Relaxation‐compensated CEST‐MRI at 7 T for mapping of creatine content and pH – preliminary application in human muscle tissue in vivo

Abstract

The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (≈ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B1. However, strong B1 fields also label semi-solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T1 relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange-dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and--by using the AREX-ratio of two RF irradiation amplitudes B1--purely exchange-rate-weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by (31)P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: cCr,rest=24.5±3.74mM to cCr,ex=38.32±13.05mM. The CEST-based pH method shows a pH decrease during exercise, whereas a slight increase was observed by (31)P NMR spectroscopy.

3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T

“…Chemical exchange saturation transfer (CEST) allows for indirect detection of diluted molecules by their saturation transfer to the abundant water pool . Many different diluted solutes were reported to be detectable with CEST such as peptides and proteins, with dependency on protein conformation, creatine, glutamate, or even injected solutes such as iopamidol, glucose, and glucose derivatives …”

“…On the other hand, physicists aim to sample the Z‐spectrum with high spectral resolution in order to facilitate accurate and reliable fitting of model peaks known to exist from studies at ultra‐high field (UHF) strengths. UHF studies at 9.4 and 7T have revealed spectrally selective CEST effects related to proteins, including amide, amine, and nuclear overhauser effect (NOE) effects, as well as smaller peaks potentially related to creatine and choline phospholipids . Moreover, spatial correlations between isolated amide CEST and gadolinium ring enhancement have been reported .…”

CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4 T

“…The long irradiation and cumulative exchange cause detectable alterations in the water signal, and enhance the sensitivity for indirectly detecting the solute molecules via the water signal . In biological tissues, CEST effects have been observed for a number of endogenous metabolites and molecules, including proteins/peptides, creatine, glutamate, glucose, myo‐inositol, glycogen, and glycosaminoglycans . In principle, CEST can provide high‐sensitivity and high‐spatial‐resolution imaging of selected proton pools in vivo , which complements some of the limitations of conventional MRS.…”

An overview of CEST MRI for non-MR physicists

“…Conventionally, in vivo detection of Cr was only feasible via MR spectroscopy [59]. High-resolution Cr-CEST in skeletal muscle (axial section of the calf) showing increased creatine levels immediately after exercise and decrease to normal level during a recovery period has been reported [21, 60]. The ability to map muscular energy metabolism may be useful in the study of myocardial disorders [61].…”