R1ρ sensitivity to pH and other compounds at clinically accessible spin‐lock fields in the presence of proteins

Abstract

Numerous human diseases involve abnormal metabolism, and proton exchange is an effective source of magnetic resonance imaging (MRI) contrast for assessing metabolism. One MRI technique that capitalizes on proton exchange is R 1 relaxation in the rotating frame (R 1ρ ). Here we investigated the sensitivity of R 1ρ to various proton-exchange mechanisms at spin-lock pulses within FDA safety guidelines for radiofrequency-induced heating. We systematically varied pH known to change the rate of proton exchange as well as the glucose and lysine concentrations, thus changing the number of amide, hydroxyl, and amine exchangeable sites in a series of egg-white albumin phantoms. The resulting effects on quantitative relaxation time measurements of R 1ρ , R 1 , and R 2 were observed at 3T. Using spin-lock amplitudes available for human imaging (less than 23.5μT) at near physiologic temperatures, we found R 1ρ was more sensitive to physiologic changes in pH than to changes in glucose and lysine concentrations. In addition, R 1ρ was more sensitive to pH changes than R 1 and R 2 . Models of proton exchange fit to the relaxation measurements suggest that amide groups were the primary source of pH sensitivity. Together, these experiments suggest an optimal spin-lock amplitude for measuring pH changes while not exceeding FDA subject heating limitations.

Proton Exchange Magnetic Resonance Imaging: Current and Future Applications in Psychiatric Research

“…The resulting T1r map is shown in C) and the color scale on the far right corresponds to the relaxation times in C. FIGURE 11 | Relationship between T1r and metabolites (pH and glucose) in an egg white albumin phantom. T1r shows a much greater response to pH changes in the physiological range as compared to glucose in physiological range (59).…”

“…T1r values has been shown to be sensitive to the concentrations of molecules including glucose (56-58) in phantom studies. T1r imaging is also sensitive to pH (Figure 11) (56, 59, 60), the amount of water that is present in tissue (56,61), macromolecular density (60), and temperature (59). Several studies have assessed the reliability of T1r relaxation times at 3T and found good scan/re-scan reliability with differences on the order of 2% or less (59,62) between scans.…”

“…While, it has been shown that collecting multiple spin-lock amplitudes as well spin-lock durations can help to identify individual metabolic contributions (54), more work is still needed to identifying how different imaging parameters effect the sensitivity of T1r to different mechanisms or molecules especially in vivo. The factors contributing to T1r relaxation time is a highly relevant topic that is still being investigated by several groups (54,59,60).…”

“…Johnson et al proposed an optimal sampling of the spin-lock durations when the approximate values of the T1r relaxation times are known in advance (92) to improve the T1r imaging efficiency. Owusu et al have also recently shown that a spin-lock amplitude of 14.1µT (600Hz) may be optimal for in vivo imaging the brain at 3T when considering tissue heating / SAR constraints (59).…”

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study

“…This relationship held across a wide range of magnetic field strengths (3.0-9.4 T) and spin-lock amplitudes (2.9-94 mT). In addition, Owusu et al (11) found that the strongest contribution to changes appears to be pH at 3-T using spin-lock amplitudes that can be achieved with U.S. Food and Drug Administration limits of subject heating. Other studies (7,(12)(13)(14) have evaluated the use of T 1 rho MRI to examine brain pH, and some have explored the potential utility of this technique in distinguishing the pathologies underlying panic disorder (15), bipolar disorder (16,17), and premanifest Huntington's disease (18).…”