MR imaging of the amide‐proton transfer effect and the pH‐insensitive nuclear overhauser effect at 9.4 T

Abstract

The amide proton transfer (APT) effect has emerged as a unique endogenous molecular imaging contrast mechanism with great clinical potentials. However, in vivo quantitative mapping of APT using the conventional asymmetry analysis is difficult due to the confounding Nuclear Overhauser Effect (NOE) and the asymmetry of the magnetization transfer (MT) effect. Here we showed that the asymmetry of MT contrast from immobile macromolecules is highly significant, and the wide spectral separation associated with a high magnetic field of 9.4 T delineates APT and NOE peaks in a Z-spectrum. Therefore, high resolution apparent APT and NOE maps can be obtained from measurements at three offsets. The apparent APT value was greater in gray matter compared to white matter in normal rat brain, and was sensitive to tissue acidosis and correlated well with ADC in the rat focal ischemic brain. In contrast, no ischemia-induced contrast was observed in the apparent NOE map. The concentration-dependence and the pH insensitivity of NOE were confirmed in phantom experiments. Our results demonstrate that in vivo apparent APT and NOE maps can be easily obtained at high magnetic fields, and the pH-insensitive NOE may be a useful indicator of mobile macromolecular contents.

Chemical Exchange Saturation Transfer (CEST) MR Technique for Liver Imaging at 3.0 Tesla: an Evaluation of Different Offset Number and an After-Meal and Over-Night-Fast Comparison

“…However, since the fat suppression was applied prior to acquisition, this MTR asym should not be dominated by the contamination of lipid at −3.5 ppm relative to water resonance, the opposite side on Z-spectrum [40]. Therefore, the contribution of possible upfield nuclear Overhauser enhancement (NOE) effects to the MTR asym difference should be small [37, 38]. According to a 500 MHz proton NMR study of Cer and its analogs in deuterated chloroform (CDCl3) at 25° C by Li et al [42], −NH in Cers has a chemical shift of ~6.3 ppm, about 1.6 ppm relative to water (4.7 ppm chemical shift).…”

Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

“…3 and 4, two z-spectra overlapped relatively well on the right. Therefore, the contribution of possible upfield nuclear Overhauser enhancement (NOE) effects to the MTR asym difference should be small [42, 43]. According to a 500MHz proton NMR study of Cer and its analogues in deuterated chloroform (CDCl3) at 25°C by Li et al [44], -NH in Cers has a chemical shift of ~6.3ppm, about 1.6ppm relative to water (4.7ppm chemical shift).…”

Downfield‐NOE‐suppressed amide‐CEST‐MRI at 7 Tesla provides a unique contrast in human glioblastoma

“…Two distinct saturation transfer (ST) effects apparent in vivo are attributed to protons of mobile proteins: at 3.5 ppm the backbone amide signals with their base catalyzed proton transfer (APT) and at -3.5 ppm the nuclear Overhauser enhancement (NOE) mediated aliphatic proton magnetization transfer (so called exchangerelayed NOE or relayed-NOE (rNOE) ST) (8,9). For these protein ST effects, several interesting correlations have been shown that might play a role in vivo and especially in pathologies: dependence on intracellular pH (5,(10)(11)(12)(13), protein concentration (8,13), or protein folding (14,15) and aggregation states (16). Already, the use for brain tumor detection (6,(17)(18)(19)(20), grading (21), and possible differentiation of tumor recurrence and radiation necrosis (22) has been shown to be feasible by proteinbased saturation transfer MRI.…”