Creatine mapping of the brain at 3T by CEST MRI

Abstract

PurposeTo assess the feasibility of CEST‐based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance.MethodsWild type and knockout mice with guanidinoacetate N‐methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein‐based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two‐step Bloch–McConnell fitting was used to fit the extracted CrCEST line‐shape and multi‐B1 Z‐spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping.ResultsBrain Z‐spectra of wild type and guanidinoacetate N‐methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes ∼23% to the GuanCEST signal at B1 = 0.8 μT, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200–300 s−1 was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B1 is less than 0.4 μT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B1 is greater than 0.4 μT with the same pH drop.ConclusionsCrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.

Simultaneous creatine and phosphocreatine mapping of skeletal muscle by CEST MRI at 3T

“…(D) The corresponding ΔZ spectra extracted by PLOF method for 3D EPI with different saturation times (0. 38 it is advisable to set the CrCEST offset to 2 ppm instead of the previously utilized value of 1.8 ppm. 23 The multi-pool Lorentzian fitting was recently used to separate creatine from phosphocreatine in CEST measurements on human muscle at 3T.…”

“…To estimate the Cr exchange rate in muscle, we used a two-step Bloch-McConnell (BM) fitting procedure that has been detailed previously. 33,38 Briefly, it includes water and MTC pools in the first step to obtain the MTC parameters and then to fit for CrCEST lineshape with the background fixed in the second step.…”

“…21,36 Due to its rapid exchange rate, CrCEST coalesces with water at 3T as observed in phantoms, 21,26 which poses a significant challenge for the extraction of CrCEST at low fields. However, recent Cr line-shape and multiple B 1 studies of CrCEST on both high field 33,37 and 3T 38 have suggested that the in vivo CrCEST exchange rate is around 270 s −1 in brain, 33,37,38 which is far less than that in phantom. This provides an opportunity to simultaneously extract PCr/CrCEST in tissues with the PLOF approach at 3T.…”

Mitochondrial Oxidative Phosphorylation Capacity in Skeletal Muscle Measured by Ultrafast Z-Spectroscopy (UFZ) MRI at 3T

“…For 3D EPI readout (41,42), UFZ MRI images were acquired with TFE factor 32 Additionally, high-resolution T2 weighted images were collected for anatomical referencing using TSE sequence with a resolution of 0.44 × 0.44 × 4.0 mm 3 . T1 maps on human leg were acquired using the Dual Flip Angle (DFA) method as detailed previously (33).…”

“…PLOF enhances the specificity of Cr and PCr CEST signal extraction, especially in brain and muscle tissues at higher magnetic field strengths (22,23,29,30). Recent research indicates that the CrCEST exchange rate is approximately 270 s -1 in the brain (30)(31)(32) and less than 150 s -1 in skeletal muscle (33). Based on these findings, the PLOF method was applied to simultaneously extract PCr/CrCEST signals in skeletal muscle at 3T (33).…”