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Resonating tattoos interest radiology researcher Swartz

"Do you have a tattoo on your lower arm or leg? Volunteers needed for a developing medical research device." So read a rash of bright-orange notices recently posted in the hallways of DMS. Any students so adorned were asked to contact Harold Swartz, M.D., Ph.D., a professor of radiology and of physiology who also has adjunct appointments in engineering and chemistry.

The bulletin boards of a medical school might seem an unlikely place to troll for what were once the hallmarks of society's fringes. Tattoos are much more common on college campuses than they used to be, however, and Swartz has found several willing subjects. But what would a radiology researcher want with college students who could audition —sans makeup—for Tennessee Williams's Rose Tattoo or Ray Bradbury's Illustrated Man?

Carbon: Swartz's interest has to do with carbon—the primary component of the India ink used for tattoos. Carbon, it turns out, allows researchers to determine the concentration of oxygen in cells, which can be valuable information because well-oxygenated tissues respond better to radiation therapy.

After earning his M.D. at the University of Illinois, a master's in public health at the University of North Carolina, and a Ph.D. at Georgetown, Swartz plunged into what is still his consuming research interest—magnetic resonance. Atoms and molecules are hotbeds of magnetic spin systems, which can absorb energy at specific resonant frequencies when placed in an externally generated magnetic field. When the external frequency is in synchrony with the natural energy levels that are separated by the external magnetic field, unique signals are generated that make it possible to study precise structural features of the atom or molecule.

Hal Swartz works on one of his tattooed volunteers, in an effort to use the carbon particles in tattoo ink to measure the oxygen content of tissues.

Photo: Mark Austin-Washburn

For example, nuclear magnetic resonance reveals not only the presence of an atomic nucleus, but also details about its interactions with other nuclei nearby. Similarly, an electron has magnetic properties by virtue of orbital rotation about its nucleus and also due to rotation, or spin, about its own axis.

Resonance: Swartz has specialized further in the resonance of unpaired electrons, which exist in free radicals—especially reactive atoms. This area of study is known as electron paramagnetic resonance (EPR). A singular advantage of this methodology in theory is that it can ignore everything else present in a complex mixture and hone in precisely on the free radical species.

Molecular oxygen is actually a stable diradical, and therefore it will readily interact with other free radical species in the body. Measuring these radical species provides indirect measurement of the oxygen tension at various anatomic sites. Methods for measuring oxygen tension in vivo have been sought for a variety of clinical purposes for some time.

Swartz's group has experimented with several paramagnetic oxygen sensors over the years, and the one that seems to have the most desirable properties is elemental carbon in the form of microparticles. The team first performed experiments in animals, finding that carbon particles injected into various anatomic sites gave the appropriate signals for trapped oxygen free radicals and that the signals varied in intensity as the oxygen tension was modified.

In most locations in the body, however, carbon particles tend to be cleared by the immune system, so Swartz went in search of a site that would be cleared more slowly or not at all. Once the idea of skin presented itself, several other aspects of the study fell into place: India ink is an aqueous suspension of lampblack, which is basically fine particles of carbon, and one of the incidental uses for India ink is as the blue-black pigment in tattoos. Although other colors are often used in tattoos, the outline and sometimes the entire pattern is made with India ink.

Plan: The eventual plan is to implant at several sites a "medical tattoo"—a small, perhaps barely visible deposit of India ink at a slightly greater depth in the skin than a conventional tattoo. These deposits could conceivably remain in place over a lifetime, permitting measurements of oxygen tension whenever they are needed. The fact that India ink has been used extensively in human subjects, not only for tattooing but also to mark surgical fields and to trace lymphatic systems, makes it likely that approval for its use in human subjects will not be a problem. There are other, perhaps even better, sensors available, but the Food and Drug Administration would likely require more extensive and prolonged testing before approving any new substance.

A significant application of this technique would be in the management of peripheral vascular disease. Although many different approaches are available to manage this complex condition, it has been difficult in the past to evaluate their relative effectiveness. With continuous, minute-to-minute readings of the actual oxygen tension in tissues at several sites, as opposed to measurements of the oxygen saturation of the blood, it should become much easier to identify those interventions that are truly effective.

Application: Swartz anticipates, however, that the major application of this technique will be in optimizing radiation treatment for cancer. Tumors are highly variable in their response to radiation. If one irradiates 100 tumors of similar size, a certain percentage will vanish completely and a certain percentage will not respond at all.

Tissue oxygen tension appears to be one of the major variables accounting for this difference. The higher the oxygen tension in the tumor, the more favorable is the response to radiation. This effect apparently has to do with there being more opportunities for efficient DNA repair mechanisms at low oxygen tension. If India ink were inserted directly into a tumor, the radiation therapist could deliver treatment at periods coinciding with high oxygen tension.

In the meantime, Swartz has a continuing need for highly decorated volunteers.

Roger P. Smith, Ph.D.

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