Simultaneous in vivo pH and temperature mapping using a PARACEST-MRI contrast agent

Area of Science:

• Biomedical Imaging
• Chemical Exchange Saturation Transfer (CEST) MRI
• In Vivo Molecular Imaging

Background:

• Altered tissue temperature and pH are hallmarks of pathological conditions like tumors and stroke, indicating metabolic distress.
• In vivo pH and temperature measurements can serve as critical biomarkers for disease detection and treatment monitoring.
• Current methods for in vivo pH and temperature assessment face limitations in accuracy and simultaneous measurement capabilities.

Purpose of the Study:

• To develop and validate a novel chemical exchange saturation transfer (CEST) MRI method for simultaneous in vivo pH and temperature mapping.
• To utilize a thulium (Tm3+) complex with DOTAM-Glycine-Lysine ligand for pH and temperature quantification.
• To demonstrate the feasibility of this technique in preclinical models.

Main Methods:

• Employing a thulium (Tm3+) complex (Tm3+-DOTAM-Gly-Lys) as a CEST agent.
• Determining pH from the linewidth of the chemical exchange saturation transfer spectrum's asymmetry curve.
• Obtaining simultaneous temperature maps using the chemical shift of the CEST peak.
• Validating pH measurements across a range of 6.0-8.0 pH units at 37°C with high precision.

Main Results:

• Achieved pH mapping with an inter-pixel standard deviation below 0.1 pH units in phantom studies.
• Demonstrated simultaneous temperature and pH mapping in a mouse leg model (N=3).
• Reported in vivo measurements of mean pH as 7.2 ± 0.2 and temperature as 37.4 ± 0.5°C in the mouse leg.

Conclusions:

• The developed CEST-based method enables accurate and simultaneous in vivo pH and temperature mapping.
• This technique holds promise as a valuable tool for non-invasive monitoring of metabolic changes in various diseases.
• Further research can explore its application in clinical settings for improved disease diagnosis and management.