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Molecular Imaging and Biology

, Volume 19, Issue 5, pp 645–655 | Cite as

Fluorescence Imaging for Cancer Screening and Surveillance

  • K. E. Tipirneni
  • E. L. Rosenthal
  • L. S. Moore
  • A. D. Haskins
  • N. Udayakumar
  • A. H. Jani
  • W. R. Carroll
  • A. B. Morlandt
  • M. Bogyo
  • J. Rao
  • Jason M. Warram
Review Article

Abstract

The advent of fluorescence imaging (FI) for cancer cell detection in the field of oncology is promising for both cancer screening and surgical resection. Particularly, FI in cancer screening and surveillance is actively being evaluated in many new clinical trials with over 30 listed on Clinical Trials.gov. While surgical resection forms the foundation of many oncologic treatments, early detection is the cornerstone for improving outcomes and reducing cancer-related morbidity and mortality. The applications of FI are twofold as it can be applied to high-risk patients in addition to those undergoing active surveillance. This technology has the promise of highlighting lesions not readily detected by conventional imaging or physical examination, allowing disease detection at an earlier stage of development. Additionally, there is a persistent need for innovative, cost-effective imaging modalities to ameliorate healthcare disparities and the global burden of cancer worldwide. In this review, we outline the current utility of FI for screening and detection in a range of cancer types.

Key words

Cancer screening Early detection of cancer Neoplasms Diagnostic imaging Optical imaging Molecular imaging 

Notes

Acknowledgements

We have no acknowledgements and there is no funding involved with the preparation of this manuscript.

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interest.

Funding Sources

This work was supported by the National Institutes of Health (T32CA091078).

References

  1. 1.
    Tsu VD, Jeronimo J, Anderson BO (2013) Why the time is right to tackle breast and cervical cancer in low-resource settings. Bull World Health Organ 91:683–690CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Frangioni JV (2008) New technologies for human cancer imaging. J Clin Oncol 26:4012–4021CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Joshi BP, Duan X, Kwon RS et al (2016) Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's neoplasia. Endoscopy 48:A1–A13CrossRefPubMedGoogle Scholar
  4. 4.
    Smith RA, Cokkinides V, Eyre HJ (2006) American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin 56:11–25 quiz 49-50CrossRefPubMedGoogle Scholar
  5. 5.
    Bosch FX, Lorincz A, Munoz N et al (2002) The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55:244–265CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Chesson HW, Dunne EF, Hariri S, Markowitz LE (2014) The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 41:660–664CrossRefPubMedGoogle Scholar
  7. 7.
    Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRefPubMedGoogle Scholar
  8. 8.
    Ferlay JSI, Ervik M, Dikshit R, et al. (2013) GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013Google Scholar
  9. 9.
    Bychkovsky BL, Ferreyra ME, Strasser-Weippl K et al (2016) Cervical cancer control in Latin America: a call to action. Cancer 122:502–514CrossRefPubMedGoogle Scholar
  10. 10.
    Julius JM, Ramondeta L, Tipton KA et al (2011) Clinical perspectives on the role of the human papillomavirus vaccine in the prevention of cancer. Pharmacotherapy 31:280–297CrossRefPubMedGoogle Scholar
  11. 11.
    Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R (2013) Screening for cervical cancer: a systematic review and meta-analysis. Systematic reviews 2:35CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Grant BD, Schwarz RA, Quang T et al (2015) High-resolution microendoscope for the detection of cervical neoplasia. Methods Mol Biol 1256:421–434CrossRefPubMedGoogle Scholar
  13. 13.
    Pierce MC, Guan Y, Quinn MK et al (2012) A pilot study of low-cost, high-resolution microendoscopy as a tool for identifying women with cervical precancer. Cancer Prev Res (Phila) 5:1273–1279CrossRefGoogle Scholar
  14. 14.
    Cronje HS, Parham GP, Cooreman BF et al (2003) A comparison of four screening methods for cervical neoplasia in a developing country. Am J Obstet Gynecol 188:395–400CrossRefPubMedGoogle Scholar
  15. 15.
    Thekkek N, Richards-Kortum R (2008) Optical imaging for cervical cancer detection: solutions for a continuing global problem. Nat Rev Cancer 8:725–731CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bedard N, Schwarz RA, Hu A et al (2013) Multimodal snapshot spectral imaging for oral cancer diagnostics: a pilot study. Biomed Opt Express 4:938–949CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    American Cancer Society (2016) Cancer Facts & Figures 2016. American Cancer Society, AtlantaGoogle Scholar
  18. 18.
    Chen AY, Myers JN (2001) Cancer of the oral cavity. Disease-a-month: DM 47:275–361CrossRefPubMedGoogle Scholar
  19. 19.
    Moore SR, Johnson NW, Pierce AM, Wilson DF (2000) The epidemiology of mouth cancer: a review of global incidence. Oral Dis 6:65–74CrossRefPubMedGoogle Scholar
  20. 20.
    Schwarz RA, Gao W, Redden Weber C et al (2009) Noninvasive evaluation of oral lesions using depth-sensitive optical spectroscopy. Cancer 115:1669–1679CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    National Comprehensive Cancer Network Guidelines. Head and Neck Cancers. Version 2.2013. NCCN.org. Accessed 29 Aug 2016.
  22. 22.
    Pierce MC, Schwarz RA, Bhattar VS et al (2012) Accuracy of in vivo multimodal optical imaging for detection of oral neoplasia. Cancer Prev Res (Phila) 5:801–809CrossRefGoogle Scholar
  23. 23.
    Lane PM, Gilhuly T, Whitehead P et al (2006) Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt 11:024006CrossRefPubMedGoogle Scholar
  24. 24.
    Sweeny L, Dean NR, Magnuson JS et al (2011) Assessment of tissue autofluorescence and reflectance for oral cavity cancer screening. Otolaryngology—head and neck surgery: official journal of American Academy of Otolaryngology-Head and Neck Surgery 145:956–960CrossRefGoogle Scholar
  25. 25.
    Lalla Y, Matias MA, Farah CS (2016) Assessment of oral mucosal lesions with autofluorescence imaging and reflectance spectroscopy. J Am Dent Assoc 147:650–660CrossRefPubMedGoogle Scholar
  26. 26.
    Houghton O, McCluggage WG (2009) The expression and diagnostic utility of p63 in the female genital tract. Adv Anat Pathol 16:316–321CrossRefPubMedGoogle Scholar
  27. 27.
    Pawinski A, Sylvester R, Kurth KH et al (1996) A combined analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council Working Party on Superficial Bladder Cancer. J Urology 156:1934–1940 discussion 1940-1931CrossRefGoogle Scholar
  28. 28.
    Thomas F, Noon AP, Rubin N et al (2013) Comparative outcomes of primary, recurrent, and progressive high-risk non-muscle-invasive bladder cancer. Eur Urology 63:145–154CrossRefGoogle Scholar
  29. 29.
    Botteman MF, Pashos CL, Redaelli A et al (2003) The health economics of bladder cancer: a comprehensive review of the published literature. PharmacoEconomics 21:1315–1330CrossRefPubMedGoogle Scholar
  30. 30.
    Rink M, Babjuk M, Catto JW et al (2013) Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature. Eur Urology 64:624–638CrossRefGoogle Scholar
  31. 31.
    Zaak D, Kriegmair M, Stepp H et al (2001) Endoscopic detection of transitional cell carcinoma with 5-aminolevulinic acid: results of 1012 fluorescence endoscopies. Urology 57:690–694CrossRefPubMedGoogle Scholar
  32. 32.
    Jichlinski P, Forrer M, Mizeret J et al (1997) Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: preliminary results. Lasers Surg Med 20:402–408CrossRefPubMedGoogle Scholar
  33. 33.
    Marti A, Jichlinski P, Lange N et al (2003) Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX distribution in human bladder cancer. J Urology 170:428–432CrossRefGoogle Scholar
  34. 34.
    Kausch I, Sommerauer M, Montorsi F et al (2010) Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urology 57:595–606CrossRefGoogle Scholar
  35. 35.
    Stenzl A, Penkoff H, Dajc-Sommerer E et al (2011) Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy: a multicenter randomized, double-blind, placebo-controlled trial. Cancer 117:938–947CrossRefPubMedGoogle Scholar
  36. 36.
    Jocham D, Witjes F, Wagner S et al (2005) Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urology 174:862–866 discussion 866CrossRefGoogle Scholar
  37. 37.
    Schmidbauer J, Witjes F, Schmeller N et al (2004) Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy. J Urology 171:135–138CrossRefGoogle Scholar
  38. 38.
    Zaak D, Hungerhuber E, Schneede P et al (2002) Role of 5-aminolevulinic acid in the detection of urothelial premalignant lesions. Cancer 95:1234–1238CrossRefPubMedGoogle Scholar
  39. 39.
    Pan Y, Volkmer JP, Mach KE et al (2014) Endoscopic molecular imaging of human bladder cancer using a CD47 antibody. Sci Transl Med 6:260ra148CrossRefPubMedGoogle Scholar
  40. 40.
    Society AC (2015) Global cancer facts & figures, 3rd edn. American Cancer Society, AtlantaGoogle Scholar
  41. 41.
    Brown LM, Devesa SS, Chow WH (2008) Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst 100:1184–1187CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Bird-Lieberman EL, Fitzgerald RC (2009) Early diagnosis of oesophageal cancer. Br J Cancer 101:1–6CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Pohl H, Welch HG (2005) The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 97:142–146CrossRefPubMedGoogle Scholar
  44. 44.
    Solaymani-Dodaran M, Logan RF, West J et al (2004) Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux. Gut 53:1070–1074CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kariv R, Plesec TP, Goldblum JR et al (2009) The Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol. Clin Gastroenterol Hepatol 7:653–658 quiz 606CrossRefPubMedGoogle Scholar
  46. 46.
    Freitag CP, Barros SG, Kruel CD et al (1999) Esophageal dysplasias are detected by endoscopy with Lugol in patients at risk for squamous cell carcinoma in southern Brazil. Dis Esophagus 12:191–195CrossRefPubMedGoogle Scholar
  47. 47.
    Reddymasu SC, Sharma P (2008) Advances in endoscopic imaging of the esophagus. Gastroenterol Clin N Am 37:763–774 viiCrossRefGoogle Scholar
  48. 48.
    Dawsey SM, Fleischer DE, Wang GQ et al (1998) Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China. Cancer 83:220–231CrossRefPubMedGoogle Scholar
  49. 49.
    Hashimoto CL, Iriya K, Baba ER et al (2005) Lugol’s dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer. Am J Gastroenterol 100:275–282CrossRefPubMedGoogle Scholar
  50. 50.
    Wei WQ, Abnet CC, Lu N et al (2005) Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China. Gut 54:759–763CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Protano MA, Xu H, Wang G et al (2015) Low-cost high-resolution microendoscopy for the detection of esophageal squamous cell neoplasia: an international trial. Gastroenterology 149:321–329CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Winawer SJ, Zauber AG, Ho MN et al (1993) Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup The New England journal of medicine 329:1977–1981CrossRefPubMedGoogle Scholar
  53. 53.
    Zauber AG, Winawer SJ, O'Brien MJ et al (2012) Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 366:687–696CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917CrossRefPubMedGoogle Scholar
  55. 55.
    Heresbach D, Barrioz T, Lapalus MG et al (2008) Miss rate for colorectal neoplastic polyps: a prospective multicenter study of back-to-back video colonoscopies. Endoscopy 40:284–290CrossRefPubMedGoogle Scholar
  56. 56.
    Leufkens AM, van Oijen MG, Vleggaar FP, Siersema PD (2012) Factors influencing the miss rate of polyps in a back-to-back colonoscopy study. Endoscopy 44:470–475CrossRefPubMedGoogle Scholar
  57. 57.
    Rex DK, Cutler CS, Lemmel GT et al (1997) Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology 112:24–28CrossRefPubMedGoogle Scholar
  58. 58.
    Diamond SJ, Enestvedt BK, Jiang Z et al (2011) Adenoma detection rate increases with each decade of life after 50 years of age. Gastrointest Endosc 74:135–140CrossRefPubMedGoogle Scholar
  59. 59.
    Rabeneck L, Paszat LF, Hilsden RJ et al (2008) Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology 135:1899–1906 1906 e1891CrossRefPubMedGoogle Scholar
  60. 60.
    Hassan C, Pickhardt PJ, Rex DK (2010) A resect and discard strategy would improve cost-effectiveness of colorectal cancer screening. Clin Gastroenterol Hepatol 8:865–869 869 e861-863CrossRefPubMedGoogle Scholar
  61. 61.
    Chang SS, Shukla R, Polydorides AD et al (2013) High resolution microendoscopy for classification of colorectal polyps. Endoscopy 45:553–559CrossRefPubMedGoogle Scholar
  62. 62.
    Vogelstein B, Papadopoulos N, Velculescu VE et al (2013) Cancer genome landscapes. Science 339:1546–1558CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Parikh ND, Perl D, Lee MH et al (2015) In vivo classification of colorectal neoplasia using high-resolution microendoscopy: improvement with experience. J Gastroenterol Hepatol 30:1155–1160CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Zhou J, Joshi BP, Duan X et al (2015) EGFR overexpressed in colonic neoplasia can be detected on wide-field endoscopic imaging. Clin Transl Gastroenterol 6:e101CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Spano JP, Lagorce C, Atlan D et al (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16:102–108CrossRefPubMedGoogle Scholar
  66. 66.
    Porebska I, Harlozinska A, Bojarowski T (2000) Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumour Biol 21:105–115CrossRefPubMedGoogle Scholar
  67. 67.
    Sano T, Sasako M, Kinoshita T, Maruyama K (1993) Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer 72:3174–3178CrossRefPubMedGoogle Scholar
  68. 68.
    Namikawa T, Kobayashi M, Kitagawa H et al (2009) Differentiated adenocarcinoma with a gastric phenotype in the stomach: difficulties in clinical and pathological diagnoses. Clin J Gastroenterol 2:268–274CrossRefPubMedGoogle Scholar
  69. 69.
    Okabayashi T, Kobayashi M, Nishimori I et al (2008) Clinicopathological features and medical management of early gastric cancer. Am J Surg 195:229–232CrossRefPubMedGoogle Scholar
  70. 70.
    So J, Rajnakova A, Chan YH et al (2013) Endoscopic tri-modal imaging improves detection of gastric intestinal metaplasia among a high-risk patient population in Singapore. Diges Dis Sci 58:3566–3575CrossRefGoogle Scholar
  71. 71.
    Namikawa T, Inoue K, Uemura S et al (2014) Photodynamic diagnosis using 5-aminolevulinic acid during gastrectomy for gastric cancer. J Surg Oncol 109:213–217CrossRefPubMedGoogle Scholar
  72. 72.
    Correa P, Chen VW (1994) Gastric cancer. Cancer Surv 19-20:55–76PubMedGoogle Scholar
  73. 73.
    Namikawa T, Inoue K, Shuin T, Hanazaki K (2015) Photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid. In: Dip DF, Ishizawa T, Kokudo N, Rosenthal JR (eds) Fluorescence imaging for surgeons: concepts and applications. Springer International Publishing, Cham, pp 195–201CrossRefGoogle Scholar
  74. 74.
    Namikawa T, Yatabe T, Inoue K et al (2015) Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer. World J Gastroenterol 21:8769–8775CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F (2009) Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy 41:751–757CrossRefPubMedGoogle Scholar
  76. 76.
    Abe S, Oda I, Suzuki H et al (2013) Short- and long-term outcomes of endoscopic submucosal dissection for undifferentiated early gastric cancer. Endoscopy 45:703–707CrossRefPubMedGoogle Scholar
  77. 77.
    Rogers HW, Weinstock MA, Harris AR et al (2010) Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 146:283–287CrossRefPubMedGoogle Scholar
  78. 78.
    Lim L, Nichols B, Migden MR et al (2014) Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis. J Biomed Opt 19:117003CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Howlader NNA, Krapcho M, Neyman N, Aminou R, Waldron W, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA, Edwards BK (eds) (1975-2008) SEER cancer statistics review. National Cancer Institute, BethesdaGoogle Scholar
  80. 80.
    Moreno G, Tran H, Chia AL, Lim A, Shumack S (2007) Prospective study to assess general practitioners’ dermatological diagnostic skills in a referral setting. Australas J Dermatol 48:77–82CrossRefPubMedGoogle Scholar
  81. 81.
    Tran H, Chen K, Lim AC, Jabbour J, Shumack S (2005) Assessing diagnostic skill in dermatology: a comparison between general practitioners and dermatologists. Australas J Dermatol 46:230–234CrossRefPubMedGoogle Scholar
  82. 82.
    Elbaum M, Kopf AW, Rabinovitz HS et al (2001) Automatic differentiation of melanoma from melanocytic nevi with multispectral digital dermoscopy: a feasibility study. J Am Acad Dermatol 44:207–218CrossRefPubMedGoogle Scholar
  83. 83.
    Gutkowicz-Krusin D, Elbaum M, Jacobs A et al (2000) Precision of automatic measurements of pigmented skin lesion parameters with a MelaFind(TM) multispectral digital dermoscope. Melanoma Res 10:563–570CrossRefPubMedGoogle Scholar
  84. 84.
    Michalska M, Chodorowska G, Krasowska D (2004) SIAscopy—a new non-invasive technique of melanoma diagnosis. Ann Univ Mariae Curie Sklodowska Med 59:421–431PubMedGoogle Scholar
  85. 85.
    Patel JK, Konda S, Perez OA et al (2008) Newer technologies/techniques and tools in the diagnosis of melanoma. Eur J Dermatol 18:617–631PubMedGoogle Scholar
  86. 86.
    Rosenthal EL, Warram JM, Bland KI, Zinn KR (2015) The status of contemporary image-guided modalities in oncologic surgery. Ann Surg 261:46–55CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Del Rosal B, Villa I, Jaque D, Sanz-Rodriguez F (2016) In vivo autofluorescence in the biological windows: the role of pigmentation. J Biophotonics 9:1059–1067CrossRefPubMedGoogle Scholar
  88. 88.
    Quinn MK, Bubi TC, Pierce MC et al (2012) High-resolution microendoscopy for the detection of cervical neoplasia in low-resource settings. PLoS One 7:e44924CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Daneshmand S, Schuckman AK, Bochner BH et al (2014) Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA. Nat Rev Urol 11:589–596PubMedGoogle Scholar

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • K. E. Tipirneni
    • 1
  • E. L. Rosenthal
    • 2
  • L. S. Moore
    • 3
  • A. D. Haskins
    • 3
  • N. Udayakumar
    • 4
  • A. H. Jani
    • 5
  • W. R. Carroll
    • 3
  • A. B. Morlandt
    • 6
  • M. Bogyo
    • 7
  • J. Rao
    • 8
  • Jason M. Warram
    • 3
    • 9
  1. 1.Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of OtolaryngologyStanford UniversityStanfordUSA
  3. 3.Department of OtolaryngologyUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of BiologyUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.School of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  6. 6.Department of Oral and Maxillofacial SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  7. 7.Department of PathologyStanford UniversityStanfordUSA
  8. 8.Department of RadiologyStanford UniversityStanfordUSA
  9. 9.Departments of Otolaryngology, Neurosurgery, & RadiologyThe University of Alabama at BirminghamBirminghamUSA

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