Real-time MR artifacts filtering during continuous EEG/fMRI acquisition

The purpose of this study was the development of a real-time filtering procedure of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI acquisition. The development of a combined EEG and fMRI technique has increased in the past few years. Preliminary “spike-triggered” applications have been possible because in this method, EEG knowledge was only necessary to identify a trigger signal to start a delayed fMRI acquisition. In this way, the two methods were used together but in an interleaved manner. In real simultaneous applications, like event-related fMRI study, artifacts induced by MRI events on EEG traces represent a substantial obstacle for a right analysis. Up until now, the methods proposed to solve this problem are mainly based on procedures to remove post-processing artifacts without the possibility to control electrophysiological behavior of the patient during fMRI scan. Moreover, these methods are not characterized by a strong “prior knowledge” of the artifact, which is an imperative condition to avoid any loss of information on the physiological signals recovered after filtering. In this work, we present a new method to perform simultaneous EEG/fMRI study with real-time artifacts filtering characterized by a procedure based on a preliminary analytical study of EPI sequence parameters-related EEG-artifact shapes. Standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes included: high-performance acquisition device; electrodes/cap/wires/cables materials and geometric design; shielding box for EEG signal receiver; optical fiber link; and software. The effects of the RF pulse and time-varying magnetic fields were minimized by using a correct head cap wires-locked environment montage and then removed during EEG/fMRI acquisition with a subtraction algorithm that takes in account the most significant EPI sequence parameters. The on-line method also allows a further post-processing utilization.     

Empirical mathematical model for dynamic manganese-enhanced MRI of the murine pancreas for assessment of β-cell function

Autoimmune ablation of pancreatic β-cells and alteration of its microvasculature may be a predictor of Type I diabetes development. A dynamic manganese-enhanced MRI (MEMRI) approach and an empirical mathematical model were developed to monitor whole pancreatic β-cell function and vasculature modifications in mice. Normal and streptozotocin-induced diabetic FVB/N mice were imaged on a 9.4 T MRI system using a 3D magnetization prepared rapid acquisition gradient echo pulse sequence to characterize low dose manganese kinetics in the pancreas head, body and tail. Average signal enhancement in the pancreas (head, body, and tail) as a function of time was fit by a novel empirical mathematical model characterizing contrast uptake/washout rates and yielding parameters describing peak signal, initial slope, and initial area under the curve. Signal enhancement from glucose-induced manganese uptake was fit by a linear function. The results demonstrated that the diabetic pancreatic tail had a significantly lower contrast uptake rate, smaller initial slope/initial area under the curve, and a smaller rate of Mn uptake following glucose activation (p < 0.05) compared to the normal pancreatic tail. These observations parallel known patterns of β-cell loss and alteration in supportive vasculature associated with diabetes. Dynamic MEMRI is a promising technique for assessing β-cell functionality and vascular perfusion with potential applications for monitoring diabetes progression and/or therapy.     

A novel functional magnetic resonance imaging compatible search-coil eye-tracking system

Measuring eye movements (EMs) using the search-coil eye-tracking technique is superior to video-based infrared methods [Collewijn H, van der Mark F, Jansen TC. Precise recording of human eye movements. Vision Res 1975;15(3):447-50], which suffer from the instability of pupil size, blinking behavior and lower temporal resolution. However, no conventional functional magnetic resonance imaging (fMRI)-compatible search-coil eye tracker exists. The main problems for such a technique are the interaction between the transmitter coils and the magnetic gradients used for imaging as well as the limited amount of space in a scanner. Here we present an approach to overcome these problems and we demonstrate a method to record EMs in an MRI scanner using a search coil. The system described has a spatial resolution of 0.07 degrees (visual angle) and a high temporal resolution (22 kHz). The transmitter coils are integrated into the visual presentation system and the control/analysis unit is portable, which enables us to integrate the eye tracker with an MRI scanner. Our tests demonstrate low noise in the recorded eye traces and scanning with minimal artifact. Furthermore, the induced current in the search coil caused by the RF pulses does not lead to measurable heating. Altogether, this MR-compatible search-coil eye tracker can be used to precisely monitor EMs with high spatial and temporal resolution during fMRI. It can therefore be of great importance for studies requiring accurate fixation of a target, or measurement and study of the subject's oculomotor system.     

Accounting for nonspecific enhancement in neuronal tract tracing using manganese enhanced magnetic resonance imaging

Manganese enhanced MRI (MEMRI) is an emerging technique for tracing neuronal pathways in vivo. However, manganese may leak into blood vessels or cerebrospinal fluid (CSF) after local injection and can be circulated to and taken up by brain regions that may not have connections to the targeted pathways. Comparing enhancement time courses after intranasal injection with intravenous infusion of MnCl₂ in rats, the early enhancements in the pituitary gland (Pit) and hippocampus indicate the contrasts in those regions in the olfactory tract-tracing experiment were caused by such systemic effects. Since the Pit has easy access to manganese from the blood and its signal is proportional to other brain regions after intravenous infusion, it was used as an internal reference for the systemic effects. Applying intensity normalization by the Pit signal to tract-tracing data from the olfactory bulb led to reduced contrast in the hippocampus. These results demonstrate that nonspecific enhancements in MEMRI tract-tracing studies may have to be taken into account and that normalization by the Pit signal can compensate these effects.     

Statistical methods for detecting activated regions in functional MRI of the brain

Two statistical tests for detecting activated pixels in functional MRI (fMRI) data are presented. The first test (t-test) is the optimal solution to the problem of detecting a known activation signal in Gaussian white noise. The results of this test are shown to be equivalent to the cross-correlation method that is widely used for activation detection in fMRI. The second test (F test) is the optimal solution when the measured data are modeled to consist of an unknown activation signal that lies in a known lower dimensional subspace of the measurement space with added Gaussian white noise. A model for the signal subspace based on a truncated trigonometric Fourier series is proposed for periodic activation–baseline imaging paradigms. The advantage of the second method is that it does not assume any information about the shape or delay of the activation signal, except that it is periodic with the same period as the activation–baseline pattern. The two models are applied to experimental echo-planar fMRI data sets and the results are compared.     

Partial volume effect compensation for improved reliability of quantitative blood-brain barrier permeability

INTRODUCTION: Blood-brain barrier (BBB) plays an important role in the pathophysiology of many central nervous system disorders. In the past, a number of laboratory techniques have been proposed to quantify permeability coefficient, k(i), an important index of barrier function. Recently, MRI has been used to estimate k(i) based on the unidirectional tracer kinetics model in one compartment as proposed by Patlak et al. and has been found to be in good agreement with the gold standard quantitative autoradiography technique. Rapid data acquisition, a prerequisite of this MRI-based technique, causes a compromise in spatial resolution resulting in partial volume (PV) averaging, an effect that is seldom explicitly compensated for in quantitative neuroimaging studies. This may have profound effect on the reliability of estimates obtained using quantitative methods. Existing PV compensation techniques that use complex statistical algorithms perform corrections on stationary images. In this proof-of-principle study, the effect of PV averaging on BBB permeability coefficient has been evaluated using a simulation model, and a postprocessing technique that makes use of dynamic information has been proposed for PV compensation in order to improve the reliability of this quantitative method. MATERIALS AND METHODS: A computer simulation model is presented, which evaluates the effect of PV averaging on permeability coefficient estimates. Beginning with a known k(i), a PV compensation technique is proposed, which aims at correcting calculated k(i) to obtain the original estimate. The application of the PV compensation technique is demonstrated in a rat stroke brain model. Magnetic resonance imaging experiments were performed in Wistar rats (n=2) on a 4.7-T scanner. After acquiring localizer, T2-weighted and diffusion-weighted images, a rapid T1 mapping protocol was implemented to acquire one pre-gadolinium-diethylenetriaminepentaacetic acid baseline data set followed by a series of postinjection data sets. The data were postprocessed without and with application of PV compensation technique to obtain a k(i) estimate. RESULTS AND DISCUSSION: The issue of PV averaging as a result of limited spatial resolution is often not addressed in quantitative MRI studies. In this work, simulation experiments have provided useful insight into the PV effects on permeability coefficient estimate. The findings of the simulation experiments agree well with the results obtained from MR experiments. Results from the MR experiments suggest that it may be important to perform PV compensation in order to improve the reliability of permeability coefficient estimates. Future work involves classification of tissue component into gray and white matter and CSF to improve the accuracy of the compensation technique and to investigate repeatability of the technique in a larger group of animals.     

Respiratory noise correction using phase information

Respiratory noise is a confounding factor in functional magnetic resonance imaging (MRI) data analysis. A novel method called Respiratory noise Correction using Phase information is proposed to retrospectively correct for the respiratory noise in functional MRI (fMRI) time series. It is demonstrated that the respiratory movement and the phase of functional MRI images are highly correlated in time. The signal fluctuation due to respiratory movements can be effectively estimated from the phase variation and removed from the functional MRI time series using a Wiener filtering technique. In our experiments, this new method is compared with RETROICOR, which requires recording respiration signal simultaneously in an fMRI experiment. The two techniques show comparable performance with respect to the respiratory noise correction for fMRI time series. However, this technique is more advantageous because there is no need for monitoring the subjects’ respiration or changing functional MRI protocols. This technique is also potentially useful for correcting respiratory noise from abnormal breathing or when the respiration is not periodic.     

Functional MRI using intravascular contrast agents: detrending of the relative cerebrovascular (rCBV) time course

In pharmacological fMRI experiments in animal models, blood pool contrast agents may be used to map cerebral blood volume change as a surrogate for neural activation. When the background signal drift due to contrast agent washout is non-negligible over the duration of the signal changes of interest, time-course detrending is essential for accurate interpretation of the experiment. Detrending approaches based on estimation of the background signal from a baseline period of the time course prior to pharmacological (or functional) challenge were evaluated with the aim of identifying a robust method of estimating the contrast agent washout contribution to the background signal drift. For fMRI studies in the rat, it was found that a constrained fit of a mono-exponential washout model was more accurate than a constant background approximation and unconstrained fits for experiments investigating the functional response to rapid pharmacological challenges such as cocaine and amphetamine. Moreover, the constrained fitting approach allows shorter baseline periods than unconstrained extrapolation, reducing the required duration of the experiment.     

Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is widely used for measuring perfusion and blood volume, especially cerebral blood volume (CBV). In case of blood-brain barrier (BBB) disruption, the conventional techniques only partially determine the pharmacokinetic parameters of contrast medium (CM) exchange between different compartments. Here a modified pharmacokinetic model is applied, which is based on the bidirectional CM exchange between blood and two interstitial compartments in terms of the fractional volumes of the compartments and the vessel permeabilities between them. The evaluation technique using this model allows one to quantify the fractional volumes of the different compartments (blood, cells, slowly and fast enhancing interstitium) as well as the vessel permeabilities and cerebral blood flow (CBF) with a single T1-weighted dynamic MRI measurement. The method has been successfully applied in 25 glioma patients for generating maps of all of these parameters. The fractional volume maps allow for the differentiation of glioma vascularization types. The maps show a good correlation with the histological grading of these tumors. Furthermore, regions with enhanced interstitial volumes are found in high-grade gliomas. Differences in permeability maps of Gd-DTPA apart from BBB disruption do not exist between different tissue types. CBF measured in high-grade glioma is less pronounced than it would be expected from their blood volume. Therefore pharmacokinetic imaging provides an additional tool for glioma characterization.     

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.     

Use of dynamic contrast-enhanced MRI to measure subtle blood-brain barrier abnormalities

There is growing interest in investigating the role of subtle changes in blood-brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences.     

Changes in MRI signal intensity during hypercapnic challenge under conscious and anesthetized conditions

Most functional magnetic resonance imaging (fMRI) studies in animals are conducted under anesthesia to minimize motion artifacts. However, methods and techniques have been developed recently for imaging fully conscious rats. Functional MRI studies on conscious animals report enhanced BOLD signal changes as compared to the anesthetized condition. In this study, rats were exposed to different concentrations of carbon dioxide (CO(2)) while conscious and anesthetized to test whether cerebrovascular reactivity may be contributing to these enhanced BOLD signal changes. Hypercapnia produced significantly greater increases in MRI signal intensity in fully conscious animals (6.7-13.3% changes) as when anesthetized with 1% isoflurane (3.2-4.9% changes). In addition, the response to hypercapnia was more immediate in the conscious condition (< 30s) with signal risetimes twice as fast as in the anesthetized state (60s). Both cortical and subcortical brain regions showed a robust, dose- dependent increase in MRI signal intensity with hypercapnic challenge while the animals were conscious but little or no change when anesthetized. Baseline variations in MRI signal were higher while animals were conscious but this was off set by greater signal intensity changes leading to a greater contrast-to-noise ratio, 13.1 in conscious animals, as compared to 8.0 in the anesthetized condition. In summary, cerebral vasculature appears to be more sensitive to hypercapnic challenge in the conscious condition resulting in enhanced T2* MRI signal intensity and the potential for better BOLD signal changes during functional imaging.     

增强低场下脑功能磁共振成像显著性的研究

实现了基于低场0.35 T磁共振成像系统的大脑功能磁共振成像（functional Magnetic Resonance Imaging,fMRI）的研究. 基于质子密度加权的快速自旋回波(Turbo Spin Echo,TSE)图像,重点研究增强低场fMRI显著性的方法,目的在于提高低场fMRI的可用性. 结果表明：健康受试者在执行手动任务期间,大脑运动区的信号强度变化可以由基于血管外质子信号增强 (Signal Enhancement by Extravascular water Protons,EEP)的对比机制探测. 优化TSE序列参数能提高图像SNR和扫描速度,并在统计分析中增加外在屏蔽图像,可以有效地提高低场下fMRI研究结果的显著性.     

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high resolution fast low angle shot (FLASH) technique (matrix size 128²). The FLASH technique was applied additionally with a 64² matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64² matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and postior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 128² compared to FLASH 64² and EPI 64², whereas the activated areas proved to be smaller in FLASH 128² functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 128². Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.     

脑功能核磁共振成像在精神疾病中的应用

主要介绍了几种脑功能核磁共振成像方法以及在精神疾病中的研究情况.血氧水平依赖fMRI (BOLD-fMRI)是目前应用最广泛的fMRI技术,可利用神经激活后对局部血流的影响,间接显示神经活动.灌注加权成像是直接测定脑血流的fMRI技术,但由于它的时间分辨率比较低,对快速的脑功能难以进行研究.扩散加权象目前主要用于脑缺血的早期诊断,利用该技术也可示踪神经通路.化学位移成像能够检测局部组织代谢产物的含量,可反映不同脑区能量和物质代谢的状况,也是一种脑功能的研究手段.尽管这些技术在神经、心理学领域已经取得非常可喜的进展,目前fMRI在精神疾病方面的工作较少,相信随着技术的改进,fMRI必将在精神疾病方面大显身手.     

Comparison of α-chloralose,medetomidine and isoflurane anesthesia for functional connectivity mapping in the rat

Functional connectivity measures based upon low-frequency blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) signal fluctuations have become a widely used tool for investigating spontaneous brain activity in humans. Still unknown, however, is the precise relationship between neural activity, the hemodynamic response and fluctuations in the MRI signal. Recent work from several groups had shown that correlated low-frequency fluctuations in the BOLD signal can be detected in the anesthetized rat — a first step toward elucidating this relationship. Building on this preliminary work, through this study, we demonstrate that functional connectivity observed in the rat depends strongly on the type of anesthesia used. Power spectra of spontaneous fluctuations and the cross-correlation-based connectivity maps from rats anesthetized with α-chloralose, medetomidine or isoflurane are presented using a high-temporal-resolution imaging sequence that ensures minimal contamination from physiological noise. The results show less localized correlation in rats anesthetized with isoflurane as compared with rats anesthetized with α-chloralose or medetomidine. These experiments highlight the utility of using different types of anesthesia to explore the fundamental physiological relationships of the BOLD signal and suggest that the mechanisms contributing to functional connectivity involve a complicated relationship between changes in neural activity, neurovascular coupling and vascular reactivity.     

Developments in active noise control sound systems for magnetic resonance imaging

Magnetic resonance imaging (MRI) scanners can produce noise measuring over 130 dB SPL. This noise stimulates the auditory nervous system, limiting the dynamic range for stimulus driven activity in functional MRI (fMRI) experiments and can influence other brain functions. Even for structural scans it causes subject anxiety and discomfort in addition to the impediment to communications. Here we describe the realization and validation of a sound system for sound presentation inside an MRI scanner and the modifications to a standard active noise control technique for use in the noisy and compact environment of the scanner. This paper provides a review of the technology available for the presentation of audio stimuli in an MRI environment and the modifications required for the active control of scanner noise. Some of the content has been previously published [Chambers J, Akeroyd MA, Summerfield AQ, Palmer AR. Active control of the volume acquisition noise in functional magnetic resonance imaging: method and psychoacoustical evaluation. J Acoust Soc Am 2001;110(6):3041-54; Levitt H. Transformed up-down methods in psychoacoustics. J Acoust Soc Am 1971;49:467-77], but this paper goes further in describing the stages of development as the system performance was optimised. The performance of the system and both the objective and subjective reduction of the scanner noise are reported. Finally, we discuss recent improvements to the system that are currently being evaluated and describe the theory of opto-acoustical transducers that operate on the principle of light modulation. These are immune from, and do not create, electro-magnetic interference (EMI) and radio-frequency interference (RFI).     

一种具有自触发功能的高精度梯度波形发生器

提出一种具有自触发功能的高精度梯度波形发生器,其主要特点在于其采用了高精度（24 位）DAC,并具有自触发功能,使梯度波形发生器能独立于脉冲序列发生器工作,从而解决了高精度DAC群延时的问题.     

Characterization of cryoinjury-induced infarction with manganese-and gadolinium-enhanced MRI and optical spectroscopy in pig hearts

Purpose

To investigate progression of cryoinjury in pigs using contrast-enhanced magnetic resonance imaging (MRI) as well as optical spectroscopy and imaging.

Methods

Cryoinjury was produced in 16 pigs in vivo and investigated using Gd-and Mn-enhanced MRI, optical imaging/spectroscopy and histology in acute and chronic setting up to 4 weeks after the injury.

Results

(1) Acute cryoinjury resulted in formation of a lesion with a severely reduced rate of sub-epicardial indocyanine green (intravascular optical flow tracer) passage. In vivo late Gd-enhanced MRI showed a ∼10 mm deep hypointense area that was surrounded by a hyperintense rim while ex vivo Mn-enhanced MRI (MEMRI) detected a homogenous hypointense zone. Histological and spectroscopic examination revealed embolic erythrocytes blockages within the cryolesion with a thin necrotic rim neighboring the normal myocardium. (2) Chronic 4-week cryoinjury was characterized by uniform Gd-enhancement, whereas MEMRI revealed reduced Mn²⁺enhancement. Histological examination showed replacement of the cryoinjured myocardium by scar tissue.

Conclusions

Acute cryoinjury resulted in formation of a no-reflow core embolized by erythrocytes and surrounded by a rim of necrotic tissue. Upon injury progression, the no-reflow zone shrunk and was completely replaced with scar tissue by 4 weeks after injury.     

Functional phantom for fMRI: a feasibility study

Functional magnetic resonance imaging (fMRI) reveals changes in blood oxygen level-dependent (BOLD) signal after considerable processing. This paper describes the implementation and testing of an fMRI phantom where electric current applied to a thin wire within a proton-rich medium substituted BOLD distortion of the magnetic field; the scanner detects these two distortions as practically identical signal changes. The magnitude of the change depended on the current strength. The phantom has a number of possible applications. Signal changes across sessions, days, instruments and individuals could be monitored. Placing the phantom close to a subject during an fMRI experiment could allow differentiating sensitivity changes in the scanner due to instrumentation from changes in the subject's state and performance during the experiment. The spatial extent of brain activations and effects of various changes in the chain of image formation could be analyzed using current-induced "activations". Furthermore, the phantom could expedite fMRI sequence development by reducing the need to scan human subjects, who introduce uncertainty to the signal. Thus, this fMRI phantom could be useful for both cognitive fMRI studies and scanner calibration.