Gold nanorods within the blood vessels of a mouse ear appear green. The lower right shows vessels within a tumor that lies under the skin. Credit: de la Zerda lab
The technique, called MOZART (for MOlecular imaging and characteriZation of tissue noninvasively At cellular ResoluTion), could one day allow scientists to detect tumors in the skin, colon or esophagus, or even to see the abnormal blood vessels that appear in the earliest stages of macular degeneration – a leading cause of blindness. The technique could allow doctors to monitor how an otherwise invisible tumor under the skin is responding to treatment, or to understand how individual cells break free from a tumor and travel to distant sites.
A technique exists for peeking into a live tissue several millimeters under the skin, revealing a landscape of cells, tissues and vessels. But that technique, called optical coherence tomography, OCT, isn’t sensitive or specific enough to see the individual cells or the molecules that the cells are producing.
Image: Overview of MOZART and its in vivo imaging capabilities. (a) Conventional OCT scan of the mouse pinna shows micro-anatomic structures in 2D (B-scan), 2D en face slice, and volumetric rendering. The dashed lines on the volumetric rendering of the OCT structure show the locations of the B-scan and en face slice. (b) MOZART combines SD-OCT with large GNRs (LGNRs) as contrast agents that are detected with custom adaptive post-processing algorithms. This approach can be used to create images that contain additional functional information in vivo. The MOZART image reveals subcutaneously-injected LGNRs with two different spectra (green and cyan) draining into lymph vessels as well as flow in blood vessels (overlay in red). The conventional OCT and MOZART 3D images depict the same region (each volume is 4 mm × 4 mm × 1 mm).
What the team needed were nanorods, but big ones. Longer nanorods vibrate at lower frequencies, or wavelengths, of light. Those vibrations scatter the light, which the microscope detects. If all the other tissues are vibrating in a white noise of higher frequencies, longer nanorods would stand out.
SoRelle’s challenge was to manufacture longer nanorods that were nontoxic, stable and very bright. The next challenge was filtering out the nanorods’ frequency from the surrounding tissue. With SoRelle’s large nanorods and Liba’s sensitive algorithms, de la Zerda and his team had solved the initial problem of detecting specific structures in three-dimensional images of living tissues. The resulting 3D, high-resolution images were so big – on the order of gigapixels – that the team needed to develop additional algorithms for analyzing and storing such large images.
The team tested their technology in the ear of a living mouse, where they were able to watch as the nanorods were taken up into the lymph system and transported through a network of valves. They were able to distinguish between 2 different size nanorods that resonated at different wavelengths in separate lymph vessels, and they could distinguish between those two nanorods in the lymph system and the blood vessels. In one study, they could watch individual valves within the lymph vessels open and close to control the flow of fluid in a single direction. This detailed imaging was de la Zerda’s initial goal when he started his lab in 2012, though he was frequently told it would be impossible.
Having shown that the gold nanorods can be seen in living tissue, the next step is to show that those nanorods can bind to specific kinds of cells, like skin cancer or abnormal vessels in early stage macular degeneration. Then, the technique could be used to learn more about how those diseases progress at the molecular level and also evaluate treatments in individual patients. http://news.stanford.edu/pr/2016/pr-mozart-imaging-nanorods-031816.html  http://www.nature.com/articles/srep23337
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