequence may pose some problems if the results are displayed in the magnitude mode. First, at short decay times, the echo may be corrupted by unwanted signals. Secondly, in that case, the amplitude of the resulting signal can evolve unexpectedly and differently as a function of the phase of the second pulse. Thirdly, at long decay times, the echo maximum occurs earlier than expected. All these problems in principle disappear with a complete four-step phase cycling scheme and the echo decay curve yields reliably the spin-spin relaxation time T ₂ (associated with off-diagonal elements). This theory allowed the exploitation of many test experiments performed at different frequencies on hexamethylenetetramine (HMT) and sodium nitrite.     

Relaxation of excited molecules in a medium with memory at short and long times

Two qualitatively different approaches to the dynamics of vibrational wave packets in the presence of medium-induced relaxation, with taking into account relaxation memory effects and without taking them into account (Makovian approximation) were compared for a molecular system with one vibrational degree of freedom (the Morse oscillator) in a medium. The time evolution of the populations of levels, mean system energy, and response of “pumping-probing” experiments were calculated. It was found that, as distinct from the Markovian approximation, the approach including memory effects can predict the evolution of a molecular system satisfying the detailed equilibrium principle. The two approaches specified also predict the existence of a qualitative difference of phase characteristics in the behavior of the system at short times.     

Quantitative in vivo1H-spectroscopy of healthy and tumorous human brain tissue at 4 tesla

In 35 healthy volunteers 79 hydrogen spectra were measured from the parietal lobe, parieto-occipital lobe, frontal lobe, temporal lobe, thalamus and insular region. Voxels were selected with a double spin-echo sequence at TE 71, 135 and 270 ms. The spectra were quantitatively evaluated by fitting a Lorentzian model to the resonances of the creatine pool at 3.02 ppm and the choline pool at 3.22 ppm. No differences were found in the intensities of either metabolite in the 6 investigated regions. Creatine and choline were equally distributed in these regions. The interindividual reproducibility of the spectra decreases with longer echo delays. The coefficients of variation of the areas of creatine and choline corrected for the number of acquisitions and the voxel size are ±13% at TE 71 ms, ±23% at TE 135 ms, ±43% at TE 270 ms. This is caused by an interindividual variation in T₂ by ±15%, which affects all resonances of a spectrum. Signal variations from the fit, the Q-factor of the RF-coil loaded with different subjects and variations in the flip angle are less than 10% at each echo delay. The intraindividual variation without repositioning of the subject was better than 10%. Using creatine as an internal reference the ratios of the amplitudes of N-acetyl-aspartate (NAA) at 2.01 ppm and γ-methylene protons of glutamic acid at 2.34 ppm were not specific for special regions of the brain. Only in the temporal lobe the ratio of NAA and creatine was reduced. A mean concentration ratio of 1.7 for NAA and Cre was measured as an average over all subjects and the investigated brain regions with the exception of the temporal lobe. Initial applications of the method to 7 patients with brain tumors are described.     

Determination of T1- and T2-relaxation times in the spleen of patients with splenomegaly

Twenty-nine patients with known splenomegaly and seven healthy volunteers were examined. The T1 and T2 relaxation times were read out from a region of interest centrally in the spleen. Even though different mean T1 and T2 relaxation times were found between the groups, the great scatter and the considerable overlap between the groups makes the contribution of relaxation time measurements to the differential diagnosis of splenomegaly of limited value.     

Natural radiative lifetimes in the1 P 1 and1 F 3 sequences of Sr I

We have measured radiative lifetimes in the 5s n p ¹ P ₁ (n=5–29) and 5s n f ¹ F ₃ (n=4–11) Rydberg series in neutral strontium. The measurements were performed with single-step laser excitation starting from the ground state or from a metastable state populated by collisions. The decay photons were detected using delayed coincidence technique or a transient recorder. The presence of configuration interaction in the 5s n p ¹ P ₁ series can be observed aroundn=8. The perturbation in the 5s n f ¹ F ₃ series is not reflected in the behaviour of the lifetime values.     

共振峰编辑法区别鼻化元音中口、鼻音共振峰的实证探究*

为解决司法话者识别中利用鼻化元音构建元音声学空间图时如何准确判别鼻化元音的口、鼻音共振峰的问题。本文通过计算机语音工作站对语音样本的共振峰进行编辑操作，利用生成的语音样本构建不同的对照组分别进行听辨。结果表明，口音、鼻音共振峰分别被衰减后的语音变化特点呈现一定规律，使用此方法可以准确区分鼻化元音的口、鼻共振峰的阶次。本文建立的“共振峰编辑”与“听觉感知”相结合的判别方法，可以为司法话者识别及语音感知、识别等相关领域通过构建元音声学空间图进行声学特征研究的模型提供口音、鼻音共振峰的判别依据。