Dimo Ivanov

Isotropic Submillimeter fMRI in the Human Brain at 7 T: Combining Reduced Field-of-View Imaging and Partially Parallel Acquisitions

Echo‐planar imaging is the most widely used imaging sequence for functional magnetic resonance imaging (fMRI) due to its fast acquisition. However, it is prone to local distortions, image blurring, and signal voids. As these effects scale with echo train length and field strength, it is essential for high‐resolution echo‐planar imaging at ultrahigh field to address these problems. Partially parallel acquisition methods can be used to improve the image quality of echo‐planar imaging. However, partially parallel acquisition can be affected by aliasing artifacts and noise enhancement. Another way to shorten the echo train length is to reduce the field‐of‐view (FOV) while maintaining the same spatial resolution. However, to achieve significant acceleration, the resulting FOV becomes very small. Another problem occurs when FOV selection is incomplete such that there is remaining signal aliased from the region outside the reduced FOV. In this article, a novel approach, a combination of reduced FOV imaging with partially parallel acquisition, is presented. This approach can address the problems described above of each individual method, enabling high‐quality single‐shot echo‐planar imaging acquisition, with submillimeter isotropic resolution and good signal‐to‐noise ratio, for fMRI at ultrahigh field strength. This is demonstrated in fMRI of human brain at 7T with an isotropic resolution of 650 μm. Magn Reson Med, 2012.

Cortical lamina-dependent blood volume changes in human brain at 7 T

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

Physiologically informed dynamic causal modeling of fMRI data

The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses - such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal process and offer new ways of inferring changes in local neuronal activity and effective connectivity from fMRI.

Slab-selective, BOLD-corrected VASO at 7 tesla provides measures of cerebral blood volume reactivity with high signal-to-noise ratio.

MRI methods sensitive to functional changes in cerebral blood volume (CBV) may map neural activity with better spatial specificity than standard functional MRI (fMRI) methods based on blood oxygen level dependent (BOLD) effect. The purpose of this study was to develop and investigate a vascular space occupancy (VASO) method with high sensitivity to CBV changes for use in human brain at 7 Tesla (T).

A Simple Low-SAR Technique for Chemical-Shift Selection with High-Field Spin-Echo Imaging

We have discovered a simple and highly robust method for removal of chemical shift artifact in spin‐echo MR images, which simultaneously decreases the radiofrequency power deposition (specific absorption rate). The method is demonstrated in spin‐echo echo‐planar imaging brain images acquired at 7 T, with complete suppression of scalp fat signal. When excitation and refocusing pulses are sufficiently different in duration, and thus also different in the amplitude of their slice‐select gradients, a spatial mismatch is produced between the fat slices excited and refocused, with no overlap. Because no additional radiofrequency pulse is used to suppress fat, the specific absorption rate is significantly reduced compared with conventional approaches. This enables greater volume coverage per unit time, well suited for functional and diffusion studies using spin‐echo echo‐planar imaging. Moreover, the method can be generally applied to any sequence involving slice‐selective excitation and at least one slice‐selective refocusing pulse at high magnetic field strengths. The method is more efficient than gradient reversal methods and more robust against inhomogeneities of the static (polarizing) field (B0). Magn Reson Med, 2010.

Whole-brain mapping of venous vessel size in humans using the hypercapnia-induced BOLD effect.

Measuring the morphology of the cerebral microvasculature by vessel-size imaging (VSI) is a promising approach for clinical applications, such as the characterization of tumor angiogenesis and stroke. Despite the great potential of VSI, this method has not yet found widespread use in practice due to the lack of experience in testing it on healthy humans. Since this limitation derives mainly from the need for an invasive injection of a contrast agent, this work explores the possibility to employ instead the easily accessible blood oxygenation level dependent (BOLD) effect for VSI of the venous microstructure. It is demonstrated that BOLD-VSI in humans can be realized by a hypercapnic challenge using a fast gradient-echo (GE) and spin-echo (SE) sequence at 7T. Reproducible maps of the mean venous vessel radius, based on the BOLD-induced changes in GE and SE relaxation rates, could be obtained within a scan time of 10min. Moreover, the method yields maps of venous blood volume and vessel density. Owing to its non-invasive character, BOLD-VSI provides a low-risk method to analyze the venous microstructure, which will not only be useful in clinical applications, but also provide a better understanding of BOLD effect.

The effect of spatial resolution on decoding accuracy in fMRI multivariate pattern analysis.

Multivariate pattern analysis (MVPA) in fMRI has been used to extract information from distributed cortical activation patterns, which may go undetected in conventional univariate analysis. However, little is known about the physical and physiological underpinnings of MVPA in fMRI as well as about the effect of spatial smoothing on its performance. Several studies have addressed these issues, but their investigation was limited to the visual cortex at 3T with conflicting results. Here, we used ultra-high field (7T) fMRI to investigate the effect of spatial resolution and smoothing on decoding of speech content (vowels) and speaker identity from auditory cortical responses. To that end, we acquired high-resolution (1.1mm isotropic) fMRI data and additionally reconstructed them at 2.2 and 3.3mm in-plane spatial resolutions from the original k-space data. Furthermore, the data at each resolution were spatially smoothed with different 3D Gaussian kernel sizes (i.e. no smoothing or 1.1, 2.2, 3.3, 4.4, or 8.8mm kernels). For all spatial resolutions and smoothing kernels, we demonstrate the feasibility of decoding speech content (vowel) and speaker identity at 7T using support vector machine (SVM) MVPA. In addition, we found that high spatial frequencies are informative for vowel decoding and that the relative contribution of high and low spatial frequencies is different across the two decoding tasks. Moderate smoothing (up to 2.2mm) improved the accuracies for both decoding of vowels and speakers, possibly due to reduction of noise (e.g. residual motion artifacts or instrument noise) while still preserving information at high spatial frequency. In summary, our results show that - even with the same stimuli and within the same brain areas - the optimal spatial resolution for MVPA in fMRI depends on the specific decoding task of interest.

Ultra-high field magnetic resonance imaging of the basal ganglia and related structures

Deep brain stimulation is a treatment for Parkinsons disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2* and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinsons disease and related disorders.

High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1

Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases.

Techniques for blood volume fMRI with VASO: From low-resolution mapping towards sub-millimeter layer-dependent applications.

&NA; Quantitative cerebral blood volume (CBV) fMRI has the potential to overcome several specific limitations of BOLD fMRI. It provides direct physiological interpretability and promises superior localization specificity in applications of sub‐millimeter resolution fMRI applications at ultra‐high magnetic fields (7 T and higher). Non‐invasive CBV fMRI using VASO (vascular space occupancy), however, is inherently limited with respect to its data acquisition efficiency, restricting its imaging coverage and achievable spatial and temporal resolution. This limitation may be reduced with recent advanced acceleration and reconstruction strategies that allow two‐dimensional acceleration, such as in simultaneous multi‐slice (SMS) 2D‐EPI or 3D‐EPI in combination with CAIPIRINHA field‐of‐view shifting. In this study, we sought to determine the functional sensitivity and specificity of these readout strategies with VASO over a broad range of spatial resolutions; spanning from low spatial resolution (3 mm) whole‐cortex to sub‐millimeter (0.75 mm) slab‐of‐cortex (for cortical layer‐dependent applications). In the thermal‐noise‐dominated regime of sub‐millimeter resolutions, 3D‐EPI‐VASO provides higher temporal stability and sensitivity to detect changes in CBV compared to 2D‐EPI‐VASO. In this regime, 3D‐EPI‐VASO unveils task activation located in the cortical laminae with little contamination from surface veins, in contrast to the cortical surface weighting of GE‐BOLD fMRI. In the physiological‐noise‐dominated regime of lower resolutions, however, 2D‐SMS‐VASO shows superior performance compared to 3D‐EPI‐VASO. Due to its superior sensitivity at a layer‐dependent level, 3D‐EPI VASO promises to play an important role in future neuroscientific applications of layer‐dependent fMRI. HighlightsLimitations of sub‐millimeter fMRI are discussed.CBV‐sensitive fMRI is combined with 2D and 3D‐sEPI imaging.At ultra‐high resolutions, novel contrast and acquisition schemes are needed.At high‐res: 1.) CBV fMRI outperforms GE‐BOLD 2.) 3D‐EPI outperforms 2D‐EPI.CBV fMRI based on 3D‐EPI allow layer‐dependent fMRI applications.