Whole brain high-resolution functional imaging at ultra high magnetic fields: an application to the analysis of resting state networks

Whole-brain functional magnetic resonance imaging (fMRI) allows measuring brain dynamics at all brain regions simultaneously and is widely used in research and clinical neuroscience to observe both stimulus-related and spontaneous neural activity. Ultrahigh magnetic fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution and specificity compared to clinical fields (1.5T and 3T). High-resolution 7T fMRI, however, has been mostly limited to partial brain coverage with previous whole-brain applications sacrificing either the spatial or temporal resolution. Here we present whole-brain high-resolution (1, 1.5 and 2mm isotropic voxels) resting state fMRI at 7T, obtained with parallel imaging technology, without sacrificing temporal resolution or brain coverage, over what is typically achieved at 3T with several fold larger voxel volumes. Using Independent Component Analysis we demonstrate that high resolution images acquired at 7T retain enough sensitivity for the reliable extraction of typical resting state brain networks and illustrate the added value of obtaining both single subject and group maps, using cortex based alignment, of the default-mode network (DMN) with high native resolution. By comparing results between multiple resolutions we show that smaller voxels volumes (1 and 1.5mm isotropic) data result in reduced partial volume effects, permitting separations of detailed spatial features within the DMN patterns as well as a better function to anatomy correspondence.     

Modulation of CNS pain circuitry by intravenous and sublingual doses of buprenorphine

Buprenorphine (BUP) is a partial agonist at μ-, δ- and ORL1 (opioid receptor-like)/nociceptin receptors and antagonist at the κ-opioid receptor site. BUP is known to have both analgesic as well as antihyperalgesic effects via its central activity, and is used in the treatment of moderate to severe chronic pain conditions. Recently, it was shown that intravenous (IV) administration of 0.2 mg/70 kg BUP modulates the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to acute noxious stimuli in healthy human subjects. The present study extends these observations by investigating the effects of BUP dose and route of administration on central nervous system (CNS) pain circuitry. Specifically, the modulation of evoked pain BOLD responses and resting state functional connectivity was measured following IV (0.1 and 0.2 mg/70 kg) and sublingual (SL) (2 mg) BUP administration in healthy human subjects. While 0.1 mg/70 kg IV BUP is sub-analgesic, both 0.2 mg/70 kg IV BUP and 2.0 mg SL BUP are analgesic doses of the drug. Evoked BOLD responses were clearly modulated in a dose-dependent manner. The analgesic doses of BUP by both routes of administration yielded a potentiation in limbic/mesolimbic circuitry and attenuation in sensorimotor/sensory-discriminative circuitry. In addition, robust decreases in functional connectivity between the putamen and the sensorimotor/sensory-discriminative structures were observed at the two analgesic doses subsequent to measuring the maximum plasma BUP concentrations (C_max). The decreases in functional connectivity within the sensorimotor/sensory-discriminative circuitry were also observed to be dose-dependent in the IV administration cohorts. These reproducible and consistent functional CNS measures at clinically effective doses of BUP demonstrate the potential of evoked pain fMRI and resting-state functional connectivity as objective tools that can inform the process of dose selection. Such methods may be useful during early clinical phase evaluation of potential analgesics in drug development.     

Ultrasound Phase Contrast Thermal Imaging with Reflex Transmission Imaging Methods in Tissue Phantoms

Thermal imaging measurements using ultrasound phase contrast have been performed in tissue phantoms heated with a focused ultrasound source. Back projection and reflex transmission imaging principles were used to detect sound speed–induced changes in the phase caused by an increase in the temperature. The temperature was determined from an empirical relationship for the temperature dependence on sound speed. The phase contrast was determined from changes in the sound field measured with a hydrophone scan conducted before and during applied heating. The lengthy scanning routine used to mimic a large two-dimensional array required a steady-state temperature distribution within the phantom. The temperature distribution in the phantom was validated with magnetic resonance (MR) thermal imaging measurements. The peak temperature was found to agree within 1°C with MR, and good agreement was found between the temperature profiles. The spatial resolution was 0.3 × 0.3 × 0.3 mm, comparing favorably with the 0.625 × 0.625 × 1.5-mm MR spatial resolution. (E-mail: cfarny@bwh.harvard.edu)     

Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV-V of the rat whisker-barrel cortex

The spatiotemporal characteristics of the hemodynamic response to increased neural activity were investigated at the level of individual intracortical vessels using BOLD-fMRI in a well-established rodent model of somatosensory stimulation at 11.7 T. Functional maps of the rat barrel cortex were obtained at 150 × 150 × 500 μm spatial resolution every 200 ms. The high spatial resolution allowed separation of active voxels into those containing intracortical macro vessels, mainly vein/venules (referred to as macrovasculature), and those enriched with arteries/capillaries and small venules (referred to as microvasculature) since the macro vessel can be readily mapped due to the fast T2* decay of blood at 11.7 T. The earliest BOLD response was observed within layers IV-V by 0.8 s following stimulation and encompassed mainly the voxels containing the microvasculature and some confined macrovasculature voxels. By 1.2 s, the BOLD signal propagated to the macrovasculature voxels where the peak BOLD signal was 2-3 times higher than that of the microvasculature voxels. The BOLD response propagated in individual venules/veins far from neuronal sources at later times. This was also observed in layers IV-V of the barrel cortex after specific stimulation of separated whisker rows. These results directly visualized that the earliest hemodynamic changes to increased neural activity occur mainly in the microvasculature and spread toward the macrovasculature. However, at peak response, the BOLD signal is dominated by penetrating venules even at layers IV-V of the cortex.     

Gray matter nulled and vascular space occupancy dependent fMRI response to visual stimulation during hypoxic hypoxia

Two cerebral blood volume (CBV)-weighted fMRI techniques, gray matter nulled (GMN) and vascular space occupancy (VASO)-dependent techniques at spatial resolution of 2 × 2 × 5 mm³, were compared in the study investigating functional responses in the human visual cortex to stimulation in normoxia (inspired O₂ = 21%) and mild hypoxic hypoxia (inspired O₂ = 12%). GMN and VASO signals and T₂* were quantified in activated voxels. While the CBV-weighted signal changes in voxels activated by visual stimulation were similar in amplitude in both fMRI techniques in both oxygenation conditions, the number of activated voxels during hypoxic hypoxia was significantly reduced by 72 ± 22% in GMN fMRI and 66 ± 23% in VASO fMRI. T₂* prolonged in GMN and VASO activated voxels in normoxia by 1.6 ± 0.5 ms and 1.7 ± 0.5 ms, respectively. In hypoxia, however, T₂* shortened in GMN-activated voxels by 0.7 ± 0.6 ms (p < 0.001 relative to normoxia), but prolonged in VASO-activated ones by 1.1 ± 0.6 ms (p < 0.05 relative to normoxia). The data show that the hemodynamic responses to visual stimulation were not affected by hypoxic hypoxia, but T₂* increases by both CBV-weighted fMRI techniques were smaller in activated voxels in hypoxia. The mechanisms influencing GMN fMRI signal in both oxygenation conditions were explored by simulating effects of the oxygen extraction fraction (OEF) and partial voluming with cerebral spinal fluid (CSF) and white matter in imaging voxels. It is concluded that while GMN fMRI data point to increased, rather than decreased OEF during visual stimulation in hypoxia, partial voluming by CSF is likely to affect the CBV quantification by GMN fMRI under the experimental conditions used.     

Role of nucleus accumbens in neuropathic pain: Linked multi-scale evidence in the rat transitioning to neuropathic pain

Despite recent evidence implicating the nucleus accumbens (NAc) as causally involved in the transition to chronic pain in humans, underlying mechanisms of this involvement remain entirely unknown. Here we elucidate mechanisms of NAc reorganizational properties (longitudinally and cross-sectionally), in an animal model of neuropathic pain (spared nerve injury [SNI]). We observed interrelated changes: (1) In resting-state functional magnetic resonance imaging (fMRI), functional connectivity of the NAc to dorsal striatum and cortex was reduced 28 days (but not 5 days) after SNI; (2) Contralateral to SNI injury, gene expression of NAc dopamine 1A, 2, and κ-opioid receptors decreased 28 days after SNI; (3) In SNI (but not sham), covariance of gene expression was upregulated at 5 days and settled to a new state at 28 days; and (4) NAc functional connectivity correlated with dopamine receptor gene expression and with tactile allodynia. Moreover, interruption of NAc activity (via lidocaine infusion) reversibly alleviated neuropathic pain in SNI animals. Together, these results demonstrate macroscopic (fMRI) and molecular reorganization of NAc and indicate that NAc neuronal activity is necessary for full expression of neuropathic pain-like behavior.     

TE-dependent spatial and spectral specificity of functional connectivity

Previous studies suggest that spontaneous fluctuations in the resting-state fMRI (RS-fMRI) signal may reflect fluctuations in transverse relaxation time (T₂^?) rather than spin density (S₀). However, such S₀ and T₂^? features have not been well characterized. In this study, spatial and spectral characteristics of functional connectivity on sensorimotor, default-mode, dorsal attention, and primary visual systems were examined using a multiple gradient-echo sequence at 3 T. In the spatial domain, we found broad, local correlations at short echo times (TE ≤ 14 ms) due to dominant S₀ contribution, whereas long-range connections mediated by T₂^? became explicit at TEs longer than 22 ms. In the frequency domain, compared with the flat spectrum of S₀, spectral power of the T₂^?-weighted signal elevated significantly with increasing TE, particularly in the frequency ranges of 0.008-0.023 Hz and 0.037-0.043 Hz. Using the S₀ spectrum as a reference, we propose two indices to measure spectral signal change (SSC) and spectral contrast-to-noise ratio (SCNR), respectively, for quantifying the RS-fMRI signal. These indices demonstrated TE dependency of connectivity-related fluctuation strength, resembling functional contrasts in activation-based fMRI. These findings further confirm that large-scale functional circuit connectivity based on BOLD contrast may be constrained within specific frequency ranges in every brain network, and the spectral features of S₀ and T₂^? could be valuable for interpreting and quantifying RS-fMRI data.     

Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance

Sleep deprivation (SD) can alter extrinsic, task-related fMRI signal involved in attention, memory and executive function. However, its effects on intrinsic low-frequency connectivity within the Default Mode Network (DMN) and its related anti-correlated network (ACN) have not been well characterized. We investigated the effect of SD on functional connectivity within the DMN, and on DMN-ACN anti-correlation, both during the resting state and during performance of a visual attention task (VAT). 26 healthy participants underwent fMRI twice: once after a normal night of sleep in rested wakefulness (RW) and once following approximately 24 h of total SD. A seed-based approach was used to examine pairwise correlations of low-frequency fMRI signal across different nodes in each state. SD was associated with significant selective reductions in DMN functional connectivity and DMN-ACN anti-correlation. This was congruent across resting state and VAT analyses, suggesting that SD induces a robust alteration in the intrinsic connectivity within and between these networks.     

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM.     

White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain. The underlying structural basis of this functional connectivity pattern is still widely unexplored. We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure underlying default mode connectivity. We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus with lateral temporal lobes, medial temporal lobes, and precuneus. This was demonstrated at the p < 0.001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach. In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data. Our findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based on distinct pattern of anatomical connectivity within the cerebral white matter.     

Spatial homogeneity and task-synchrony of the trial-related hemodynamic signal

There is growing evidence that functional brain images in alert task-engaged subjects contain task-related but stimulus-independent signals in addition to stimulus-evoked responses. It is important to separate these different components when analyzing the neuroimaging signal. Using intrinsic-signal optical imaging combined with electrophysiology we had earlier reported a particular ‘trial-related signal’ in the primary visual cortex (V1) of alert monkeys performing periodic fixation tasks. This signal periodically modulated V1 tissue blood volume, in time with anticipated trial onsets. Unlike visually evoked blood volume changes, however, this signal was present even in total darkness. Further, it could not be predicted by concurrently recorded spiking or local field potentials. Here we use our earlier recording techniques to analyze the spatial distribution of this trial-related signal over our imaged area (10 mm square, subdivided into a 16 × 16 grid, i.e. at 625 μm resolution). We show that the signal is spatially coherent and essentially homogeneous over the imaged region and fails to be predicted by concurrent electrode recordings even at the resolution of a single grid square at the electrode tip. As a corollary we show that the signal is critically linked to the animals' engagement in a task. Not only does the trial-related signal entrain accurately and precisely to any task timing at which the animal was willing to perform; the signal also loses the entrained trial-locked pattern dramatically, within a single trial, when the animal stops performing correctly. Thus the signal is very unlikely to be an ongoing task-independent vascular oscillation. These findings will help categorize the likely distinct varieties of non-stimulus-related signals evoked during behavioral tasks, and lead to a further understanding of the elements comprising the net neuroimaging response.     

Dynamic gray matter changes within cortex and striatum after short motor skill training are associated with their increased functional interaction

Gray matter (GM) changes have been described after short learning tasks that lasted for 7 days or after external stimulation that lasted for 5 days. However, the early time course of training-dependent GM changes is still unknown. We investigated whether shorter motor training sessions (four times of 30 min training) would induce GM changes. Therefore, T1-weighted MRIs were acquired daily. Because reported GM changes were induced by learning, a close relationship was assumed between the functional activity and the GM changes. Therefore, fMRI was performed in addition to daily T1-weighted MRIs.At the end of the four training sessions (at time point “post”), the test results of the trained motor skill were associated with an increase of GM in secondary cortical motor areas (dPMC_right, dPMC_left, SMA_left and the right inferior parietal lobule, IPL_right). The earliest time point at which a GM change was detected was 1 day before in the right ventral striatum (by contrasting daily T1-weighted MRI vs. baseline). To analyze whether this very early GM change within the right ventral striatum is associated with those GM changes at time point post (which were associated with motor skill performance), their functional connectivity was investigated over the time period of motor skill training. This analysis revealed an increase of functional coupling between these regions (striatum and cortex) over the training days.The current data demonstrate training-induced short GM plasticity is paralleled by their temporally dynamical process of functional interaction between the cortex and the striatum in response to a motor skill training.     

Changes occur in resting state network of motor system during 4 weeks of motor skill learning

We tested whether the resting state functional connectivity of the motor system changed during 4 weeks of motor skill learning using functional magnetic resonance imaging (fMRI). Ten healthy volunteers learned to produce a sequential finger movement by daily practice of the task over a 4 week period. Changes in the resting state motor network were examined before training (Week 0), two weeks after the onset of training (Week 2), and immediately at the end of the training (Week 4). The resting state motor system was analyzed using group independent component analysis (ICA). Statistical Parametric Mapping (SPM) second-level analysis was conducted on independent z-maps generated by the group ICA. Three regions, namely right postcentral gyrus, and bilateral supramarginal gyri were found to be sensitive to the training duration. Specifically, the strength of resting state functional connectivity in the right postcentral gyrus and right supramarginal gyrus increased from Week 0 to Week 2, during which the behavioral performance improved significantly, and decreased from Week 2 to Week 4, during which there was no more significant improvement in behavioral performance. The strength of resting state functional connectivity in left supramarginal gyrus increased throughout the training. These results confirm changes in the resting state network during slow-learning stage of motor skill learning, and support the premise that the resting state networks play a role in improving performance.     

Dynamical stability of intrinsic connectivity networks

Functional connectivity MRI (fcMRI) has become a widely used technique in recent years for measuring the static correlation of activity between cortical regions. Using a publicly available resting state dataset (n = 961 subjects), we obtained high spatial-resolution maps of functional connectivity between a lattice of 7266 regions covering the gray matter. Average whole brain functional correlations were calculated, with high reproducibility within the dataset and across sites. Since correlation measures not only represent pairwise connectivity information, but also shared inputs from other brain regions, we approximate pairwise connection strength by representing each region as a linear combination of the others by performing a Cholesky decomposition of the pairwise correlation matrix. We then used this weighted connection strength between regions to iterate relative brain activity in discrete temporal steps, beginning both with random initial conditions, and with initial conditions reflecting intrinsic connectivity networks using each region as a seed. In whole brain simulations based on weighted connectivity from healthy adult subjects (mean age 27.3), there was consistent convergence to one of two inverted states, one representing high activity in the default mode network, the other representing low relative activity in the default mode network. Metastable intermediate states in our simulation corresponded to combinations of characterized functional networks. Convergence to a final state was slowest for initial conditions on the borders of the default mode network.     

Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions

Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive–affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI–rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing.     

Migraine and the Hippocampus

Purpose of Review

The hippocampus is involved in pain processing, pain-related attention and anxiety, and stress response. The present review compiles the present knowledge of hippocampal volume, activity, and connectivity regarding migraine.

Recent Findings

For hippocampal volume, a longitudinal study discovered decreased volume in newly diagnosed migraine patients after 1 year. Two cross-sectional studies suggested an adaptive increase of volume at low headache frequency and a maladaptive decrease of volume at higher headache frequency. Patients who carried a COMT Val homozygous were found to have larger hippocampi on both sides compared with healthy controls with the same polymorphism. For hippocampal activation, one study showed greater nociceptive activation in patients with migraine compared to healthy controls, with the activity correlated to headache frequency. Another study showed greater deactivation and higher functional connectivity linked to other pain-processing regions in low frequency compared to high-frequency migraineurs. At resting state, intraregional functional connectivity of hippocampus was demonstrated to be lower, and connectivity of the hippocampus with other brain regions was different in patients carrying specific genetic variants. For structural connectivity, two studies suggest a stronger connectivity between the hippocampus and other corticolimbic regions, and the altered connectivities are responsible for migraine-associated allodynia or placebo effect of migraine.

Summary

Factors including headache frequency, accumulative number of migraine attacks, anxiety score, depression score, and genetic variants are related to hippocampal morphology and functional changes in people with migraine. Future studies should select participants precisely and appropriately control for genetic variants to investigate the complex relationship between the hippocampus and migraine.

     

Identification of cortical lamination in awake monkeys by high resolution magnetic resonance imaging

Brodmann divided the neocortex into 47 different cortical areas based on histological differences in laminar myeloarchitectonic and cytoarchitectonic defined structure. The ability to do so in vivo with anatomical magnetic resonance (MR) methods in awake subjects would be extremely advantageous for many functional studies. However, due to the limitations of spatial resolution and contrast, this has been difficult to achieve in awake subjects. Here, we report that by using a combination of MR microscopy and novel contrast effects, cortical layers can be delineated in the visual cortex of awake subjects (nonhuman primates) at 4.7 T. We obtained data from 30-min acquisitions at voxel size of 62.5 × 62.5 × 1000 μm³ (4 nl). Both the phase and magnitude components of the T₂*-weighted image were used to generate laminar profiles which are believed to reflect variations in myelin and local cell density content across cortical depth. Based on this, we were able to identify six layers characteristic of the striate cortex (V1). These were the stripe of Kaes-Bechterew (in layer II/III), the stripe of Gennari (in layer IV), the inner band of Baillarger (in layer V), as well as three sub-layers within layer IV (IVa, IVb, and IVc). Furthermore, we found that the laminar structure of two extrastriate visual cortex (V2, V4) can also be detected. Following the tradition of Brodmann, this significant improvement in cortical laminar visualization should make it possible to discriminate cortical regions in awake subjects corresponding to differences in myeloarchitecture and cytoarchitecture.     

Fast and tissue-optimized mapping of magnetic susceptibility and T2* with multi-echo and multi-shot spirals

Gradient-echo MRI of resonance-frequency shift and T2* values exhibit unique tissue contrast and offer relevant physiological information. However, acquiring 3D-phase images and T2* maps with the standard spoiled gradient echo (SPGR) sequence is lengthy for routine imaging at high-spatial resolution and whole-brain coverage. In addition, with the standard SPGR sequence, optimal signal-to-noise ratio (SNR) cannot be achieved for every tissue type given their distributed resonance frequency and T2* value. To address these two issues, a SNR optimized multi-echo sequence with a stack-of-spiral acquisition is proposed and implemented for achieving fast and simultaneous acquisition of image phase and T2* maps. The analytical behavior of the phase SNR is derived as a function of resonance frequency, T2* and echo time. This relationship is utilized to achieve tissue optimized SNR by combining phase images with different echo times. Simulations and in vivo experiments were designed to verify the theoretical predictions. Using the multi-echo spiral acquisition, whole-brain coverage with 1 mm isotropic resolution can be achieved within 2.5 min, shortening the scan time by a factor of 8. The resulting multi-echo phase map shows similar SNR to that of the standard SPGR. The acquisition can be further accelerated with non-Cartesian parallel imaging. The technique can be readily extended to other multi-shot readout trajectories besides spiral. It may provide a practical acquisition strategy for high resolution and simultaneous 3D mapping of magnetic susceptibility and T2*.     

Investigation of spatial resolution, partial volume effects and smoothing in functional MRI using artificial 3D time series

This work addresses the balance between temporal signal-to-noise ratio (tSNR) and partial volume effects (PVE) in functional magnetic resonance imaging (fMRI) and investigates the impact of the choice of spatial resolution and smoothing. In fMRI, since physiological time courses are monitored, tSNR is of greater importance than image SNR. Improving SNR by an increase in voxel volume may be of negligible benefit when physiological fluctuations dominate the noise. Furthermore, at large voxel volumes, PVE are more pronounced, leading to an overall loss in performance. Artificial fMRI time series, based on high-resolution anatomical data, were used to simulate BOLD activation in a controlled manner. The performance was subsequently quantified as a measure of how well the resulted activation matched the simulated activation. The performance was highly dependent on the spatial resolution. At high contrast-to-noise ratio (CNR), the optimal voxel volume was small, i.e. in the region of 2(3) mm(3). It was also shown that using a substantially larger voxel volume in this case could potentially negate the CNR benefits. The optimal smoothing kernel width was dependent on the CNR, being larger at poor CNR. At CNR >1, little or no smoothing proved advantageous. The use of artificial time series gave an opportunity to quantitatively investigate the effects of partial volume and smoothing in single subject fMRI. It was shown that a proper choice of spatial resolution and smoothing kernel width is important for fMRI performance.     

基于fMRI功能连接度分析正常人相关脑区在运动过程中的参与程度

目的 在运动及静息两种状态下,观察初级运动区(M1)与其他运动相关区域之间功能连接程度,分析特定功能区在运动执行过程中的作用.方法 选取6名正常人作为研究对象,进行血氧水平依赖功能磁共振成像(BOLD-fMRI)检查.功能成像分为静息功能、右手运动功能、左手运动功能三部分.运动功能采用Block设计,采取手指顺序对指任务.扫描结果 采用统计参数图 (SPM2)进行数据分析和脑功能区定位.功能连接度采用时间相关算法,选取运动任务时对应的最强激活点(均为一侧M1区)作为种子点,分别在静息功能数据和运动功能数据中将该种子区与相应全脑做相关分析,计算不同脑区与种子区之间的相关性,以Z值反映其功能连接程度,并观察同一脑区在运动及静息两种状态下与种子点之间Z值的变化.结果 在静息状态下,与种子点相关联的区域为双侧躯体感觉运动区(SMC)、辅助运动区(SMA)及同侧顶上小叶(SPL);在运动状态下,与种子点相关联的区域为双侧SMC、SMA、同侧SPL及小脑前叶(ALC);在运动状态下双侧SMC及SMA之间功能联系的Z值较静息状态下普遍增大.结论 静息状态下双侧SMC、SMA及同侧SPL之间存在比较稳定的功能联系;运动状态下双侧SMC及SMA之间功能联系增强.运动肢体同侧ALC参与运动任务的执行,但不参与静息状态下运动区之间的功能连接.