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Using India Ink as a Sensor for Oximetry: Evidence of its Safety as a Medical Device

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Oxygen Transport to Tissue XXXIX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 977))

Abstract

Clinical EPR spectroscopy is emerging as an important modality, with the potential to be used in standard clinical practice to determine the extent of hypoxia in tissues and whether hypoxic tissues respond to breathing enriched oxygen during therapy. Oximetry can provide important information useful for prognosis and to improve patient outcomes. EPR oximetry has many potential advantages over other ways to measure oxygen in tissues, including directly measuring oxygen in tissues and being particularly sensitive to low oxygen, repeatable, and non-invasive after an initial injection of the EPR-sensing material is placed in the tumor. The most immediately available oxygen sensor is India ink, where two classes of carbon (carbon black and charcoal) have been identified as having acceptable paramagnetic properties for oximetry. While India ink has a long history of safe use in tattoos, a systematic research search regarding its safety for marking tissues for medical uses and an examination of the evidence that differentiates between ink based on charcoal or carbon black has not been conducted. Methods. Using systematic literature search techniques, we searched the PubMed and Food and Drug Administration databases, finding ~1000 publications reporting on adverse events associated with India/carbon based inks. The detailed review of outcomes was based on studies involving >16 patients, where the ink was identifiable as carbon black or charcoal. Results. Fifty-six studies met these criteria. There were few reports of complications other than transient and usually mild discomfort and bleeding at injection, and there was no difference in charcoal vs. carbon black India ink. Conclusions. India ink was generally well tolerated by patients and physicians reported that it was easy to use in practice and used few resources. The risk is low enough to justify its use as an oxygen sensor in clinical practice.

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References

  1. Vaupel P, Mayer A (2015) The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal 10:878–879. doi:10.1089/ars.2014.6155

    Article  Google Scholar 

  2. Gallez B (2003) Packaging of paramagnetic materials in oximetry and other applications. In: Berliner LJ (ed) In Vivo EPR (ESR): theory and application. Springer, New York, pp 259–283. doi:10.1007/978-1-4615-0061-2

    Chapter  Google Scholar 

  3. Charlier N, Beghein N, Gallez B (2004) Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. NMR Biomed 17:303–310. doi:10.1002/nbm.902

    Article  CAS  PubMed  Google Scholar 

  4. Jordan BF, Baudelet C, Gallez B (1998) Carbon-centered radicals as oxygen sensors for in vivo electron paramagnetic resonance: screening for an optimal probe among commercially available charcoals magnetic resonance materials in physics. Biol Med 7:121–129

    CAS  Google Scholar 

  5. Swartz HM, Williams BB, Hou H, Khan N, Jarvis LA, Chen EY, Schaner P, Ali AN, Gallez B, Kuppusamy P, Flood AB (2016) Direct and repeated clinical measurements of p02 for enhancing cancer therapy and other applications. Adv Exp Med Biol 923:95–104

    Article  PubMed  Google Scholar 

  6. Swartz HM, Williams BB, Zaki BI, Hartford AC, Jarvis LA, Chen E, Comi RJ, Ernstoff MS, Hou H, Khan N, Swarts SG, Flood AB, Kuppusamy P (2014) Clinical EPR: unique opportunities and some challenges. Acad Radiol 21(2):197–206

    Article  PubMed  PubMed Central  Google Scholar 

  7. Long CM, Nascarella MA, Valberg PA (2013) Carbon black vs. black carbon and other airborne materials containing elemental carbon: physical and chemical distinctions. Environ Pollut 181:271–286

    Article  CAS  PubMed  Google Scholar 

  8. Dorfer L, Moser M, Spindler K, Bahr F, Egarter-Vigl E, Dohr G (1998) 5200-year-old acupuncture in central Europe? Science 282:242–243

    Article  CAS  PubMed  Google Scholar 

  9. Dorfer L, Moser M, Bahr F, Spindler K, Egarter-Vigl E, Giullén S, Dohr G, Kenner T (1999) A medical report from the stone age? Lancet 354:1023–1025

    Article  CAS  PubMed  Google Scholar 

  10. Kean WF, Tocchio S, Kean M, Rainsford KD (2013) The musculoskeletal abnormalities of the similaun iceman (“Ötzi”): clues to chronic pain and possible treatments. Inflammopharmacology 21(1):11–20

    Article  PubMed  Google Scholar 

  11. Pabst MA, Letofsky-Pabst I, Bock E, Moser M, Dorfer L, Egarter–Vigl E, Hofer E (2009) The tattoos of the tyrolean iceman: a light microscopical, ultrastructural and element analytical study. J Archaeol Sci 36:2335–2341

    Article  Google Scholar 

  12. Sperry K (1992) Tattoos and tattooing. Part II: gross pathology, histopathology, medical complications, and applications. Am J Forensic Med Pathol 13(1):7–17

    Article  CAS  PubMed  Google Scholar 

  13. Fujita H, Nishil Y, Yamashita K, Kawamata A, Yoshikawa K (1988) The uptake and long-term storage of India ink particles and latex beads by fibroblasts in the dermis and subcutis of mice, with special regard to the non-inflammatory defense reaction by fibroblasts. Arch Histol Cytol 51(3):285–294

    Article  CAS  PubMed  Google Scholar 

  14. Lea PJ, Pawlowski A (1987) Human tattoo. Electron microscopic assessment of epidermis, epidermal-dermal junction, and dermis. Int J Dermatol 26:453–458

    Article  CAS  PubMed  Google Scholar 

  15. Aboosy N, Mulder CJ, Berends FJ, Meijer JW, Sorge AA (2005) Endoscopic tattoo of the colon might be standardized to locate tumors intraoperatively. Rom J Gastroenterol 14(3):245–248

    PubMed  Google Scholar 

  16. Cipe G, Cengiz MB, Idiz UO et al (2016) The effects of preoperative endoscopic tattooing on distal surgical margin and ileostomy rates in laparoscopic rectal cancer surgery: a prospective randomized study. Surg Laparosc Endosc Percutan Tech 26(4):301–303

    Article  PubMed  Google Scholar 

  17. Fennerty MB, Sampliner RE, Hixson LJ, Garewal HS (1992) Effectiveness of India ink as a long-term colonic mucosal marker. Am J Gastroenterol 87(1):79–81

    CAS  PubMed  Google Scholar 

  18. Hwang MR, Sohn DK, Park JW et al (2010) Small-dose India ink tattooing for preoperative localization of colorectal tumor. J Laparoendosc Adv Surg Tech. Part A 20(9):731–734

    Article  Google Scholar 

  19. McArthur CS, Roayaie S, Waye JD (1999) Safety of preoperation endoscopic tattoo with india ink for identification of colonic lesions. Surg Endosc 13(4):397–400

    Article  CAS  PubMed  Google Scholar 

  20. Park JW, Sohn DK, Hong CW et al (2008) The usefulness of preoperative colonoscopic tattooing using a saline test injection method with prepackaged sterile India ink for localization in laparoscopic colorectal surgery. Surg Endosc 22(2):501–505

    Article  CAS  PubMed  Google Scholar 

  21. Salomon P, Berner JS, Waye JD (1993) Endoscopic India ink injection: a method for preparation, sterilization, and administration. Gastrointest Endosc 39(6):803–805

    Article  CAS  PubMed  Google Scholar 

  22. Shaffer RT, Francis JM, Carrougher JG et al (1998) India ink tattooing in the esophagus. Gastrointest Endosc 47(3):257–260

    Article  CAS  PubMed  Google Scholar 

  23. Shatz BA, Thavorides V (1991) Colonic tattoo for follow-up of endoscopic sessile polypectomy. Gastrointest Endosc 37(1):59–60

    Article  CAS  PubMed  Google Scholar 

  24. Sun L, Si J, Chen S, Liu W, Zhao L, Wang L (2009) The establishment and clinical appliance of technique of mucosa marking targeting biopsy. Hepatogastroenterology 56(89):59–62

    PubMed  Google Scholar 

  25. Chami L, Hartl D, Leboulleux S et al (2015) Preoperative localization of neck recurrences from thyroid cancer: charcoal tattooing under ultrasound guidance. Thyroid : Off J Am Thyroid Assoc 25(3):341–346

    Article  Google Scholar 

  26. Kang TW, Shin JH, Han BK et al (2009) Preoperative ultrasound-guided tattooing localization of recurrences after thyroidectomy: safety and effectiveness. Ann Surg Oncol 16(6):1655–1659

    Article  PubMed  Google Scholar 

  27. Tirelli G, Cova MA, Boscolo-Rizzo P, Da Mosto MC, Makuc E, Gardenal N (2016) Charcoal suspension tattoo: a new technique for intraoperative detection of small tumors of the parotid gland. Ann Otol Rhinol Laryngol 125(7):529–535

    Article  PubMed  Google Scholar 

  28. Ko K, Han BK, Jang KM et al (2007) The value of ultrasound-guided tattooing localization of nonpalpable breast lesions. Korean J Radiol 8(4):295–301

    Article  PubMed  PubMed Central  Google Scholar 

  29. Langlois SL, Carter ML (1991) Carbon localisation of impalpable mammographic abnormalities. Australas Radiol 35(3):237–241

    Article  CAS  PubMed  Google Scholar 

  30. Rose A, Collins JP, Neerhut P, Bishop CV, Mann GB (2003) Carbon localisation of impalpable breast lesions. Breast (Edinburgh/Scotland) 12(4):264–269

    Article  CAS  Google Scholar 

  31. Svane G (1983) A stereotaxic technique for preoperative marking of non-palpable breast lesions. Acta Radiol Diagn 24(2):145–151

    Article  CAS  Google Scholar 

  32. Azavedo ESG, Auer G (1989) Stereotactic fine-needle biopsy in 2594 mammographically detected non-palpable lesions. Lancet 1(8646):1033–1036

    Article  CAS  PubMed  Google Scholar 

  33. Cavalcanti TC, Malafaia O, Nassif PA et al (2012) Non-palpable breast lesions marked with coal suspension: evaluation of anatomopathological aspects, viability of interpretation and inflammatory response. Revista do Colegio Brasileiro de Cirurgioes 39(6):469–475

    Article  PubMed  Google Scholar 

  34. Mazy S, Galant C, Berliere M, Mazy G (2001) Localization of non-palpable breast lesions with black carbon powder (experience of the Catholic University of Louvain). J Radiol 82(2):161–164

    CAS  PubMed  Google Scholar 

  35. Mullen DJ, Eisen RN, Newman RD, Perrone PM, Wilsey JC (2001) The use of carbon marking after stereotactic large-core-needle breast biopsy. Radiology 218(1):255–260

    Article  CAS  PubMed  Google Scholar 

  36. Rathod S, Munshi A, Agarwal J (2012) Skin markings methods and guidelines: a reality in image guidance radiotherapy era. South Asian J Cancer 1(1):27–29

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mathieu MC, Bonhomme-Faivre L, Rouzier R, Seiller M, Barreau-Pouhaer L, Travagli JP (2007) Tattooing breast cancers treated with neoadjuvant chemotherapy. Ann Surg Oncol 14(8):2233–2238

    Article  PubMed  Google Scholar 

  38. Choy N, Lipson J, Porter C et al (2015) Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Ann Surg Oncol 22(2):377–382

    Article  PubMed  Google Scholar 

  39. Khan N, Hou H, Hein P et al (2005) Black magic and EPR oximetry: from lab to initial clinical trials. Adv Exp Med Biol 566:119–125

    Article  PubMed  Google Scholar 

  40. Kirchoff DD, Hang JH, Cekic V et al (2014) Endoscopic tattooing to mark distal margin for low anterior rectal and select sigmoid resections. Surg Innov 21:376–380

    Article  PubMed  Google Scholar 

  41. Food and Drug Administration (2012). Tattoos & permanent makeup: fact sheet http://www.fda.gov/ Cosmetics/ProductsIngredients/Products/ucm108530.htm . Accessed 20 Aug 2016

  42. Islam PS, Chang C, Selmi C, Generali E, Huntley A, Teuber SS, Gershwin E (2016) Medical complications of tattoos: a comprehensive review. Clin Rev Allergy Immunol 50(2):273–286

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Institutes of Health (National Cancer Institute grant P01 CA190193).

Disclosures

ABF and HMS are owners of Clin-EPR, LLC, which manufacturers EPR devices for investigational clinical applications.

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Correspondence to Ann Barry Flood .

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Flood, A.B., Wood, V.A., Swartz, H.M. (2017). Using India Ink as a Sensor for Oximetry: Evidence of its Safety as a Medical Device. In: Halpern, H., LaManna, J., Harrison, D., Epel, B. (eds) Oxygen Transport to Tissue XXXIX. Advances in Experimental Medicine and Biology, vol 977. Springer, Cham. https://doi.org/10.1007/978-3-319-55231-6_40

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