Photoacoustic Tomography Helps Detect Deep Cancer Cells

Genetically modifying glioblastoma cells with a bacterial phytochrome enables them to be identified as deep as one centimeter inside tissue using photoacoustic tomography (PAT).

Researchers at Washington University (WUSTL; St. Louis, MO, USA) and Albert Einstein College of Medicine (New York, NY, USA) successfully combined deep-penetration, high-resolution PAT with a BphP1, a reversibly switchable, phytochrome derived from Rhodopseudomonas palustris bacterium. Since BphP1 has the ability to differentiate between red and near-infrared (NIR) light-absorption states, the researchers took images of the modified cancerous tissue using the two types of light and compared them to get a highly sensitive, high-resolution image of the cancer cells.

Furthermore, the combined single-wavelength PAT and efficient BphP1 photo-switching between red and NIR states enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth, and improved spatial resolution. This allowed the researchers to monitor tumor growth and metastasis with 100-μm resolution at depths approaching 10 mm and image individual cancer cells with a sub-optical diffraction resolution of about 140 nm. The study was published on November 9, 2015, in Nature Methods.

“This technique is extremely useful for cancer imaging. When we first look at the early-stage cancer, cancer tissue does not differ much from the background, healthy tissue; because the abundant blood gives strong signals, the cancer cells don't stand out,” said lead author biomedical engineer Junjie Yao, PhD, of WUSTL. “Now, with this new technology, we can see cancer cells in a tiny bit of tissue when the cancer is small.”

“Genetic encoding of the protein allows us to image and track targeted biological processes deep in tissue. The optical switching property of the protein enables new imaging capability,” said senior author Lihong Wang, PhD, of WUSTL. “This technology provides a promising new tool to biologists for high-resolution, deep imaging of cancer with genetic specificity as well as for drug screening in living tissue.”

PAT of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity.

Related Links:
Washington University
Albert Einstein College of Medicine