Medical imaging has a pretty big toolbox: x-ray radiography, ultrasonography, endoscopy, elastography, thermography, magnetic resonance, computerized tomography, positron emission tomography, and simple photography (including smart phone pictures for distance monitoring. Something they all have in common, assuming proper use, is cost effectiveness by reducing the length of hospital stays—for example, a $1,000 MRI vs. $3,000/day for a hospital bed. Most of imaging innovation is additive—that is, improvements of existing modes, though some may be more additive than others. Royal Philips and MIT are researching ultrasound and physiological modeling as a less invasive, and less expensive, way to assess intracranial pressure from brain injuries. Philips, General Electric, Siemens, Samsung and other makers of MRI and CT machines may be looking over their shoulder at what IBM is doing with artificial intelligence to better interpret less expensive technology. And, possibly moving in a more expensive direction, the University of California at Davis is working on a $15.5m NIH grant to develop a whole-body positron emission tomography scanner. PET shows more than the anatomy of MRI or CT imaging; it reveals how tissues function. All high energy scanning could benefit from quicker results and less radiation exposure. Meanwhile, improved illumination agents, such as a “lumifluor” (fluorescent protein) from deep sea shrimp, or synthetic diamonds, offer better ways to see things like tumors, arterial blockages and early signs of Alzheimer’s disease. But a true “game changed” in imaging hasn’t yet reached clinical medicine; it’s still in lab development: nanomicroscopy. Diseases “present” at different observable levels in organs and tissues, but all are rooted in molecules within cells (even a single cell). Aberrations of DNA, RNA, proteins, in particular, represent a chain of events—that is, DNA sends its instructions in RNA messages, and RNA assembles amino acids into proteins. Nucleic acid errors are well established pathologies, but a protein, after forming normally, can undergo shape changing events that cause or contribute to a disease. Some of these faults can be seen in high energy microscopes, but such observation kills cells. To see disease where it originates, at the molecular level in living cells, is nanomicroscopy’s potential and present reality with two designs: photoactivated localization and lattice light sheet microscopes. Both rely on genetically encoded green fluorescent proteins—originally discovered in jellyfish. Recombinant DNA techniques link the fluorescent and target proteins, which viral vectors (or other means) introduce into live cells. Under two wavelengths of light, the fluorescence can be turned on or off at will, showing a particular molecule’s location in, say, a cell’s interior membrane. The lattice light sheet refinement illuminates the fluorescent markers with light intersecting at perpendicular angles. Multiple images are stacked into a computer-sharpened ultra-high resolution final picture. One of the pioneers in this field of nanoscopy is Eric Betzig, a group leader at the Howard Hughes Medical Institute’s Janelia Research Park in Ashburn, VA. For this work he shared the 2014 Nobel Prize in Chemistry.