脑功能磁共振成像在人类嗅觉研究中的应用

在人类的5种主要感觉中,嗅觉是最广泛、古老、直接和内在的感觉.这些特性使人们对人类嗅觉的研究异常艰难,以致于直到今天人们对嗅觉的功能仍不清楚,而对大脑的功能机制所知更少.与其他基于物理原理的方法一样,磁共振成像技术的广泛应用极大地推动了整个生命科学的发展.脑功能磁共振成像的优势（高分辨率、高对比度、无损性和无放射性等）为人们研究嗅觉高级中枢以及与嗅觉相关行为的脑机制等提供了强有力的技术手段.文章在简单介绍嗅觉知识的基础上,着重讨论了近十年来,脑功能磁共振成像技术在人类嗅觉研究中所取得的成果.     

脑功能磁共振成像在人类嗅觉研究中的应用

在人类的5种主要感觉中,嗅觉是最广泛、古老、直接和内在的感觉.这些特性使人们对人类嗅觉的研究异常艰难,以致于直到今天人们对嗅觉的功能仍不清楚,而对大脑的功能机制所知更少.与其他基于物理原理的方法一样,磁共振成像技术的广泛应用极大地推动了整个生命科学的发展.脑功能磁共振成像的优势(高分辨率、高对比度、无损性和无放射性等)为人们研究嗅觉高级中枢以及与嗅觉相关行为的脑机制等提供了强有力的技术手段.文章在简单介绍嗅觉知识的基础上,着重讨论了近十年来,脑功能磁共振成像技术在人类嗅觉研究中所取得的成果.     

The role of nonlinearity in computing graph-theoretical properties of resting-state functional magnetic resonance imaging brain networks

In recent years, there has been an increasing interest in the study of large-scale brain activity interaction structure from the perspective of complex networks, based on functional magnetic resonance imaging (fMRI) measurements. To assess the strength of interaction (functional connectivity, FC) between two brain regions, the linear (Pearson) correlation coefficient of the respective time series is most commonly used. Since a potential use of nonlinear FC measures has recently been discussed in this and other fields, the question arises whether particular nonlinear FC measures would be more informative for the graph analysis than linear ones. We present a comparison of network analysis results obtained from the brain connectivity graphs capturing either full (both linear and nonlinear) or only linear connectivity using 24 sessions of human resting-state fMRI. For each session, a matrix of full connectivity between 90 anatomical parcel time series is computed using mutual information. For comparison, connectivity matrices obtained for multivariate linear Gaussian surrogate data that preserve the correlations, but remove any nonlinearity are generated. Binarizing these matrices using multiple thresholds, we generate graphs corresponding to linear and full nonlinear interaction structures. The effect of neglecting nonlinearity is then assessed by comparing the values of a range of graph-theoretical measures evaluated for both types of graphs. Statistical comparisons suggest a potential effect of nonlinearity on the local measures-clustering coefficient and betweenness centrality. Nevertheless, subsequent quantitative comparison shows that the nonlinearity effect is practically negligible when compared to the intersubject variability of the graph measures. Further, on the group-average graph level, the nonlinearity effect is unnoticeable.     

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.

Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.     

Real-time animal functional magnetic resonance imaging and its application to neuropharmacological studies

In pharmacological magnetic resonance imaging (phMRI) with anesthetized animals, there is usually only a single time window to observe the dynamic signal change to an acute drug administration since subsequent drug injections are likely to result in altered response properties (e.g., tolerance). Unlike the block-design experiments in which fMRI signal can be elicited with multiple repetitions of a task, these single-event experiments require stable baseline in order to reliably identify drug-induced signal changes. Such factors as subject motion, scanner instability and/or alterations in physiological conditions of the anesthetized animal could confound the baseline signal. The unique feature of such functional MRI (fMRI) studies necessitates a technique that is able to monitor MRI signal in a real-time fashion and to interactively control certain experimental procedures. In the present study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. It is also shown that this technique can be applied to monitor baseline physiological conditions in conventional fMRI experiments using blood oxygenation level-dependent (BOLD) contrast, further demonstrating the versatility of this technique.     

Real-time functional magnetic resonance imaging: methods and applications

Functional magnetic resonance imaging (fMRI) has been limited by time-consuming data analysis and a low signal-to-noise ratio, impeding online analysis. Recent advances in acquisition techniques, computational power and algorithms increased the sensitivity and speed of fMRI significantly, making real-time analysis and display of fMRI data feasible. So far, most reports have focused on the technical aspects of real-time fMRI (rtfMRI). Here, we provide an overview of the different major areas of applications that became possible with rtfMRI: online analysis of single-subject data provides immediate quality assurance and functional localizers guiding the main fMRI experiment or surgical interventions. In teaching, rtfMRI naturally combines all essential parts of a neuroimaging experiment, such as experimental design, data acquisition and analysis, while adding a high level of interactivity. Thus, the learning of essential knowledge required to conduct functional imaging experiments is facilitated. rtfMRI allows for brain-computer interfaces (BCI) with a high spatial and temporal resolution and whole-brain coverage. Recent studies have shown that such BCI can be used to provide online feedback of the blood-oxygen-level-dependent signal and to learn the self-regulation of local brain activity. Preliminary evidence suggests that this local self-regulation can be used as a new paradigm in cognitive neuroscience to study brain plasticity and the functional relevance of brain areas, even being potentially applicable for psychophysiological treatment.     

Ictal imaging using functional magnetic resonance

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. This noninvasive technique can also map the coritical activation that occurs during focal seizures, as demonstrated here by the results obtained using a conventional 1.5 T clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. FLASH images (TE = 60 ms) were acquired every 10 s over a period of 25 min, and activation images derived by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. These results demonstrate (a) that functional MRI can potentially provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure; and (b) that there is the possibility of obtaining similar information in the absence of clinical seizures, suggesting the potential for studies in patients with interictal electrical disturbances.     

Acoustic noise during functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) enables sites of brain activation to be localized in human subjects. For studies of the auditory system, acoustic noise generated during fMRI can interfere with assessments of this activation by introducing uncontrolled extraneous sounds. As a first step toward reducing the noise during fMRI, this paper describes the temporal and spectral characteristics of the noise present under typical fMRI study conditions for two imagers with different static magnetic field strengths. Peak noise levels were 123 and 138 dB re 20 microPa in a 1.5-tesla (T) and a 3-T imager, respectively. The noise spectrum (calculated over a 10-ms window coinciding with the highest-amplitude noise) showed a prominent maximum at 1 kHz for the 1.5-T imager (115 dB SPL) and at 1.4 kHz for the 3-T imager (131 dB SPL). The frequency content and timing of the most intense noise components indicated that the noise was primarily attributable to the readout gradients in the imaging pulse sequence. The noise persisted above background levels for 300-500 ms after gradient activity ceased, indicating that resonating structures in the imager or noise reverberating in the imager room were also factors. The gradient noise waveform was highly repeatable. In addition, the coolant pump for the imager's permanent magnet and the room air-handling system were sources of ongoing noise lower in both level and frequency than gradient coil noise. Knowledge of the sources and characteristics of the noise enabled the examination of general approaches to noise control that could be applied to reduce the unwanted noise during fMRI sessions.     

Generalized relative entropy in functional magnetic resonance imaging

The generalized Kullback-Leibler distance D_q (q is the Tsallis parameter) is shown to be an useful measure for analysis of functional magnetic resonance imaging (fMRI) data series. This generalized form of entropy is used to evaluate the “distance” between the probability functions p₁ and p₂ of the signal levels related to periods of stimulus and non-stimulus in event-related fMRI experiments. The probability densities of the mean distance (averaged over the N epochs of the entire experiment) are obtained through numerical simulations for different values of signal-to-noise ratio (SNR) and found to be fitted very well by Gamma distributions (χ²<0.0008) for small values of N (N<30). These distributions allow us to determine the sensitivity and specificity of the method by construction of the receiver operating characteristic (ROC) curves. The performance of the method is also investigated in terms of the parameters q and L (number of signal levels) and our results indicate that the optimum choice is q=0.8 and L=3. The entropic index q is found to exert control on both sensitivity and specificity of the method. As q (q>0) is raised, sensitivity increases but specificity decreases. Finally, the method is applied in the analysis of a real event-related fMRI motor stimulus experiment and the resulting maps show activation in primary and secondary motor brain areas.     

Task-specific deactivation patterns in functional magnetic resonance imaging

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function.     

Development of sound measurement systems for auditory functional magnetic resonance imaging

Auditory functional magnetic resonance imaging (fMRI) requires quantification of sound stimuli in the magnetic environment and adequate isolation of background noise. We report the development of two novel sound measurement systems that accurately measure the sound intensity inside the ear, which can simultaneously provide the similar or greater amount of scanner- noise protection than ear-muffs. First, we placed a 2.6 x 2.6-mm microphone in an insert phone that was connected to a headphone [microphone-integrated, foam-tipped insert-phone with a headphone (MIHP)]. This attenuated scanner noise by 37.8+/-4.6 dB, a level better than the reference amount obtained using earmuffs. The nonmetallic optical microphone was integrated with a headphone [optical microphone in a headphone (OMHP)] and it effectively detected the change of sound intensity caused by variable compression on the cushions of the headphone. Wearing the OMHP reduced the noise by 28.5+/-5.9 dB and did not affect echoplanar magnetic resonance images. We also performed an auditory fMRI study using the MIHP system and presented increase in the auditory cortical activation following 10-dB increment in the intensity of sound stimulation. These two newly developed sound measurement systems successfully achieved the accurate quantification of sound stimuli with maintaining the similar level of noise protection of wearing earmuffs in the auditory fMRI experiment.     

Neonatal auditory activation detected by functional magnetic resonance imaging

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.     

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.     

Alkali lasers for magnetic resonance imaging

Spin-polarized nuclei of such gases as ³He and ¹²⁹Xe are successfully used for magnetic resonance imaging of lungs and other organs of human body. To produce large numbers of spin-polarized nuclei required for this medical application, a high power narrowband tunable laser source is required. Diode pumped alkali lasers, developed during last several years can be an ideal source for this application. In this paper we present our latest achievements in diode pumped alkali lasers development. We describe optically pumped Cs laser tunable in the range of 14 GHz and operating in single transverse mode with a linewidth less than 3 MHz. We also present continuous wave diode pumped Rb and Cs lasers with output power 17 W and 20 W.     

Integration of structural and functional magnetic resonance imaging improves mild cognitive impairment detection

The identification of mild cognitive impairments (MCI) via either structural magnetic resonance imaging (sMRI) or functional MRI (fMRI) has great potential due to the non-invasiveness of the techniques. Furthermore, these techniques allow longitudinal follow-ups of single subjects via repeated measurements. sMRI- or fMRI-based biomarkers have been adopted separately to diagnose MCI; however, there has not been a systematic effort to integrate sMRI- and fMRI-based features to increase MCI detection accuracy. This study investigated whether the detection of MCI can be improved via the integration of biomarkers identified from both sMRI and fMRI modalities. Regional volume sizes and neuronal activity levels of brains from MCI subjects were compared with those from healthy controls and used to identify biomarkers from sMRI and fMRI data, respectively. In the subsequent classification phase, MCI was automatically detected using a support vector machine algorithm that employed the identified sMRI- and fMRI-based biomarkers as an input feature vector. The results indicate that the fMRI-based biomarkers provided more information for detecting MCI than the sMRI-based biomarkers. Moreover, the integrated feature sets using the sMRI- and fMRI-based biomarkers consistently showed greater detection accuracy than the feature sets based only on the fMRI-based biomarkers. The results demonstrate that integration of sMRI and fMRI modalities can provide supplemental information to improve the diagnosis of MCI relative to either the sMRI or fMRI modalities alone.