Lasers let scientists watch red blood cells in living mice and an alternative to biopsies

Seeing Red: A new imaging technique produces video-quality images of red blood cells in living tissue. Researchers used the technology to observe red blood cells (shown) moving through the capillaries of live mice.
Credit: Sunney Xie/Harvard University

MIT Technology Review reports that scientists at Harvard University have developed a noninvasive imaging technique that captures images at the molecular level so quickly that they can “watch” red blood cells move through the capillaries of a live mouse. The team is working to adapt the techniques to MRI which would enable scans of the surface of deeper tissues and organs to enable for screening for colon cancer and other diseases.

The system uses two laser beams set at different frequencies to excite specific types of molecules in the skin. A custom-designed detector picks up the excited molecular signal and translates it into an image.

Sunney Xie, professor of chemistry and chemical biology at Harvard, says the technique could be a noninvasive alternative to often painful and time-consuming skin biopsies.

Currently, systems like magnetic resonance imaging (MRI) and positron emission tomography (PET) serve as windows into the molecular world. Clinicians use these tools to identify diseases like cancer. To detect specific molecules or cancerous cells, MRI requires the patient to ingest or inject contrast agents, and PET requires low doses of radioactive substances. However, scientists have found that these compounds, also referred to as “labels,” may harm or alter normal cellular processes.

In contrast, Xie’s technique is label-free, drawing upon a noninvasive imaging system called Raman spectroscopy. Named after Indian scientist C.V. Raman, the technique takes advantage of the fact that certain molecular bonds vibrate at specific frequencies. When a monochromatic laser illuminates a molecular sample, the molecules scatter the light back in various ways depending on their natural vibrations

To improve sensitivity (and pick up the weak signal), Xie and graduate students Brian Saar and Christian Freudiger developed a high-speed imaging setup with two lasers instead of the conventional one, exploiting a process known as stimulated Raman spectroscopy. The scientists’ goal is to produce label-free images of a wide range of molecules in living animals and humans.

So far, Xie and his colleagues have only been able to image at a depth of 100 microns, mostly due to the limitations of laser-based techniques. Xie says a solution may be to pair the technique with an imaging system like MRI, which can produce images deeper in the body, though with less clarity.

The team is working with mechanical engineer Eric Seibel at the University of Washington to design an endoscope that can house the two-laser system, in order to thread it through the body and create detailed images of tissues and organs. With such a capability, says Ji-Xin Cheng, associate professor of biomedical engineering at Purdue University, doctors may be able to identify other diseases that manifest on the surface of organs other than skin.

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