Central Nervous System Molecular Imaging

It has been over 40 years since the advent of in vivo molecular imaging within the brain, first accomplished with a nonmetabolized analog of glucose, namely ¹⁸F-fluorodeoxyglucose and positron emission tomography (PET). Those initial studies paved the way for quantitative brain imaging of a variety of neurotransmitter systems, enzymes, transporters, cells, and synapses, all of which are being pursued to understand normal physiology and neuropsychiatric disease. Furthermore, new modalities have been developed beyond PET for interrogating-and in some cases manipulating-brain activity. In addition to detection of disease, physicians and investigators increasingly use neuromolecular imaging for target engagement and receptor occupancy in the service of drug development, identifying appropriate patients for clinical trials and ultimately for clinical management and determining prognosis-the latter to be augmented as more molecular brain imaging data are available and analyzed using artificial intelligence. In addition to the neurons themselves, molecular imaging within the brain is pivoting toward understanding the immune environment, for example, neuroinflammation, in analogy to shifts seen in cancer imaging research. Mechanism-guided, targeted imaging is the coin of the realm with a view to enhancing precision medicine for central nervous system disorders.