A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

Abstract

A new interpretation is proposed for stimulus-induced signal changes in diffusion-weighted functional MRI. T(2)-weighted spin-echo echo-planar images were acquired at different diffusion-weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus-correlated response and post-stimulus undershoot (PSU) in the functional time-courses were found to follow different trends as a function of b-value. Data were analysed using a three-compartment signal model, with one compartment being purely vascular and the other two dominated by fast- and slow-diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus-induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast-diffusion phase displays a substantial PSU, while the slow-diffusion phase demonstrates a highly reproducible and stimulus-correlated time-course with minimal undershoot. The decomposed responses are interpreted in terms of the spin-echo blood oxygenation level dependent (SE-BOLD) effect, and it is proposed that the signal produced by fast- and slow-diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule- and capillary-sized vessels, respectively. This interpretation suggests that diffusion-weighted SE-BOLD imaging may provide subtle information about the haemodynamic and neuronal responses.

An Explanation of Signal Changes in DW-fMRI: Monte Carlo Simulation Study of Restricted Diffusion of Water Molecules Using 3D and Two-Compartment Cortical Cell Models

“…For instance, a study showed decreased apparent diffusion coefficient, implying increased normalized signal intensity for about 1.57% with b-value of 1443-1461 mm 2 /s and this result was consistent with our result that the normalized signal intensities increased for about 2.17% with b-value of 1400 mm 2 /s, Δ of 30 ms, and r of 10.1 μm [1]. In other studies, 1-2% increases of the raw signal intensities with the b-value of 1600-1800 mm 2 /s were reported [2], [3], [5]. In our simulations, we obtained 2.15-2.18% increases in the normalized signal intensities with the b-value of 1600-1800 mm 2 /s, Δ of 30 ms, and r of 10.1 μm.…”

Evidence for a vascular contribution to diffusion FMRI at high b value

“…During activation, they hypothesize that the compartment with slower diffusion increases (because of cell swelling), causing the overall diffusion to decrease and the signal to therefore increase. However, a similar effect could arise for compartments with fixed volume (no swelling) that had different diffusion coefficients and T 2 values (40). As the b value changes, the signal contribution of the T 2 BOLD effect in each compartment would be determined by its diffusion coefficient, and the percent signal change would therefore depend on b value.…”

BOLD background gradient contributions in diffusion‐weighted fMRI—comparison of spin‐echo and twice‐refocused spin‐echo sequences

“…Also, our model simplifies the diffusion properties of water in brain matter, which cannot be described assuming isotropic diffusion characterized by a single diffusion coefficient (40). In a very recent study, Kershaw et al (11) explained their findings in DFMRI experiments by means of a model that considers a slow-and a fast-diffusing pool, indicating that the diffusion characteristics could be crucial to explain DFRMI findings.…”

“…Thus, one can safely assume that it is exclusively caused by the interaction between diffusion weighting gradients and background gradients. In the study by Fujita (41), a scaling law, b ¼ DÁTE/r 2 , was derived that allows a set of results calculated for a specific diffusion constant (D) and vessel radius (r) to be applied to a situation with the same b but different D and r. Noting that the largest extravascular SE-BOLD signal changes occur when b lies between 2 and 4, it is possible to estimate the range of vessel sizes that are most sensitive for molecules diffusing with a specific diffusion coefficient (11). Our results suggest that this range also depends on the size of the bvalue if a sequence is chosen that does not minimize cross-terms.…”

“…At the cortical surface, a small decrease in the ADC was found (10), which may also have arisen from a functional reduction in the partial volume of the cerebrospinal fluid. In a very recent contribution, Kershaw et al (11) have proposed that the observation of an overall decrease in diffusion can be explained by decomposing the signal in fractions from slow-and fast-diffusing molecules with distinct BOLD signal characteristics. The interpretation and the observability of the diffusion changes during activation as observed using FMRI is still a matter of debate.…”