New Approaches to Deep-Tissue Imaging

New Approaches to Deep-Tissue Imaging

Near infrared fluorescent proteins (NIR FPs) are probes that allow for optical imaging of molecules and structures deep within tissues. Modern NIR FPs are engineered from bacterial phytochromes (photoreceptors that plants and some bacteria use to detect light) that are complexed with biliverdin (a breakdown product of heme, the hemoglobin subunit that gives blood its red color). In November, scientists led by Vladislav Verkhusha, Ph.D., published two papers, in Chemistry & Biology and in Nature Methods. The Chemistry & Biology paper introduced several new—and so far brightest—NIR FPs and explained, for the first time, the molecular basis for the diverse fluorescent colors produced by NIR FPs. This study also offered a molecular engineering strategy for rationally designing multicolor NIR FPs. The Nature Methods paper involved a hybrid imaging technology called photoacoustic tomography (PAT). In PAT, biological material is zapped with laser pulses and the absorbed laser energy is converted into heat, which causes the targeted tissue to briefly expand and emit ultrasound. Ultrasonic transducers detect these ultrasound waves, which yield images when analyzed. In this study, Dr. Verkhusha for the first time carried out NIR imaging by combining PAT with a non-fluorescent natural bacterial phytochrome. He obtained deep-tissue imaging with improved sensitivity and resolution compared with standard PAT. This new imaging approach can be used for studying health problems including brain disorders and cancer by targeting the phytochrome probes to specific subsets of cells and even subcellular compartments. Dr. Verkhusha is professor of anatomy & structural biology.