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Researchers develop first technique for viewing cells and tissues in 3D under the skin.

Scientists have many tools at their disposal for looking at preserved tissue under a microscope in incredible detail, or peering into the living body at lower resolution. What they haven’t had is a way to do both, namely create a three-dimensional real-time image of individual cells or even molecules in a living animal.  Now, researchers at Stanford University have done just that by developing a nanoimaging technique which can glimpse under the skin of a living animal, showing intricate real-time details in three dimensions of the lymph and blood vessels.  The team state that the technique, called MOZART (for MOlecular imaging and characteriZation of tissue noninvasively At cellular ResoluTion), could allow scientists to detect tumours 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 opensource study is published in the journal Scientific Reports.

Previous studies show that a technique exists for peeking into a live tissue several millimeters under the skin, revealing a landscape of cells, tissues and vessels. The technique, called optical coherence tomography, or OCT, isn’t sensitive or specific enough to see the individual cells or the molecules that the cells are producing.  A major issue has also been finding a way of differentiating between cells or tissues; for example, picking out the cancerous cells beginning to multiply within an overall healthy tissue. In other forms of microscopy, researchers have created tags that latch onto molecules or structures of interest to illuminate those structures and provide a detailed view of where they are in the cell or body. The current study developed the first technique for viewing cells and tissues in three dimensions under the skin.

The current study developed computer algorithms that could separate out the frequencies of light scattered by nontoxic nanorods of various lengths and differentiate those from surrounding tissue.  Results, using the ear of a living mouse, show that the nanorods are taken up into the lymph system and transported through a network of valves. Data findings show that by distinguishing between two different size nanorods resonating at different wavelengths in separate lymph vessels, the distinction can be made between those two nanorods in the lymph system and the blood vessels.

The lab state that they could watch individual valves within the lymph vessels open and close to control the flow of fluid in a single direction, something that no other study has achieved before to their knowledge.  They go on to conclude that their technique could allow doctors to monitor how an otherwise invisible tumour under the skin is responding to treatment, or to understand how individual cells break free from a tumour and travel to distant sites.

The team surmise that 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. For the future, the researchers state their technique could be used to learn more about how those diseases progress at the molecular level and also evaluate treatments in individual patients, something that previously hadn’t been possible.

Source: Stanford Bio-X

Blood Vessels in the Ear of a Mouse.  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.
Blood Vessels in the Ear of a Mouse. 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.

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