Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (P<10(-7)) and area (P<10(-8)) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties.     

Increased BOLD sensitivity in the orbitofrontal cortex using slice-dependent echo times at 3 T

Functional magnetic resonance imaging (fMRI) exploits the blood oxygenation level dependent (BOLD) effect to detect neuronal activation related to various experimental paradigms. Some of these, such as reversal learning, involve the orbitofrontal cortex and its interaction with other brain regions like the amygdala, striatum or dorsolateral prefrontal cortex. These paradigms are commonly investigated with event-related methods and gradient echo-planar imaging (EPI) with short echo time of 27 ms. However, susceptibility-induced signal losses and image distortions in the orbitofrontal cortex are still a problem for this optimized sequence as this brain region consists of several slices with different optimal echo times. An EPI sequence with slice-dependent echo times is suitable to maximize BOLD sensitivity in all slices and might thus improve signal detection in the orbitofrontal cortex. To test this hypothesis, we first optimized echo times via BOLD sensitivity simulation. Second, we measured 12 healthy volunteers using a standard EPI sequence with an echo time of 27 ms and a modified EPI sequence with echo times ranging from 22 ms to 47 ms. In the orbitofrontal cortex, the number of activated voxels increased from 87±44 to 549±83 and the maximal t-value increased from 4.4±0.3 to 5.4±0.3 when the modified EPI was used. We conclude that an EPI with slice-dependent echo times may be a valuable tool to mitigate susceptibility artifacts in event-related whole-brain fMRI studies with a focus on the orbitofrontal cortex.     

Steady-state activation in somatosensory cortex after changes in stimulus rate during median nerve stimulation

Passive electrical stimulation activates various human somatosensory cortical systems including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII) and bilateral insula. The effect of stimulation frequency on blood oxygenation level-dependent (BOLD) activity remains unclear. We acquired 3-T functional magnetic resonance imaging (fMRI) in eight healthy volunteers during electrical median nerve stimulation at frequencies of 1, 3 and 10 Hz. During stimulation BOLD signal changes showed activation in the contralateral SI, bilateral SII and bilateral insula. Results of fMRI analysis showed that these areas were progressively active with the increase of rate of stimulation. As a major finding, the contralateral SI showed an increase of peak of BOLD activation from 1 to 3 Hz but reached a plateau during 10-Hz stimulation. Our finding is of interest for basic research and for clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.     

Analysis of the distribution of diffusion coefficients in cat brain at 9.4 T using the inverse Laplace transformation

In this work, the usefulness of the inverse Laplace transformation (ILT) in the characterization of diffusion processes in the brain has been investigated. The method has been implemented on both phantom and in vivo cat brain data acquired at high resolution at 9.4 T. The results were compared with monoexponential and biexponential analyses of the same data. It is shown that in the case of diffusion restricted by white matter axonal tracts, the resulting diffusograms are in good agreement with the biexponential model. In gray matter, however, the non-monoexponential decay does not lead to a bimodal distribution in the ILT, even though the data can be fitted to a biexponential. This finding suggests the possibility of a distribution of diffusion coefficients rather than a discrete biexponential behavior. It is shown that this distribution is sensitive, for example, to experimental parameters such as the diffusion time. Thus, the ILT offers the possibility of implementing a unique tool for the analysis of heterogeneous diffusion, that is, the analysis of the diffusion coefficient distribution, which has the yet unexplored potential of being a valuable parameter in the characterization of tissue structure.     

In vivo mapping of functional domains and axonal connectivity in cat visual cortex using magnetic resonance imaging

Noninvasive cognitive neuroimaging studies based on functional magnetic resonance imaging (fMRI) are of ever-increasing importance for basic and clinical neurosciences. The explanatory power of fMRI could be greatly expanded, however, if the pattern of the neuronal circuitry underlying functional activation could be made visible in an equally noninvasive manner. In this study, blood oxygenation level-dependent (BOLD)-based fMRI and diffusion tensor imaging (DTI) were performed in the same cat visual cortex, and the foci of fMRI activation utilized as seeding points for 3D DTI fiber reconstruction algorithms, thus providing the map of the axonal circuitry underlying visual information processing. The methods developed in this study will lay the foundation for in vivo neuroanatomy and the ability for noninvasive longitudinal studies of brain development.     

Optimizing the mapping of finger areas in primary somatosensory cortex using functional MRI

Functional magnetic resonance imaging mapping of the finger somatotopy in the primary somatosensory cortex requires a reproducible and precise stimulation. The highly detailed functional architecture in this region of the brain also requires careful consideration in choice of spatial resolution and postprocessing parameters. The purpose of this study is therefore to investigate the impact of spatial resolution and level of smoothing during tactile stimulation using a precise stimuli system. Twenty-one volunteers were scanned using 2³ mm³ and 3³ mm³ voxel volume and subsequently evaluated using three different smoothing kernel widths. The overall activation reproducibility was also evaluated. Using a high spatial resolution proved advantageous for all fingers. At 2³ mm³ voxel volume, activation of the thumb, middle finger and little finger areas was seen in 89%, 67% and 50% of the volunteers, compared to 78%, 61% and 33% at 3³ mm³, respectively. The sensitivity was comparable for nonsmoothed and slightly smoothed (4 mm kernel width) data; however, increasing the smoothing kernel width from 4 to 8 mm resulted in a critical decrease (50%) in sensitivity. In repeated measurements of the same subject at six different days, the localization reproducibility of all fingers was within 4 mm (1 S.D. of the mean). The precise computer-controlled stimulus, together with data acquisition at high spatial resolution and with only minor smoothing during evaluation, could be a very useful strategy in studies of brain plasticity and rehabilitation strategies in hand and finger disorders and injuries.     

Sources of functional magnetic resonance imaging signal fluctuations in the human brain at rest: a 7 T study

Signal fluctuations in functional magnetic resonance imaging (fMRI) can result from a number of sources that may have a neuronal, physiologic or instrumental origin. To determine the relative contribution of these sources, we recorded physiological (respiration and cardiac) signals simultaneously with fMRI in human volunteers at rest with their eyes closed. State-of-the-art technology was used including high magnetic field (7 T), a multichannel detector array and high-resolution (3 mm³) echo-planar imaging. We investigated the relative contribution of thermal noise and other sources of variance to the observed fMRI signal fluctuations both in the visual cortex and in the whole brain gray matter. The following sources of variance were evaluated separately: low-frequency drifts due to scanner instability, effects correlated with respiratory and cardiac cycles, effects due to variability in the respiratory flow rate and cardiac rate, and other sources, tentatively attributed to spontaneous neuronal activity. We found that low-frequency drifts are the most significant source of fMRI signal fluctuations (3.0% signal change in the visual cortex, TE=32 ms), followed by spontaneous neuronal activity (2.9%), thermal noise (2.1%), effects due to variability in physiological rates (respiration 0.9%, heartbeat 0.9%), and correlated with physiological cycles (0.6%). We suggest the selection and use of four lagged physiological noise regressors as an effective model to explain the variance related to fluctuations in the rates of respiration volume change and cardiac pulsation. Our results also indicate that, compared to the whole brain gray matter, the visual cortex has higher sensitivity to changes in both the rate of respiration and the spontaneous resting-state activity. Under the conditions of this study, spontaneous neuronal activity is one of the major contributors to the measured fMRI signal fluctuations, increasing almost twofold relative to earlier experiments under similar conditions at 3 T.     

Biphasic time course of brain water ADC observed during the first month of life in term neonates with severe perinatal asphyxia is indicative of poor outcome at 3 years

In severe perinatal asphyxia, the prognostic value of apparent diffusion coefficient (ADC) measurements is still open to question. We hypothesized that temporal and anatomical changes of brain ADC values occurring early after the hypoxic-ischemic insult could predict the outcome at 36 months. To demonstrate this, mean ADC values were calculated for 16 brain structures in 59 term neonates who underwent an MR examination during the first month of life. Neonates were divided into two groups according to their 36-month outcome: unfavorable (death/severe disability) or favorable outcome. ADC values were plotted against age at scan.In neonates with favorable outcomes (n=32), ADC values were constant over the study period. In babies with unfavorable outcomes (n=27), ADCs exhibited two different patterns. In infratentorial structures, ADCs were constant and normal. In supratentorial areas, ADCs followed a biphasic temporal evolution: ADC values were at their lowest at day 2, showed a rapid increase until Days 5-7, and were thereafter similar to those of neonates with favorable outcomes. Using receiver operating characteristic analysis, during the first 3-5 days of life, all neonates with decreased ADC had an unfavorable outcome.These temporal and anatomical changes of ADC values imply that individual prognosis of asphyxiated neonates can only be predicted by measurement of ADC in supratentorial areas within the first 3-5 days of life.     

Post-stimulus response in hemodynamics observed by functional magnetic resonance imaging--difference between the primary sensorimotor area and the supplementary motor area

The blood oxygen level dependency (BOLD) contrast is a useful tool for functional neuroimaging based on the hemodynamic response to neuronal activation. We observed different hemodynamic responses in the BOLD signal between the primary sensorimotor area (SM1) and the supplementary motor area (SMA) in the sequential finger movement task. In the SMA, a stronger initial overshoot and a post-stimulus overshoot were observed. It was hypothesized from the time course analysis that the stronger initial overshoot reflected the activation of the SMA for motor control programming in the initial phase. Although the post-stimulus overshoot may be partially explained by cerebral blood flow (CBF) cerebral blood volume (CBV) uncoupling, its mechanism remained unknown. In the SM1, only the initial overshoot was observed and the level of BOLD signal was almost constant after the initial overshoot during the task period. These observations suggested that the BOLD signal is characterized by both CBF-CBV uncoupling and the neuronal activation characteristics in each region.     

Intersubject variability in the analysis of diffusion tensor images at the group level: fractional anisotropy mapping and fiber tracking techniques

Introduction

Diffusion tensor imaging (DTI) provides comprehensive information about quantitative diffusion and connectivity in the human brain. Transformation into stereotactic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The objective of the present study was to optimize technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level.

Methods

Different averaging methods for mean diffusion-weighted images containing DTI information were compared, i.e., region of interest-based fractional anisotropy (FA) mapping, fiber tracking (FT) and corresponding tractwise FA statistics (TFAS). The novel technique of intersubject FT that takes into account directional information of single data sets during the FT process was compared to standard FT techniques. Application of the methods was shown in the comparison of normal subjects and subjects with defined white matter pathology (alterations of the corpus callosum).

Results

Fiber tracking was applied to averaged data sets and showed similar results compared with FT on single subject data. The application of TFAS to averaged data showed averaged FA values around 0.4 for normal controls. The values were in the range of the standard deviation for averaged FA values for TFAS applied to single subject data. These results were independent of the applied averaging technique. A significant reduction of the averaged FA values was found in comparison to TFAS applied to data from subjects with defined white matter pathology (FA around 0.2).

Conclusion

The applicability of FT techniques in the analysis of different subjects at the group level was demonstrated. Group comparisons as well as FT on group averaged data were shown to be feasible. The objective of this work was to identify the most appropriate method for intersubject averaging and group comparison which incorporates intersubject variability of the directional information.     

High resolution diffusion weighted magnetic resonance imaging of the pancreas using reduced field of view single-shot echo-planar imaging at 3 T

Diffusion weighted magnetic resonance imaging (DWI) has been mostly acquired using single-shot echo-planar imaging (ss EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in ss EPI especially for abdominal imaging, even with the advances in parallel imaging. A novel method of reduced Field of View ss EPI (rFOV ss EPI) has achieved high resolution DWI in human carotid artery, spinal cord with reduced blurring and higher spatial resolution than conventional ss EPI, but it has not been used to pancreas imaging. In the work, comparisons between the full FOV ss-DW EPI and rFOV ss-DW EPI in image qualities and ADC values of pancreatic tumors and normal pancreatic tissues were performed to demonstrate the feasibility of pancreatic high resolution rFOV DWI. There were no significant differences in the mean ADC values between full FOV DWI and rFOV DWI for the 17 subjects using b = 600 s/mm² (P = 0.962). However, subjective scores of image quality was significantly higher at rFOV ss DWI (P = 0.008 and 0.000 for b-value = 0 s/mm² and 600 s/mm² respectively). The spatial resolution of DWI for pancreas was increased by a factor of over 2.0 (from almost 3.0 mm/pixel to 1.25 mm/pixel) using rFOV ss EPI technique. Reduced FOV ss EPI can provide good DW images and is promising to benefit applications for pancreatic diseases.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.     

Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort.     

High-resolution in vivo diffusion tensor imaging of the injured cat spinal cord using self-navigated,interleaved, variable-density spiral acquisition (SNAILS-DTI)

Diffusion tensor magnetic resonance imaging (DTI) is useful for studying the microstructural changes in the spinal cord following traumatic injury; however, image quality is generally poor due to the small size of the spinal cord, physiological motion and susceptibility artifacts. Self-navigated, interleaved, variable-density spiral diffusion tensor imaging (SNAILS-DTI) is a distinctive pulse sequence that bypasses many of the challenges associated with DTI of the spinal cord, particularly if imaging gradient hardware is of conventional quality. In the current study, we have demonstrated the feasibility of implementing SNAILS-DTI on a clinical 3.0-T MR scanner and examined the effect of navigator filter parameters on image quality and reconstruction time. Results demonstrate high-quality, high-resolution (546 μm×546 μm) in vivo DTI images of the cat spinal cord after traumatic spinal cord injury.