Direct and fast detection of neuronal activation in the human brain with diffusion MRI

Abstract

Using MRI, we found that a slowly diffusing water pool was expanding (1.7 ؎ 0.3%) upon activation on the human visual cortex at the detriment of a faster diffusing pool. The time course of this water phase transition preceded the activation-triggered vascular response detected by usual functional MRI by several seconds. The observed changes in water diffusion likely reflect early biophysical events that take place in the activated cells, such as cell swelling and membrane expansion. Although the exact mechanisms remain to clarify, access to such an early and direct physiological marker of cortical activation with MRI will provide opportunities for functional neuroimaging of the human brain.ur current model of neuronal activation places great importance on transient electrical and biochemical events associated with the excitation processes. However, there is compelling evidence that activation is accompanied by other important physical phenomena. Microstructural changes in excited tissues have been observed, first from optical birefringence measurements (1, 2) and later more directly by using piezoelectric transducers (3). Those studies have revealed, for instance, that in the brain cell swelling is one of the physiological responses associated with neuronal activation (4, 5).However, such biophysical events have been monitored at the microscopic level by using invasive techniques in neuronal cell cultures or slices, and do not necessarily reflect physiological conditions (6, 7). Observing changes in cortical cell configuration in animals or humans would, thus, have a tremendous impact, because they would be directly linked to neuronal events, such as membrane expansion, and bridge the gap with current approaches to obtain images of human brain activation. Those approaches, such as blood oxygen level-dependent (BOLD) MRI, are based on blood flow changes and only indirectly and remotely related to cortical activation (8,9).A small decrease of the water diffusion coefficient during activation of human visual cortex has been previously reported by using diffusion MRI (10). Diffusion MRI provides valuable information on the microscopic obstacles which hinder diffusing molecules, such as membranes or macromolecules, and in turn, on the tissue cellular structure (11). Based on other MRI reports of water diffusivity decrease during intense neuronal activation (12, 13) or during other physiological or pathological conditions inducing cell swelling (14-17), the observed diffusion findings have been putatively ascribed to a transient swelling of cortical cells and a shrinking of the extracellular space, increasing its tortuosity (18) for diffusing molecules. However, no confirmation has been found so far for this mechanism. The aim of this report is to demonstrate that a decrease in water mobility can readily been observed in the human brain with diffusion MRI upon activation, and to provide evidence that this effect results from an early neuronal activation event that precedes the blood flow response by a sizeable time am...

Water-Diffusion Slowdown in the Human Visual Cortex on Visual Stimulation Precedes Vascular Responses

“…However, it is well established that the decrease in deoxy-Hb content produced during activation leads to a decrease of the diffusion-sensitized signal (equivalent to a pseudo ADC increase), because the local gradients artifactually decrease the b value (Does et al, 1999;Kiselev, 2004;Zhong, 1991;Zhong et al, 1998). This is opposite to our current findings and the results of others (Jin and Kim, 2008;Le Bihan et al, 2006;Yacoub et al, 2008). In any case the crossterm contribution is expected to be negligible in our setting: We used a diffusion SE sequence made of a double pair of gradient pulses of opposite polarities, designed to mitigate the effects of the crossterms with local magneticsusceptibility gradients (Finsterbusch, 2008).…”

“…The amplitude of the diffusion response was larger than that of SE-BOLD response, but was smaller than that of the GE-BOLD response, as previously reported (Le Bihan et al, 2006). The poststimulus undershoot for the diffusion signal was very small and not distinguishable from noise.…”

“…At high b values (strong diffusion sensitization), as used in both this study and in a previous work (Le Bihan et al, 2006), the direct contribution of the vascular compartment to the diffusion MRI signal is negligible (Jin and Kim, 2008;Yacoub et al, 2008). First, the intravascular signal is crushed, because the diffusion coefficient of blood water is B2.5 times greater than that of brain tissue water (B0.8 Â 10 À3 mm 2 /sec).…”

“…(B) A custom-made cushion was used to set the optical fibers on the occipital area in the supine body position. magnetic field-gradient pulses applied simultaneously along all three axes (Le Bihan et al, 2006;Reese et al, 2003). The acquisition parameters were as follows: matrix = 96 Â 96 Â 10; interleaved slice acquisition; voxel size = 2 Â 2 Â 3 mm 2 ; echo time (TE) = 89 ms; repetition time (TR) = 1.5 sec; 6/8 partial k-space; and bandwidth = 1,302 Hz/pix.…”

“…In other words, the raw diffusion-weighted signal is the sum of a unique, true tissue diffusion component (apparent diffusion coefficient; ADC) and a local magnetic-susceptibility tissue component (T2* t ), which is common with BOLD SE signals. The tissue diffusion response can be isolated by using images acquired with different degree of diffusion sensitization, as it increases with the b value (Jin and Kim, 2008;Le Bihan et al, 2006;Yacoub et al, 2008), though this approach is time consuming.…”