Nanosensors for the Chemical Imaging of Acetylcholine Using Magnetic Resonance Imaging.
Yi LuoEric H KimChris A FlaskHeather A ClarkPublished in: ACS nano (2018)
A suite of imaging tools for detecting specific chemicals in the central nervous system could accelerate the understanding of neural signaling events critical to brain function and disease. Here, we introduce a class of nanoparticle sensors for the highly specific detection of acetylcholine in the living brain using magnetic resonance imaging. The nanosensor is composed of acetylcholine-catalyzing enzymes and pH-sensitive gadolinium contrast agents co-localized onto the surface of polymer nanoparticles, which leads to changes in T1 relaxation rate (1/ T1). The mechanism of the sensor involves the enzymatic hydrolysis of acetylcholine leading to a localized decrease in pH which is detected by the pH-sensitive gadolinium chelate. The concomitant change in 1/ T1 in vitro measured a 20% increase from 0 to 10 μM acetylcholine concentration. The applicability of the nanosensors in vivo was demonstrated in the rat medial prefrontal cortex showing distinct changes in 1/ T1 induced by pharmacological stimuli. The highly specific acetylcholine nanosensor we present here offers a promising strategy for detection of cholinergic neurotransmission and will facilitate our understanding of brain function through chemical imaging.
Keyphrases
- magnetic resonance imaging
- high resolution
- contrast enhanced
- resting state
- white matter
- prefrontal cortex
- functional connectivity
- computed tomography
- magnetic resonance
- oxidative stress
- cerebral ischemia
- nitric oxide
- hydrogen peroxide
- multiple sclerosis
- fluorescence imaging
- cerebrospinal fluid
- photodynamic therapy
- mass spectrometry
- blood brain barrier
- subarachnoid hemorrhage
- brain injury
- anaerobic digestion