Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis

Abstract

Purpose To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. Procedures Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. Results There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. Conclusions Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

Diagnostic performance between contrast enhancement, proton MR spectroscopy, and amide proton transfer imaging in patients with brain tumors

“…First, despite several researches including the current study, the origin of APT signal still remains unclear. Many researchers have demonstrated some biological signature such as cytosolic protein including folding status or amount of specific protein contributes APT signal . Furthermore, there are some discussions about the confounding effects of asymmetry of the solid‐phase MT effect and possible intra‐ and intermolecular nuclear Overhauser effects (NOE) of aliphatic protons and the T 1 value of the tissue to the APT‐weighted image .…”

Clinical applications of chemical exchange saturation transfer (CEST) MRI

“…Although the amides of semisolid proteins have a broad range of MR frequencies and short T 1 and T 2 relaxation time constants that can generate MT effects, mobile proteins and peptides have longer relaxation times and have amide groups that exhibit a more narrow range of MR frequencies centered at ∼3.5 ppm. The concentration of amide groups in endogenous mobile peptides and proteins is ∼5–8 mM in most tissues . These three conditions are appropriate for detection of amide protons with CEST MRI.…”

“…APT MRI has been used empirically to analyze solid tumors, although the interpretation of the imaging contrast is still under study. Strong evidence indicates that the concentrations of mobile proteins and peptides are higher in tumors, which generate higher APT MRI contrast . Metabolically active tumors produce excess lactic acid in the extracellular tumor microenvironment as a consequence of enhanced aerobic glycolysis, known as the Warburg effect .…”

Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury

“…APT imaging is an important molecular MRI technique that can generate contrast based on tissue pH (Jin et al, 2012; Sun et al, 2007; Tietze et al, 2014; Zhou and van Zijl, 2011) or concentrations of endogenous mobile proteins and peptides (Jiang et al, 2016; Yan et al, 2015; Zhou et al, 2013). The most important novel finding of this study was that APTw signals increased significantly in the perilesional brain regions of untreated TBI rats at 3 and 7 days.…”