Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts

Abstract

Amide proton transfer (APT) imaging is a variant of magnetization transfer (MT) imaging, in which the contrast is determined by a change in water intensity due to chemical exchange with saturated amide protons of endogenous mobile proteins and peptides. In this study, eight Fisher 344 rats implanted with 9L gliosarcoma cells and six nude rats implanted with human glioblastoma cells were imaged at 4.7 T. There were increased signal intensities in tumors in the APT-weighted images. The contrast of APT imaging between the tumor and contralateral brain tissue was about 3.9% in water intensity (1.49% ± 0.66% versus −2.36% ± 0.19%) for the more uniformly hypercellular 9L brain tumors, and it was reduced to 1.6% (−1.18% ± 0.60% versus −2.77% ± 0.42%) for the human glioblastoma xenografts that contained hypocellular zones of necrosis. The preliminary results show that the APT technique at the protein level may provide a unique MRI contrast for the characterization of brain tumors.

In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma

“…Normal, healthy brain tissue displayed negative and lower APT values compared with tumor at baseline and 1 wk ( Fig. 2A, white arrow) as reported in previous literature (16). In all untreated control animals, the enhanced area increased drastically at 1 wk relative to baseline (7. ; P = 0.87).…”

“…The images obtained at 29 frequency offsets were first collected to obtain a z-spectrum. The z-spectrum was fitted on a pixel-by-pixel basis according to the procedure using the 12th-order polynomial fitting on positive and negative sides of frequency offsets, respectively, as previously reported (16,17). Subsequently, the original z-spectrum was corrected pixel-wise for the any B 0 inhomogeneity through interpolation and centering of the z-spectrum.…”

Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging

“…The high APT signal in tumours can be attributed to abundant concentration of mobile proteins and peptides in cellular cytoplasm. Higher cell density reported in HGGs in a human study [22] and animal study [23] would be a cause of higher concentration of mobile proteins and peptides. The present results revealed that the ADC did not differ between the high and low grades, indicating that the cell density was not very different between the grades whereas the APT signals were clearly different between the grades.…”

Understanding quantitative pulsed CEST in the presence of MT

“…Chemical exchange was first investigated by nuclear magnetic resonance (NMR) (1)(2)(3)(4) and was proposed as an MRI method by Wolff and Balaban (5); however, it was only recently introduced as a clinical technique (6). Its utility as a contrast mechanism has been demonstrated in brain tumors (7,8) and in identification of reperfusable regions of stroke damage (9). As the chemical exchange is sensitive to hydrogen ion concentration, CEST experiments may allow quantification of pH as well.…”