New laser method facilitates screening of cancerous moles under skin surface

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New laser method facilitates screening of cancerous moles under skin surface
Dec 1, 2007
Ilya Petrou, M.D.
Dermatology Times

Key Points

-New laser technique allows doctors to screen cancerous moles and skin cancer before surgical excision
-Molecular signatures can be seen that are not available through conventional methods
-This method is able to scan and produce a full 3D reconstructed image of the mole

Durham, N.C. Û Dermatologists are confronted with the daily task of diagnosing moles and skin cancers, but sometimes making an accurate diagnosis can be challenging due to a sometimes morphologic ambiguity of lesions.

Researchers at Duke University have developed a laser-based system that can produce 3D images of the cellular and structural makeup of a lesion, helping physicians secure an accurate diagnosis of a given lesion without classic histologic evaluation.

"Conventional dermatology is limited by the fact that by eye, we can only see a few microns below the surface of the pigmented mole. So without actually excising the mole, it is extraordinarily difficult to try to make some judgment as to whether a lesion is suspect or not. This is where our novel laser technology can make a difference," says Warren S. Warren, Ph.D., the James B. Duke professor of chemistry, radiology and biomedical engineering and director of Duke's new Center for Molecular and Biomedical Imaging.

Imaging methods

Some optical imaging methods can go significantly deeper using infrared light at wavelengths where moles are transparent. Near-infrared light (800 nm) in normal tissue can penetrate down 5 or 10 cm, but Dr. Warren says the basic problem is the lack of microscopic resolution due to scattering.

For other imaging applications, methods have been developed that can get deeper into tissue and still keep microscopic resolution. One such method uses lasers, which give extremely short pulses emitted infrequently Û so-called "ultra-fast" laser pulses.

However, this method requires that the target tissue create visible or ultraviolet light in response to the laser pulses, and melanomas are so dark that such light, even if created, is usually reabsorbed.

"The method that we came up with actually involves a similar kind of laser where the average power is less than a laser pointer, but the peak power is very high because it comes in very short bursts. Our method uses a delicate interplay between two laser beams, each emitting a different color of light.

"By using two different colors of lasers Û and by using a technology that we invented and patented about 10 years ago that allows us to sculpt the individual laser pulses to change their shapes Û we are able to extract signatures that do not fluoresce strongly, and that turns out to be critical for the dermatology application in respect to pigmented lesions," Dr. Warren tells Dermatology Times.

Dr. Warren says this method can measure eumelanin and pheomelanin at the same time, differentiate their molecular signatures, as well as measure the vascular structure and visualize the hemoglobin and deoxyhemoglobin deep into tissue. As a result, a lot of molecular signatures that just are not available by any conventional method can be realized.

Laser advantage

Using the laser, Dr. Warren was able to capture high-resolution signatures of human melanomas grown on mouse models. The major advantage of this method is that it can generate full 3D images that the computer can slice in any direction one wishes, without excising the mole.

"So in effect you are doing a virtual excision and you can pull out many more molecular signatures than the conventional methods would do anyway," Dr. Warren says.

"The signature that we are most interested in is the eumelanin and pheomelanin ratio, as we know that when moles become deranged, the production of pheomelanin tends to increase. But if you can look at the spatial distribution of the pheomelanin and eumelanin, which our method lets us do, the clinical evidence from older chemical studies says that is very likely to be a very strong correlate, whether the internal chemistry has changed and something is becoming malignant," Dr. Warren says.

According to Dr. Warren, the melanin ratio is the most promising molecular signature; however, vascular structures are also an important signature and are different in moles. He says in virtually every cancer, there is an angiogenesis pattern that can be used as a useful marker, such as metabolic rate. The general concern, in particular for melanomas, is the changes in metabolic rates, which are almost always associated with changes in the vasculature. Using this method, one can visualize the vasculature structure without excising it to help determine the nature of a given lesion.

Dr. Warren says when performing a histology, one usually only examines a representative 5- to 10-micron slice somewhere in the middle of the mole. This method is capable of scanning, and would actually be able to look at a full 3D reconstructed image of the mole.

"So, if instead of having to be lucky in finding a representative 10-micron slice of tissue, in principle, you could actually be looking at overall metrics on it, and be able to make a better judgment," Dr. Warren says.

"I believe that this method is not going to replace the standard ABCD rules in identifying whether a mole is suspect or not, but in many ambiguous cases, it can definitely help the clinician reach a clear diagnosis without performing a surgery. In addition, I would say that it would be something that would be useful on small moles, say less than 6 mm, that are commonly ignored by the rules," Dr. Warren says.

With this method, he says, more moles can be screened, and melanoma can be identified at an earlier stage.

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