Improved shimming for fMRI specifically optimizing the local BOLD sensitivity

Vascular component analysis of hyperoxic and hypercapnic BOLD contrast

Application of k-space energy spectrum analysis to susceptibility field mapping and distortion correction in gradient-echo EPI

Revealing Brain Activity and White Matter Structure Using Functional and Diffusion-Weighted Magnetic Resonance Imaging

Functional MRI (fMRI) is a non-invasive technique widely used to map brain-functions. Nevertheless, its hemodynamic basis and spatial precision with which fMRI reflects sites of neuronal activity are not completely understood. We therefore combined fMRI, based on the blood oxygenation level dependent (BOLD) effect, with optical recording of intrinsic signals (ORIS), a technique, which has a better spatial and temporal resolution. Furthermore, ORIS can distinguish between localized changes in deoxyhemoglobin, and more widespread changes in cerebral blood volume/flow. In gerbils hemodynamic responses over the contralateral barrel cortex were studied with both methods, using identical stimulation of a single vibrissae and identical integration and correlation analysis strategies. Analysis of integration maps and of the spatial distribution and temporal correlation with the block-design of vibrissal stimulation revealed that the BOLD signal, at the site of neuronal activation, does not reflect a depletion of deoxyhemoglobin, as generally assumed. Instead, its positive polarity is likely due to an increase in cerebral blood volume (CBV) whose highly dynamic effect on the BOLD signal exceeds that of the increase in deoxyhemoglobin remaining elevated during prolonged stimulation. This is so, because we show, that blood flow does wash out deoxyhemoglobin but at a rate which is to decrease the deoxyhemoglobin concentration in the voxel below resting level. The wash out causes an accumulation of deoxyhemoglobin in the draining venous side, but at a time window which can be clearly distinguished from the specific activity by applying an analysis strategy based on correlation functions. Therefore, draining veins do not appear as confounding problem. This knowledge could be useful to model the BOLD effect more accurately and improve the spatial resolution of fMRI.

PurposeTo quantitatively assess the effects of high degree and order (1st–4th+) relative to 1st–2nd degree B0 shimming at 7 Tesla (T) on gradient‐echo echo planar imaging (GE‐EPI) and blood‐oxygen‐level dependent (BOLD) activation.MethodsSimulations and GE‐EPI were performed at (2mm)3 and (3mm)3 resolution, evaluating the temporal signal‐to‐noise ratio (tSNR), transverse relaxivity (R2*), BOLD % signal change and activated pixel counts in a breath‐hold task.ResultsComparing the 1st–4th+ degree with 1st–2nd degree shimmed B0 maps generated spatially varying regions of Δ|B0|=|B01−2|−|B01−4+|. As binned in 10‐Hz intervals, the two center Δ|B0| (±10 Hz) bins maintained the B0 offset of 48.6% of gray‐matter pixels. In the positive Δ|B0| bins greater than 10 Hz, the 1st–4th+degree shimming improved the B0 offset in 41.1%; in negative Δ|B0| bins less than −10 Hz, the offset worsened in 10.2% of the pixels. In the positive Δ|B0| bins, we found variable but significant increases in BOLD sensitivity; the negative Δ|B0| bins showed significant decreases. In the breath‐hold studies, positive bins showed significantly increased activated pixel numbers (+5–29%), whereas negative bins showed −18 to 0% decline.Conclusion1st–4th+ degree shimming maintained B0 homogeneity over central brain regions while improving most of the other regions, including the inferior frontal lobe. Magn Reson Med 78:1734–1745, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

A novel sequence has been introduced that combines multiband imaging with a multi-echo acquisition for simultaneous high spatial resolution pseudo-continuous arterial spin labeling (ASL) and blood-oxygenation-level dependent (BOLD) echo-planar imaging (MBME ASL/BOLD). Resting-state connectivity in healthy adult subjects was assessed using this sequence. Four echoes were acquired with a multiband acceleration of four, in order to increase spatial resolution, shorten repetition time, and reduce slice-timing effects on the ASL signal. In addition, by acquiring four echoes, advanced multi-echo independent component analysis (ME-ICA) denoising could be employed to increase the signal-to-noise ratio (SNR) and BOLD sensitivity. Seed-based and dual-regression approaches were utilized to analyze functional connectivity. Cerebral blood flow (CBF) and BOLD coupling was also evaluated by correlating the perfusion-weighted timeseries with the BOLD timeseries. These metrics were compared between single echo (E2), multi-echo combined (MEC), multi-echo combined and denoised (MECDN), and perfusion-weighted (PW) timeseries. Temporal SNR increased for the MECDN data compared to the MEC and E2 data. Connectivity also increased, in terms of correlation strength and network size, for the MECDN compared to the MEC and E2 datasets. CBF and BOLD coupling was increased in major resting-state networks, and that correlation was strongest for the MECDN datasets. These results indicate our novel MBME ASL/BOLD sequence, which collects simultaneous high-resolution ASL/BOLD data, could be a powerful tool for detecting functional connectivity and dynamic neurovascular coupling during the resting state. The collection of more than two echoes facilitates the use of ME-ICA denoising to greatly improve the quality of resting state functional connectivity MRI.

Functional MRI (fMRI) generally employs gradient-echo echo-planar imaging (GE-EPI) to measure blood oxygen level-dependent (BOLD) signal changes that result from changes in tissue relaxation time T(*) (2) between activation and rest. Since T(*) (2) strongly varies across the brain and BOLD contrast is maximal only where the echo time (TE) equals the local T(*) (2), imaging at a single TE is a compromise in terms of overall sensitivity. Furthermore, the long echo train makes EPI very sensitive to main field inhomogeneities, causing strong image distortion. A method is presented that uses accelerated parallel imaging to reduce image artifacts and acquire images at multiple TEs following a single excitation, with no need to increase TR. Sensitivity gains from the broadened T(*) (2) coverage are optimized by pixelwise weighted echo summation based on local T(*) (2) or contrast-to-noise ratio (CNR) measurements. The method was evaluated using an approach that allows differential BOLD CNR to be calculated without stimulation, as well as with a Stroop experiment. Results obtained at 3 T showed that BOLD sensitivity improved by 11% or more in all brain regions, with larger gains in areas typically affected by strong susceptibility artifacts. The use of parallel imaging markedly reduces image distortion, and hence the method should find widespread application in functional brain imaging.

PurposeSensitivity and specificity of blood oxygenation level–dependent (BOLD) functional MRI (fMRI) is sensitive to magnetic field strength and acquisition methods. We have investigated gradient‐echo (GE)‐ and spin‐echo (SE)‐BOLD fMRI at ultrahigh fields of 9.4 and 15.2 Tesla.MethodsBOLD fMRI experiments responding to forepaw stimulation were performed with 3 echo times (TE) at each echo type and B 0 in α‐chloralose–anesthetized rats. The contralateral forelimb somatosensory region was selected for quantitative analyses.ResultsAt 9.4 T and 15.2 T, average baseline T 2 * (n = 9) was 26.6 and 17.1 msec, whereas baseline T 2 value (n = 9) was 35.7 and 24.5 msec, respectively. Averaged stimulation‐induced ΔR 2 * was –1.72 s–1 at 9.4 T and –3.09 s–1 at 15.2 T, whereas ΔR 2 was –1.19 s–1 at 9.4 T and –1.97 s–1 at 15.2 T. At the optimal TE of tissue T 2 * or T 2, BOLD percent changes were slightly higher at 15.2 T than at 9.4 T (GE: 7.4% versus 6.4% and SE: 5.7% versus 5.4%). The ΔR 2 * and ΔR 2 ratio of 15.2 T to 9.4 T was 1.8 and 1.66, respectively. The ratio of the macrovessel‐containing superficial to microvessel‐dominant parenchymal BOLD signal was 1.73 to 1.76 for GE‐BOLD versus 1.13 to 1.19 for SE‐BOLD, indicating that the SE‐BOLD contrast is less sensitive to macrovessels than GE‐BOLD.ConclusionSE‐BOLD fMRI improves spatial specificity to microvessels compared to GE‐BOLD at both fields. BOLD sensitivity is similar at the both fields and can be improved at ultrahigh fields only for thermal‐noise–dominant ultrahigh‐resolution fMRI.

Functional magnetic resonance imaging (fMRI) is a unique window to the brain, enabling scientists to follow changes in brain activity in response to hormones, ageing, environment, drugs of abuse and other stimuli. There are two features that make fMRI unique when compared with other imaging modalities used in behavioural neuroscience. First, it can be entirely noninvasive: each animal can serve as its own control over the natural course of its life, vital for following neuroadaptation and other developmental processes critical to understanding behaviour. Second, fMRI has the spatial and temporal resolution to observe patterns of neuronal activity across the entire brain in less than a minute. Although fMRI does not have the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, synchronised changes in neuronal activity across multiple brain areas seen with functional MRI can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviours. Thus, fMRI affords a systems approach to the study of the brain, complementing and building from other neurobiological techniques to understand how behaviour is organised across multiple brain regions. In this review, we present a general background to fMRI and the different imaging modalities that can be used in fMRI studies. Included are examples of the application of fMRI in behavioural neuroscience research, along with discussion of the advantages and disadvantages of this technology.

The purpose of this chapter is to introduce the novice NMR imager to blood oxygen level dependent (BOLD) contrast as well as remind the seasoned veteran of its beauty. Introduction to many of the factors that influence the BOLD signal is given higher priority than pursuing any subset in exquisite detail. Instead, references are given for readers seeking intense investigations into a given aspect. The hope is that this overview inspires the reader with the elegant simplicity of BOLD contrast while not, at first, intimidating too much with the underlying complexity. As one's knowledge of NMR matures so too will one's understanding, appreciation, and application of BOLD MRI. BOLD contrast derives from variations in the magnetic susceptibility of blood due to variations in the concentration of deoxyhemoglobin. These magnetic susceptibility effects produce local magnetic fields around blood vessels that can result in phase dispersion of nearby spins and, therefore, changes in signal intensity in NMR images. After providing brief historical context for BOLD, this chapter will follow the trail of magnetic susceptibility through definition, its source and location in vivo, and how the source and location in vivo interact with anatomical (e.g., blood vessel size) and imaging considerations (e.g., pulse sequence) to influence the BOLD signal. We will conclude by briefly highlighting clinical and preclinical applications using BOLD contrast.

Echo-planar imaging (EPI) is very sensitive to patient-induced field inhomogeneity caused by susceptibility changes between different anatomical regions. This results in geometric and intensity distortions in the image, especially near tissue/air and tissue/bone interfaces. A new approach is presented to reduce geometric and intensity distortions in EPI. A phase-encoded multireference scan is used to estimate the amplitude and phase errors in the measured signals due to the field inhomogeneity. The EPI data is corrected using both the amplitude and phase of the measured errors. This technique has been evaluated using EPI pulse sequences implemented with conventional gradients and implemented with imaging systems that have special resonating gradients and fast analog to digital converters. The results in both phantom and human studies show that in the absence of object motion the new correction technique can effectively reduce the geometric and intensity distortions.

Brain activation is known to lead to enhanced perfusion which, together with other physiological changes (e.g. blood volume, oxygen consumption), results in a decreased deoxyhaemoglobin concentration in regions of neuronal activity (Ogawa et al. 1990). This effect is referred to as the BOLD (blood oxygenation level dependent) effect and is by far the most commonly used method for fMRI studies and manifests itself as a slight increase in the strongly T2* (or T2) weighted MR images used for fMRI studies. BOLD signal changes occur both in the tissue (extra-vascular BOLD effect) and within the vasculature (intra-vascular BOLD effect). Non-BOLD related intra-vascular signal changes can also occur within larger vessels due to in-flow effects.

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flow-sensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an interleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes can be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 +/- 11 SD ml/100 g tissue/min and 43 +/- 16 SD % (n = 12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previous results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.

Echo planar images (EPI) suffer from geometric distortions caused by static-field inhomogeneity. Correction techniques have been suggested based on field maps obtained before or after the EPI acquisition. However, when a relatively long time series of images is required, as in fMRI studies, the inhomogeneity varies from image to image because of gross motion and physiological activity such as respiration and cardiac motion. It is not ideal to approximate the varying maps of field inhomogeneity by means of one map. To overcome this limitation, multiple field maps are desirable for correcting the distortions that are dynamically changing. Some groups have explored the possibility of acquiring multiple field maps, but either the increased scan time is not affordable for most fMRI studies or the field map acquisition is embedded in EPI pulse sequence, which produces a map of insufficient resolution to support a complete distortion correction. In this paper, we propose a dynamic field mapping technique that uses a single reference image and a single corresponding acquired field map and the phase information extracted from the complex image data of each EPI image in the time series. From this information, a separate field map is then derived individually for each EPI image. The derived field maps are then used for distortion correction. This approach, which is particularly suitable for fMRI studies, can correct for image distortion that varies dynamically without sacrificing temporal resolution. We validate this technique using simulated data, and the experimental results show improved performance in comparison to correction using a single field map.

Mapping the static magnetic field via the phase evolution over gradient echo scans acquired at two or more echo times is an established method. A number of possibilities exist, however, for combining phase data from multi-channel coils, denoising and thresholding field maps for high field applications. Three methods for combining phase images when no body/volume coil is available are tested: (i) Hermitian product, (ii) phase-matching over channels, and (iii) a new approach based on calculating separate field maps for each channel. The separate channel method is shown to yield field maps with higher signal-to-noise ratio than the Hermitian product and phase-matching methods and fewer unwrapping errors at low signal-to-noise ratio. Separate channel combination also allows unreliable voxels to be identified via the standard deviation over channels, which is found to be the most effective means of denoising field maps. Tests were performed using multichannel coils with between 8 and 32 channels at 3 T, 4 T, and 7 T. For application in the correction of distortions in echo-planar images, a formulation is proposed for reducing the local gradient of field maps to eliminate signal pile-up or swapping artifacts. Field maps calculated using these techniques, implemented in a freely available MATLAB toolbox, provide the basis for an effective correction for echo-planar imaging distortions at high fields.