Magnetic resonance imaging of the Amine–Proton EXchange (APEX) dependent contrast

Abstract

Chemical exchange between water and labile protons from amino-acids, proteins and other molecules can be exploited to provide tissue contrast with magnetic resonance imaging (MRI) techniques. Using an off-resonance Spin-Locking (SL) scheme for signal preparation is advantageous because the image contrast can be tuned to specific exchange rates by adjusting SL pulse parameters. While the amide-proton transfer (APT) contrast is obtained optimally with steady-state preparation, using a low power and long irradiation pulse, image contrast from the faster amine-water proton exchange (APEX) is optimized in the transient state with a higher power and a shorter SL pulse. Our phantom experiments show that the APEX contrast is sensitive to protein and amino acid concentration, as well as pH. In vivo 9.4-T SL MRI data of rat brains with irradiation parameters optimized to slow exchange rates have a sharp peak at 3.5 ppm and also broad peak at −2 to −5 ppm, inducing negative contrast in APT-weighted images, while the APEX image has large positive signal resulting from a weighted summation of many different amine-groups. Brain ischemia induced by cardiac arrest decreases pure APT signal from ~1.7% to ~0%, and increases the APEX signal from ~8% to ~16%. In the middle cerebral artery occlusion (MCAO) model, the APEX signal shows different spatial and temporal patterns with large inter-animal variations compared to APT and water diffusion maps. Because of the similarity between the chemical exchange saturation transfer (CEST) and SL techniques, APEX contrast can also be obtained by a CEST approach using similar irradiation parameters. APEX may provide useful information for many diseases involving a change in levels of proteins, peptides, amino-acids, or pH, and may serve as a sensitive neuroimaging biomarker.

Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness

“…However, it has been recently proven that CEST effect from glutamine’s fast-exchanging amine protons cannot be detected under physiological and pathological pHs [12, 17]. Recently, researchers intended to assign CEST at +2 ppm to amine protons in general [67, 68]. Particularly, Jin et al .…”

Advanced MR Methods in Differential Diagnosis of Brain Tumors

“…Amino and hydroxyl protons usually fall in the slow to medium exchange regime (Δω/k exchange ~ 1), but it has been shown that glucose and glycogen can be detected with CEST in animal models at high magnetic field strengths (>9 T, (Chan et al 2012;Nasrallah et al 2013;van Zijl et al 2007)). Recently it was proposed that spin-locking (SL) techniques are more suited for the intermediate exchange regime (Lin et al 2011;Jin et al 2012) and pilot studies could detect myoinositol (Haris et al 2011) and glutamate (Cai et al 2012) using this method. However, no applications in oncology are published yet; thus, a description of these methods would be beyond the scope of this short overview.…”

Amide Proton Transfer Imaging in Clinics: Basic Concepts and Current and Future Use in Brain Tumors and Stroke

“…For the amine proton, which has a peak centered around 3 ppm, the CEST effects appear to increase as pH decreases in the physiologic range (3,8,38,60).…”