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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 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.

“To identify a solid tumor, tumor margins, and metastasis requires cutting and slicing tissue, staining it with dye, and looking at it under a microscope in a pathology lab next door—a process that could take 15 to 20 minutes,” says Xie. “Here, we don’t need a biopsy; we can obtain almost identical images without cutting the tissue.”

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.

However, Xie says, the signal from Raman spectroscopy is weak, particularly when applied to living tissue, where molecular composition is heterogeneous. A specific molecular signal could be lost amidst other backscattered noise. To improve sensitivity, 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.

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Credit: Brian Saar & Christian Freudiger / Harvard University
Video by Sunney Xie/Harvard University

Tagged: Biomedicine, imaging, MRI, molecular imaging, PET

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