Sensing intracellular calcium ions using a manganese-based MRI contrast agent

Area of Science:

• Biomedical Imaging
• Neuroscience
• Cellular Biology

Background:

• Calcium ions are crucial for cellular signal transduction and various physiological processes.
• Optical probes for intracellular calcium imaging face limitations in deep tissue and intact organisms.
• Noninvasive detection of deep tissue calcium signaling remains a significant challenge.

Purpose of the Study:

• To develop a novel manganese-based contrast agent for intracellular calcium monitoring using MRI.
• To enable noninvasive detection of calcium signaling in optically inaccessible tissues.
• To validate a new probe for real-time measurement of neural activation.

Main Methods:

• Synthesis of a manganese-based paramagnetic contrast agent, ManICS1-AM.
• Cell loading with ManICS1-AM and stimulation with pharmacological agents or optogenetics.
• Intracellular calcium level monitoring using Magnetic Resonance Imaging (MRI).
• Application of ManICS1-AM in rodent brains for neural activation measurement.

Main Results:

• ManICS1-AM successfully permeated cells and allowed for intracellular calcium level monitoring via MRI.
• Changes in MRI contrast correlated directly with signals from fluorescent calcium indicators.
• MRI-based measurement of neural activation in rodent brain regions was achieved.

Conclusions:

• ManICS1-AM is a validated calcium sensor for MRI-based imaging.
• The probe overcomes limitations of optical methods for deep tissue and brain imaging.
• ManICS1-AM facilitates noninvasive monitoring of neural activity in vivo.