On the mechanism of painful burn sensation in tattoos on magnetic resonance imaging (MRI). Magnetic substances in tattoo inks used for permanent makeup (PMU) identified: Magnetite, goethite, and hematite

Abstract Background Persons with cosmetic tattoos occasionally experience severe pain and burning sensation on magnetic resonance imaging (MRI). Objective To explore the culprit magnetic substances in commonly used permanent makeup inks. Material and methods 20 inks used for cosmetic tattooing of eyebrows, eyeliners, and lips were selected. Ink bottles were tested for magnetic behavior with a neodymium magnet. Eight iron oxide inks qualified for the final study. Metals were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP‐MS). The magnetic fraction of inks was isolated and analyzed by X‐ray fluorescence (XRF). Magnetic iron compounds were characterized by Mössbauer spectroscopy and powder X‐ray diffraction (XRD). Results ICP‐MS showed iron in all magnetic samples, and some nickel and chromium. Mössbauer spectroscopy and XRD detected ferromagnetic minerals, particularly magnetite, followed by goethite and hematite. Conclusion This original study of cosmetic ink stock products made with iron oxide pigments reports magnetic impurities in inks for cosmetic tattooing, e.g., magnetite, goethite, and hematite. These may be the main cause of MRI burn sensation in cosmetic tattoos. The mechanism behind sensations is hypothesized to be induction of electrical stimuli of axons from periaxonal pigment/impurity activated by magnetic force. Magnetite is considered the lead culprit.


INTRODUCTION
Hazards and adverse effects from ferromagnetic material such as metal implants may occur in MRI procedures. 1,2 Tattoo ink stock products are known to contain metallic ingredients and impurities; [3][4][5] thus, adverse reactions may occur in tattooed skin on exposure to forceful magnetic fields. 6 A review of the literature finds reports of burn sensations of varying degree without associated physical signs albeit erythema and edema in the tattoo occasionally may occur. The literature has misinterpreted the feeling of burn and claimed the sensation to be a real thermal insult induced by MRI; 7-10 inks exposed to MRI show no temperature increase. 7 Permanent makeup is in the medical literature indicated to carry a special risk of MRI-induced complication due to the commonly used iron oxide pigments in this type of inks. 6,7 MRI adverse events of decorative tattoos on trunk and extremities have been sporadically reported, but events are exceptional relative to the popularity of these adornments. 11,12 Iron oxide pigments of high purity are usually not magnetic, and MRI events of tattoos made with this class of chemicals are suspected to be due to magnetic contaminants or impurities in the crude raw material used in production. Ink production is industrial, widely unregulated, and not quality assured through good manufacturing practice (GMP) standards.
The word magnet comes from the ancient Greek city Magnesia founded by the Magnete tribe; rocks in this city are ferromagnetic. Iron oxide pigments in tattoo inks often originate from some natural source of raw material supply and, thus, are likely to be variably contaminated with metals and minerals, including nickel, cobalt, chromium, and copper. 3,5,7,13 However, even high iron oxide content is not automatically associated with magnetism, as the magnetic properties depend on several chemical and physical factors such as oxidation level, the configuration of electrons in the material's atoms, and the crystal structure.
Thus, some iron oxides may have paramagnetic or ferromagnetic properties; meaning it is attracted by magnets. Some can in the laboratory become permanently magnetic.
The aim of this study was to identify magnetic substances in commercial ink stock products often used in cosmetic tattooing. This was to our best knowledge not explored in the past. Identification of magnetic culprit substances in tattoo inks may result in the future manufacturing of MRI-safe tattoo inks. Burn sensation in a tattoo often interrupts and invalidates the MRI procedure, and MRI is essential in the diagnosis of, for example, cancer.

Selection of commercial ink stock products by magnets test: initial off-the-shelf test
One investigator (J. Serup) visited a local cosmetic tattoo studio, Diana Hvas Perfecting Beauty, Rødovre, Denmark. Ink stock products exclusively made for cosmetic tattooing e.g., eyebrows, eyeliners, and lips were randomly selected from the studio ink portfolio. A simple F I G U R E 1 Flowchart of the study test using a handheld magnet was introduced to identify ink bottles with magnetic behavior. 14 In this primary screening, using a solid neodymium magnet strength of 0.3 tesla (T) measured with a handheld Gaussmeter, the ink bottles were exposed to a static magnetic field. A product was deemed test positive if the whole ink bottle when lying horizontally could be rolled on a flat surface, drawn by the magnet. The test is used with caution as asymmetry of the ink bottle, labeling, and sometimes a metal nut for stirring might produce false-positive or -negative outcomes. Therefore, in case of doubtful outcomes, a confirmatory test was conducted. In a transparent Petri dish, a single drop of ink was dosed in the center of the dish. A handheld neodymium magnet was moved under the Petri dish, and the ink drop was visually inspected for surface structure changes referenced to a Rosensweig instability, or horizontal move of the entire drop of ink following movement of the magnet under the bottom of the Petri dish. 15 All ink bottles were categorized as magnetic or nonmagnetic ( Figure 1). Nonmagnetic samples were with one exception excluded from more detailed analysis. 6 M was reconsidered and concluded nonmagnetic and served as a negative control in further testing.

Separation of magnetic particles in magnetic inks
In a 100 ml beaker, 1.0 gram of each magnetic tattoo ink was weighed. The ink was then dissolved in 25 mL of demineralized water. To isolate the magnetic pigment particles, a powerful permanent magnet (diameter 2.4 cm × height 1.5 cm) was held under the beaker, and the ink dilutions were centrifuged in the glass for 30 s. This was to locate and retain the ferromagnetic particles after the supernatant was gently discarded. The procedure was repeated until suspensions of particles were transparent; 40-60 extractions were required.
The isolated magnetic particles were then mixed with a small amount of demineralized water in a pre-weighed vial and placed on a heating plate for 8 h to dehydrate. Thereafter, the dehydrated pigment powder was weighed and analyzed by solid-state methodology (see Section 2.4).

Analysis of elements in separated magnetic particles by X-ray fluorescence (XRF)
A Niton™ XL3t GOLDD, a handheld high-performance portable Xray fluorescence elemental analyzer from Thermo Scientific was used. 16

Mössbauer spectroscopy to identify magnetic chemicals/constituents
Fe-57 Mössbauer spectra were obtained at room temperature (298 K) on air-dry powdered sample packed into a Perspex sample holder, using a conventional constant acceleration spectrometer and a collimated source of Co-57 in Rh. The spectrometer was calibrated using a 12.5 mm foil of natural Fe at room temperature, and isomer shifts were given with respect to the center of the spectrum of the absorber. In this experiment, no thickness corrections were applied to the spectra. Spectra were fitted using a combination of doublet and sextet components having Lorentzian line shapes.

X-ray powder diffraction
Powder X-ray diffraction (PXRD) analyses were conducted with a Bruker D8 Advance diffractometer using CuKα radiation. The CuKβ radiation was suppressed using a Ni filter. All analyses were performed at room temperature in the angular range 10-60 • 2θ with a step size of 0.02 • 2θ and a dwell time of 10 s per step. The energy window of the Lynxeye detector was set to reduce the noise caused by the Fe fluorescence effects excited by the Cu emission radiation from the iron-rich samples.

RESULTS
Twenty random cosmetic ink products from the cosmetic tattoo clinic were enrolled (flowchart; Figure 1). Tables 1A and 1B show the Table 1A, and nonmagnetic samples in Table 1B. However, using the confirmatory Petri dish test, one sample (no. 6 M) turned out false positive. This was confirmed by no detection of iron or other metals in the chemical analysis program (

TA B L E 2 Elements analyzed by ICP-MS of magnetic inks
The TA B L E 3 Elements in dry powder sediment with concentrated magnetic pigment measured by handheld X-ray fluorescence (XRD) I.D., under the detection limit.

Content of elements in magnetic ink sediment
Ten nonmagnetic cosmetic inks were used as controls (no. 1C-10C) in the first part of the analytical program, e.g., measurement of elements ( Table 2). They were negative in both magnet tests; thus, con-  (Table 2).
After separation of the magnetic particles (1 M-10 M), the retained dry pigment powder presented with dark brown or black colors, thus, the same color as the ink stock product.
Analysis of the dry powder pigment with a handheld XRF device showed high proportions of iron expressed as a percentage, and minor proportions of titanium, chromium, magnesium, zinc, silicon, and sulfur (Table 3). Consistent finding of silicon indicates some ore is the origin of the raw material.
Prior to analysis by Mössbauer spectroscopy, two samples were excluded. One sample was lost; another was depleted since too little material was available for further analysis (Figure 1  iron. Confirmatory analysis using powder X-ray diffraction supported findings by Mössbauer spectroscopy (Table 4).

DISCUSSION
All magnetic ink samples contained metals particularly iron oxides and, as an original finding, the classical iron oxide minerals known from the literature to be magnetic, e.g., magnetite, goethite, and hematite. Magnetic chemicals in the inks are supposed to be outside the recipe and thus not added deliberately; they were seen as impurities originating from the crude pigment raw material.
The concentration of magnetic iron oxide impurities in tattoo inks is not supposed to be linearly correlated to the magnetic property of the product since magnetic property is known in physics to depend on several factors such as oxidation level and crystallographic structure. For instance, both hematite and magnetite are iron oxides but represent different crystal classes with distinct magnetic properties. Hematite is a hexagonal mineral and a spin-canted antiferromagnet leading to only feeble magnetization whereas magnetite is a hexoctahedral mineral, in an inverse spinel structure leading to a magnetization hundred times stronger. Therefore, these minerals are bound to behave very differently when exposed to MRI conditions. Magnetite is the stronger one. Tattoo pigment is by electron microscopy of tattooed skin observed directly in the perineurium of cutaneous nerves; closeness between pigment and nerve supports the hypothesis that MRI-induced magnetic activation of perineural pigment can trigger an electrical signal that makes the sensory nerves lead impulses to the brain, with the sensation being read and felt as burn and pain. 20 The electron microscopy study includes particle position and physical orientation under the influence of MRI fields; a physical drag effect on pigment particles was so far not observed. 21 There determining pigment aggregation ink stock products, are supposed to depend on the electrical potential of the particle surface, measured as the zeta. The zeta potential is influenced by pigment coatings commonly used in ink manufacturing independent of pigment class. 25 The zeta potential of iron oxides, carbon black, and most other pigments are measured negative. Differences between the potential of particles and the close surrounding create electrical fields, which under the influence of a powerful magnetic field might induce a sensory response. Our observation that iron oxide-based ink stock products commonly are magnetic contrasts no indication that every person tattooed with magnetic ink will risk MRI burn sensation. Present clinical evidence indicates only 1-2% of tattooed patients react in their tattoo on MRI. 6 Obviously, strong individual and local prerequisites or factors diminish the response rate; it may be the density and closeness of pigment in situ nearby the axon; it may be variable axonal threshold for this kind of sensation; and it may be the coating of pigment particles to influence their electrical surface potential and the electrical field relative to the pigment core. There may also be a window of increased sensitivity to MRI in the fresh tattoo in the healing phase before washout of tattoo pigment and metals seeded by tattoo needling is effective. 30

CONCLUSION
We report the original observation that iron oxide pigments used in cosmetic tattoo ink stock products commonly contain magnetic iron oxide impurities namely magnetite, goethite, and hematite. Magnetite is considered the main component responsible for instant burn sensations in cosmetic tattoos exposed to MRI. A simple magnet test of ink stock products with a handheld magnet can be used to distinguish magnetic and nonmagnetic inks. Used for product screening as a safety measure, the test is limited by many false-positive outcomes versus clinical adverse response. A range of individual and local factors and other ink-related conditions appear involved. It is hypothesized that the mechanism of MRI tattoo reactions is a magnet-electrical induction of pigment particles nearby neurons resulting in direct excitation of sensory neurons in the tattoo with a sensory signal read by the central nervous system as a painful burn sensation in the tattoo.

ACKNOWLEDGMENTS
The authors extend their appreciation Diana Hvas, Permanent Makeup Artist, who donated samples of cosmetic tattoo ink samples from her studio.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.