Improved pH measurements with a single PARACEST MRI contrast agent

Area of Science:

• Biomedical Imaging
• Magnetic Resonance Imaging
• Chemical Exchange Saturation Transfer (CEST)

Background:

• Accurate extracellular pH measurement is vital for assessing pH-dependent and pH-altering therapies.
• Current methods may have limitations in precision and applicability.
• Paramagnetic chemical exchange saturation transfer (PARACEST) offers a potential avenue for pH imaging.

Purpose of the Study:

• To evaluate a novel PARACEST MRI contrast agent, Yb-DO3A-oAA, for accurate and precise extracellular pH measurement.
• To establish the correlation between the agent's CEST effects and physiological pH.
• To assess the influence of various factors on pH measurement accuracy.

Main Methods:

• Utilized a Yb-DO3A-oAA PARACEST MRI contrast agent.
• Measured CEST effects dependent on pH.
• Derived a ratio from CEST effects to correlate with pH.
• Assessed measurement precision, accuracy, and independence from concentration and T1 relaxation times.
• Investigated temperature dependency and the impact of MR coalescence.

Main Results:

• A linear correlation was established between the derived CEST ratio and pH across the physiological range.
• pH measurement achieved a precision of 0.21 pH units and accuracy of 0.09 pH units.
• The pH measurement was independent of agent concentration and T1 relaxation times.
• Temperature was found to influence measurements, and MR coalescence effects were observed, particularly at high pH.

Conclusions:

• The single PARACEST MRI contrast agent, Yb-DO3A-oAA, can accurately measure extracellular pH.
• Ratiometric analysis of CEST effects can mitigate challenges like MR coalescence.
• Empirical calibration under specific conditions is necessary for reliable subsequent measurements.