颞叶癫痫的功能MRI研究进展

颞叶癫■（TLE）是癫■中最常见的难治性类型,临床上对于药物难以控制的癫■,手术切除致■灶具有良好的治疗效果。随着MRI技术的迅速发展,功能磁共振成像（fMRI）在癫■研究中的优势越来越显著,尤其在癫■灶的定侧、定位方面明显优于常规MRI,具有更好的临床应用价值。fMRI对TLE脑网络、认知功能的研究,及在TLE病因、病理生理机制、治疗预后等方面的应用取得了诸多进展。     

Real-time display of artifact-free electroencephalography during functional magnetic resonance imaging and magnetic resonance spectroscopy in an animal model of epilepsy.

Simultaneous recording of electroencephalogram (EEG) and functional MRI (fMRI) or MR spectroscopy (MRS) can provide further insight into our understanding of the underlying mechanisms of neurologic disorders. Current technology for simultaneous EEG and MRI recording is limited by extensive postacquisition processing of the data. Real-time display of artifact-free EEG recording during fMRI/MRS studies is essential in studies that involve epilepsy to ensure that they address specific EEG features such as epileptic spikes or seizures. By optimizing the EEG recording equipment to maximize the common mode rejection ratio of its amplifiers, a unique EEG system was designed and tested that allowed real-time display of the artifact-free EEG during fMRI/MRS in an animal model of epilepsy. Spike recordings were optimized by suppression of the background EEG activity using fast-acting and easily controlled inhalational anesthesia. Artifact suppression efficiency of 70-100% was achieved following direct subtraction of referentially recorded filtered EEG tracings from active electrodes, which were located in close proximity to each other (over homologous occipital cortices) and a reference electrode. Two independent postacquisition processing tools, independent component analysis and direct subtraction of unfiltered digital EEG data in MATLAB, were used to verify the accuracy of real-time EEG display.     

Age dependence of cerebral perfusion assessed by magnetic resonance continuous arterial spin labeling

PURPOSE: To study the normal dependence of cerebral perfusion changes on age, to measure values of perfusion early in life, and to create a reference dataset. MATERIALS AND METHODS: Perfusion maps were collected from a total of 44 healthy subjects (from four to 78 years old) using the arterial spin labeling (ASL) technique. The population was retrospectively divided into three age groups: children, teenagers, and adults. For each group, mean values of cerebral blood flow (CBF) were calculated in gray matter (GM) and white matter (WM). Results were compared across the three different age groups. RESULTS: CBF values decreased with age (97+/-5 mL/100 g/minute in GM and 26+/-1 mL/100 g/minute in WM for the children, GM 79+/-3 mL/100 g/minute and WM 22+/-1 mL/100 g/minute for the teenagers, and GM 58+/-4 mL/100 g/minute, WM 20+/-1 mL/100 g/minute for the adults). The quantitative results suggest a rapid drop, rather than a gradual decrease, in cerebral perfusion between children and adult subjects, especially in the GM. This step in CBF occurs during adolescence, at approximately the 16th year of age. CONCLUSION: ASL is a practical and quantitative technique suitable for perfusion measurement in children as well as adults. Perfusion measurements with ASL appear sensitive to neurophysiological changes occurring during brain maturation.     

~1H-MRS磁共振波谱分析对海马硬化诊断的评价

目的分析原发性颞叶癫痫与海马硬化之间的关系,探讨磁共振波谱成像(1H-MRS)在海马硬化早期诊断中的应用价值。方法回顾性分析30例经手术证实的海马硬化患者的临床表现、1H-MRS资料,重点分析1H-MRS的NAA、Cr、Cho波峰特点。结果 1H-MRS发现异常28例(93%),2例在MRI及1H-MRS均未见异常。结论 1H-MRS可对海马硬化或伴有海马胶质细胞增生者进行早期诊断,提高了海马硬化诊断的敏感性。     

Detrimental effects of BOLD signal in arterial spin labeling fMRI at high field strength.

Arterial spin labeling (ASL) MRI is a useful technique for noninvasive measurement of cerebral blood flow (CBF) in humans. High field strength provides a unique advantage for ASL because of longer blood T(1) relaxation times, making this technique a promising quantitative approach for functional brain mapping. However, higher magnetic field also introduces new challenges. Here it is shown that the CBF response determined using ASL functional MRI (fMRI) at 3.0 T contains significant contamination from blood-oxygenation-level-dependent (BOLD) effects. Due to interleaved acquisitions of label and control images, difference in blood oxygenation status between these two scans can cause incomplete cancellation of the static signal upon image subtraction, resulting in a BOLD-related artifact in the estimated CBF hemodynamics. If not accounted for, such an effect can complicate the interpretation of the ASL results, e.g., causing a delayed onset and offset of the response, or inducing an artifactual poststimulus undershoot. The BOLD contribution also decreases the sensitivity of ASL-based fMRI. Correction methods are proposed to reduce the artifact, giving increased number of activated voxels (18+/-5%, P=0.006) and more accurate estimation of CBF temporal characteristics.     

Quantification of rodent cerebral blood flow (CBF) in normal and high flow states using pulsed arterial spin labeling magnetic resonance imaging

PURPOSE: To implement a pulsed arterial spin labeling (ASL) technique in rats that accounts for cerebral blood flow (CBF) quantification errors due to arterial transit times (dt)-the time that tagged blood takes to reach the imaging slice-and outflow of the tag. MATERIALS AND METHODS: Wistar rats were subjected to air or 5% CO(2), and flow-sensitive alternating inversion-recovery (FAIR) perfusion images were acquired. For CBF calculation, we applied the double-subtraction strategy (Buxton et al., Magn Reson Med 1998;40:383-396), in which data collected at two inversion times (TIs) are combined. RESULTS: The ASL signal fell off more rapidly than expected from TI = one second onward, due to outflow effects. Inversion times for CBF calculation were therefore chosen to be larger than the longest transit times, but short enough to avoid systematic errors caused by outflow of tagged blood. Using our method, we observed a marked regional variability in CBF and dt, and a region dependent response to hypercapnia. CONCLUSION: Even when flow is accelerated, CBF can be accurately determined using pulsed ASL, as long as dt and outflow of the tag are accounted for.     

Noise reduction in multi-slice arterial spin tagging imaging.

Attenuating the static signal in arterial spin tagging (ASSIST) was initially developed for 3D imaging of cerebral blood flow. To enable the simultaneous collection of cerebral blood flow and BOLD data, a multi-slice version of ASSIST is proposed. As with the 3D version, this sequence uses multiple inversion pulses during the tagging period to suppress the static signal. To maintain background suppression in all slices, the multi-slice sequence applies additional inversion pulses between slice acquisitions. The utility of the sequence was demonstrated by simultaneously acquiring ASSIST and BOLD data during a functional task and by collecting resting-state ASSIST data over a large number of slices. In addition, the temporal stability of the perfusion signal was found to be 60% greater at 3 T compared to 1.5 T, which was attributed to the insensitivity of ASSIST to physiologic noise.     

In vivo estimation of the flow-driven adiabatic inversion efficiency for continuous arterial spin labeling: a method using phase contrast magnetic resonance angiography.

The accurate quantification of perfusion with arterial spin labeling (ASL) requires consideration of a number of factors, including the efficiency of the inversion and control pulses used for spin labeling. In this study the effects of spin velocity on continuous ASL efficiency when using the amplitude modulated control strategy were investigated using simulations of the Bloch equations. The inversion efficiency was determined in vivo by combining the simulations with phase-contrast velocity mapping data acquired at the level of the tagging plane. Using this novel method, an average inversion efficiency of 69% was calculated for a group of 28 subjects, in good agreement with experimental data reported previously. There was, however, a large range in inversion efficiency measured across the subject group (50-76%), indicating that the velocity dependence of the amplitude modulated control efficiency may introduce additional variability into the perfusion calculations if not properly taken into account.     

颞叶癫痫患者前额叶背外侧的定量质子磁共振波谱研究

目的:利用氢质子磁共振波谱(1H-MRS)研究颞叶癫痫(TLE)患者前额叶背外侧区(DLPFC)的生化改变,探讨额叶在TLE发病代谢机制中的作用.方法:纳入TLE患者(TLE组)及健康志愿者(健康对照组)各20例.根据24h视频脑电图(VEEG)所提示致痫灶所在部位将TLE组分为左侧TLE亚组及右侧TLE亚组.利用单体素1 H-MRS点分辨波谱序列(PRESS)进行扫描,并采用LCModel软件进行后处理,获取所有被试者双侧DLPFC区氮乙酰天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)、肌醇(Ins)及谷氨酸/谷氨酰胺复合物(Glx)的绝对浓度.然后分别对比健康对照组及TLE患者左侧DLPFC区与右侧DLPFC区、健康对照组与TLE患者同侧DLPFC区之间各代谢物浓度的差异.结果:健康对照组左右侧DLPFC区NAA浓度分别为(7.24±0.57) mmol/L、(6.76±0.87) mmol/L,左侧NAA浓度显著高于右侧(P=0.024);而TLE患者上述NAA不对称性消失,左右侧NAA浓度分别为(6.58±0.56) mmol/L、(6.31±0.62)mmol/L(P=0.092).与健康对照相比,TLE患者左侧DLPFC区NAA、Cr及Ins浓度显著降低(P=0.000、0.014、0.025),右侧DLPFC区仅Ins浓度显著降低(P=0.013),而Cho、Glx浓度在左右侧DLPFC区均无显著改变.分层分析进一步揭示左侧TLE亚组的左侧DLPFC区NAA、Cr及Ins浓度较对照组显著降低(P=0.001、0.047、0.007),右侧DLPFC区Ins浓度较对照组显著降低(P=0.002);而右侧TLE组仅有左侧DLPFC区NAA浓度显著降低(P=0.037).结论:颞叶癫痫患者的额叶也存在生化代谢异常,且以左侧额叶改变为主,说明额叶在TLE发病的代谢机制中可能起着重要作用.     

Perfusion-based fMRI: insights from animal models

Modern functional neuroimaging techniques, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and optical imaging of intrinsic signals (OIS), rely on a tight coupling between neural activity and cerebral blood flow (CBF) to visualize brain activity using CBF as a surrogate marker. Because CBF is a uniquely defined physiological parameter, fMRI techniques based on CBF contrast have the advantage of being specific to tissue signal change, and the potential to provide more direct and quantitative measures of brain activation than blood oxygenation level-dependent (BOLD)- or cerebral blood volume (CBV)-based techniques. The changes in CBF elicited by increased neural activity are an excellent index of the magnitude of electrical activity. Increases in CBF are more closely localized to the foci of increased electrical activity, and occur more promptly to the stimulus than BOLD- or CBV-based contrast. In addition, CBF-based fMRI is less affected by confounds from venous drainage common to BOLD. Animal studies of brain activation have yielded considerable insights into the advantages of CBF-based fMRI. Based on results provided by animal studies, CBF fMRI may offer a means of better assessing the magnitude, spatial extent, and temporal response of neural activity, and may be more specific to tissue state. These properties are expected to be particularly useful for longitudinal and quantitative fMRI studies.     

Functional magnetic resonance imaging activation detection: fuzzy cluster analysis in wavelet and multiwavelet domains

PURPOSE: To present novel feature spaces, based on multiscale decompositions obtained by scalar wavelet and multiwavelet transforms, to remedy problems associated with high dimension of functional magnetic resonance imaging (fMRI) time series (when they are used directly in clustering algorithms) and their poor signal-to-noise ratio (SNR) that limits accurate classification of fMRI time series according to their activation contents. MATERIALS AND METHODS: Using randomization, the proposed method finds wavelet/multiwavelet coefficients that represent the activation content of fMRI time series and combines them to define new feature spaces. Using simulated and experimental fMRI data sets, the proposed feature spaces are compared to the cross-correlation (CC) feature space and their performances are evaluated. In these studies, the false positive detection rate is controlled using randomization. To compare different methods, several points of the receiver operating characteristics (ROC) curves, using simulated data, are estimated and compared. RESULTS: The proposed features suppress the effects of confounding signals and improve activation detection sensitivity. Experimental results show improved sensitivity and robustness of the proposed method compared to the conventional CC analysis. CONCLUSION: More accurate and sensitive activation detection can be achieved using the proposed feature spaces compared to CC feature space. Multiwavelet features show superior detection sensitivity compared to the scalar wavelet features.     

Quantitative magnetic resonance imaging of the fetal brain in utero: Methods and applications

Application of modern magnetic resonance imaging (MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and accepted ultrasonographic approach are the subject of a continuing debate; however the focus of this review is on the even younger field of quantitative MRI as applied to non-invasive studies of fetal brain development. The techniques covered under this header include structural MRI when followed by quantitative (e.g., volumetric) analysis, as well as quantitative analyses of diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. The majority of the published work reviewed here reflects information gathered from normal fetuses scanned during the 3^rd trimester, with relatively smaller number of studies of pathological samples including common congenital pathologies such as ventriculomegaly and viral infection.     

Physiological origin of low‐frequency drift in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)

We investigated the biophysical mechanism of low‐frequency drift in blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) (0.00–0.01 Hz), by exploring its spatial distribution, dependence on imaging parameters, and relationship with task‐induced brain activation. Cardiac and respiratory signals were concurrently recorded during MRI scanning and subsequently removed from MRI data. It was found that the spatial distribution of low‐frequency drifts in human brain followed a tissue‐specific pattern, with greater drift magnitude in the gray matter than in white matter. In gray matter, the dependence of drift magnitudes on TE was similar to that of task‐induced BOLD signal changes, i.e., the absolute drift magnitude reached the maximum when TE approached T whereas relative drift magnitude increased linearly with TE. By systematically varying the flip angle, it was found that drift magnitudes possessed a positive dependence on image intensity. In phantom experiments, the observed drift was not only much smaller than that of human brain, but also showed different dependence on TE and flip angle. In fMRI studies with visual stimulation, a strong positive correlation between drift effects at baseline and task‐induced BOLD signal changes was observed both across subjects and across activated pixels within individual participants. We further demonstrated that intrinsic, physiological drift effects are a major component of the spontaneous fluctuations of BOLD fMRI signal within the frequency range of 0.0–0.1 Hz. Our study supports brain physiology, as opposed to scanner instabilities or cardiac/respiratory pulsations, as the main source of low‐frequency drifts in BOLD fMRI. Magn Reson Med 61, 2009. © 2009 Wiley‐Liss, Inc.     

Water chemical shift in 1H NMR of red cells: effects of pH when transmembrane magnetic susceptibility differences are low

The (1)H magic angle spinning (MAS) NMR spectrum of water in erythrocyte suspensions shows peaks from each of the intracellular and extracellular water pools. The splitting is a true chemical shift and is brought about by the elimination of water exchange under MAS conditions due to physical separation of the two water populations. The size of the chemical shift difference is determined by the concentration of intracellular protein affecting the average extent of hydrogen bonding of water. We present here a model of the chemical shift behavior for water in erythrocytes under normal high-resolution NMR conditions based on results from MAS experiments on these cells exposed to different pH and osmotic conditions. The model accurately predicts the chemical shift of water for a static sample, and the results demonstrate that in high-resolution NMR experiments the chemical shift of water will appear to be invariant if differences in magnetic susceptibility across the cell membrane are minimal (<10% of the magnetic susceptibility of water). Thus, changes in the shape and chemical shift of the water resonance are not due to pH changes in the physiological range. The findings are fundamental to an interpretation of the mechanism of chemical shift effects on the water resonance that may occur in functional MRI.     

Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

Introduction

The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways.

Materials and methods

Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated.

Results

The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA.

Discussion

Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed.

Conclusion

The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF).     

Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: Evidence from resting-state fMRI

Objective

The hippocampus expresses high levels of thyroid hormone receptors, suggesting that hippocampal functions, including cognition and regulation of mood, can be disrupted by thyroid pathology. Indeed, structural and functional alterations within the hippocampus have been observed in hyperthyroid patients. In addition to internal circuitry, hippocampal processing is dependent on extensive connections with other limbic and neocortical structures, but the effects of hyperthyroidism on functional connectivity (FC) with these areas have not been studied. The purpose of this study was to investigate possible abnormalities in the FC between the hippocampus and other neural structures in hyperthyroid patients using resting-state fMRI.

Methods

Seed-based correlation analysis was performed on resting-state fMRI data to reveal possible differences in hippocampal FC between hyperthyroid patients and healthy controls. Correlation analysis was used to investigate the relationships between the strength of FC in regions showing significant group differences and clinical variables.

Results

Compared to controls, hyperthyroid patients showed weaker FC between the bilateral hippocampus and both the bilateral anterior cingulate cortex (ACC) and bilateral posterior cingulate cortex (PCC), as well as between the right hippocampus and right medial orbitofrontal cortex (mOFC). Disease duration was negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC and PCC. Levels of depression and anxiety were negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC.

Conclusion

Decreased functional connectivity between the hippocampus and bilateral ACC, PCC, and right mOFC may contribute to the emotional and cognitive dysfunction associated with hyperthyroidism.