Contradiction between amide‐CEST signal and pH in breast cancer explained with metabolic MRI

Abstract

Purpose Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods In this study we combined APT MRI and 31P‐MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty‐two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

In vivo characterization of downfield peaks at 9.4 T: T2 relaxation times, quantification, pH estimation, and assignments

“…There are many exchangeable amide protons with resonances between 5.0 and 10.0 ppm. The CEST amide proton transfer signal has shown improved contrast between healthy and diseased tissue in diseases such as cancer or stroke 9‐11 . The CEST amide signal has, however, a strong dependence on both the concentration of mobile amide protons and pH, as demonstrated by simulations 12 and on rat brain metastasis 13 .…”

Comparative Study of Amide Proton Transfer‐Weighted Imaging and Intravoxel Incoherent Motion Imaging in Breast Cancer Diagnosis and Evaluation

“…For example, Klomp et al 14 assessed the reproducibility of APTWI in the breast at 7.0T MRI, and Zaric et al 15 explored the value of APTWI in the evaluation of tumor grade and cell proliferation in breast cancer. Also, some reports also have explored its reliability in the evaluation of lymphatic metastasis of breast cancer 16 and normal fibroglandular breast tissue 17 . However, these studies did not discuss the differences in APTWI‐related parameters between benign and malignant lesions and the correlations of these parameters with prognostic factors.…”

Simultaneous proteoglycans and hypoxia mapping of chondrosarcoma environment by frequency selective CEST MRI

“…Some authors reported a decrease of the CEST effect on the pH, 49,50 whereas others observed the opposite. 51,52 Most of these APT CEST effects were obtained after performing the so-called magnetization transfer ratio asymmetry analysis. The key assumption in this data processing is that for negative offsets, only the direct water saturation effect is recorded.…”