Functional cerebral blood volume mapping with simultaneous multi-slice acquisition

Sub-millimeter resolution functional magnetic resonance imaging (fMRI) at ultra-high field (≥ 7T) has offered an unprecedented opportunity to probe mesoscopic computations at a columnar or laminar level. However, its application has been primarily restricted to the neocortex. Inferior brain regions, particularly the hippocampus (HC), are challenging targets for laminar fMRI. Recent developments in acquisition methods have shown the feasibility of laminar recordings in the HC using gradient-echo blood oxygenation level-dependent (BOLD) contrast. Nonetheless, the spatial specificity of the BOLD signal is compromised by the draining veins’ bias. Cerebral blood volume (CBV)-sensitive sequences including vascular space occupancy (VASO) have emerged as a promising approach to capture the laminar activity with mitigated venous bias. Yet, its feasibility in the HC is unclear and challenged by methodological constraints. Here, we optimized VASO to mitigate the macrovasculature contribution in HC. By evaluating a series of advanced acquisition strategies tailored to HC, we obtained improved VASO signal quality with minimal artifacts. The optimized protocol was further validated with an autobiographical memory task. Our findings show that combining the high detection power of gradient-echo BOLD with the vein-bias-mitigated VASO contrast allows for differentiation between neural activity-related BOLD signals and those biased by draining veins. These results demonstrate the feasibility of submillimeter VASO acquired with conventional 7T scanners in the HC to map the circuit-level mechanisms of memory retrieval across HC subfields, laying a foundation to investigate the microcircuitry of HC-driven complex cognitive functions and their alterations in neurodegeneration and epilepsy.

Simultaneous Multi-Slice (SMS) magnetic resonance imaging (MRI) is a rapidly evolving technique for increasing imaging speed. Controlled aliasing techniques utilize periodic undersampling patterns to help mitigate the loss in signal-to-noise ratio (SNR) in SMS MRI. To evaluate the performance of different undersampling patterns, a quantitative description of the image SNR loss is needed. Additionally, eddy current effects in echo planar imaging (EPI) lead to slice-specific Nyquist ghosting artifacts. These artifacts cannot be accurately corrected for each individual slice before or after slice-unaliasing. In this work, we propose a hybrid-space sensitivity encoding (SENSE) reconstruction framework for SMS MRI by adopting a three-dimensional representation of the SMS acquisition. Analytical SNR loss maps are derived for SMS acquisitions with arbitrary phase encoding undersampling patterns. Moreover, we propose a matrix-decoding correction method that corrects the slice-specific Nyquist ghosting artifacts in SMS EPI acquisitions. Brain images demonstrate that the proposed hybrid-space SENSE reconstruction generates images with comparable quality to commonly used split-slice-generalized autocalibrating partially parallel acquisition reconstruction. The analytical SNR loss maps agree with those calculated by a Monte Carlo based method, but require less computation time for high quality maps. The analytical maps enable a fair comparison between the performances of coherent and incoherent SMS undersampling patterns. Phantom and brain SMS EPI images show that the matrix-decoding method performs better than the single-slice and slice-averaged Nyquist ghosting correction methods under the hybrid-space SENSE reconstruction framework.

Improved cortical-layer specificity of vascular space occupancy fMRI with slab inversion relative to spin-echo BOLD at 9.4 T

Dynamics of respiratory and cardiac CSF motion revealed with real-time simultaneous multi-slice EPI velocity phase contrast imaging

Diffusion tensor imaging (DTI) of the brain provides essential information on the white matter integrity and structural connectivity. However, it suffers from a low signal-to-noise ratio (SNR) and requires a long scan time to achieve high spatial and/or diffusion resolution and wide brain coverage. With recent advances in parallel and simultaneous multislice (multiband) imaging, the SNR efficiency has been improved by reducing the repetition time (TR ). However, due to the limited number of RF coil channels available on preclinical MRI scanners, simultaneous multislice acquisition has not been practical. In this study, we demonstrate the ability of multiband DTI to acquire high-resolution data of the mouse brain with 84 slices covering the whole brain in 0.2 mm isotropic resolution without a coil array at 9.4 T. Hadamard-encoding four-band pulses were used to acquire four slices simultaneously, with the reduction in the TR maximizing the SNR efficiency. To overcome shot-to-shot phase variations, Hadamard decoding with a self-calibrated phase was developed. Compared with single-band DTI acquired with the same scan time, the multiband DTI leads to significantly increased SNR by 40% in the white matter. This SNR gain resulted in reduced variations in fractional anisotropy, mean diffusivity, and eigenvector orientation. Furthermore, the cerebrospinal fluid signal was attenuated, leading to reduced free-water contamination. Without the need for a high-density coil array or parallel imaging, this technique enables highly efficient preclinical DTI that will facilitate connectome studies.

Resting-state brain activity has been widely investigated using blood oxygenation level dependent (BOLD) contrast techniques. However, BOLD signal changes reflect a combination of the effects of cerebral blood flow (CBF), cerebral blood volume (CBV), as well as the cerebral metabolic rate of oxygen (CMRO2). In this study, resting-state brain activation was detected and compared using the following techniques: (a) BOLD, using a gradient-echo echo planar imaging (GE-EPI) sequence; (b) CBV-weighted signal, acquired using gradient and spin echo (GRASE) based vascular space occupancy (VASO); and (c) CBF, using pseudo-continuous arterial spin labeling (pCASL). Reliable brain networks were detected using VASO and ASL, including sensorimotor, auditory, primary visual, higher visual, default mode, salience and left/right executive control networks. Differences between the resting-state activation detected with ASL, VASO and BOLD could potentially be due to the different temporal signal-to-noise ratio (tSNR) and the short post-labeling delay (PLD) in ASL, along with differences in the spin-echo readout of VASO. It is also possible that the dynamics of spontaneous fluctuations in BOLD, CBV and CBF could differ due to biological reasons, according to their location within the brain.

The Effect of Slice Order and Thickness on fMRI Activation Data Using Multislice Echo-Planar Imaging

Simultaneous multi-slice (SMS) echo-planar imaging has had a huge impact on the acceleration and routine use of diffusion-weighted MRI (DWI) in neuroimaging studies in particular the human connectome project; but also holds the potential to facilitate DWI of moving subjects, as proposed by the new technique developed in this paper. We present a novel registration-based motion tracking technique that takes advantage of the multi-plane coverage of the anatomy by simultaneously acquired slices to enable robust reconstruction of neural microstructure from SMS DWI of moving subjects. Our technique constitutes three main components: 1) motion tracking and estimation using SMS registration, 2) detection and rejection of intra-slice motion, and 3) robust reconstruction. Quantitative results from 14 volunteer subject experiments and the analysis of motion-corrupted SMS DWI of 6 children indicate robust reconstruction in the presence of continuous motion and the potential to extend the use of SMS DWI in very challenging populations.

To achieve motion-robust diffusion compartment imaging (DCI) in near continuously moving subjects based on simultaneous multi-slice, diffusion-weighted brain MRI. Simultaneous multi-slice (SMS) acquisition enables fast and dense sampling of k- and q-space. We propose to achieve motion-robust DCI via slice-level motion correction by exploiting the rigid coupling between simultaneously acquired slices. This coupling provides 3D coverage of the anatomy that substantially constraints the slice-to-volume alignment problem. This is incorporated into an explicit model of motion dynamics that handles continuous and large subject motion in robust DCI reconstruction. We applied the proposed technique, called Motion Tracking based on Simultanous Multislice Registration (MT-SMR) to multi b-value SMS diffusion-weighted brain MRI of healthy volunteers and motion-corrupted scans of 20 pediatric subjects. Quantitative and qualitative evaluation based on fractional anisotropy in unidirectional fiber regions, and DCI in crossing-fiber regions show robust reconstruction in the presence of motion. The proposed approach has the potential to extend routine use of SMS DCI in very challenging populations, such as young children, newborns, and non-cooperative patients.

A new method for designing radiofrequency (RF) pulses with numerical optimization in the wavelet domain is presented. Numerical optimization may yield solutions that might otherwise have not been discovered with analytic techniques alone. Further, processing in the wavelet domain reduces the number of unknowns through compression properties inherent in wavelet transforms, providing a more tractable optimization problem. This algorithm is demonstrated with simultaneous multi-slice (SMS) spin echo refocusing pulses because reduced peak RF power is necessary for SMS diffusion imaging with high acceleration factors. An iterative, nonlinear, constrained numerical minimization algorithm was developed to generate an optimized RF pulse waveform. Wavelet domain coefficients were modulated while iteratively running a Bloch equation simulator to generate the intermediate slice profile of the net magnetization. The algorithm minimizes the L2-norm of the slice profile with additional terms to penalize rejection band ripple and maximize the net transverse magnetization across each slice. Simulations and human brain imaging were used to demonstrate a new RF pulse design that yields an optimized slice profile and reduced peak energy deposition when applied to a multiband single-shot echo planar diffusion acquisition. This method may be used to optimize factors such as magnitude and phase spectral profiles and peak RF pulse power for multiband simultaneous multi-slice (SMS) acquisitions. Wavelet-based RF pulse optimization provides a useful design method to achieve a pulse waveform with beneficial amplitude reduction while preserving appropriate magnetization response for magnetic resonance imaging.

BackgroundWhole-body magnetic resonance imaging (WB-MRI) is an increasingly used guideline-based imaging modality for oncological and non-oncological pathologies during childhood and adolescence. While diffusion-weighted imaging (DWI), a part of WB-MRI, enhances image interpretation and improves sensitivity, it also requires the longest acquisition time during a typical WB-MRI scan protocol. Interleaved short tau inversion recovery (STIR) DWI with simultaneous multi-slice (SMS) acquisition is an effective way to speed up examinations.ObjectiveIn this study of children and adolescents, we compared the acquisition time, image quality, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values of an interleaved STIR SMS-DWI sequence with a standard non-accelerated DWI sequence for WB-MRI.Materials and methodsTwenty children and adolescents (mean age: 13.9 years) who received two WB-MRI scans at a maximum interval of 18 months, consisting of either standard DWI or SMS-DWI MRI, respectively, were included. For quantitative evaluation, the signal-to-noise ratio (SNR) was determined for b800 images and ADC maps of seven anatomical regions. Image quality evaluation was independently performed by two experienced paediatric radiologists using a 5-point Likert scale. The measurement time per slice stack, pause between measurements including shim and total measurement time of DWI for standard DWI and SMS-DWI were extracted directly from the scan data.ResultsWhen including the shim duration, the acquisition time for SMS-DWI was 43% faster than for standard DWI. Qualitatively, the scores of SMS-DWI were higher in six locations in the b800 images and four locations in the ADC maps. There was substantial agreement between both readers, with a Cohen’s kappa of 0.75. Quantitatively, the SNR in the b800 images and the ADC maps did not differ significantly from one another.ConclusionWhole body-MRI with SMS-DWI provided equivalent image quality and reduced the acquisition time almost by half compared to the standard WB-DWI protocol.

Methodological advancements of functional Magnetic Resonance Imaging (fMRI) in recent years allow researchers to approach the mesoscopic spatial regime of cortical layers and cortical columns. In principle, this could revolutionize the ability to tackle cortical information processing within micro-circuits and across brain systems. One of the major limitations of conventional gradient-echo BOLD fMRI, however, is that it probes neuronal activity changes only indirectly via evoked cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2) changes. Since, the resulting gradient-echo BOLD signal is mostly sensitive to ascending veins in the tissue and to pial veins, the achievable spatial specificity to neuronal activation is limited. Furthermore, the non-linear interaction of CBF, CBV and CMRO2 at high resolutions can hamper quantitative interpretations of the BOLD signal across cortical layer and columns with different baseline physiology. Measuring CBF, CBV or CMRO2 directly on a laminar and columnar level can overcome these limitations. This presentation will introduce laminar non-BOLD fMRI methods, summarize resent advancements, and provide an overview of how to use these methods to improve the neuroscientific interpretability in application studies. First, I will review the physiology of the cortical blood supply in the sub-millimeter regime and the corresponding practical challenges in high-resolution fMRI. Then, I will review the most-widely used non-BOLD fMRI methods to measure high-resolution CBF, CBV and CMRO2 responses and discuss them with respect to their sequence parameter space, sensitivity, specificity and applicability. Specific focus will be on the methods of arterial spin labeling (ASL), vascular space occupancy (VASO) and calibrated fMRI. Finally, I will conclude that non-BOLD methods at submillimeter resolution have an inherently low signal-to-noise ratio (SNR) are thus still challenging. However, their spatial specificity is improved, they are quantifiable, and, hence, the obtained results are physiologically interpretable. Therefore, they can potentially be superior alternatives to conventional GE-BOLD never the less. This conclusion will be discussed in the light of recent neuroscientific application studies that pinpoint laminar and columnar microcircuits in visual cortex, sensorimotor cortex, and prefrontal cortex. References 1. Polimeni, J.R., Fischl, B., Greve, D.N., and Wald, L.L. (2010). Laminar analysis of 7T BOLD using an imposed spatial activation pattern in human V1. Neuroimage 52, 1334–1346. 2. Kay, K., Jamison, K., Vizioli, L., Zhang, R., Margalit, E., and Ugurbil, K. (2018). A critical assessment of data quality and venous effects in ultra-high-resolution fMRI. BioRxiv 1–45. 3. Kim, S.-G., and Ogawa, S. (2012). Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J. Cereb. Blood Flow Metab. 32, 1188–1206. 4. Goense, J.B.M., Whittingstall, K., and Logothetis, N.K. (2012). Neural and BOLD responses across the brain. Wiley Interdiscip. Rev. Cogn. Sci. 3, 75–86. 5. Huber, L., Uludaǧ, K., and Möller, H.E. (2017). Non-BOLD contrast for laminar fMRI in humans: CBF, CBV, and CMRO2. Neuroimage ahead of print. 6. Huber, Finn, Handwerker ... Bandettini (2018). Unique functional digit representation in human motor cortex across columns and layers. In 48th Society for Neuroscience, p. 675.03. 7. Finn, Huber, Jangraw, and Bandettini (2018). Layer-dependent activity in human prefrontal cortex during working memory. BioRxiv 425249. 8. Huber, Handwerker, Jangraw ... Bandettini (2017). High-resolution CBV-fMRI allows mapping of laminar activity and connectivity of cortical cortical input and output in human M1.

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO2 inhalation with continuous acquisition of blood oxygen level-dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O2 inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi-slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two-dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO2 and O2 inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p=0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p=0.3). On a voxel-wise level, approximately 20-30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.

Baseline GABA concentration and fMRI response

Improved laminar specificity and sensitivity by combining SE and GE BOLD signals