Precision neuroradiology: mapping the nodes and networks that link genes to behaviour

What is the future of neuroradiology in the era of precision medicine? As with any big change, this transformation in medicine presents both challenges and opportunities, and to flourish in this new environment we will have to adapt. It is difficult to predict exactly how neuroradiology will evolve in this shifting landscape, but there will be changes in both what we image and what we do. In terms of imaging, we will need to move beyond simply imaging brain anatomy and toward imaging function, both at the molecular and circuit level. In terms of what we do, we will need to move from the periphery of the clinical enterprise toward its center, with a new emphasis on integrating imaging with genetic and clinical data to form a comprehensive picture of the patient that can be used to direct further testing and care. The payoff is that these changes will align neuroradiology with the emerging field of precision psychiatry, which promises to replace symptom-based diagnosis and trial-and-error treatment of psychiatric disorders with diagnoses based on quantifiable genetic, imaging, physiologic, and behavioural criteria and therapies targeted to the particular pathophysiology of individual patients. Here we review some of the recent developments in behavioural genetics and neuroscience that are laying the foundation for precision psychiatry. By no means comprehensive, our goal is to introduce some of the perspectives and techniques that are likely to be relevant to the precision neuroradiologist of the future.

DNA microscopy: Optics-free spatio-genetic imaging by a stand-alone chemical reaction

Analyzing the spatial organization of molecules in cells and tissues is a cornerstone of biological research and clinical practice. However, despite enormous progress in profiling the molecular constituents of cells, spatially mapping these constituents remains a disjointed and machinery-intensive process, relying on either light microscopy or direct physical registration and capture. Here, we demonstrate DNA microscopy, a new imaging modality for scalable, optics-free mapping of relative biomolecule positions. In DNA microscopy of transcripts, transcript molecules are tagged in situ with randomized nucleotides, labeling each molecule uniquely. A second in situ reaction then amplifies the tagged molecules, concatenates the resulting copies, and adds new randomized nucleotides to uniquely label each concatenation event. An algorithm decodes molecular proximities from these concatenated sequences, and infers physical images of the original transcripts at cellular resolution. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system.