# CEST Contrasts Exhibit Significant Regional Variations in the Human Brain at 3 T

## TL;DR

This study shows that CEST MRI contrast varies significantly across different brain regions, which is important for detecting subtle changes in neurological diseases.

## Contribution

The study provides a baseline reference for regional CEST contrast variability in healthy brains at 3T, aiding in clinical interpretation.

## Key findings

- CEST contrasts show significant regional differences in gray and white matter across brain regions.
- Lower GM signals were observed in the frontal lobe and higher in the calcarine sulcus for most CEST contrasts.
- Low intersubject variability was found, offering robust normative values for future clinical comparisons.

## Abstract

Chemical exchange saturation transfer (CEST) MRI is a promising molecular imaging technique with established clinical relevance in neuro‐oncology. While CEST contrast differences between gray matter (GM) and white matter (WM) are documented, brain region–specific contrast variations remain underexplored. This study investigates the regional variability of CEST contrasts in healthy brains to provide a baseline reference, which could enhance the detection of subtle pathological changes in clinical settings. Ten healthy volunteers (five female, mean age 25 ± 3.1 years) underwent 3D CEST imaging on a 3‐T Siemens Prisma scanner. Using a custom segmentation tool, GM and WM regions of interest (ROIs) were automatically selected in the frontal, parietotemporal, and occipital regions and the calcarine sulcus to analyze regional contrast changes for the relaxation‐compensated MTRRex and asymmetry‐based APTw CEST contrasts. Individual and grouped analyses showed significant regional differences in GM and WM for all CEST contrasts. Globally, significant GM‐WM differences were also detected for the APTw, MTRRex AMIDE, and MTRRex ssMT, which demonstrated higher GM contrast values for APTw and MTRRex AMIDE and lower GM contrast values for the MTRRex ssMT. Regionally, all contrasts showed reduced GM signals in the frontal lobe and increased signals in the calcarine sulcus when compared to the occipital and parietotemporal lobe; however, these differences were less pronounced for MTRRex rNOE and MTRRex ssMT. Relaxation‐compensated CEST and APTw CEST contrast values exhibit significant regional variation in the healthy brain, highlighting the importance of consistent ROI placement in clinical studies. At the same time, low intersubject variability was observed, providing robust normative values for future comparisons. These regional reference values can aid in the detection of subtle pathological changes in CEST MRI by offering a reliable baseline for interpreting deviations in patient data.

Both relaxation‐compensated and asymmetry‐based APTw CEST contrasts show significant regional variability in healthy human brains.

These findings expand our knowledge about CEST contrasts and highlight the need for consistent placement of control ROIs in neuroimaging, which is particularly crucial in pathologies that only lead to subtle differences in CEST contrast.