Dataset Information

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 t_mix = 10 ms and 40 ms, respectively. Fast-exchanging components reached the highest saturation when using a B₁ = 2.8 μT and t_mix = 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.

SUBMITTER: Schmitz-Abecassis B

PROVIDER: S-EPMC9290048 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole-dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple-pool Lorentzian fits, and the three-point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple-pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three-point method significantly underestimates both APT and rNOE saturation transfer at -3.5 ppm (NOE(-3.5)). The multiple-pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (?1 ?T at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non-Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 ?T were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(-3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed quantification methods.