Cucurbit[6]uril Hyperpolarized Chemical Exchange Saturation Transfer Pulse Sequence Parameter Optimization and...

Area of Science:

• Medical Imaging
• Biophysics
• Nanotechnology

Background:

• Molecular imaging is key for personalized medicine, requiring effective contrast agents.
• Hyperpolarized ¹²⁹ Xe MRI with chemical exchange saturation transfer (HyperCEST) offers high efficiency.
• Cucurbit[6]uril (CB6) shows promise as a HyperCEST agent but needs clinical optimization.

Purpose of the Study:

• Optimize MRI pulse sequence parameters for CB6 in clinical settings.
• Evaluate the performance of different depolarization pulse shapes.
• Determine the detectability limit of CB6 in blood using optimized sequences.

Main Methods:

• Optimized MRI pulse sequence parameters for CB6 in phosphate-buffered saline (PBS) and bovine blood.
• Tested four depolarization pulse shapes: sinusoidal, 3-lobe sinc (3LS), rectangular, and hyperbolic secant.
• Assessed CB6 detectability limits in a clinical 3.0T MRI scanner.

Main Results:

• The 3-lobe sinc (3LS) pulse shape yielded the best performance, achieving 24% depletion in a 25 μM CB6 PBS solution.
• CB6 detectability limit in citrated bovine blood was 100 μM, with 30% ±9% HyperCEST depletion.
• The ¹²⁹ Xe HyperCEST effect was observed in red blood cells for the first time, comparable to plasma.

Conclusions:

• Optimized 3LS pulse sequences significantly enhance CB6 performance in clinical MRI scanners.
• Achieved a clinically relevant detectability limit for CB6 in blood, paving the way for in vivo applications.
• Demonstrated the feasibility of observing the ¹²⁹ Xe HyperCEST effect within red blood cells, expanding its molecular imaging potential.