Remote Clinical Decision Support and AI Tools: Current & Future Perspectives

The first medical device to bring the advantages of oral mucosal fluorescence visualization (FV) to dentistry was the VELscope system (LED Dental, Vancouver BC), launched in 2006. In 2023, fluorescence is being increasingly used as part of comprehensive oral soft tissue evaluations in dentistry as an adjunctive aid in patient assessment. VELscope’s use as an oral mucosal screening tool has been extensively reported in the scientific literature. A review of the literature found 38 reviews and or meta-analyses^1–38 involving VELscope, 49 papers evaluating the VELscope as an oral mucosal screening tool in clinical or case studies^39–87 and another 11 studies/reviews^88–98 related to VELscope helping to delineate surgical margins. The utility of VELscope fluorescence visualization has been extended to other areas, most notably in identifying necrotic vs viable bone during surgical treatment of Medication Related Osteonecrosis of the Jaw^99–114; although from a commercial and regulatory perspective, this is strictly off-label use.

FV in oral mucosal screening is mainstream although a debate has developed regarding the appropriate uses of FV. FV devices, including the VELscope are, by definition and regulatory approval, adjuncts to the traditional oral exam. They are designed as supplementary visual aids that complement the visual and tactile exam by making abnormalities visually apparent that might otherwise have been overlooked. They help to visualize tissue changes that are suggestive not only of malignancy or potential malignancy but also a multitude of other potential diseases. The subsequent process of investigating these findings, identifying and removing proximate causes, and assessing the need for biopsy and definitive treatment, involves a clear protocol that is well-defined.
Concern has been expressed about “false positives” incorrectly attributed to FV-based devices when their use is treated as providing a definitive diagnostic outcome (positive or negative) for cancer or other diagnoses. Such findings are not false positives but mucosal conditions that merit further consideration since some may represent signs of significant local or systemically initiated mucosal change that require definitive diagnosis and management.

The authors have been closely involved with a Clinical Decision Support Service (CDSS) instituted by LED Dental Inc. (LED) for its VELscope customers to provide remote support to the dental practices in their efforts to make appropriate decisions in the management of the soft tissue lesions. This first, commercially-based, widely marketed service has been available to VELscope customers for more than 10 years, significantly predating a teledentistry-based program that helps in managing soft tissue lesions based on white light and fluorescence images.¹¹⁵

Practitioners are clearly advised that LED’s CDSS clinical case comments are in no way intended to be viewed as a definitive diagnosis and/or action plan but should be seen as suggestions that the clinician may consider in managing the patient. CDSS requirements include anonymous patient data, lesion history, prescribed medications, and white light reflectance and fluorescence photographs of the tissue of concern.

This information is forwarded to a highly qualified oral medicine specialist (Dr. Edmond Truelove) who reviews the information, and provides observations and suggestions based on the submitted information. The report contains the following elements:

• Description of the findings from examination of the supplied white light and fluorescence photographs.
• A summary of the patient and lesion history as provided by the practice.
• A list of clinical conditions that are recommended to be included as part of the differential diagnosis of the referring clinician.
• A discussion of the above listed conditions in the context of the findings and the patient and lesion history.
• Some suggestions to help guide the management of the patient moving forward (e.g. suggestions for lesion resolution, follow-up recommendations, etc.).

A clinical example (Image Smiles Dental – Dr. Jim Yeganegi Inc. & Associates, Vancouver, BC, Canada) is illustrative of the value provided by the service.

A 72 yr. old female presented for routine dental recall examination. She reported no oral symptoms or changes. Her medical history was negative for significant risk of mucosal disease and was only positive for hypothyroidism and rheumatoid arthritis. Medications in use at the time included Synthroid and Hydroxychloroquine. The area viewed with traditional white light illumination is shown in Fig. 1 and the fluorescence response is shown in Fig.2.
Conditions suggested by the CDSS to be considered in the clinician’s differential diagnosis included:

• Epithelial dysplasia/carcinoma
• Chronic infection with fistula from adjacent odontogenic or periodontal infection
• Malignant tumor of accessory salivary gland
• Unintended factitial trauma

Fig. 1

Fig. 2

The discussion section of the report provided the following guidance: “Lack of symptoms increases odds that the lesion represents significant risk of disorders included in the differential diagnosis. The loss of fluorescence could represent inflammatory or dysplastic change. Careful follow up to rule out local odontogenic infection and assessment to determine if risk of dysplastic change or progressive mucosal disease is significant enough that biopsy and other testing be initiated.”

This service is currently offered at no charge for VELscope users. The increasing costs of maintaining the service and expanding it may require a review of this policy. More than 15,000 dental practices in North America have purchased VELscope units. In 2022, a total of 237 clinical cases were processed through the service. Only a small minority of VELscope users take advantage of the CDSS consulting service. Those that do generally find it has great value.

The current submission process is email-based. By late 2023, the submission process for clinical cases will become cloud-based. To submit a case, a clinician will complete an online submission form which will be viewed, and responded to, by an oral medicine specialist. An important characteristic of this new form will be the use of fields with predefined selection choices as opposed to free-form text fields. This will make it easier to submit the case and the specialist should be able to respond more quickly. A comprehensive PDF report, containing all the submitted information and specialist case comments in one document, will be automatically emailed to the patient’s clinician.

LED intends to grow the service through ease-of-use and automation. They will conduct an outreach to their existing customers to significantly increase participation in the program. LED will recruit additional oral medicine specialists to increase capacity.

An additional motivation for moving to a predefined choices format is to facilitate the development of an AI-based algorithm that can provide automated guidance. AI-based algorithms based on analysis of reflectance and/or autofluorescence images of oral mucosal lesions are being explored.^116–122 LED and its partner, KELLS (www.getkells.com), are working on a comprehensive AI approach based on image data plus patient and lesion history information.

Initially, the algorithm will be based on historical data obtained through:

a) Clinical cases processed through the LED’s CDSS service to date. Algorithm training will be based on the clinical case data, the oral medicine specialists’ proposed differential diagnosis and suitably categorized, recommended actions for follow-up with the patient.

b) Clinical case histories supplied by specialists with white light and fluorescence photographs and patient data where biopsies have been performed and histopathological diagnoses obtained.

Moving forward, LED plans to incentivize practices to provide follow-up information on the final resolution of a case including histopathology diagnosis if a biopsy was performed. Referencing the final diagnostic outcomes of cases will strengthen the development of an AI-based algorithm.

It is not anticipated that an AI algorithm could replace clinical case support by an oral medicine specialist. However, its very valuable role could be:

a) A precursor step to 1) submitting a case through the service to engage an oral medicine specialist, or 2) referral and/or consultation with a specialist.

b) Integration into the CDSS through oral medicine specialists to facilitate and streamline their own analysis of the case.

The final form of the AI-algorithm’s deployment will depend upon its performance once it has been sufficiently trained, but LED is certain that it will contribute value to the dental community in helping to identify and manage oral soft tissue lesions.

Oral Health welcomes this original article.

Authors Disclaimer: David Morgan is Chief Technology Officer at LED Dental Inc, manufacturer of the VELscope system. Edmond Truelove receives remuneration from LED Dental Inc. for his role as a clinical consultant in LED’s Clinical Decision Support Service.

References

1. Kim DH, Kim SW, Hwang SH. Efficacy of non-invasive diagnostic methods in the diagnosis and screening of oral cancer and precancer. Braz J Otorhinolaryngol. 2022 Dec;88(6):937–47.
2. Mendonca P, Sunny SP, Mohan U, Birur N P, Suresh A, Kuriakose MA. Non-invasive imaging of oral potentially malignant and malignant lesions: A systematic review and meta-analysis. Oral Oncol. 2022 Jul;130:105877.
3. Flores Dos Santos LC, Fernandes JR, Lima IFP, Bittencourt L da S, Martins MD, Lamers ML. Applicability of autofluorescence and fluorescent probes in early detection of oral potentially malignant disorders: A systematic review and meta-data analysis. Photodiagnosis Photodyn Ther. 2022 Jun;38:102764.
4. Coll Y, Geddes A, Thomson E. The light at the end of the tunnel? Can light-based tests increase the accuracy of our diagnoses of pre-cancerous/cancerous lesions? Evid Based Dent. 2022 Mar;23(1):16–7.
5. Chaurasia A, Alam SI, Singh N. Oral cancer diagnostics: An overview. Natl J Maxillofac Surg. 2021 Dec;12(3):324–32.
6. Mazur M, Ndokaj A, Venugopal DC, Roberto M, Albu C, Jedliński M, et al. In Vivo Imaging-Based Techniques for Early Diagnosis of Oral Potentially Malignant Disorders-Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2021 Nov 10;18(22).
7. Buenahora MR, Peraza-L A, Díaz-Báez D, Bustillo J, Santacruz I, Trujillo TG, et al. Diagnostic accuracy of clinical visualization and light-based tests in precancerous and cancerous lesions of the oral cavity and oropharynx: a systematic review and meta-analysis. Clin Oral Investig. 2021 Jun;25(6):4145–59.
8. Lima IFP, Brand LM, de Figueiredo JAP, Steier L, Lamers ML. Use of autofluorescence and fluorescent probes as a potential diagnostic tool for oral cancer: A systematic review. Photodiagnosis Photodyn Ther. 2021 Mar;33:102073.
9. Abati S, Bramati C, Bondi S, Lissoni A, Trimarchi M. Oral Cancer and Precancer: A Narrative Review on the Relevance of Early Diagnosis. Int J Environ Res Public Health. 2020 Dec 8;17(24).
10. 1Kim DH, Kim SW, Hwang SH. Autofluorescence imaging to identify oral malignant or premalignant lesions: Systematic review and meta-analysis. Head Neck. 2020 Dec;42(12):3735–43.
11. Tatehara S, Satomura K. Non-Invasive Diagnostic System Based on Light for Detecting Early-Stage Oral Cancer and High-Risk Precancerous Lesions-Potential for Dentistry. Cancers. 2020 Oct 29;12(11).
12. Tiwari L, Kujan O, Farah CS. Optical fluorescence imaging in oral cancer and potentially malignant disorders: A systematic review. Oral Dis. 2020 Apr;26(3):491–510.
13. Tomo S, Miyahara GI, Simonato LE. History and future perspectives for the use of fluorescence visualization to detect oral squamous cell carcinoma and oral potentially malignant disorders. Photodiagnosis Photodyn Ther. 2019 Dec;28:308–17.
14. K Chaitanya NCS, Chavva S, Surekha E, Priyanka V, Akhila M, Ponnuru HK, et al. A Meta-analysis on efficacy of auto fluorescence in detecting the early dysplastic changes of oral cavity. South Asian J Cancer. 2019 Dec;8(4):233–6.
15. Cicciù M, Cervino G, Fiorillo L, D’Amico C, Oteri G, Troiano G, et al. Early Diagnosis on Oral and Potentially Oral Malignant Lesions: A Systematic Review on the VELscope(®) Fluorescence Method. Dent J. 2019 Sep 4;7(3).
16. Crossan L, Conway DI. Another oral cancer clinical guideline – but does it propose changes to dental practice? Evid Based Dent. 2019 Mar;20(1):7–8.
17. Amaechi BT, Owosho AA, Fried D. Fluorescence and Near-Infrared Light Transillumination. Dent Clin North Am. 2018 Jul;62(3):435–52.
18. Cicciù M, Herford AS, Cervino G, Troiano G, Lauritano F, Laino L. Tissue Fluorescence Imaging (VELscope) for Quick Non-Invasive Diagnosis in Oral Pathology. J Craniofac Surg. 2017 Mar;28(2):e112–5.
19. Jitender S, Sarika G, Varada HR, Omprakash Y, Mohsin K. Screening for oral cancer. J Exp Ther Oncol. 2016 Nov;11(4):303–7.
20. Nagi R, Reddy-Kantharaj YB, Rakesh N, Janardhan-Reddy S, Sahu S. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review. Med Oral Patol Oral Cirugia Bucal. 2016 Jul 1;21(4):e447-455.
21. Giovannacci I, Vescovi P, Manfredi M, Meleti M. Non-invasive visual tools for diagnosis of oral cancer and dysplasia: A systematic review. Med Oral Patol Oral Cirugia Bucal. 2016 May 1;21(3):e305-315.
22. Awan KH, Patil S. Efficacy of Autofluorescence Imaging as an Adjunctive Technique for Examination and Detection of Oral Potentially Malignant Disorders: A Systematic Review. J Contemp Dent Pract. 2015 Sep 1;16(9):744–9.
23. Balasubramaniam AM, Sriraman R, Sindhuja P, Mohideen K, Parameswar RA, Muhamed Haris KT. Autofluorescence based diagnostic techniques for oral cancer. J Pharm Bioallied Sci. 2015 Aug;7(Suppl 2):S374-377.
24. Spivakovsky S, Gerber MG. Little evidence for the effectiveness of chemiluminescence and autofluorescent imaging devices as oral cancer screening adjuncts. Evid Based Dent. 2015 Jun;16(2):48.
25. Chhabra N, Chhabra S, Sapra N. Diagnostic modalities for squamous cell carcinoma: an extensive review of literature-considering toluidine blue as a useful adjunct. J Maxillofac Oral Surg. 2015 Jun;14(2):188–200.
26. Rashid A, Warnakulasuriya S. The use of light-based (optical) detection systems as adjuncts in the detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2015 May;44(5):307–28.
27. Nair DR, Pruthy R, Pawar U, Chaturvedi P. Oral cancer: Premalignant conditions and screening–an update. J Cancer Res Ther. 2012 Jan;8 Suppl 1:S57-66.
28. Mercadante V, Paderni C, Campisi G. Novel non-invasive adjunctive techniques for early oral cancer diagnosis and oral lesions examination. Curr Pharm Des. 2012;18(34):5442–51.
29. Mehrotra R, Gupta DK. Exciting new advances in oral cancer diagnosis: avenues to early detection. Head Neck Oncol. 2011 Jul 28;3:33.
30. Olivo M, Bhuvaneswari R, Keogh I. Advances in bio-optical imaging for the diagnosis of early oral cancer. Pharmaceutics. 2011 Jul 11;3(3):354–78.
31. López-Jornet P, De la Mano-Espinosa T. The efficacy of direct tissue fluorescence visualization in screening for oral premalignant lesions in general practice: an update. Int J Dent Hyg. 2011 May;9(2):97–100.
32. Balevi B. Assessing the usefulness of three adjunctive diagnostic devices for oral cancer screening: a probabilistic approach. Community Dent Oral Epidemiol. 2011 Apr;39(2):171–6.
33. Fricain JC. [Autofluorescence for the detection of potentially malignant and malignant lesions of the oral cavity lining]. Rev Stomatol Chir Maxillofac. 2011 Feb;112(1):16–21.
34. Rhodus NL. Oral cancer and precancer: improving outcomes. Compend Contin Educ Dent Jamesburg NJ 1995. 2009 Oct;30(8):486–8, 490–4, 496-498 passim; quiz 504, 520.
35. Trullenque-Eriksson A, Muñoz-Corcuera M, Campo-Trapero J, Cano-Sánchez J, Bascones-Martínez A. Analysis of new diagnostic methods in suspicious lesions of the oral mucosa. Med Oral Patol Oral Cirugia Bucal. 2009 May 1;14(5):E210-216.
36. Fedele S. Diagnostic aids in the screening of oral cancer. Head Neck Oncol. 2009 Jan 30;1:5.
37. Patton LL, Epstein JB, Kerr AR. Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. J Am Dent Assoc 1939. 2008 Jul;139(7):896–905; quiz 993–4.
38. Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol. 2008 Jan;44(1):10–22.
39. Amirchaghmaghi M, Mohtasham N, Delavarian Z, Shakeri MT, Taghizadeh A, Khazaeni K, et al. Analyzing the relationship between tissue color observed in VELscope examination and histopathological factors in OSCC patients. Photodiagnosis Photodyn Ther. 2022 Dec 21;41:103248.
40. Li C, Zhang Q, Sun K, Jia H, Shen X, Tang G, et al. Autofluorescence imaging as a noninvasive tool of risk stratification for malignant transformation of oral leukoplakia: A follow-up cohort study. Oral Oncol. 2022 Jul;130:105941.
41. Wang C, Qi X, Zhou X, Liu H, Li M. Diagnostic value of objective VELscope fluorescence methods in distinguishing oral cancer from oral potentially malignant disorders (OPMDs). Transl Cancer Res. 2022 Jun;11(6):1603–15.
42. Sharma A, Sharma A, Bansal AK, Goyal C, Mankotia S, Parmar M, et al. To Evaluate the Efficacy of Tissue Autofluorescence (Velscope) in the Visualization of Oral Premalignant and Malignant Lesions among High-Risk Population Aged 18 Years and Above in Haroli Block of Una, Himachal Pradesh. J Int Soc Prev Community Dent. 2022 Jun;12(3):365–75.
43. Vibhute NA, Jagtap SV, Patil SV. Velscope guided oral cancer screening: A ray of hope in early oral cancer diagnosis. J Oral Maxillofac Pathol JOMFP. 2021 Dec;25(3):548–9.
44. Jain S, Jain K, Bais PS, Shinkar SV, Saify F. Role of Fluorescence Imaging Device in Screening of Oral Cancer: A Cross-Sectional Study in Chhattisgarh Population. Indian J Community Med Off Publ Indian Assoc Prev Soc Med. 2021 Dec;46(4):622–5.
45. Srubar J, Uhrikova T, Delongova P. Atypical carcinoma detected after regression of a “benign” oral white lesion. A case report. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslov. 2021 Jun;165(2):229–32.
46. Giovannacci I, Magnoni C, Pedrazzi G, Vescovi P, Meleti M. Clinicopathological Features Associated with Fluorescence Alteration: Analysis of 108 Oral Malignant and Potentially Malignant Lesions. Photobiomodulation Photomed Laser Surg. 2021 Jan;39(1):53–61.
47. Schorn L, Rana M, Madry A, Ipaktchi R, Möllmann H, Gellrich NC, et al. Does autofluorescence help detect recurrent squamous cell carcinoma? A prospective clinical study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020 Sep;130(3):258–63.
48. Leuci S, Coppola N, Turkina A, Bizzoca ME, Favia G, Spagnuolo G, et al. May VelScope Be Deemed an Opportunistic Oral Cancer Screening by General Dentists? A Pilot Study. J Clin Med. 2020 Jun 5;9(6).
49. Shah S, Waknis P, Saha A, Setiya S, Ratra T, Vaswani V. The use of Velscope to assess cellular changes occuring in oral premalignancy. J Oral Biol Craniofacial Res. 2020 Jun;10(2):99–103.
50. Meleti M, Giovannacci I, Vescovi P, Pedrazzi G, Govoni P, Magnoni C. Histopathological determinants of autofluorescence patterns in oral carcinoma. Oral Dis. 2020 Feb 11;
51. Shah AM, Bansal S, Shirsat PM, Prasad P, Desai RS. Exophytic verrucous hyperplasia in oral submucous fibrosis: A single-center study. J Oral Maxillofac Pathol JOMFP. 2019 Dec;23(3):393–9.
52. Pentenero M, Todaro D, Marino R, Gandolfo S. Interobserver and intraobserver variability affecting the assessment of loss of autofluorescence of oral mucosal lesions. Photodiagnosis Photodyn Ther. 2019 Dec;28:338–42.
53. Shi L, Li C, Shen X, Zhou Z, Liu W, Tang G. Potential role of autofluorescence imaging in determining biopsy of oral potentially malignant disorders: A large prospective diagnostic study. Oral Oncol. 2019 Nov;98:176–9.
54. Farah CS, Dost F, Do L. Usefulness of optical fluorescence imaging in identification and triaging of oral potentially malignant disorders: A study of VELscope in the LESIONS programme. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2019 Aug;48(7):581–7.
55. Amirchaghmaghi M, Mohtasham N, Delavarian Z, Shakeri MT, Hatami M, Mosannen Mozafari P. The diagnostic value of the native fluorescence visualization device for early detection of premalignant/malignant lesions of the oral cavity. Photodiagnosis Photodyn Ther. 2018 Mar;21:19–27.
56. Cânjău S, Todea DCM, Sinescu C, Pricop MO, Duma VF. Fluorescence influence on screening decisions for oral malignant lesions. Romanian J Morphol Embryol Rev Roum Morphol Embryol. 2018;59(1):203–9.
57. Ganga RS, Gundre D, Bansal S, Shirsat PM, Prasad P, Desai RS. Evaluation of the diagnostic efficacy and spectrum of autofluorescence of benign, dysplastic and malignant lesions of the oral cavity using VELscope. Oral Oncol. 2017 Dec;75:67–74.
58. Yamamoto N, Kawaguchi K, Fujihara H, Hasebe M, Kishi Y, Yasukawa M, et al. Detection accuracy for epithelial dysplasia using an objective autofluorescence visualization method based on the luminance ratio. Int J Oral Sci. 2017 Nov 10;9(11):e2.
59. Burian E, Schulz C, Probst F, Palla B, Tröltzsch M, Maglitto F, et al. Fluorescence based characterization of early oral squamous cell carcinoma using the Visually Enhanced Light Scope technique. J Cranio-Maxillo-fac Surg Off Publ Eur Assoc Cranio-Maxillo-fac Surg. 2017 Sep;45(9):1526–30.
60. Ohnishi Y, Fujii T, Ugaki Y, Yasui H, Watanabe M, Dateoka S, et al. Usefulness of a fluorescence visualization system for the detection of oral precancerous and early cancerous lesions. Oncol Rep. 2016 Jul;36(1):514–20.
61. Kordbacheh F, Bhatia N, Farah CS. Patterns of differentially expressed genes in oral mucosal lesions visualised under autofluorescence (VELscope(TM) ). Oral Dis. 2016 May;22(4):285–96.
62. Scheer M, Fuss J, Derman MA, Kreppel M, Neugebauer J, Rothamel D, et al. Autofluorescence imaging in recurrent oral squamous cell carcinoma. Oral Maxillofac Surg. 2016 Mar;20(1):27–33.
63. Jané-Salas E, Blanco-Carrión A, Jover-Armengol L, López-López J. Autofluorescence and Diagnostic Accuracy of Lesions of Oral Mucosa: A Pilot Study. Braz Dent J. 2015 Dec;26(6):580–6.
64. Awan KH, Morgan PR, Warnakulasuriya S. Assessing the accuracy of autofluorescence, chemiluminescence and toluidine blue as diagnostic tools for oral potentially malignant disorders–a clinicopathological evaluation. Clin Oral Investig. 2015 Dec;19(9):2267–72.
65. Sawan D, Mashlah A. Evaluation of premalignant and malignant lesions by fluorescent light (VELscope). J Int Soc Prev Community Dent. 2015 Jun;5(3):248–54.
66. Kaur J, Jacobs R. Combination of Autofluorescence imaging and salivary protoporphyrin in Oral precancerous and cancerous lesions: Non-invasive tools. J Clin Exp Dent. 2015 Apr;7(2):e187-191.
67. Ayoub HM, Newcomb TL, McCombs GB, Bonnie M. The Use of Fluorescence Technology versus Visual and Tactile Examination in the Detection of Oral Lesions: A Pilot Study. J Dent Hyg JDH. 2015 Feb;89(1):63–71.
68. Bhatia N, Matias MAT, Farah CS. Assessment of a decision making protocol to improve the efficacy of VELscopeTM in general dental practice: a prospective evaluation. Oral Oncol. 2014 Oct;50(10):1012–9.
69. Laronde DM, Williams PM, Hislop TG, Poh C, Ng S, Bajdik C, et al. Influence of fluorescence on screening decisions for oral mucosal lesions in community dental practices. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2014 Jan;43(1):7–13.
70. Hanken H, Kraatz J, Smeets R, Heiland M, Assaf AT, Blessmann M, et al. The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscopeTM) – a single blinded clinical evaluation. Head Face Med. 2013 Aug 23;9:23.
71. Bhatia N, Lalla Y, Vu AN, Farah CS. Advances in optical adjunctive AIDS for visualisation and detection of oral malignant and potentially malignant lesions. Int J Dent. 2013;2013:194029.
72. McNamara KK, Martin BD, Evans EW, Kalmar JR. The role of direct visual fluorescent examination (VELscope) in routine screening for potentially malignant oral mucosal lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Nov;114(5):636–43.
73. Rana M, Zapf A, Kuehle M, Gellrich NC, Eckardt AM. Clinical evaluation of an autofluorescence diagnostic device for oral cancer detection: a prospective randomized diagnostic study. Eur J Cancer Prev Off J Eur Cancer Prev Organ ECP. 2012 Sep;21(5):460–6.
74. Marzouki HZ, Tuong Vi Vu T, Ywakim R, Chauvin P, Hanley J, Kost KM. Use of fluorescent light in detecting malignant and premalignant lesions in the oral cavity: a prospective, single-blind study. J Otolaryngol – Head Neck Surg J Oto-Rhino-Laryngol Chir Cervico-Faciale. 2012 Jun 1;41(3):164–8.
75. Farah CS, McIntosh L, Georgiou A, McCullough MJ. Efficacy of tissue autofluorescence imaging (VELScope) in the visualization of oral mucosal lesions. Head Neck. 2012 Jun;34(6):856–62.
76. Huber MA. Adjunctive diagnostic aids in oral cancer screening: an update. Tex Dent J. 2012 May;129(5):471–80.
77. Truelove EL, Dean D, Maltby S, Griffith M, Huggins K, Griffith M, et al. Narrow band (light) imaging of oral mucosa in routine dental patients. Part I: Assessment of value in detection of mucosal changes. Gen Dent. 2011 Aug;59(4):281–9; quiz 290–1, 319–20.
78. Paderni C, Compilato D, Carinci F, Nardi G, Rodolico V, Lo Muzio L, et al. Direct visualization of oral-cavity tissue fluorescence as novel aid for early oral cancer diagnosis and potentially malignant disorders monitoring. Int J Immunopathol Pharmacol. 2011 Jun;24(2 Suppl):121–8.
79. Matsumoto K. [Detection of potentially malignant and malignant lesions of oral cavity using autofluorescence visualization device]. Kokubyo Gakkai Zasshi. 2011 Jun;78(2):73–80.
80. Scheer M, Neugebauer J, Derman A, Fuss J, Drebber U, Zoeller JE. Autofluorescence imaging of potentially malignant mucosa lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 May;111(5):568–77.
81. Awan KH, Morgan PR, Warnakulasuriya S. Evaluation of an autofluorescence based imaging system (VELscopeTM) in the detection of oral potentially malignant disorders and benign keratoses. Oral Oncol. 2011 Apr;47(4):274–7.
82. Mehrotra R, Singh M, Thomas S, Nair P, Pandya S, Nigam NS, et al. A cross-sectional study evaluating chemiluminescence and autofluorescence in the detection of clinically innocuous precancerous and cancerous oral lesions. J Am Dent Assoc 1939. 2010 Feb;141(2):151–6.
83. Huber MA. Assessment of the VELscope as an adjunctive examination tool. Tex Dent J. 2009 Jun;126(6):528–35.
84. Huff K, Stark PC, Solomon LW. Sensitivity of direct tissue fluorescence visualization in screening for oral premalignant lesions in general practice. Gen Dent. 2009 Feb;57(1):34–8.
85. Comisi JC. Oral human papillomavirus lesion identified using VELscope instrumentation: case report. Gen Dent. 2008 Oct;56(6):548–50.
86. Poh CF, Ng SP, Williams PM, Zhang L, Laronde DM, Lane P, et al. Direct fluorescence visualization of clinically occult high-risk oral premalignant disease using a simple hand-held device. Head Neck. 2007 Jan;29(1):71–6.
87. Lane PM, Gilhuly T, Whitehead P, Zeng H, Poh CF, Ng S, et al. Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt. 2006;11(2):024006.
88. Fernandes JR, Dos Santos LCF, Lamers ML. Applicability of autofluorescence and fluorescent probes in the trans-surgical of oral carcinomas: A systematic review. Photodiagnosis Photodyn Ther. 2022 Dec 9;41:103238.
89. Sun LF, Wang CX, Cao ZY, Han W, Guo SS, Wang YZ, et al. Evaluation of autofluorescence visualization system in the delineation of oral squamous cell carcinoma surgical margins. Photodiagnosis Photodyn Ther. 2021 Dec;36:102487.
90. Biamonte F, Buffone C, Santamaria G, Battaglia AM, Mignogna C, Fortunato L, et al. Gene expression analysis of autofluorescence margins in leukoplakia and oral carcinoma: A pilot study. Oral Dis. 2021 Mar;27(2):193–203.
91. Durham JS, Brasher P, Anderson DW, Yoo J, Hart R, Dort JC, et al. Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Otolaryngol– Head Neck Surg. 2020 Dec 1;146(12):1149–55.
92. Kain JJ, Birkeland AC, Udayakumar N, Morlandt AB, Stevens TM, Carroll WR, et al. Surgical margins in oral cavity squamous cell carcinoma: Current practices and future directions. The Laryngoscope. 2020 Jan;130(1):128–38.
93. Farah CS, Kordbacheh F, John K, Bennett N, Fox SA. Molecular classification of autofluorescence excision margins in oral potentially malignant disorders. Oral Dis. 2018 Jul;24(5):732–40.
94. Tirelli G, Zacchigna S, Boscolo Nata F, Quatela E, Di Lenarda R, Piovesana M. Will the mininvasive approach challenge the old paradigms in oral cancer surgery? Eur Arch Oto-Rhino-Laryngol Off J Eur Fed Oto-Rhino-Laryngol Soc EUFOS Affil Ger Soc Oto-Rhino-Laryngol – Head Neck Surg. 2017 Mar;274(3):1279–89.
95. Poh CF, Anderson DW, Durham JS, Chen J, Berean KW, MacAulay CE, et al. Fluorescence Visualization-Guided Surgery for Early-Stage Oral Cancer. JAMA Otolaryngol– Head Neck Surg. 2016 Mar;142(3):209–16.
96. Elvers D, Braunschweig T, Hilgers RD, Ghassemi A, Möhlhenrich SC, Hölzle F, et al. Margins of oral leukoplakia: autofluorescence and histopathology. Br J Oral Maxillofac Surg. 2015 Feb;53(2):164–9.
97. Poh CF, MacAulay CE, Zhang L, Rosin MP. Tracing the “at-risk” oral mucosa field with autofluorescence: steps toward clinical impact. Cancer Prev Res Phila Pa. 2009 May;2(5):401–4.
98. Poh CF, Zhang L, Anderson DW, Durham JS, Williams PM, Priddy RW, et al. Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients. Clin Cancer Res Off J Am Assoc Cancer Res. 2006 Nov 15;12(22):6716–22.
99. Tomo S, da Cruz TM, Figueira JA, Cunha JLS, Miyahara GI, Simonato LE. Fluorescence-guided surgical management of medication-related osteonecrosis of the jaws. Photodiagnosis Photodyn Ther. 2020 Dec;32:102003.
100. Ristow O, Nehrbass D, Zeiter S, Arens D, Moratin J, Pautke C, et al. Differences between auto-fluorescence and tetracycline-fluorescence in medication-related osteonecrosis of the jaw-a preclinical proof of concept study in the mini-pig. Clin Oral Investig. 2020 Dec;24(12):4625–37.
101. Rupp M, Henssler L, Brochhausen C, Zustin J, Geis S, Pfeifer C, et al. Can necrotic bone be objectively identified in chronic fracture related infections? – First clinical experience with an intraoperative fluorescence imaging technique. Injury. 2020 Nov;51(11):2541–5.
102. Giudice A, Bennardo F, Barone S, Antonelli A, Figliuzzi MM, Fortunato L. Can Autofluorescence Guide Surgeons in the Treatment of Medication-Related Osteonecrosis of the Jaw? A Prospective Feasibility Study. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2018 May;76(5):982–95.
103. Ristow O, Otto S, Geiß C, Kehl V, Berger M, Troeltzsch M, et al. Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study. Int J Oral Maxillofac Surg. 2017 Feb;46(2):157–66.
104. Otto S, Ristow O, Pache C, Troeltzsch M, Fliefel R, Ehrenfeld M, et al. Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study. J Cranio-Maxillo-fac Surg Off Publ Eur Assoc Cranio-Maxillo-fac Surg. 2016 Aug;44(8):1073–80.
105. Yoshiga D, Sasaguri M, Matsuo K, Yoshida S, Uehara M, Habu M, et al. Fluorescence-guided bone resection by using Visually Enhanced Lesion Scope in diffuse chronic sclerosingosteomyelitis of the mandible: Clinical and pathological evaluation. J Clin Exp Dent. 2015 Oct;7(4):e548-551.
106. Yoshiga D, Sasaguri M, Matsuo K, Kokuryou S, Habu M, Oda M, et al. Intraoperative detection of viable bone with fluorescence imaging using Visually Enhanced Lesion Scope in patients with bisphosphonate-related osteonecrosis of the jaw: clinical and pathological evaluation. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2015 Jul;26(7):1997–2006.
107. Ristow O, Otto S, Troeltzsch M, Hohlweg-Majert B, Pautke C. Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ). J Cranio-Maxillo-fac Surg Off Publ Eur Assoc Cranio-Maxillo-fac Surg. 2015 Mar;43(2):290–3.
108. Ristow O, Pautke C. Auto-fluorescence of the bone and its use for delineation of bone necrosis. Int J Oral Maxillofac Surg. 2014 Nov;43(11):1391–3.
109. Assaf AT, Zrnc TA, Riecke B, Wikner J, Zustin J, Friedrich RE, et al. Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope) in patients with bisphosphonate related osteonecrosis of the jaw (BRONJ). J Cranio-Maxillo-fac Surg Off Publ Eur Assoc Cranio-Maxillo-fac Surg. 2014 Jul;42(5):e157-164.
110. Otto S, Baumann S, Ehrenfeld M, Pautke C. Successful surgical management of osteonecrosis of the jaw due to RANK-ligand inhibitor treatment using fluorescence guided bone resection. J Cranio-Maxillo-fac Surg Off Publ Eur Assoc Cranio-Maxillo-fac Surg. 2013 Oct;41(7):694–8.
111. 1Otto S, Sotlar K, Ehrenfeld M, Pautke C. Osteonecrosis of the jaw as a possible rare side effect of annual bisphosphonate administration for osteoporosis: A case report. J Med Case Reports. 2011 Sep 23;5:477.
112. Pautke C, Bauer F, Otto S, Tischer T, Steiner T, Weitz J, et al. Fluorescence-guided bone resection in bisphosphonate-related osteonecrosis of the jaws: first clinical results of a prospective pilot study. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2011 Jan;69(1):84–91.
113. Pautke C, Bauer F, Bissinger O, Tischer T, Kreutzer K, Steiner T, et al. Tetracycline bone fluorescence: a valuable marker for osteonecrosis characterization and therapy. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2010 Jan;68(1):125–9.
114. Pautke C, Bauer F, Tischer T, Kreutzer K, Weitz J, Kesting M, et al. Fluorescence-guided bone resection in bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2009 Mar;67(3):471–6.
115. Vetchaporn S, Rangsri W, Ittichaicharoen J, Rungsiyakull P. Validity and Reliability of Intraoral Camera with Fluorescent Aids for Oral Potentially Malignant Disorders Screening in Teledentistry. Int J Dent. 2021;2021:6814027.
116. Caughlin K, Duran-Sierra E, Cheng S, Cuenca R, Ahmed B, Ji J, et al. Aligning Small Datasets using Domain Adversarial Learning: Applications in Automated In Vivo Oral Cancer Diagnosis. IEEE J Biomed Health Inform. 2022 Oct 24;PP.
117. Kim JS, Kim BG, Hwang SH. Efficacy of Artificial Intelligence-Assisted Discrimination of Oral Cancerous Lesions from Normal Mucosa Based on the Oral Mucosal Image: A Systematic Review and Meta-Analysis. Cancers. 2022 Jul 19;14(14).
118. Jeng MJ, Sharma M, Sharma L, Huang SF, Chang LB, Wu SL, et al. Novel Quantitative Analysis Using Optical Imaging (VELscope) and Spectroscopy (Raman) Techniques for Oral Cancer Detection. Cancers. 2020 Nov 13;12(11).
119. Awais M, Ghayvat H, Krishnan Pandarathodiyil A, Nabillah Ghani WM, Ramanathan A, Pandya S, et al. Healthcare Professional in the Loop (HPIL): Classification of Standard and Oral Cancer-Causing Anomalous Regions of Oral Cavity Using Textural Analysis Technique in Autofluorescence Imaging. Sensors. 2020 Oct 12;20(20).
120. Jeng MJ, Sharma M, Chao TY, Li YC, Huang SF, Chang LB, et al. Multiclass classification of autofluorescence images of oral cavity lesions based on quantitative analysis. PloS One. 2020;15(2):e0228132.
121. Song B, Sunny S, Uthoff RD, Patrick S, Suresh A, Kolur T, et al. Automatic classification of dual-modalilty, smartphone-based oral dysplasia and malignancy images using deep learning. Biomed Opt Express. 2018 Nov 1;9(11):5318–29.
122. Huang TT, Huang JS, Wang YY, Chen KC, Wong TY, Chen YC, et al. Novel quantitative analysis of autofluorescence images for oral cancer screening. Oral Oncol. 2017 May;68:20–6.

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About the Author

David Morgan PhD (physics) graduated the University of British Columbia. After research positions at Cambridge University and BC Cancer Research Centre, he began a 25-year career in medical device research and product development. He is currently the Chief Technology Officer at LED Dental Inc.

Dr. Truelove graduated in Oral Medicine, Indiana University. Now Professor Emeritus, he established the Department of Oral Medicine, University of Washington, and was Department Chair until 2010. He has published 200+ scientific articles, earned numerous research grants, and was appointed Chair, American Board of Oral Medicine and Council of Scientific Affairs at the ADA.