# Development and Validation of Four Different Methods to Improve MRI-CEST Tumor pH Mapping in Presence of Fat

## TL;DR

This paper introduces four new methods to improve tumor pH measurements using MRI by addressing interference from fat signals.

## Contribution

The novel contribution is the development and validation of four post-processing methods to correct fat signal interference in CEST-MRI pH measurements.

## Key findings

- Four post-processing approaches were tested to correct fat signal interference in CEST-MRI.
- Only the water pool Lorentzian fitting method provided highly accurate pH measurements in tumor-bearing mice.
- The methods enable accurate tumor pH measurements even with moderate to high fat fractions.

## Abstract

CEST-MRI is an emerging imaging technique suitable for various in vivo applications, including the quantification of tumor acidosis. Traditionally, CEST contrast is calculated by asymmetry analysis, but the presence of fat signals leads to wrong contrast quantification and hence to inaccurate pH measurements. In this study, we investigated four post-processing approaches to overcome fat signal influences and enable correct CEST contrast calculations and tumor pH measurements using iopamidol. The proposed methods involve replacing the Z-spectrum region affected by fat peaks by (i) using a linear interpolation of the fat frequencies, (ii) applying water pool Lorentzian fitting, (iii) considering only the positive part of the Z-spectrum, or (iv) calculating a correction factor for the ratiometric value. In vitro and in vivo studies demonstrated the possibility of using these approaches to calculate CEST contrast and then to measure tumor pH, even in the presence of moderate to high fat fraction values. However, only the method based on the water pool Lorentzian fitting produced highly accurate results in terms of pH measurement in tumor-bearing mice with low and high fat contents.