People with light-skin or red
hair are often prone to hard-to-detect melanomas, often caused by
properties of pigments within skin called melanins.
People with fair
skin have a higher concentration of the melanin known as pheomelanin in
their skin, and a corresponding higher probability of developing
melanoma - in particular, a difficult-to-detect subtype known as
amelanotic melanoma. In high concentrations, pheomelanin is responsible
for the orange-reddishness in hair, but is essentially invisible in
‘With a refined classic Raman-based technique, researchers succeeded in imaging the two dominant melanin molecules - a breakthrough that could lead to early detection of melanoma.’
While eumelanin, the brown-black pigment found in most melanomas,
can be easily seen, the light colored pheomelanin is difficult to
detect; even with advances in modern microscopy, understanding the
pheomelanin molecule and its role in melanoma has eluded scientists.
Recently, researchers at Massachusetts General Hospital's Wellman
Center for Photomedicine have made a breakthrough for spotting and
studying this elusive molecule in skin. Sam Osseiran, a scientist on the
team lead by Harvard University professor Conor Evans, will present
their findings at the OSA Biophotonics Congress: Optics in the Life Sciences meeting.
The Evans group's research centers around the use of a
high-resolution imaging technique called coherent anti-Stokes Raman
Scatterings (CARS) microscopy, a variant of the more widely used Raman
spectroscopy that enables chemically-specific imaging by means of
detecting molecular vibrations.
Evans, whose translational research group specializes in microscopy
and spectroscopy for understanding cancer and dermatology afflictions,
says the common assumption about locating and imaging pheomelanin is
that "there's really no good way to see this mostly invisible pigment
when it occurs in skin."
But Massachusetts General's chief of dermatology, David Fischer,
approached Evans and they decided to collaborate. Evans' research team
took on the pheomelanin imaging challenge. "So my team put our heads
together, scouring for ways to see it," Evans said.
While another optical technology, called transient absorption
microscopy, does offer possibilities for studying pheomelanin, this
method is complex and does not easily lend itself to clinical practice.
"We started to look through the Raman literature," Evans said.
"Raman spectroscopy is a very mature technique that allows you to detect
molecules by their unique chemical vibrations, which are themselves
derived from the structure of the molecules. CARS microscopy is a
coherent Raman tool that is akin to using a tuning fork to specifically
detect molecular structures."
Fortunately, CARS microscopy proved successful for imaging
pheomelanin. "Pheomelanin has a unique chemical structure, there is
nothing else like it in the body," Evans said. "So, we started to look
at the molecular structure and noticed there was a corresponding unique
molecular vibration that might be useful for imaging the pigment with
Evans gives much of the credit to his research team, Sam Osseiran
and post-doctoral researcher Tracy Wang, for leading the way in
developing and refining the CARS microscopy method for imaging
pheomelanin. In general, CARS microscopy utilizes two lasers focused on a
sample whose energy difference is "tuned" to specific molecular
vibrations to generate high resolution imaging information.
"The work led by Tracy was really rather novel application of CARS
microscopy to target this biomolecule which no one else has tried to do
before," Osseiran said. "We adjusted our system and aligned and tuned
everything so that we could specifically target this one melanin
Serendipitously, while developing their CARS imaging method, the
group found a complementary method that could be used for the
simultaneous detection of eumelanin called sum-frequency absorption
(SFA) microscopy. SFA makes use of a signal modulation scheme that can
detect both species of melanin. This additional imaging tool is
important, as most humans produce both species within skin, making
mapping the distribution and quantity of both pigments important.
"Sum-frequency absorption imaging allows you to visualize where all
the melanin absorbers are within tissue," said Evans. "As both CARS and
SFA can be carried out at the same time, these two techniques can be
used together to simultaneously image both melanin pigments."
Wang and Osseiran believe their CARS and SFA method could be very
helpful for future research on melanoma and its treatment, as well as
observing the changes that occur with melanin species in different
states. "We are adding another tool to our utility belt here in our
investigations of melanoma," Osseiran said.
The study's original motivator, David Fischer, believes that a very
important benefit of the work might be its potential role in diagnosing
"This may offer a brand-new tool for early diagnosis for some of the
most lethal melanomas, possibly at a stage when they might still be
curable," said Fisher. "Time and time again, it is proven that early
diagnosis saves lives."