WO2008074052A1 - Tattooing method for radiation therapy - Google Patents

Tattooing method for radiation therapy Download PDF

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Publication number
WO2008074052A1
WO2008074052A1 PCT/AU2007/001770 AU2007001770W WO2008074052A1 WO 2008074052 A1 WO2008074052 A1 WO 2008074052A1 AU 2007001770 W AU2007001770 W AU 2007001770W WO 2008074052 A1 WO2008074052 A1 WO 2008074052A1
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WIPO (PCT)
Prior art keywords
ink
skin
tattoos
tattoo
black
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PCT/AU2007/001770
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French (fr)
Inventor
Margaux Clare Smolinski
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Margaux Clare Smolinski
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Priority claimed from AU2006907317A external-priority patent/AU2006907317A0/en
Application filed by Margaux Clare Smolinski filed Critical Margaux Clare Smolinski
Publication of WO2008074052A1 publication Critical patent/WO2008074052A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39Markers, e.g. radio-opaque or breast lesions markers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3937Visible markers
    • A61B2090/3941Photoluminescent markers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/39Markers, e.g. radio-opaque or breast lesions markers
    • A61B2090/3937Visible markers
    • A61B2090/395Visible markers with marking agent for marking skin or other tissue

Definitions

  • the invention relates to radiation therapy.
  • the invention relates to the tattooing of patients to aid in field positioning during radiation treatment.
  • India ink (or Indian ink) is a basic black ink once commonly used for printing and writing, but now used mostly for drawing.
  • the ink is made from a black carbon pigment suspended in an aqueous adhesive or other binding medium.
  • the ink has been certified non- toxic by the Art and Creative Materials Institute (website http://www.acminet.org/asp/CPSearchFrames.ASP) and is widely used in radiation therapy departments for positioning tattoos.
  • the permanent tattoos created during the patient's simulation session are documented and, if a CT scan is to be performed, highlighted using wire or another radio-opaque material so they can be easily visualised on the scan.
  • the patient's set-up is referenced to the localisation tattoos.
  • an isocentre can be positioned within the patient by moving the treatment bed with reference to the tattoo.
  • an SSD to a tattoo can determine the isocentre depth within the patient.
  • the object of the invention is to provide an alternative to black ink in the tattooing of patients for radiation treatment.
  • a method of tattooing skin for radiation therapy comprising injection into the skin of the patient at the desired site an ink which is visible under UV light (hereafter referred to as a UV ink).
  • UV ink in the preparation of a medicament for tattooing skin for radiation therapy.
  • the UV ink used in the method and use defined in the previous paragraphs can be any suitable ink which does not radiate in the visible light range but radiates when subjected to light in the UV range 4-400 nm (http://imagers.gsfc.nasa.gov/ems/uv.html).
  • the ink must preferably be hypoallergenic and non toxic.
  • the UV ink is injected using any of the techniques suitable for subdermally administering a fluid. Methods include applying the UV ink to the skin at the tattoo site then using a sterile needle or lance to pierce the skin to thus deposit the fluid subdermally.
  • Figure 1 a Failure of ink droplets on the skin. When black ink was placed directly on the pig skin, the result was an area of staining around the tattoo itself.
  • the tattoo on the left was created with a 21 -gauge needle, the one on the right with a lance.
  • Figure Ib Various tattooing methods. The tattoo methods were (from left) 21 -gauge needle inserted perpendicular to the skin, 21 -gauge needle inserted at a thirty-degree angle to the skin, lance inserted perpendicular to the skin and lance inserted at a thirty-degree angle to the skin.
  • FIGS. 2a-2b Coffee-stained pig skin (2a) shows the pig skin during staining complete with excess coffee and four hours later (2b), upon removal of the remaining coffee.
  • FIGS. 2c-2d Tea-stained pig skin (2c) shows the pig skin during staining - the excess tea leaves are clearly visible and four hours later (2d), after removal of the tea leaves.
  • Figures 2e-2f Pig skin coloured with red and green food colouring (2e) shows the pig skin after application of the colouring (dye is still wet) and four hours after application (2f), the dye had dried and soaked into the skin. Little excess remained to be removed.
  • Figures 3a-3b UV-ink ⁇ tattooed, untinted pig skin.
  • the photograph on the left (3a) was taken under normal lighting conditions, and the one on the right (3 b) was taken under a UV light.
  • the UV tattoos are easily visualised under the UV light, but virtually invisible in normal light.
  • Figure 3c-3d Black ink-tattooed, untinted pig skin. The photograph (3c) was taken under normal lighting conditions, and photograph (3d) was taken under a UV light. The black ink tattoos are clearly seen under both lighting conditions.
  • Figures 3e-3f Black ink and UV ink tattoos on coffee-stained pig skin. The photographs were taken in normal light (3e) and UV light (3f). The black ink tattoo can be seen towards the top of both images, indicated with an arrow. The UV ink tattoo, however, is not visible on either image.
  • CT Computerised Tomography
  • UV Ultra-violet QSRL: Q-switched ruby laser
  • the materials required for the testing of the tattooing technique included a lance, a 21- gauge needle, black ink, pig skin, alcohol wipes and a camera for documentation.
  • the procedure was performed as follows: the 21 -gauge needle was dipped into the black ink and inserted approximately 2mm into the pig skin, with the needle held perpendicular to the surface of the skin. The needle was removed and the area was wiped over with an alcohol wipe. This step was repeated with the lance. Next, the 21 -gauge needle was dipped into the black ink and inserted approximately 2mm into the pig skin, with the needle held at an angle to the skin surface of approximately thirty degrees. The needle was removed and the area was wiped with an alcohol wipe. This step was also repeated with a 21 gauge needle. The results of the various tattooing methods were photographed. The best technique was the angled method using a 21- gauge needle. This technique was chosen to be used in Part 3 of the experiment.
  • the coffee- stained piece of pig skin from Part 1 of the experiment was tattooed using the same technique, once with a needle dipped in black ink and once with a needle dipped in UV ink. All three pieces of pig skin were photographed under normal lighting conditions and under a black light.
  • Pig skin was chosen to simulate human skin due to the similarity in texture and colour.
  • the skin was stored in a plastic freezer bag in the refrigerator before and after tattooing to maintain freshness. It was not frozen, as freezing of the UV ink is not recommended (from the Chameleon Body Art Supply website, http://www.crazychameleonbodyartsupply.com/bmx- 1000-chameleon-tattoo-inks.htm).
  • the tattoos although similar, are larger when created by the 21 -gauge needle, and larger still when inserted at an angle.
  • the technique that produced the largest tattoo was chosen for use in Part 3 because, although large, garish tattoos are undesirable in radiation therapy, it was assumed that the more UV ink inserted into the skin, the more the tattoo will fluoresce under a black light.
  • the size of the UV tattoo under normal light is not an issue, because it cannot be seen without the aid of a black light.
  • Figures 2a-2f show the results from Part 2 of the experiment.
  • Figures 2a and 2b show the pig skin stained with coffee granules, 2a before and 2b after removal of the excess coffee.
  • Figures 2c and 2d show the same for the tea leaves and Figures 2e and 2f for the green and red food colouring.
  • the food-coloured skin had dried after the four hour wait and only a small amount of dye was removed; the remaining dye had soaked into the pig skin. It is easy to see through these photographs why the coffee-stained skin was chosen to replicate dark- pigmented human skin, as it is quite uniform in colour and a similar shade to some skin tones.
  • the results from Part 3 of the experiment using the pale, untinted pig skin were extremely successful.
  • Figure 3a shows a piece of untinted pig skin containing nine UV tattoos arranged in a square.
  • Figure 3b shows the same piece of pig skin under a black light.
  • the tattoos can be easily visualised under the black light but are practically invisible in normal light.
  • the black tattoos are quite large and easily seen under normal lighting, Figure 3c, but harder to see under the black light, Figure 3d.
  • the testing of the black ink under the black light was mostly for completeness, as it would be entirely unnecessary to examine a black ink tattoo under a black light in a clinical setting.
  • Inks such as gentian violet, henna and permanent markers have been previously applied as reference marks to guide field set-up, but by far the most effective means of field localisation is to use permanent tattoos. Unlike the other inks, these tattoos do not wash off or wear out over time and act as a visual history of treatment if the patient returns for further therapy.
  • black ink tattoos are not always visualised easily on certain skin types, can cause allergic reactions in some patients and act as a perpetual reminder to the wearer of their cancer treatment. It is for these reasons that an alternative to the black ink tattoos was investigated.
  • tattooing involves piercing of the skin with needles that contain a pigment.
  • the needle generally only penetrates the skin one to two millimetres, through the epidermis and just into the papillary and reticular dermis, but no deeper. This results in pigment from the needle being deposited under the skin.
  • the needle causes superficial dermal capillary damage and a blood droplet forms on the surface of the skin. This blood then clots and some plasma and tissue fluid may be produced from the site of the tattoo for a few hours following the perforation.
  • the pierced skin reacts by becoming red and inflamed (erythematous) and then swollen (oedematous).
  • the tattoo appears raised and has a reddish border which can extend into the untattooed skin for up to one centimetre. This reaction tends to abate within a few hours after the tattoo was created, however some slight inflammatory remains, extending no more than one to two millimetres beyond the tattoo site.
  • the pigment-soaked needle deposits its ink in the epidermis and all of the superficial dermal layers. Over the next few days, the superficial and regenerative basal epidermal layers will peel off and fall away until only the pigment within the dermis remains. These epidermal layers will grow back normally and the tattoo will be seen in the underlying dermis through the epidermis. It takes about two weeks for the epidermis to completely regenerate, however, the body will react to the tattoo ink as a foreign entity for life. Dermal macrophages absorb pigment particles and carry them into the local lymphatics. Some macrophages will only move a short distance from the tattoo within the dermis, causing a blurring and spreading of the tattoo. This effect is exacerbated by chronic exposure to sunlight. (Sperry, 1992)
  • India ink tattoos are permanent if untreated, however, it is possible to have them removed.
  • Tattoo removal has been conducted on many patients for varying reasons since the 1960s. Many removal techniques exist. However, many leave scars which can be more disfiguring than the original tattoo itself.
  • a frequently used tattoo removal technique in the past was dermabrasion, during which the epidermis overlying the tattoo was virtually sanded back and caustic chemicals like tannic acid or silver nitrate were applied to the exposed, pigment-containing dermis to enhance pigment extrusion. This technique often left behind a significant scar.
  • Cryosurgery where the tattooed skin is frozen with liquid nitrogen, causing the pigmented skin to become necrotic and eventually fall away, can be successful, but only for small tattoos.
  • Another more basic technique for tattoo removal is to re-tattoo the area with a needle containing no ink, and after exposing the pigmented dermis, soak the region in warm, salty water for several days and leach the pigment out.
  • One cutting-edge tattoo removal technique claims to successfully remove tattoos without significant scarring.
  • the method uses a Q-switched ruby laser (QSRL).
  • QSRL Q-switched ruby laser
  • the newest generation of QSRLs emit nanosecond-domain pulses of light, which is readily absorbed by tattoo pigments, especially blue-black pigments such as India ink.
  • the exact way in which the pigment absorbs the photons is quite complex, but basically the pigment granules heat up and destroy the cell which contains them.
  • the problem with this approach arises when patients require further radiation therapy treatment.
  • the permanent tattoos act as a history of past treatment sites and prevent overlapping of fields, which in turn prevents necrosis of over-irradiated tissue. If radiation therapy tattoos are removed, this history is somewhat lost, and although all measures are taken to document fields locations through photographs and charts, change in the patient's physiology through weight gain or loss and skin sag can blur the boundaries.
  • a permanent tattoo is invaluable in these circumstances.
  • Black ink tattoos are not always easily visualised. On very dark-skinned or heavily- freckled patients, black ink tattoos can be hard to locate, even with the aid of anatomical references.
  • a solution to this is to mark the tattoo on with a permanent marker, and apply a thin, adhesive plastic film to the tattoo location. This aids in tattoo location and visibility from day to day. This film, however, is not permanent and needs to be changed and the marks reapplied during treatment. Also, the sticky plastic can be irritating to the patient, especially if it is in an awkward location. This approach does not solve the problem of difficulty in locating the tattoo if the patient returns for treatment.
  • Radiation therapy needs a hypo-allergenic tattoo ink which is permanent, invisible under normal light and easily visualised in all skin types. This is where UV ink comes into play.
  • UV ink tattoos are applied in the same way as black ink tattoos, it is reasonable to assume that they would be permanent.
  • UV ink tattoos are invisible under normal lighting. This is because the natural pigment of skin masks the small amount of ink in the dermis. This characteristic of the UV ink would make it ideal in the radiation therapy environment because it would eliminate the need for tattoo removal. If the tattoos could be unseen in everyday light but remain on the skin, a permanent record of past treatment, the patient could feel less self-conscious of the marks and the radiation staff could still locate the tattoos in case of re-treatment.
  • UV ink tattoos are more easily visualised than black ink tattoos on dark or freckled skin.
  • the test attempted to show UV tattoos on dark pigmented skin, however, only the superficial epidermis of the pig skin could be dyed. This differs from live human skin, as the melanocytes are actually located in the basal layer of the epidermis. It is the melanocytes which produce melanin, the pigment in normal skin. It is assumed that this is the reason the UV tattoo could not be seen in the dark pig skin. It is uncertain, but likely that the black light was prevented from reaching the ink by the superficial layer of dye. As the light could not reach the tattoo in order for it to fluoresce, it could not be visualised in the image. The black ink tattoo could be seen on the pigmented skin, however, as expected, it was poorly visualised, as the skin was quite dark. .
  • any black light will do.
  • the light used in the experiment above was a small, hand-held LED-based UV torch, located in the lid of a felt pen containing UV ink.
  • the device was purchased on eBay for AU$5.75 plus shipping costs from seller Prosound Electronics Funstuff (website http://stores.ebay.com.au/Prosound- Electronics-Funstuff)
  • the torch when held over the tattooed pig skin, effectively illuminated the UV tattoos.
  • a larger black light could be used in a clinical setting, but a convenient, pen- sized light seems more than adequate.
  • the highlighter ink experiment mentioned earlier describes attaching lights to various objects in the treatment room.
  • India ink is fairly inexpensive, a 30ml-bottle available from one eBay online store for AU$7.00 plus postage and handling (http://stores.ebay.com.au/Red-Branch). 60ml of the Chameleon brand UV ink was purchased for the experiment from their online store
  • UV ink could serve as an alternative to India ink when tattooing patients undergoing radiation therapy treatment.
  • the ink is virtually invisible under normal lighting circumstances but still easily identifiable under a black light.
  • UV ink could potentially save health departments money in the future by eliminating the need for tattoo removal.
  • UV ink has the potential to act as a successful medium for creating radiation therapy tattoos.
  • the term "comprise” and variants of the term such as “comprises” or “comprising” are used herein to denote the inclusion of a stated integer or stated integers but not to exclude any other integer or any other integers, unless in the context or usage an exclusive interpretation of the term is required.

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Abstract

The invention relates to radiation therapy. In particular, the invention relates to a method of tattooing patients using ink visible under UV light to aid in field positioning during radiation treatment.

Description

TECHNICAL FIELD
The invention relates to radiation therapy. In particular, the invention relates to the tattooing of patients to aid in field positioning during radiation treatment.
BACKGROUND ART
In the past, various temporary inks have been used to create marks on the skin of cancer patients to assist in their positioning prior to receiving radiation therapy. These ink markings, made with substances such as henna, gentian violet and even permanent marker ink had to be re-drawn several times throughout treatment and washed away once treatment was completed. This repetitive application was time consuming, and the non-permanent quality of the inks meant that if the patient came back for further treatment, no history of beam placement existed on the patient's skin. To overcome this issue, most radiation therapy departments around the world today routinely use black India ink to create permanent tattoos on patients undergoing treatment to assist in daily straightening, levelling and field localisation. The tattooing technique is variable and the tattoos vary in size, number and position dependant on the location of the field, the beam geometry and the particular department protocols.
India ink (or Indian ink) is a basic black ink once commonly used for printing and writing, but now used mostly for drawing. The ink is made from a black carbon pigment suspended in an aqueous adhesive or other binding medium. The ink has been certified non- toxic by the Art and Creative Materials Institute (website http://www.acminet.org/asp/CPSearchFrames.ASP) and is widely used in radiation therapy departments for positioning tattoos.
In radiation therapy departments, the permanent tattoos created during the patient's simulation session are documented and, if a CT scan is to be performed, highlighted using wire or another radio-opaque material so they can be easily visualised on the scan. After the patient's beam arrangements and positions have been determined, the patient's set-up is referenced to the localisation tattoos. During set-up, an isocentre can be positioned within the patient by moving the treatment bed with reference to the tattoo. Also, an SSD to a tattoo can determine the isocentre depth within the patient. Some departments will use tattoos on a patient's sides to align with the transverse lasers in order to level the patient. By aligning these tattoos and an anterior tattoo can also allow for monitoring and reproducibility of pelvic tilt. Breast cancer patients require several tattoos to localise fields borders and beam entry and exit points. Although not routine, if stabilisation shells are unavailable, a patient undergoing a head and neck treatment may require tattoos to be placed in obvious areas such as the neck. The list of tattoo locations is endless, but without these tattoos, patient set-up would become more time consuming and far less accurate.
Various reasons exist to investigate a suitable alternative to black ink for radiation therapy tattoos. Some research has been published about allergies to radiation therapy tattoos displayed by some patients, and evidence exists that the permanent and visible nature of the tattoos can be detrimental to the patient and a constant reminder of their cancer experience. Patients may also refuse to have tattoos done for their treatment. Reasons vary from cultural and personal beliefs to cosmetic issues. Some patient's religious beliefs oppose any form of tattooing or skin marking. On occasion, older patients may refuse to be tattooed due to societal stereotypes. And although most departments try not to tattoo patients in obvious places, even tattooing the stomach or chest may have an effect on, for example, a young lady undergoing breast cancer treatment who may become self-conscious of these marks whilst wearing swimwear. It is possible to have the tattoos removed, but often the removal process can leave a scar. Also, if the patient is to be re-treated with radiation therapy, removal of the tattoo can inhibit the localisation of the previous treatment fields and make positioning of the new fields more difficult, as can having no tattoos done at all. Lastly, India ink tattoos do not show up clearly on all skin types. Heavily freckled or dark pigmented skin may make location of the positioning tattoo difficult, as the tattoo may blend in with the skin tone or be lost in a sea of freckles or moles. It is for all of these reasons that a hypo-allergenic, permanent tattoo that is invisible under normal light but clearly visualised in a clinical setting should be investigated. The object of the invention is to provide an alternative to black ink in the tattooing of patients for radiation treatment.
SUMMARY OF THE INVENTION Definitions of the specific embodiments of the invention as claimed herein follow.
According to a first embodiment of the invention, there is provided a method of tattooing skin for radiation therapy, the method comprising injection into the skin of the patient at the desired site an ink which is visible under UV light (hereafter referred to as a UV ink).
According to a second embodiment of the invention, there is provided a use of UV ink in the preparation of a medicament for tattooing skin for radiation therapy.
The UV ink used in the method and use defined in the previous paragraphs can be any suitable ink which does not radiate in the visible light range but radiates when subjected to light in the UV range 4-400 nm (http://imagers.gsfc.nasa.gov/ems/uv.html). The ink must preferably be hypoallergenic and non toxic. The UV ink is injected using any of the techniques suitable for subdermally administering a fluid. Methods include applying the UV ink to the skin at the tattoo site then using a sterile needle or lance to pierce the skin to thus deposit the fluid subdermally. Having broadly described the invention, a non-limiting example of the method will now be given with reference to the accompanying drawings briefly described hereafter.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 a: Failure of ink droplets on the skin. When black ink was placed directly on the pig skin, the result was an area of staining around the tattoo itself. The tattoo on the left was created with a 21 -gauge needle, the one on the right with a lance. Figure Ib: Various tattooing methods. The tattoo methods were (from left) 21 -gauge needle inserted perpendicular to the skin, 21 -gauge needle inserted at a thirty-degree angle to the skin, lance inserted perpendicular to the skin and lance inserted at a thirty-degree angle to the skin.
Figures 2a-2b: Coffee-stained pig skin (2a) shows the pig skin during staining complete with excess coffee and four hours later (2b), upon removal of the remaining coffee.
Figures 2c-2d: Tea-stained pig skin (2c) shows the pig skin during staining - the excess tea leaves are clearly visible and four hours later (2d), after removal of the tea leaves.
Figures 2e-2f: Pig skin coloured with red and green food colouring (2e) shows the pig skin after application of the colouring (dye is still wet) and four hours after application (2f), the dye had dried and soaked into the skin. Little excess remained to be removed.
Figures 3a-3b: UV-ink~tattooed, untinted pig skin. The photograph on the left (3a) was taken under normal lighting conditions, and the one on the right (3 b) was taken under a UV light. The UV tattoos are easily visualised under the UV light, but virtually invisible in normal light. Figure 3c-3d: Black ink-tattooed, untinted pig skin. The photograph (3c) was taken under normal lighting conditions, and photograph (3d) was taken under a UV light. The black ink tattoos are clearly seen under both lighting conditions.
Figures 3e-3f: Black ink and UV ink tattoos on coffee-stained pig skin. The photographs were taken in normal light (3e) and UV light (3f). The black ink tattoo can be seen towards the top of both images, indicated with an arrow. The UV ink tattoo, however, is not visible on either image. DETAILED DESCRIPTION OF THE INVENTION The following abbreviations are used hereafter: CT: Computerised Tomography
UV: Ultra-violet QSRL: Q-switched ruby laser
SSD: Source-to-skin distance
EXPERIMENTAL TECHNIQUE
The experiment was divided into three distinct parts: 1. To determine which tattooing technique was most successful.
2. To determine an appropriate way to dye the pig skin.
3. To compare the visibility of UV ink and black ink tattoos on pale and dark pigskin under normal and black light.
Tattooing Technique
The materials required for the testing of the tattooing technique included a lance, a 21- gauge needle, black ink, pig skin, alcohol wipes and a camera for documentation.
The procedure was performed as follows: the 21 -gauge needle was dipped into the black ink and inserted approximately 2mm into the pig skin, with the needle held perpendicular to the surface of the skin. The needle was removed and the area was wiped over with an alcohol wipe. This step was repeated with the lance. Next, the 21 -gauge needle was dipped into the black ink and inserted approximately 2mm into the pig skin, with the needle held at an angle to the skin surface of approximately thirty degrees. The needle was removed and the area was wiped with an alcohol wipe. This step was also repeated with a 21 gauge needle. The results of the various tattooing methods were photographed. The best technique was the angled method using a 21- gauge needle. This technique was chosen to be used in Part 3 of the experiment. It was assumed that the best method of tattooing using black ink would also be the best method of tattooing with UV ink. Dying of Pig Skin The materials used for the dying of the pig skin were Moccona Classic Medium Roast coffee granules, tea leaves extracted from a Bushells Blue Label Tagged tea bag, red and green Queen Food Colours, warm water, pig skin and a camera to document the results.
Three pieces of pig skin, approximately four centimetres square, were cut from a sheet. Coffee granules were dissolved in warm water and applied thickly to one piece of skin, warm- water-soaked tea leaves were applied to another square and red and green food colouring (mixed) were applied to the third piece of skin. The skin was left for approximately four hours and the excess coffee, food colouring and tea was removed. The results were photographed. The coffee-stained pig skin appeared to be the closest to dark-pigment human skin and was chosen for Part 3 of the experiment. Comparison of UV Ink and Black Ink
Chameleon UV Ink Colour UV Titanium White, black ink, pig skin (both unstained and coffee-stained), alcohol wipes, 21 -gauge needles, a black light and a camera were needed to perform and document this stage of the experiment. A piece of pale, unstained pig skin was pierced with a 21 -gauge needle dipped in black ink and inserted into the skin at approximately thirty degrees to the surface of the skin. After the needle was removed, the tattooed area was immediately wiped over with an alcohol wipe. The pig skin was tattooed nine times with the tattoos arranged in a square. The same procedure was repeated with a 21 -gauge needle dipped in UV ink on a separate piece of unstained pig skin. The coffee- stained piece of pig skin from Part 1 of the experiment was tattooed using the same technique, once with a needle dipped in black ink and once with a needle dipped in UV ink. All three pieces of pig skin were photographed under normal lighting conditions and under a black light.
EXPERIMENTAL RESULTS
Pig skin was chosen to simulate human skin due to the similarity in texture and colour. The skin was stored in a plastic freezer bag in the refrigerator before and after tattooing to maintain freshness. It was not frozen, as freezing of the UV ink is not recommended (from the Chameleon Body Art Supply website, http://www.crazychameleonbodyartsupply.com/bmx- 1000-chameleon-tattoo-inks.htm).
When testing the different tattooing methods, it was initially desirable to place the ink on the skin and on the needle or lance and then insert the needle or lance into the skin underlying the ink. Unfortunately, the pig skin absorbed the black ink quite rapidly and stained the area, making the tattoo itself quite unclear. This was documented and can be seen in Figure Ia, which shows two attempted tattoos, one from a lance and one from a needle. It was then decided that best method of applying the ink was to place the ink only on the needle or lance and to wipe the area clean with an alcohol wipe immediately after puncturing the skin.
The results from Part 1 of the experiment, shown in Figure Ib, display the difference in size of tattoos created with 21 -gauge needle and lance dipped in black ink and inserted into the skin at both a perpendicular angle and at an angle of about 30 degrees to the skin. The tattoos, although similar, are larger when created by the 21 -gauge needle, and larger still when inserted at an angle. The technique that produced the largest tattoo was chosen for use in Part 3 because, although large, garish tattoos are undesirable in radiation therapy, it was assumed that the more UV ink inserted into the skin, the more the tattoo will fluoresce under a black light. The size of the UV tattoo under normal light is not an issue, because it cannot be seen without the aid of a black light.
The results from Part 2 of the experiment are shown in Figures 2a-2f. Figures 2a and 2b show the pig skin stained with coffee granules, 2a before and 2b after removal of the excess coffee. Figures 2c and 2d show the same for the tea leaves and Figures 2e and 2f for the green and red food colouring. The food-coloured skin had dried after the four hour wait and only a small amount of dye was removed; the remaining dye had soaked into the pig skin. It is easy to see through these photographs why the coffee-stained skin was chosen to replicate dark- pigmented human skin, as it is quite uniform in colour and a similar shade to some skin tones. The results from Part 3 of the experiment using the pale, untinted pig skin were extremely successful. Figure 3a shows a piece of untinted pig skin containing nine UV tattoos arranged in a square. Figure 3b shows the same piece of pig skin under a black light. The tattoos can be easily visualised under the black light but are practically invisible in normal light. In contrast, the black tattoos are quite large and easily seen under normal lighting, Figure 3c, but harder to see under the black light, Figure 3d. The testing of the black ink under the black light was mostly for completeness, as it would be entirely unnecessary to examine a black ink tattoo under a black light in a clinical setting.
The results pertaining to the coffee-stained pig skin, however, were somewhat disappointing. The test proved that neither the black ink tattoo nor the UV tattoo are easily visualised on darker skin, as seen in Figure 3e, however, the UV tattoo on the pigmented skin did not fluoresce under the black light, shown by Figure 3f. This was most likely due to the placement of the dye, which will be discussed below.
In the past, various methods of marking radiation therapy treatment areas have been used. Inks such as gentian violet, henna and permanent markers have been previously applied as reference marks to guide field set-up, but by far the most effective means of field localisation is to use permanent tattoos. Unlike the other inks, these tattoos do not wash off or wear out over time and act as a visual history of treatment if the patient returns for further therapy. However, black ink tattoos are not always visualised easily on certain skin types, can cause allergic reactions in some patients and act as a perpetual reminder to the wearer of their cancer treatment. It is for these reasons that an alternative to the black ink tattoos was investigated.
In humans, tattooing involves piercing of the skin with needles that contain a pigment. The needle generally only penetrates the skin one to two millimetres, through the epidermis and just into the papillary and reticular dermis, but no deeper. This results in pigment from the needle being deposited under the skin. The needle causes superficial dermal capillary damage and a blood droplet forms on the surface of the skin. This blood then clots and some plasma and tissue fluid may be produced from the site of the tattoo for a few hours following the perforation. The pierced skin reacts by becoming red and inflamed (erythematous) and then swollen (oedematous). The tattoo appears raised and has a reddish border which can extend into the untattooed skin for up to one centimetre. This reaction tends to abate within a few hours after the tattoo was created, however some slight inflammatory remains, extending no more than one to two millimetres beyond the tattoo site.
The pigment-soaked needle deposits its ink in the epidermis and all of the superficial dermal layers. Over the next few days, the superficial and regenerative basal epidermal layers will peel off and fall away until only the pigment within the dermis remains. These epidermal layers will grow back normally and the tattoo will be seen in the underlying dermis through the epidermis. It takes about two weeks for the epidermis to completely regenerate, however, the body will react to the tattoo ink as a foreign entity for life. Dermal macrophages absorb pigment particles and carry them into the local lymphatics. Some macrophages will only move a short distance from the tattoo within the dermis, causing a blurring and spreading of the tattoo. This effect is exacerbated by chronic exposure to sunlight. (Sperry, 1992)
Allergies to radiation therapy tattoos are rare, but not unheard of. A case report published in Volume 43 of Australasian Radiology describes two cases of allergies to black ink tattoos in breast cancer patients. Several days after the tattoos were applied, one patient experienced stinging pain and both developed itching (pruritus) and a rash. Both reactions were classified as allergy to the pigment, however the reactions subsided with time, either with steroid cream (hydrocortisone) and/or oral antihistamine treatment. Although these reactions were not severe, for a breast cancer to develop itchy tattoos alongside other adverse skin reactions induced by radiation therapy is undesirable.
India ink tattoos are permanent if untreated, however, it is possible to have them removed. Tattoo removal has been conducted on many patients for varying reasons since the 1960s. Many removal techniques exist. However, many leave scars which can be more disfiguring than the original tattoo itself. A frequently used tattoo removal technique in the past was dermabrasion, during which the epidermis overlying the tattoo was virtually sanded back and caustic chemicals like tannic acid or silver nitrate were applied to the exposed, pigment-containing dermis to enhance pigment extrusion. This technique often left behind a significant scar. Cryosurgery, where the tattooed skin is frozen with liquid nitrogen, causing the pigmented skin to become necrotic and eventually fall away, can be successful, but only for small tattoos. Complete surgical resection of tattoos is another possibility, but will always leave a scar. Another more basic technique for tattoo removal is to re-tattoo the area with a needle containing no ink, and after exposing the pigmented dermis, soak the region in warm, salty water for several days and leach the pigment out. One cutting-edge tattoo removal technique claims to successfully remove tattoos without significant scarring. The method uses a Q-switched ruby laser (QSRL). The newest generation of QSRLs emit nanosecond-domain pulses of light, which is readily absorbed by tattoo pigments, especially blue-black pigments such as India ink. The exact way in which the pigment absorbs the photons is quite complex, but basically the pigment granules heat up and destroy the cell which contains them. The inflammatory response which follows this destruction clears away the obliterated cell and pigment debris, thus removing the tattoo. It could be assumed that super-heating pigment under the skin would create some long-term damage and scarring. However, due to the extremely short pulses generated by the QSRL (about 40 nanoseconds), residual thermal damage is prevented from injuring normal skin. (Taylor et al, 1991)
With such a successful method of tattoo removal in existence, it is surprising to many dermatologists that more radiation therapy patients are not referred for removal of positioning tattoos. In a letter to the editor entitled Laser Removal of Radiation Tattoos in the April 2002 edition of Annals of Internal Medicine, Dr. Murad Alam and Dr. Kenneth A. Arndt wrote: In our experience, positional tattoos, especially those in cosmetically sensitive locations such as the presternal area and the breast, may contribute significantly to the dehumanisation of patients grappling with a malignancy. When there is a hiatus in treatment or a prolonged remission, removal of the tattoos can be a liberating, hopeful experience. Patients understand that the tattoos are not dangerous, but they nonetheless appreciate the small kindness of physicians who offer to treat them. Erasure of the visible stigmata of the cancer can be a milestone in the process of emotional recovery. (p558). The letter goes on to outline the recent success of the Q-switched ruby lasers, outlined how radiation therapy tattoos were ideal for this treatment and stated that the tattoos could be completely removed within a few sessions.
The problem with this approach arises when patients require further radiation therapy treatment. The permanent tattoos act as a history of past treatment sites and prevent overlapping of fields, which in turn prevents necrosis of over-irradiated tissue. If radiation therapy tattoos are removed, this history is somewhat lost, and although all measures are taken to document fields locations through photographs and charts, change in the patient's physiology through weight gain or loss and skin sag can blur the boundaries. A permanent tattoo is invaluable in these circumstances.
Black ink tattoos are not always easily visualised. On very dark-skinned or heavily- freckled patients, black ink tattoos can be hard to locate, even with the aid of anatomical references. A solution to this is to mark the tattoo on with a permanent marker, and apply a thin, adhesive plastic film to the tattoo location. This aids in tattoo location and visibility from day to day. This film, however, is not permanent and needs to be changed and the marks reapplied during treatment. Also, the sticky plastic can be irritating to the patient, especially if it is in an awkward location. This approach does not solve the problem of difficulty in locating the tattoo if the patient returns for treatment.
Radiation therapy needs a hypo-allergenic tattoo ink which is permanent, invisible under normal light and easily visualised in all skin types. This is where UV ink comes into play.
The UV ink under scrutiny in this investigation claims to be safer than most regular tattoo inks. This is because the ink itself never comes into contact with the skin - the dye molecules are in fact encased in a synthetic polymer known as Polymethylmethacrylate (PMMA). PMMA has been used for decades in varying medical procedures such as dental prostheses and bone repair. This 'coating' is what makes this particular ink hypoallergenic. To date, no adverse reactions to this particular UV ink have been documented.
As UV ink tattoos are applied in the same way as black ink tattoos, it is reasonable to assume that they would be permanent.
If a light coloured ink is used, it appears that the UV ink tattoos are invisible under normal lighting. This is because the natural pigment of skin masks the small amount of ink in the dermis. This characteristic of the UV ink would make it ideal in the radiation therapy environment because it would eliminate the need for tattoo removal. If the tattoos could be unseen in everyday light but remain on the skin, a permanent record of past treatment, the patient could feel less self-conscious of the marks and the radiation staff could still locate the tattoos in case of re-treatment.
It is uncertain with the data collected if UV ink tattoos are more easily visualised than black ink tattoos on dark or freckled skin. The test attempted to show UV tattoos on dark pigmented skin, however, only the superficial epidermis of the pig skin could be dyed. This differs from live human skin, as the melanocytes are actually located in the basal layer of the epidermis. It is the melanocytes which produce melanin, the pigment in normal skin. It is assumed that this is the reason the UV tattoo could not be seen in the dark pig skin. It is uncertain, but likely that the black light was prevented from reaching the ink by the superficial layer of dye. As the light could not reach the tattoo in order for it to fluoresce, it could not be visualised in the image. The black ink tattoo could be seen on the pigmented skin, however, as expected, it was poorly visualised, as the skin was quite dark. .
A peer review published in the Spring edition of Radiation Therapist 2006 outlines an experiment using a black light-sensitive ink. The review illustrates the benefits of using a black light-sensitive ink in place of India ink for radiation therapy tattoos. In this case, the authors have experimented with everyday highlighter ink. The experiment has used raw, skinless chicken breast in place of human skin and has assumed that this material is a suitable substitute. The chicken was tattooed with various highlighter colours by injecting the ink under the skin using an 18-gauge needle (the exact technique is not described). The intensity of the colours was then measured using a rather crude but nonetheless effective method. At 12 inches (30.5cm), all tattoos were assigned an intensity value of 1. The observer would then move away from the tattooed chicken until he or she could no longer visualise the tattoo. The maximum distance at which the tattoo could be seen was recorded. The relative intensity could then be determined by dividing this recorded number by the distance at which the intensity value was 1 (30.5). The study proved that under normal light India ink was quite intense, but under black light, certain colours of highlighter ink could be just as intense. The benefit of the highlighter ink, of course, was that it was virtually invisible under normal lighting conditions. The experiment outlined the toxicity of both highlighter and India ink and it was stated that both types of ink are certified non-toxic. This, however, does not mean the highlighter ink is also hypoallergenic, and does not imply that reactions like those seen in the afore-mentioned breast cancer patient case would not occur. The report also mentions invisible fluorescent ink as a suitable alternative to highlighter ink, but quotes a price at double that of India ink. The experiment goes on to suggest mounting black lights along the treatment bed and on the gantry head for ease of tattoo localisation. The report neglects to mention the effects of working with ultra-violet light long-term.
When it comes to visualising the UV ink tattoos, any black light will do. The light used in the experiment above was a small, hand-held LED-based UV torch, located in the lid of a felt pen containing UV ink. The device was purchased on eBay for AU$5.75 plus shipping costs from seller Prosound Electronics Funstuff (website http://stores.ebay.com.au/Prosound- Electronics-Funstuff) The torch, when held over the tattooed pig skin, effectively illuminated the UV tattoos. A larger black light could be used in a clinical setting, but a convenient, pen- sized light seems more than adequate. The highlighter ink experiment mentioned earlier describes attaching lights to various objects in the treatment room. However, as the long term effects exposure to this ultra-violet light are unknown, perhaps until further studies are conducted, it would be better to err on the side of caution and use small, hand-held lights for a as short a time as possible if using UV tattoos in a therapy department.
A major issue in most health departments today is the cost of materials. India ink is fairly inexpensive, a 30ml-bottle available from one eBay online store for AU$7.00 plus postage and handling (http://stores.ebay.com.au/Red-Branch). 60ml of the Chameleon brand UV ink was purchased for the experiment from their online store
(http://www.blacklightink.com/tattoo-supplies-supply.htm) for US$35.00 which, in addition to the shipping costs, totalled around AU$60.00. This cost is a great deal more than that of the India ink. However, it is cheaper in cost for the health system if it eliminates the need for the patient to undergo a tattoo removal procedure, and cheaper in time for the radiation therapist if the patient does not have their tattoos removed. A solution to this is to make UV tattoos optional - if the patient chooses the UV ink over the India ink, a small fee may be charged. An additional cost would be that of purchasing the black lights. The black light used in the experiment was less than AU$6.00. It is when looking at these short-term costs that the long- term costs must be weighed up. A small cost up front could prevent larger costs in the future, such as the afore mentioned tattoo removal treatments, or worse, a law suit from a patient claiming emotional trauma caused by the tattoos.
In summary, UV ink could serve as an alternative to India ink when tattooing patients undergoing radiation therapy treatment. The ink is virtually invisible under normal lighting circumstances but still easily identifiable under a black light. Although slightly less cost- effective than India ink, UV ink could potentially save health departments money in the future by eliminating the need for tattoo removal. UV ink has the potential to act as a successful medium for creating radiation therapy tattoos. The term "comprise" and variants of the term such as "comprises" or "comprising" are used herein to denote the inclusion of a stated integer or stated integers but not to exclude any other integer or any other integers, unless in the context or usage an exclusive interpretation of the term is required.
Any reference to publications cited in this specification is not an admission that the disclosures constitute common general knowledge in Australia.
REFERENCES
Taylor, C. R., Anderson, R. R., Gange, R. W., Michaud, N. A., Flotte, T. J. (1991) Light and Electron Microscopic Analysis of Tattoos Treated by Q-Switched Ruby Laser, The Journal Of Investigative Dermatology, Volume 97, Number 1, ppl31-136. Sperry, K. (1991) Tattoos and tattooing. Part I: History and methodology. American journal of forensic medicine and pathology, Volume 12, Issue 4, pp313-319.
Sperry, K. (1992) Tattoos and tattooing. Part II: Gross pathology, histopathology, medical complications and applications. American journal of forensic medicine and pathology, Volume 13, Issue 1, pp7-17. Alam, M., Arndt, K. A., (2002) Laser Removal of Radiation Tattoos, Annals of Internal
Medicine, Volume 136, Number 7, pp558.
David, J. E., Castle, S. K. B., Mossi, K. M. (2006) Localisation Tattoos: An Alternative Method Using Fluorescent Inks, Radiation Therapist, Volume 15, Number 1, ppl-5.
Sewak, S., Graham, P., Nankervis, J. (1999) Tattoo allergy in patients receiving adjuvant radiotherapy for breast cancer, Australasian Radiology, Volume 42, pp558-561.
Common (Frequently Asked) Questions about Radiation Therapy, Palestine Cancer Center Website, http://drjohng.com/faq.htm#tattoos accessed 25/9/06.
Anderson, D. M., (2002) Mosby's Medical, Nursing, & Allied Health Dictionary, Sixth Edition, USA: Mosby. Wikipedia, The Free Encyclopedia, Indian Ink, http://en.wikipedia.org/wiki/India ink accessed 25/9/06.
The Art and Creative Materials Institute website, http://www.acminet.org/asp/CPSearchFrames.ASP accessed 25/9/06. eBay Online Stores: Prosound Electronics Funstuff, http://stores. ebay.com.au/Prosound-Electronics-Funstuff accessed 27/9/06.
Red Branch, Minis Cards Celtic and More, http://stores.ebay.com.au/Red-Branch accessed 27/9/06.

Claims

The claims defining the invention are as follows:
1. A method of tattooing skin for radiation therapy, the method comprising injection into the skin of the patient at the desired site a UV ink.
2. Use of UV ink in the preparation of a medicament for tattooing skin for radiation therapy.
3. The method of claim 1 or the use of claim 2, wherein the skin is human skin.
PCT/AU2007/001770 2006-12-21 2007-11-19 Tattooing method for radiation therapy WO2008074052A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4610806A (en) * 1982-10-19 1986-09-09 Rosen Gerald M Skin-marking compositions and devices, and their use
US6013122A (en) * 1998-08-18 2000-01-11 Option Technologies, Inc. Tattoo inks
US6470891B2 (en) * 1999-12-13 2002-10-29 George H. Carroll Photochromatic tattoo
WO2005046620A2 (en) * 2003-11-12 2005-05-26 The General Hospital Corporation Variable appearance tissue markings

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US4610806A (en) * 1982-10-19 1986-09-09 Rosen Gerald M Skin-marking compositions and devices, and their use
US6013122A (en) * 1998-08-18 2000-01-11 Option Technologies, Inc. Tattoo inks
US6470891B2 (en) * 1999-12-13 2002-10-29 George H. Carroll Photochromatic tattoo
WO2005046620A2 (en) * 2003-11-12 2005-05-26 The General Hospital Corporation Variable appearance tissue markings

Non-Patent Citations (2)

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Title
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DAVID J.E. ET AL.: "Localization Tattoos: An Alternative Method Using Fluorescent Inks", RADIATION THERAPEUTIST, vol. 15, no. 1, 2006, pages 1 - 5, Retrieved from the Internet <URL:http://www.people.vcu.edu/~kmmossi/downloads/Localization_Tattoos.pdf> *

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