Glowing grains: NIR ID for parathyroid glands

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  • Published: Jul 1, 2011
  • Author: David Bradley
  • Channels: Infrared Spectroscopy
thumbnail image: Glowing grains: NIR ID for parathyroid glands

Highlighting the parathyroids

Researchers have discovered that the parathyroid glands - four small organs each the size of a grain of rice located at the back of the throat - glow with a natural fluorescence in the near infrared. The finding has led to the development of an optical detector for highlighting the glands during endocrine surgery to avoid damage to these essential organs.

The parathyroid glands, located at the rear of the thyroid gland, produce parathyroid hormone that controls critical calcium concentrations in the bones, intestines and kidneys. This controls the body's calcium level within a narrow range, so that the nervous and muscular systems can function properly. Damage to these tiny organs during surgery can have deleterious, life-long effects on patient health. Inconveniently for surgeons who need to operate on surrounding tissue, the parathyroid glands are not only small but very difficult to discriminate from the thyroid itself and surrounding lymph and fatty tissues. Moreover, the parathyroid glands are not always on the posterior of the thyroid gland they can be present within the thyroid and sometimes in the chest. Spotting them with the unaided surgical eye is difficult. It usually requires a microscope to find them reliably.

Nevertheless, life-saving surgery is often needed that carries with it the risk of damage to the parathyroid glands. Tens of thousands of instances of endocrine surgery are carried out each year. More than 80,000 in the USA alone in 2004 with epidemiological predictions suggesting that the numbers will rise significantly by 2020, to more than 100,000 in the USA. Estimates suggest that invasive surgery involving treatment or removal of diseases thyroid tissue usually leads to damage to the parathyroid glands in between 8 and 19 percent of patients.

Strong glow

Now, biomedical engineer Anita Mahadevan-Jansen of Vanderbilt University in Nashville, Tennessee and her colleagues have discovered that the parathyroid glands are two to ten times more fluorescent in the NIR than any other tissue present in the neck. "We have taken measurements from more than 50 patients now and we have found this effect 100 percent of the time, even when the tissue is diseased. That is amazing. You almost never get 100 percent results in biological studies."

The strong fluorescence from these glands requires no expensive or sophisticated instrumentation to observe. A simple detector built from "off-the-shelf" components is adequate and uses a readily available low-powered infrared laser and a fibre optical probe. The laser light transmitted through the optical fibre illuminates the tissue with NIR, while neighbouring fibres feed any fluorescent light generated back to the detector. The system is currently wending its way through the patent application process.

"I was certainly impressed with how accurate this method seems to be," enthuses John Phay, an endocrine surgeon at the Ohio State University Medical Center. Phay collaborated on the research when he was at Vanderbilt. "The ability to detect the parathyroids would be a big help: the major problem in parathyroid surgery is finding them and it is very hard to avoid them in thyroid cancer surgery when you need to clear out lymph nodes." The system will be most useful when connected to a camera so that the fluorescing tissues can all be displayed on a single monitor.

The research program emerged from a difficult surgical procedure in which Lisa White, then a first-year resident in the Vanderbilt surgery department took part. "It was a very difficult case," White explains. "We were looking for the parathyroid glands and they were very hard to find. After the surgery was over, I decided that we really need a better way of identifying parathyroid tissue." White then scoured the medical literature to learn about the physiology and biochemistry of the parathyroid glands and serendipitously found a paper by Mahadevan-Jansen with another intern that described an optical technique for detecting liver cancer. White reasoned that if such a technique could spot the difference between normal and cancerous liver tissue, then it might be able to highlight the differences between other tissues.

White and Mahadevan-Jansen began a collaboration and recruited Phay. They tried several different optical techniques on available animal tissues, but none revealed anything distinctive about parathyroid tissue. Mahadevan-Jansen suggested Raman spectroscopy to fingerprint different organic molecules that might be present, but the Raman effect is, of course, rather weak and difficult to measure. However, when they inserted parathyroid tissue into the system the detector was unexpectedly saturated. Most biological fluorescence takes place in the ultraviolet and visible ranges, not at IR wavelengths.

Leaky revelations

What the team assumed was a light leak turned out to be a real effect. When the saturation phenomenon persisted across several different samples, they recognised that it was a real physical effect that would ultimately be exploited in their parathyroid detector. Biomedical engineering graduate student Constantine Paras was brought into the team and following the requisite approval tests began on human thyroid and parathyroid tissue. The researchers then grasped that they actually didn't need the Raman kit, all they required for detectable fluorescence was an NIR source and detector. The team is yet to determine the underlying cause of this parathyroid fluorescence. Nevertheless, that should not preclude its use in surgical procedures involving neck tissues and the thyroid gland in particular.

 



The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

 Infrared fluorescence of human parathyroid and thyroid tissue. The fluorescence of the parathyroid tissue on the upper left is twice as strong as that of thyroid tissue, providing an immediate way to differentiate the two. (Mehadevan-Jansen Lab)
Parathyroid glow

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