Magnetic resonance imaging of calcium ions could unlock the brain’s mysteries

Calcium ions are a key messenger in neural activity and synaptic signaling. Magnetic resonance imaging has emerged as the leading way to noninvasively measure intracellular and extracellular calcium exchanges on large scales in vertebrates of all sizes, which helps scientists discover the neural mechanisms that underlie memory, behaviors, emotional states, and more.

Recent innovations with MRI sensor technology have enabled the imaging of a wide range of chemical principles and physical mechanisms in the brain. Miller et al. summarize state-of-the-art MRI-based calcium sensors, their performance, in vivo applications, and challenges related to sensitivity.

“Our goal in compiling this review was to highlight these pioneering innovations,” said author Arnab Mukherjee. “Each one brings us another step closer to the ambitious goal of connecting brainwide calcium signals with MRI readouts.”

Traditional approaches for studying calcium fluctuations involve imaging with fluorescent dye. While this has led to numerous breakthroughs in neuroscience, it can only cover about 0.2% of a mouse’s brain at a time.

In contrast, MRI can sample larger tissue sizes and depths, which is necessary for decoding neural mechanisms, such as cognitive function and sensorimotor activity, and understanding the effects of neurodegeneration.

The authors highlight future potential for MRI calcium sensors in complimenting innovations in reporter gene technology and gene delivery to map calcium activity in genetically targeted cells. Additionally, future improvements in sensitivity will open applications to most problems in neuroscience.

Mukherjee hopes the review can serve as a reference and roadmap to inspire the next generation of calcium imaging technologies and initiate more collaborations between biologists and imaging scientists.

Source: “Calcium-responsive contrast agents for functional magnetic resonance imaging,” by Austin D. C. Miller, Harun F. Ozbakir, and Arnab Mukherjee, Chemical Physics Reviews (2021). The article can be accessed at https://doi.org/10.1063/5.0041394 .