Spin‐lock imaging of early tissue pH changes in ischemic rat brain

Abstract

We have previously reported that the dispersion of spin-lattice relaxation rates in the rotating frame (R ) of tissue water protons at high field can be dominated by chemical exchange contributions. Ischemia in brain causes changes in tissue pH, which in turn may affect proton exchange rates. Amide proton transfer (APT, a form of chemical exchange saturation transfer) has been shown to be sensitive to chemical exchange rates and able to detect pH changes non-invasively following ischemic stroke. However, the specificity of APT to pH changes is decreased because of the influence of several other factors that affect magnetization transfer. R is less influenced by such confounding factors and thus may be more specific for detecting variations in pH. Here, we applied a spin-locking sequence to detect ischemic stroke in animal models. Although R images acquired with a single spin-locking amplitude (ω ) have previously been used to assess stroke, here we use ΔR , which is the difference in R values acquired with two different locking fields to emphasize selectively the contribution of chemical exchange effects. Numerical simulations with different exchange rates and measurements of tissue homogenates with different pH were performed to evaluate the specificity of ΔR to detect tissue acidosis. Spin-lock and APT data were acquired on five rat brains after ischemic strokes induced via middle cerebral artery occlusions. Correlations between these data were analyzed at different time points after the onset of stroke. The results show that ΔR (but not R acquired with a single ω ) was significantly correlated with APT metrics consistent with ΔR varying with pH.

Enhanced CEST MRI Using the Residual of Inversed Z-Spectra for Ischemia Detection

“…Previous studies by Ref [28] and Ref [33] used AREX for T 1 normalization since T 1 can be significantly changed in stroke lesion. However, T 1 mapping is usually time-consuming.…”

Evaluation of the sensitivity of R1ρ MRI to pH and macromolecular density

“…More complicated models exist, such as methods that attempt to estimate exchange kinetics [ 32 ] and models that remove the relaxation portions due to diffusion or where random molecular motion lead to R 1ρ,H20 being equal to R 2,H20 and R 1,H2O [ 36 ], which require spin-lock fields higher than 3000 Hz [ [36] , [37] , [38] , [39] ] and cannot be achieved on our clinical system due to patient safety constraints. It may be possible to use much smaller spin-lock fields to measure pH [ 32 ], where R 1ρ is nearly indistinguishable from R 2 , however such measurements in clinical settings would be hampered by increased field non-uniformity effects that confound low spin-lock R 1ρ measurements.…”

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

“…Supporting Information Table S1 in the Supporting Information summarizes a list of APT quantification methods used for ischemic stroke imaging, including the advantages and limitations of each method. In this study, only some of the most commonly used APT quantification methods were used for analysis (underlined in Supporting Information Table S1 and defined in the Supplementary Materials), that is, magnetization transfer ratio asymmetry (MTR asym ), 13 water relaxation time T 1 -normalized MTR asym , [27][28][29] apparent exchange-dependent relaxation (AREX), 12,30,31 Lorentzian difference analysis (LDA), 12,25,26,32 and multi-Lorentzian fitting. 27,33,34 Other methods were excluded because of unsuitable experimental parameters as this was a retrospective analysis.…”