Improved sensitivity and microvascular weighting of 3T laminar fMRI with GE-BOLD using NORDIC and phase regression

Knudsen, Lasse; Bailey, Christopher J.; Blicher, Jakob Udby; Yang, Yan; Zhang, Peng; Lund, Torben Ellegaard

doi:10.1016/j.neuroimage.2023.120011

Cited by 15 publications

(17 citation statements)

References 76 publications

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“…To date, only a limited number of studies have reported on 3T layer-specific GE-BOLD fMRI (Koopmans, Barth, and Norris 2010;Scheeringa et al 2016;Irati Markuerkiaga et al 2021;Knudsen et al 2023). Among these, the study by Knudsen et al (2023) addressed the draining-vein contamination issue by employing phase regression techniques to mitigate bias toward superficial cortical layers. Phase regression operates by removing signals from vessels that generate a non-zero net phase, typically vessels that are large and oriented in a particular direction.…”

Section: Discussionmentioning

confidence: 99%

“…This study implemented the phase regression method for comparative purposes. The phase regression approach was applied to remove the macrovascular component in the BOLD signal as indicated in previous reports (Menon 2002; Knudsen et al 2023). This macrovascular component not only contributes to alterations in signal magnitude, but also introduces phase variations.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, SE-EPI is not completely free from T2* effects either due to the long readout time (Goense and Logothetis 2008) and, therefore, is not completely free from draining-vein effects. In another layer-dependent fMRI study focused on a finger-tapping task, phase regression significantly reduced the bias toward the superficial layer in the primary motor area (M1), although some residual macrovascular contribution remained (Knudsen et al 2023).…”

Section: Introductionmentioning

confidence: 99%

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Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression

Chang,

Lin,

Giovanello

2023

Preprint

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Layer-dependent functional magnetic resonance imaging (fMRI) offers a compelling avenue for investigating directed functional connectivity (FC). To construct a comprehensive map of brain-wide directed FC, several technical criteria must be met, including sub-mm spatial resolution, adequate temporal resolution, functional sensitivity, global brain coverage, and high spatial specificity. Although gradient echo (GE)–based echo planar imaging (EPI) is commonly used for rapid fMRI acquisition, it faces significant challenges due to the draining-vein effect, particularly when utilizing blood oxygen level-dependent (BOLD) contrast. In this study, we mitigated this effect by incorporating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence, opting for a 3T magnetic field strength over 7T. We also integrated several advanced techniques, such as simultaneous multi-slice (SMS) acceleration and NORDIC denoising, to enhance temporal resolution, spatial coverage, and signal sensitivity. Collectively, the VN fMRI method exhibited notable spatial specificity, as evidenced by the identification of double-peak activation patterns within the primary motor cortex (M1) during a finger-tapping task. Additionally, the technique demonstrated BOLD sensitivity in the lateral geniculate nucleus (LGN). Furthermore, our VN fMRI technique displayed superior robustness when compared to conventional fMRI approaches across participants. Our findings of directed FC elucidate several layer-specific functional relationships between different brain regions and align closely with existing literature. Given the widespread availability of 3T scanners, this technical advancement has the potential for significant impact across multiple domains of neuroscience research.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression

Chang,

Lin,

Giovanello

2023

Preprint

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“…This intermixing of the blood draining from each layer potentially reduces the laminar BOLD signal spatial specificity and results in a larger BOLD signal change near the surface, in part because they collect draining blood from the entire depth, and in part because the pial veins comprise a significant fraction of a voxel at these resolutions. Previous studies have attempted to address the draining veins issue by post-processing methods such as masking out the signal from veins (Chen et al, 2013;Koopmans et al, 2010), deconvolution (Hollander et al, 2021;Markuerkiaga et al, 2021), phase regression (Knudsen et al, 2023;Menon, 2002;Stanley et al, 2021) or by employing fMRI contrasts with higher sensitivity to microvasculature such as SE (Goense and Logothetis, 2006;Yacoub et al, 2003;Zhao et al, 2006), GREASE (Beckett et al, 2020;Martino et al, 2013;Polimeni, 2018) and VASO (Huber et al, 2014b;Lu et al, 2003).…”

Section: Monocular and Binocular Vaso Laminar Responses Peak In Lower...mentioning

confidence: 99%

Layer Dependence of Monocular and Binocular Responses in Human Ocular Dominance Columns at 7T using VASO and BOLD

Akbari

Gati

Zeman³

et al. 2023

Preprint

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The neurons located in the striate cortex (V1) preferentially respond to the input from one eye or another, forming a fingerprint-like pattern of ocular dominance columns (ODCs). At this mesoscopic scale, accessible by ultra-high field fMRI, V1 is supplied/drained by a network of surface (pial) vessels that connect to descending/ascending tangential vessels that penetrate the cortex and supply/drain a capillary bed whose density is also layer dependent. In this study, we measured the layer dependence of monocular and binocular responses of ocular dominance columns in V1 at 7T using Blood Oxygenation Level Dependent (BOLD) and VAscular Space Occupancy (VASO) contrasts. Our results indicate that the microvascular blood volume changes that give rise to VASO are well confined to the site of neural activity across the layers of the cortex and between the columns. Pial veins dominate the BOLD response and mix the signal between columns. When the GRE BOLD response was examined in only the VASO-specific voxels (thus eliminating the pial vein signal), the laminar profile was very similar to VASO, however, the columnar response was still blurred. Caution needs to be exercised in the interpretation of signal changes in BOLD at the mesoscale both in terms of feedforward/feedback effects and inhibitory and excitatory effects.

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“…10 Whereas the microvas-culature gives the most spatially specific BOLD contributions, draining pial veins are the largest source of dHb and lead to the strongest and furthest reaching BOLD effect, reducing spatial specificity of the BOLD signal. 8,9,11 Therefore, microvascular specificity - high sensitivity to microvessels and low sensitivity to macrovessels (mainly pial veins) - is desired to infer activation patterns from the fMRI data. The supralinear increase of microvascular contributions with increasing field strength versus a linear increase of macrovascular contributions has been a significant drive to build high field ( ≥ 7T) MRI systems with a promise of increased microvascular specificity.…”

Section: Introductionmentioning

confidence: 99%

Microvascular Specificity of Spin Echo BOLD fMRI: Impact of EPI Echo Train Length

van Horen,

Siero,

Bhogal

et al. 2023

Preprint

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A spatially specific fMRI acquisition requires specificity to the microvasculature that serves active neuronal sites. Macrovascular contributions will reduce the microvascular specificity but can be reduced by using spin echo (SE) sequences that use a π pulse to refocus static field inhomogeneities near large veins. The microvascular specificity of a SE-echo planar imaging (SE-EPI) scan depends on the echo train length (ETL)-duration, but the dependence is not well-characterized in humans at 7T. To determine how microvascular-specific SE-EPI BOLD is in humans at 7T, we developed a Monte Carlo voxel model that computes the signal of a proton ensemble residing in a vasculature subjected to a SE-EPI pulse sequence. We characterized the ETL-duration dependence of the microvascular specificity by simulating the BOLD signal as a function of ETL, the range adhering to experimentally realistic readouts. We performed a validation experiment for our simulation observations, in which we acquired a set of SE-EPI BOLD time series with varying ETL during a hyperoxic gas challenge. Both our simulations and measurements show an increase in macrovascular contamination as a function of ETL, with an increase of 30% according to our simulation and 60% according to our validation experiment between the shortest and longest ETL durations (23.1 - 49.7 ms). We conclude that the microvascular specificity decreases heavily with increasing ETL-durations. We recommend reducing the ETL-duration as much as possible to minimize macrovascular contamination in SE-EPI BOLD experiments. We additionally recommend scanning at high resolutions to minimize partial volume effects with CSF. CSF voxels show a large BOLD response, which can be attributed to both the presence of large veins (high blood volume) and molecular oxygen-induced T1-shortening (significant in a hyperoxia experiment). The magnified BOLD signal in a GM-CSF partial volume voxel reduces the desired microvascular specificity and, therefore, will hinder the interpretation of functional MRI activation patterns.

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Improved sensitivity and microvascular weighting of 3T laminar fMRI with GE-BOLD using NORDIC and phase regression

Cited by 15 publications

References 76 publications

Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression

Enabling brain-wide mapping of directed functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression

Layer Dependence of Monocular and Binocular Responses in Human Ocular Dominance Columns at 7T using VASO and BOLD

Microvascular Specificity of Spin Echo BOLD fMRI: Impact of EPI Echo Train Length

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