Table 1.

Main in vivo optical imaging methods that could be used as an adjunct to conventional oral examination in oral premalignant disorders screening are autofluorescence imaging (AFI), targeted fluorescence imaging (TFI), high-resolution microendoscopy (HRME), narrow band imaging (NBI), Raman spectroscopy (RS). For each method, basic principles, advantages and inconvenient are described as well as references.

In Vivo Optical Imaging Methods to Detect OPMD	Basic Principle	Advantages	Inconvenient	Interesting Studies on Methods to Detect OPMD
Autofluorescence imaging (AFI)	Visualization of the autofluorescence from endogenous fluorophores (NADH and FAD) Metabolic and morphologic changes related to carcinologic process led to autofluorescence loss. Altered/dysplastic mucosa appears darker compared with the healthy surroundings.	Practical Cost-effective Non-invasive	Low specificity: -False positives: tissues with rich micro vascularity (granulation tissue, inflammation, and oedema) -False negatives: regions with hyperkeratosis (Leukoplakia+++) or overgrowth of bacteria (producing extra fluorophores)	[5,72,73,74,75]
Targeted Fluorescence imaging (TFI)	Visualization of a fluorescence probe specifically targeting the neoplastic tissues	The targeted immune-fluorescence imaging: targeting an over-expressed protein by approved antibodies	Intra-tumour phenotype heterogeneity decreases it sensitivity	[5]
Narrow band imaging (NBI)	Visualization of the neoangiogenic patterns of tissues using an illumination light within the absorption spectrum of haemoglobin	The abnormal intra epithelial capillary loops (ICPL) patterns can be used to differentiate neoplastic from normal tissues The NBI endoscopic system is widely available	Characterization of IPCL patterns is subjective and false positive results are frequent (level of keratinization, lymphoid tissue, previous radiation or surgery, inflammation and vascular lesions)	[5,76,77]
High resolution microendoscopy (HRME)	Visualization of an emitted light by superficially applied fluorophores using a flexible fiber-optic probe placed in direct contact with the suspicious tissue	Cost effective Non-invasive High resolution High sensitivity and specificity Simple and portable device Requires minimal training High inter-rater reliability	Not commercially available The proflavine (the most commonly used contrast agent) is not approved for in vivo clinical use Limited field-of-view	[5,78]
Raman Spectroscopy (RS)	Visualization of the ‘molecular fingerprint’ (i.e., variations of chemical components) of a tissue using vibrational spectroscopic technique	Water absorption does not disturb the measurement High signal-to-noise ratio Fewer sample volumes are required for analysis.	Analyses are difficult No commercially available Too large for routine clinical use Time consuming	[5,79,80,81,82]