Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients

Abstract

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH‐weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model‐based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model‐based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model‐based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model‐based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Selecting the reference image for registration of CEST series

“…CEST maps can be substantially different in terms of quantitative UIs when different reference images are chosen during registration. In contrast to the use of S 0 as the reference image, as described in many reports (5,7–11), we showed here, in five normal volunteers and eight brain tumor patients, that S 0 is actually the worst reference image while the 3.5 ppm dynamic generates a higher, though not statistically significantly different, average UI than other saturated dynamics for APT tumor imaging.…”

“…This exchange process, typically occurring at various rates from tens of Hertz to thousands of Hertz, serves as a signal amplifier for the low-concentration biomolecules when detecting effects on the high-concentration water signal. CEST imaging has been shown to be useful in many human brain applications, such as tumors (2–4) and strokes (5,6). …”

Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla

“…The significance of using APT imaging is that the MRI contrast at the cellular protein level is achieved indirectly through the bulk water signal used in daily imaging. Many encouraging results have been reported by different research groups, regarding promising APT-weighted (APTW) signals as image biomarkers for brain tumours [22–27] and other cancers in the prostate, breast, and neck [28–31], and for cerebral ischemia [32–34], Parkinson’s disease [35], and ventral hernia [36]. To the best of our knowledge, PCNSLs have never been studied with APT imaging, and the APT-MRI parameters have also not been quantitatively compared between PCNSLs and HGGs.…”

Novel Magnetic Resonance Imaging Techniques in Brain Tumors

“…Amide proton transfer was then applied in human brain tumors by Jones et al 95 showing increased contrast in regions of tumor, which were again attributed to increased protein and peptide content. Since then, additional studies have implemented APT imaging in human gliomas at 3 T. 96,97 In addition, APT has been applied in cases of ischemia, 98,99 stroke, 100,101 and multiple sclerosis, 102 as well as imaging of the breast 103 and prostate 104 in humans and in a lung cancer mouse model. 105 The APTeffects in healthy brain tissue have also been characterized at 7 T, 106 where the effects of nuclear Overhauser enhancement are more prevalent.…”