Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH

Abstract

Purpose: Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH.

Methods: Two metrics of contrast based on R_1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R_1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations.

Results: The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH.

Conclusions: Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: MRI; X-ray agent; extracellular pH; spin lock.

FIG. 1.

Diagram of spin-locking sequence.

FIG2.

CEST Z-spectra (a) and MTR_asym spectra (b) with irradiation power of 0.5, 1, 2, 3, 4, and 5 μT on iohexol samples with pH 7.0. Note the two exchanging groups (amide and hydroxyl) on the MTR spectra.

FIG. 3.

Measured R_1ρ dispersion, ΔR_1ρ, and S_ρ on the four iohexol samples with a variety of pH but constant agent concentration (a, c, and e) and the three iohexol samples with a variety of agent concentration but constant pH (b, d, and f), respectively. Dots in all subfigures are measured data, solid lines in (a and b) are the fitted curves using Chopra’s model, and the red line in (e) is the best fit using Eq. (4).

FIG. 4

R_1ρ dispersion (a) and ΔR_1ρ dispersion difference (b) from rat brain tumors before (used as baseline) and at 10 mins and 60 mins after injecting iohexol agent. Error bars are the standard deviations across four subjects.

FIG. 5

(a) mean time course of ΔR_1ρ difference from four rat brains, (b) R_1w map, (c) ΔR_1ρ map before injection, (d) ΔR_1ρ map at 10 mins after injection, and (e) ΔR_1ρ difference map. Error bars in (a) are the standard deviations across four subjects.

FIG. 6

pH maps from the four tumor bearing rat brains. Dark area represents the omitted voxels which have no significant concentration of agent.