Distribution of brain sodium long and short relaxation times and concentrations: a multi-echo ultra-high field 23Na MRI study
Résumé
Sodium (23 Na) MRI proffers the possibility of novel information for neurological research but also particular challenges. Uncertainty can arise in in vivo 23 Na estimates from signal losses given the rapidity of T2* decay due to biexponential relaxation with both short (T 2 * short) and long (T 2 * long) components. We build on previous work by characterising the decay curve directly via multi-echo imaging at 7 T in 13 controls with the requisite number, distribution and range to assess the distribution of both in vivo T 2 * short and T 2 * long and in variation between grey and white matter, and subregions. By modelling the relationship between signal and reference concentration and applying it to in vivo 23 Na-MRI signal, 23 Na concentrations and apparent transverse relaxation times of different brain regions were measured for the first time. Relaxation components and concentrations differed substantially between regions of differing tissue composition, suggesting sensitivity of multi-echo 23 Na-MRI toward features of tissue composition. As such, these results raise the prospect of multi-echo 23 Na-MRI as an adjunct source of information on biochemical mechanisms in both physiological and pathophysiological states. In the physiological state, the maintenance of the transmembrane sodium (23 Na) concentration gradient (10-15 mM intracellular sodium concentration and ~140 mM extracellular sodium concentration) is a precondition for several critical cellular functions. These include the transport of ions, neurotransmitters and nutrients; regulation of osmotic and electrostatic forces on cells and macromolecules; as well as the transmission of action potentials 1-3. In the diseased state, multiple pathological pathways can lead to aberrations of these functions. Such alterations can lead to changes in intra-and extracellular concentrations due to a reduced ability to maintain resting conditions and due to conformational changes in cells themselves as well as the cellular environment in which they are embedded. Thus, 23 Na-MRI is a potential source of more direct and quantitative biochemical information than is generally possible with conventional proton (1 H) MRI 4. As such, there is substantial interest in 23 Na-MRI regarding a range of neurological conditions despite the additional complications of acquiring 23 Na-MRI signal, including stroke 5 , epilepsy 6 , tumors 7 and neurodegenerative diseases 8-12. The quadrupolar 23 Na nucleus (spin = 3/2) is subject to the influence of fluctuations in neighbouring electric fields due to net positive and non-uniform distribution of charge 3,13-15. In the presence of a magnetic field, 23 Na nuclei exhibit four discrete energy states, with three possible (single quantum, SQ) transitions (−1/2, +1/2 "cen-tral transition"; −3/2, −1/2 and 1/2, 3/2 "satellite transitions"). In highly motile environments such as plasma or cerebrospinal fluid (CSF), the correlation time (τ C) is much shorter than the Larmor period (ω 0 −1) (ω 0 • τ C ≪ 1), leading to monoexponential longitudinal (T 1) and transverse (T 2) relaxation. This is in contrast to tissue environments such as within cells and the interstitial spaces between cells where diffusion is restricted by interactions of the 23 Na cation with macromolecular anions. Such interactions modulate decay behaviour in a measurable way: the satellite transitions are subject to additional fast relaxation processes so that both T 1 and T 2 reflect
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