Effects of intracellular pH, blood, and tissue oxygen tension on T_1ρ relaxation in rat brain

Abstract

The effects of intracellular pH (pH i ), paramagnetic macroscopic, and microscopic susceptibility on T 1 in the rotating frame (T 1 ) were studied in rat brain. Intracellular acidosis was induced by hypercapnia and pH i , T 1 , T 2 , diffusion, and cerebral blood volume (CBV) were quantified. Taking into account the CBV contribution, a prolongation of parenchymal T 1 by 4.5% was ascribed to a change in tissue water relaxation caused by a one unit drop in pH i . Blood T 1 was found to prolong linearly with blood oxygenation saturation (Y). The macroscopic susceptibility contribution to parenchymal T 1 was assessed both through BOLD and an iron oxide contrast agent, AMI-227. The T 1 data from these experiments could be described by intravascular effects with insignificant effects of susceptibility gradients on tissue water. Tissue oxygen tension (PtO 2 ) was manipulated and monitored with microelectrodes to assess its plausible contribution to microscopic susceptibility and relaxation. Parenchymal Acute ischemia results in subtle and almost instantaneous changes in cerebral MR relaxation times, including prolongation of T 1 (1,2) and T 1 in the rotating frame (T 1 ) (3,4), shortening of T* 2 (5), and T 2 (1,6,7). These relaxation changes are expressed in global forebrain ischemia when there is no possibility for edema formation (2) and also almost immediately after the occlusion of the middle cerebral artery (3,8). The time-dependency of these relaxation changes reveals that net water accumulation to the ischemic brain tissue is not responsible for the depicted MR changes. Early T* 2 and T 2 reductions in ischemic brain have been ascribed to local increases in the level of deoxyhemoglobin, i.e., a blood oxygenation level-dependent (BOLD) phenomenon (5,6,9) and, furthermore, T 2 effects have been quantitatively modeled as intravascular susceptibility effects reflecting elevated oxygen extraction in the flow-compromised tissue (7). The presence of negative BOLD in flow-compromised brain is an index of ongoing oxidative metabolism; thus, it can reveal potentially viable tissue (10).While the transverse relaxation changes in the early moments of ischemia can be explained by both intra-and extravascular susceptibility effects, the longitudinal relaxation alterations might have a different pathophysiological background. From a general principle, tissue R 1 relaxation rate (R 1,obs ) has been proposed to receive contributions from the following physical factors:where subscripts exch, rot, and diff indicate exchange, rotational, and diffusion contributions to R 1 , respectively, and b is the fraction of bound water (11). The same relation has commonly been regarded as being applicable throughout the resonance frequency range, thus also including T 1 relaxation in the rotating frame (11,12). Knispel et al. (11) quantitatively explored T 1 relaxation and relaxation dispersion, i.e., T 1 as a function of B 1 , in tissue phantoms and they concluded that three distinct correlation times, falling into the three physical categor...

A pulse sequence for rapid in vivo spin‐locked MRI

“…The SL-EPI sequence has the advantage of rapid acquisition of T 1 data compared to a T 1 -prepared TSE sequence. This new sequence should allow studies that determine the dependence of T 1 on blood oxygenation levels in vitro (9) to be performed in vivo in a clinical setting. As an example, T 1 mapping could be used to detect ischemia in regions in the brain with some basic modifications, such as the use of an appropriate RF coil to SL flowing blood, for example, in the carotids.…”

“…Consequently, we are currently pursuing studies that compare results from T 2 , T 2 *, and T 1 -weighted fMRI experiments to elucidate mechanisms of Blood Oxygenation Level Dependent (BOLD) contrast as the relative contribution of susceptibility to the relaxation times will differ between sequences (9). Further, the magnetic susceptibility of blood affects the MR signal in brain parenchyma differently depending on the size of the vessel.…”

Pulse sequence for multislice T1ρ‐weighted MRI

“…In addition, T 1 -weighted MRI of H 2 17 O was recently used to measure cerebral and tumor perfusion (13,14). The sensitivity of T 1 to a variety of physiological parameters has also been demonstrated (15).…”

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder

“…In contrast, the physiological source of T1ρ is less well‐understood. Prior studies have shown that T1ρ is sensitive to changes in pH, with signal increasing with acidity (Heo et al., 2014; Kettunen et al., 2002). Because of this, fT1ρ signal may reflect increases in acidic metabolites such as H + , glutamate, and lactate in tissue following neuronal activation (Belanger et al., 2011).…”

“…This technique aims to quantitatively map the spin‐lock–based T1ρ relaxation time temporally and is sensitive to chemical exchange of protons between water and amide, hydroxyl, and/or amine groups (Jin, Autio, Obata, & Kim, 2011). This chemical exchange is influenced by pH and metabolite concentration (e.g., glucose and glutamate) (Jin et al., 2011; Kettunen, Gröhn, Silvennoinen, Penttonen, & Kauppinen, 2002), which have been shown to change in response to neural activation prior to changes in blood flow (Belanger, Allaman, & Magistretti, 2011). T1ρ relaxation is also sensitive to stimulus‐induced rotary saturation (SIRS), which may directly measure neuronal currents (Witzel, Lin, Rosen, & Wald, 2008).…”