Although melanoma is one of the less common types of skin cancer, experts consider it fatal because it accounts for the majority of skin cancer deaths (about 75 percent). It is a malignant tumor of melanocytes – cells found predominantly in skin, but are also found in the bowel and the eye. Despite many years of intensive laboratory and clinical research, early surgical resection of thin tumors still gives the greatest chance of cure.
So a great deal rides on the accuracy of the initial surgery, where the goal is to remove as little tissue as possible while obtaining “clean margins” all around the tumor. Until now, no imaging technique has been up to the task of resolving the melanoma accurately enough to guide surgery; this has motivated many teams, including by Lihong Wang and Younan Xia from Washington University, St. Louis.
Traditional methods tend to cut well beyond the visible margins of the lesion, since surgeons want to ensure they remove all the malignant tissue. The new solution, described in the July issue of ACS Nano, combines an innovative imaging technique and a contrast agent to enhance the precision of surgery. The imaging technique and contrast agent produce 3D images.
Although this imaging technique is new, it is actually based on the century-old photoacoustic effect discovered by Alexander Graham Bell. Bell exploited the effect in what he considered his greatest invention ever, the photophone, which converted sound to light, transmitted the light and then converted it back to sound at the receiver. The absorption of light heats a material slightly, typically by a matter of millikelvins, and the temperature rise causes thermoelastic expansion.
According to Wang, “Much the same thing happens when you heat a balloon and it expands.” If the light is pulsed at the right frequency, the material will expand and contract, generating a sound wave. “We detect the sound signal outside the tissue, and from there on it’s a mathematical problem,” he said. “We use a computer to reconstruct an image.”
Photoacoustic tomography (PAT) can detect deep structures that strongly absorb light because sound scatters much less than light in tissue. Furthermore, it’s a lot safer than other means of deep imaging. It uses photons whose energy is only a couple of electron volts, whereas X-rays have energies in the thousands of electron volts. Positron emission tomography (PET) also requires high-energy photons. “PET improves tissue transparency by two to three orders of magnitude,” says Wang.
In their study, the team explains that photoacoustic images of biological tissue can be made without the use of contrast agents, particularly if tissues are pigmented by molecules such as hemoglobin or melanin. However, photoacoustic images of melanomas are fuzzy and vague around the edges; so to improve the contrast between the malignant and normal tissue, Xia loads the malignant tissue with gold. “Gold is much better at scattering and absorbing light than biological materials,” he said. “One gold nanocage absorbs as much light as a million melanin molecules.”
The contrast agent consists of hollow gold cages; in fact, the cages are so tiny that they can only be seen through the color they collectively lend to the liquid in which they float. Alteration of the size and geometry of the particles tune them to absorb or scatter light over a wide range of wavelengths. In this way, the nanoparticles behave quite differently than bulk gold. In the case of treating and diagnosing melanoma, the injection of the gold particles seems to be helpful: they tend to accumulate in tumors because the cells that line a tumor’s blood vessels are disorganized and leaky.
One of the improvements introduced by Xia is the increase of the uptake rate. By decorating the nanoparticles with an alpha-melanocyte-stimulating hormone, scientists slightly altered the molecule to make it more stable in the body. This hormone normally stimulates the production and release of the brown pigment melanin in the skin and hair.
The study details experiments with mice, in which melanomas took up four times as many “functionalized” nanocages than nanocages coated with an inert chemical. With the contrast agent, the photoacoustic signal from the melanoma was 36 percent stronger. Subcutaneous mouse melanomas barely visible to the unaided eye show up clearly in the photoacoustic images, their subterranean peninsulas and islands of malignancy starkly revealed.
Therefore, the scientists conclude that their technique is effective.
Although the process itself can be barely traced, its effects and results are evident. “We’re essentially listening to a structure instead of looking at it,” says Wang. “Using pure optical imaging, it is hard to look deep into tissues because light is absorbed and scattered,” he notes, but then again, their new methods will help extracting melanoma with better precision.
TFOT has also covered the implantable cancer vaccine researched at Harvard University, the Laser Microscalpel developed at Texas University used to target cancers individually, and the cancer vaccination, researched at Hadassah, Israel.
For more information about the new technique that allows seeing melanoma, see Washington University’s press release.