The use of variable delay multipulse chemical exchange saturation transfer for separately assessing different CEST pools in the human brain at 7T

Abstract

Purpose Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo, while mitigating the MTC. Methods VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three‐pool Lorentzian fitting. Different B1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates. Results The results show the importance of removing MTC when applying VDMP in vivo and the influence of B1 for distinguishing different pools. Finally, the optimal B1 and mixing times to effectively saturate slow‐ and fast‐exchanging components are also reported. Slow‐exchanging amides and rNOE components could be distinguished when using B1 = 1 μT and tmix = 10 ms and 40 ms, respectively. Fast‐exchanging components reached the highest saturation when using a B1 = 2.8 μT and tmix = 0 ms. Conclusion VDMP is a powerful CEST‐editing tool, exploiting chemical exchange‐rate differences. After MTC removal, it allows separate assessment of slow‐ and fast‐exchanging solute pools in in vivo human brain.

The relayed nuclear Overhauser effect in magnetization transfer and chemical exchange saturation transfer MRI

“…6 Analyzing upfield and downfield signals separately can be achieved by Z-spectral fitting methods such as the Lorentzian difference method (or MTR residual spectrum after removing water direct saturation), 13,122 Multiple-Lorentzian fitting, 14 polynomial fitting, 123 and apparent exchangedependent relaxation (AREX) or MTR Rex analysis, 124 as well as exchange rate filtering approaches such as chemical exchange rotation transfer (CERT) 125 and variable delay multipulse (VDMP) MRI. 126 Figure 8 shows the processed Z-spectra for native and unfolded BSA at different pH and temperatures, using the so-called relaxationcompensated analysis of the Z-spectrum (AREX). 22 These AREX spectra for proteins show that the amine proton pool signal around +2.7 to +3.0 ppm (attributed mainly to amino acids asparagine, glutamine, glutamate, and lysine) is strongly influenced by pH and temperature, confirming the sensitivity of proton exchange to the physiological environment.…”

“…However, as commented upon in another review, “The success of this approach is based on a coincidental symbiotic effect of mixing the rNOE, APT and asymmetric MTC contributions” 6 . Analyzing upfield and downfield signals separately can be achieved by Z‐spectral fitting methods such as the Lorentzian difference method (or MTR residual spectrum after removing water direct saturation), 13,122 Multiple‐Lorentzian fitting, 14 polynomial fitting, 123 and apparent exchange‐dependent relaxation (AREX) or MTR Rex analysis, 124 as well as exchange rate filtering approaches such as chemical exchange rotation transfer (CERT) 125 and variable delay multipulse (VDMP) MRI 126 …”

Radiofrequency labeling strategies in chemical exchange saturation transfer MRI

“…Several groups have employed the VDMP method to separate different components with varied exchange rates. [97][98][99] For instance, Xu et al…”

Label-Free Chemically and Molecularly Selective Magnetic Resonance Imaging

“…The desirable single metabolite-targeted CEST imaging typically can be contaminated by other biomolecules as current metabolite-specific CEST pulse sequences are not specific enough. In this context, efforts have been made to develop sophisticated data acquisition schemes or methodologies and CEST imaging sequences for measuring exchange rates more accurately and quantitatively or filtering out interfering protons in a specific exchange rate range to “purify” the measured CEST signal. , It should be noted that many exogenous agents are inherently CEST contrast agents and are already entering the phases of clinical trials …”