Amide Proton Transfer MRI Research Articles

A Simple Model for Understanding the Origin of the Amide Proton Transfer MRI Signal in Tissue

Amide proton transfer (APT) imaging is a new molecular MRI technique that gives contrast at the cellular protein level. To better understand the origin of the APT signal in tissue, fresh and cooked hen eggs (n = 4) were imaged at 4.7 Tesla. The APT effect was quantified using the asymmetry in the magnetization transfer ratio (MTR(asym)) at the composite amide proton resonance frequency (3.5 ppm from the water resonance). The measured APT signals were significantly higher in the fresh egg white (20.1% ± 0.9%) than in the fresh egg yolk (-1.4% ± 1.1%; P < 0.001), and in the cooked egg white (2.8% ± 0.7%; P < 0.001), all of which have similar absolute protein contents. The data support the notion that the APT effect observed in vivo is associated with mobile proteins in tissue, such as those in the cytoplasm.

Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI—Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH

Amide proton transfer (APT) MRI is sensitive to ischemic tissue acidosis and has been increasingly used as a research tool to investigate disrupted tissue metabolism during acute stroke. However, magnetization transfer asymmetry (MTR(asym)) analysis is often used for calculating APT contrast, which only provides pH-weighted images. In addition to pH-dependent APT contrast, in vivo MTR(asym) is subject to a baseline shift (ΔMTR'(asym)) attributable to the slightly asymmetric magnetization transfer (MT) effect. Additionally, APT contrast approximately scales with T(1) relaxation time. Tissue relaxation time may also affect the experimentally obtainable APT contrast via saturation efficiency and RF spillover effects. In this study, we acquired perfusion, diffusion, relaxation and pH-weighted APT MRI data, and spectroscopy (MRS) in an animal model of acute ischemic stroke. We modeled in vivo MTR(asym) as a superposition of pH-dependent APT contrast and a baseline shift ΔMTR'(asym) (i.e., MTR(asym)=APTR(pH)+ΔMTR'(asym)), and quantified tissue pH. We found pH of the contralateral normal tissue to be 7.03±0.05 and the ipsilateral ischemic tissue pH was 6.44±0.24, which correlated with tissue perfusion and diffusion rates. In summary, our study established an endogenous and quantitative pH imaging technique for improved characterization of ischemic tissue acidification and metabolism disruption.

Amide proton transfer (APT) MRI for detecting brain tumor recurrence

Amide proton transfer (APT) MRI for detecting brain tumor recurrence

Fast multislice pH‐weighted chemical exchange saturation transfer (CEST) MRI with Unevenly segmented RF irradiation

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging technique for measuring microenvironment properties via dilute CEST labile groups. Conventionally, CEST MRI is implemented with a long radiofrequency irradiation module, followed by fast image acquisition to obtain the steady state CEST contrast. Nevertheless, the sensitivity, scan time, and spatial coverage of the conventional CEST MRI method may not be optimal. Our study proposed a segmented radiofrequency labeling scheme that includes a long primary radiofrequency irradiation module to generate the steady state CEST contrast and repetitive short secondary radiofrequency irradiation module immediately after the image acquisition so as to maintain the steady state CEST contrast for multislice acquisition and signal averaging. The proposed CEST MRI method was validated experimentally with a tissue-like pH phantom and optimized for the maximal contrast-to-noise ratio. In addition, the proposed sequence was evaluated for imaging ischemic acidosis via pH-weighted endogenous amide proton transfer MRI, which showed similar contrast as conventional amide proton transfer MRI. In sum, a fast multislice relaxation self-compensated CEST MRI sequence was developed, with significantly improved sensitivity and suitable for in vivo applications.

Investigation of optimizing and translating pH-sensitive pulsed-chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner.

Chemical exchange saturation transfer (CEST) MRI provides a sensitive detection mechanism that allows characterization of dilute labile protons usually undetectable by conventional MRI. Particularly, amide proton transfer (APT) imaging, a variant of CEST MRI, has been shown capable of detecting ischemic acidosis, and may serve as a surrogate metabolic imaging marker. For preclinical CEST imaging, continuous-wave (CW) radiofrequency (RF) irradiation is often applied so that the steady state CEST contrast can be reached. On clinical scanners, however, specific absorption rate (SAR) limit and hardware preclude the use of CW irradiation, and instead require an irradiation scheme of repetitive RF pulses (pulsed-CEST imaging). In this work, CW- and pulsed-CEST MRI were systematically compared using a tissue-like pH phantom on an imager capable of both CW and pulsed RF irradiation schemes. The results showed that the maximally obtainable pulsed-CEST contrast is approximately 95% of CW-CEST contrast, and their optimal RF irradiation powers are equal. Moreover, the pulsed-CEST sequence was translated to a 3 Tesla clinical scanner and detected pH contrast from the labile creatine amine groups (1.9 ppm). Furthermore, pilot endogenous APT imaging of normal human volunteers was demonstrated, warranting future APT MRI of stroke patients to elucidate its diagnostic value.