On the sensitivity of the diffusion MRI signal to brain activity in response to a motor cortex paradigm

Abstract

Diffusion functional magnetic resonance imaging (dfMRI) is a promising technique to map functional activations by acquiring diffusion‐weighed spin‐echo images. In previous studies, dfMRI showed higher spatial accuracy at activation mapping compared to classic functional MRI approaches. However, it remains unclear whether dfMRI measures result from changes in the intracellular/extracellular environment, perfusion, and/or T2 values. We designed an acquisition/quantification scheme to disentangle such effects in the motor cortex during a finger‐tapping paradigm. dfMRI was acquired at specific diffusion weightings to selectively suppress perfusion and free‐water diffusion, then time series of the apparent diffusion coefficient (ADC‐fMRI) and of intravoxel incoherent motion (IVIM) effects were derived. ADC‐fMRI provided ADC estimates sensitive to changes in perfusion and free‐water volume, but not to T2/T2* values. With IVIM modeling, we isolated the perfusion contribution to ADC, while suppressing T2 effects. Compared to conventional gradient‐echo blood oxygenation level‐dependent fMRI, activation maps obtained with dfMRI and ADC‐fMRI had smaller clusters, and the spatial overlap between the three techniques was below 50%. Increases of perfusion fractions were observed during task in both dfMRI and ADC‐fMRI activations. Perfusion effects were more prominent with ADC‐fMRI than with dfMRI but were significant in less than 25% of activation regions. IVIM modeling suggests that the sensitivity to task of dfMRI derives from a decrease of intracellular/extracellular diffusion and an increase of the pseudo‐diffusion signal fraction, leading to different, more confined spatial activation patterns compared to classic functional MRI.

The Mechanism of Downregulated Interstitial Fluid Drainage Following Neuronal Excitation

“…Diffusion fMRI represents a promising technique to reflect neuronal activities, but this method cannot differentiate among all water molecules on the voxel level of the cortex, including blood vessels, cells, and ECS. Notably, whether the modulation of diffusion originates from the intracellular or extracellular environment remains unclear [51]. Because of the introduction of tracers that are specifically located within the ECS, our present results showed the same diffusion changes in the deep brain nucleus and further verified that the restricted diffusion partly originated from the decrease of diffusion within the ECS.…”

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and diffusion fMRI responses in mouse visual cortex

“…Diffusion functional MRI (DfMRI) has been proposed as an alternative to blood oxygenation level dependent (BOLD) fMRI to monitor neural activity noninvasively [1]. Several studies have demonstrated that the DfMRI and BOLD fMRI responses to a variety of stimuli differed qualitatively and quantitatively (ie amplitudes and time courses of responses) [1][2][3][4][5] suggesting that mechanisms underlying BOLD and diffusion fMRI must be different, although this view has been controversial [6,7]. While BOLD fMRI relies on the indirect neurovascular coupling mechanism [8,9] the current hypothetical mechanism of DfMRI is thought to be related to the neural activation triggered cell swelling, for which there is a large body of evidence [10,11].…”

Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response

“…Blood water contributions to the MRI signal should therefore be eliminated to access changes in tissue ADC only. The inclusion of b=0 in the ADC estimation may result in BOLDlike response functions as, for instance, reported in Luca et al, 2019 andNunes et al, 2019. It is noteworthy that techniques to suppress the blood signal by injection of magnetic particles (Jin and Kim, 2008) may also introduce an indirect vascular contribution, as they generate susceptibility gradients around vessels that fluctuate with changes in vessel size. Encouragingly, studies of perfused tissues without vasculature have clearly demonstrated that neuronal activity decreases the overall diffusion coefficient (Flint et al, 2009;Tirosh and Nevo, 2013;Spees et al, 2018), although the sensitivity to physiological levels of activity has been questioned (Bai et al, 2016).…”

“…These gradients can contribute to the effective diffusion-weighting imparted in the sequence, most notably via cross-terms with the diffusion gradients Gd. Contributions from background gradients may have challenged the interpretation in Darquie et al, 2001;Autio et al, 2011;Luca et al, 2019. A sequence design that minimizes cross-terms should be preferred, e.g.…”