The ‘wet mind’: water and functional neuroimaging

Abstract

Functional neuroimaging has emerged as an important approach to study the brain and the mind. Surprisingly, although they are based on radically different physical approaches both positron emission tomography (PET) and magnetic resonance imaging (MRI) make brain activation imaging possible through measurements involving water molecules. So far, PET and MRI functional imaging have relied on the principle that neuronal activation and blood flow are coupled through metabolism. However, a new paradigm has emerged to look at brain activity through the observation with MRI of the molecular diffusion of water. In contrast with the former approaches diffusion MRI has the potential to reveal changes in the intrinsic water physical properties during brain activation, which could be more intimately linked to the neuronal activation mechanisms and lead to an improved spatial and temporal resolution. However, this link has yet to be fully confirmed and understood. To shed light on the possible relationship between water and brain activation, this introductory paper reviews the most recent data on the physical properties of water and on the status of water in biological tissues, and evaluates their relevance to brain diffusion MRI. The biophysical mechanisms of brain activation are then reassessed to reveal their intimacy with the physical properties of water, which may come to be regarded as the 'molecule of the mind'.

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

“…These results suggest that the diffusion response could reflect other dynamic events occurring in the tissue, notably changes in its cellular structure, such as cell swelling to which diffusion MRI is exquisitely sensitive (Le Bihan, 2007). Clearly the origin of the diffusion signal remains to be investigated and further work will establish whether this water diffusion signal can be used as a more direct surrogate marker of neuronal activation representing a significant departure from the neurovascular-coupling paradigm used by current neuroimaging methods, offering improved spatial and temporal resolution and specificity.…”

“…This slowdown occurs several seconds before the hemodynamic response detected by BOLD fMRI, and has been tentatively ascribed to the phase transition of a fraction of the water molecules from a faster to a slower diffusion pool in the areas of the cortex undergoing activation (Le Bihan et al, 2006). This slow-diffusion pool might consist of water molecules in close association with cell membranes, and the observed phase transition could result from the membrane expansion of cortical cells that undergo swelling during brain activation (Andrew and MacVicar, 1994;Le Bihan, 2007;Tasaki, 1999). This hypothetical mechanism, if confirmed, would be more closely associated with neuronal activation, and would mark a significant departure from the blood flow-based MRI approach, thereby potentially offering improved spatial and temporal resolution.…”

Studies of anomalous diffusion in the human brain using fractional order calculus

“…In many biologic tissues, the diffusion-induced MR signal loss deviates from monoexponential decay, exp(ÀbD) (where D is the diffusion coefficient and b is the b factor), particularly at high b values (e.g., >1500 sec/mm 2 for human brain tissues) (1). This phenomenon, sometimes referred to as anomalous diffusion, has been modeled extensively using a biexponential function:…”

Are we ready to image the incoherent molecular motion in our minds?

“…Indeed, from a theoretical point of view and free from conceptual bias with perfusion, the D and D* coefficients in ischemic stroke might be superior to the perfusion-diffusion mismatch principle because they allow us to monitor the untangled changes in cellular volume and extracellular space as well as the shift of balance between the fast and the slow diffusion water pools in the tissue [8]. As water and cell swelling are strongly associated with neuronal activation, it is reasonable to think that IVIM bears a tremendous potential to shed light on the early pathophysiology of ischemia.…”

“…Novel applications of IVIM-labeled diffusion metrics, which will provide much food for thought in the future, are the diffusion-weighted functional MRI (fMRI) and the diffusion-weighted arterial spin labeling (ASL) [8,17]. Brain activation (small) signal changes, due to cell swelling and the associated water-phase transitions, accompany the change from the resting to the activated conditions.…”