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Title: Clinical study of the use of Photodynamic Detection (PDD) in assessing suspicious oral lesions
Author: Al-Juboori, Jamal Noori Ahmed
Awarding Body: University of Dundee
Current Institution: University of Dundee
Date of Award: 2011
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Abstract:
Photodynamic Detection (PDD) is a diagnostic technique involving administration of a photosensitizer to the targeted cells that can be stimulated by short wavelength light which then leads to emission of light at a different wavelength (lower energy). The light emitted by the cells can be detected and analysed (by a spectroscope). All cells have the innate ability (due to endogenous fluorophores) to fluoresce, termed autofluorescence. Any cellular, metabolic or structural changes can alter the fluorescence intensity peaks. In this study 5-aminolevulinic acid (5-ALA) photosensitizer prodrug was used, which is metabolised in highly active cells to protoporphyrin IX (PpIX). Excitation of a cell at 405nm wavelength (light) leads to emission of autofluorescence at 500nm and PpIX at 635nm. The purpose of this investigation was to evaluate the use of compact spectroscopy together with the photosensitizer prodrug 5-ALA, in assessing clinically suspicious oral lesions. To that end the followings were assessed: • The fluorescence intensity ratio (FIR) or Red/Green ratio at 635/500nm measurements of normal anatomical sites at ten oral anatomical sites to map and create baseline readings for normal oral mucosal site fluorescence. • The effect of participants’ characteristics on the normal oral mucosal site FIR measurements. • The use the fluorescence intensity ratio (FIR) measurements to determine any differences between the lesion and the normal oral readings and whether the FIR from clinically suspicious oral lesions is associated with the histopathology grade. In addition to the sensitivity and specificity of the technique in assessing clinically suspicious (premalignant) oral lesions for potential malignant change.Prior to the trial commencing, approval were obtained from the Research Ethics Committee (REC), local NHS Research and Development (R&D), and Medicine Healthcare product Regulatory Agency (MHRA) and the University of Dundee Research Innovation Services (RIS). A total of thirty five participants with clinically suspicious oral lesions were recruited in Dundee (Dundee Dental Hospital) and Glasgow (Southern General Hospital). A Photodynamic Detection method using compact fluorescence spectroscopy and 5-ALA mouth rinse was applied. FIR measurements from ten normal anatomical sites were obtained in every patient to study the variation at different normal oral sites and the effect of the participant’s characteristics on these readings. In addition, two FIR measurements were obtained from each lesion and a further one taken from normal looking mucosa well beyond the lesion boundary (i.e. more than 5mm away) prior to biopsy. The readings were compared to study the reliability, reproducibility and efficacy of the photodynamic method in detecting mucosal abnormality. A total of 292 spectral readings obtained from normal mucosa were used to study the FIR measurements at normal oral anatomical sites. The results showed that the oral regions could be grouped into two broad categories with similar readings, the palatal and tongue readings in one group and buccal, ventral tongue, floor of the mouth, gingiva and lip mucosa on the other (essentially keratinized and non keratinized groups). The same set of readings were further analysed to study the effect of individual characteristics (age, gender, presence of oral prosthesis, metabolic diseases, smoking and alcohol consumptions) on the FIR measurements. There was no significant difference between FIR measurements within each of the groups studied, although at times sample sizes were very small.A total of 134 spectral readings obtained from 47 lesions that were biopsied from 35 patients recruited to the trial were used for the next part of the study. There were 91 spectra obtained from the lesions and 43 spectra obtained from the normal sites (more than 5mm away from the borders of the lesion) for comparison. There was a significant difference between the lesion and normal site readings. The FIR readings for the dysplastic lesions were significantly different when compared with the normal and benign hyperkeratoses. However there was no significant difference between dysplastic and inflammatory lesions (lichen planus, lichenoid lesions and candidal leukoplakia) on the one hand and inflammatory lesions and hyperkeratotic lesion on the other. Further analysis showed the sensitivity in detecting all the clinically suspicious oral lesions from the normal sites was 59.5% and specificity was 73.8%. The sensitivity in detecting dysplasia from normal sites was 100% and specificity 100%.Photodynamic Detection was able to detect a difference between the oral lesions from normal mucosa (but so is the naked eye!). However there was variation in the sensitivity and specificity in detecting a range of different pathological conditions. The technique was highly sensitive in detecting dysplasia from normal mucosa but unfortunately the technique is not able to discriminate reliably between dysplasia and inflammatory lesions whose clinical appearance can be very similar. In conclusion, the photodynamic detection method used in this study would not appear to offer a reliable screening tool for the early detection of oral dysplasia/cancer. The need to consider adjunctive tests that discriminate inflammation from dysplasia is required. Photodynamic Detection (PDD) is a diagnostic technique involving administration of a photosensitizer to the targeted cells that can be stimulated by short wavelength light which then leads to emission of light at a different wavelength (lower energy). The light emitted by the cells can be detected and analysed (by a spectroscope). All cells have the innate ability (due to endogenous fluorophores) to fluoresce, termed autofluorescence. Any cellular, metabolic or structural changes can alter the fluorescence intensity peaks. In this study 5-aminolevulinic acid (5-ALA) photosensitizer prodrug was used, which is metabolised in highly active cells to protoporphyrin IX (PpIX). Excitation of a cell at 405nm wavelength (light) leads to emission of autofluorescence at 500nm and PpIX at 635nm. The purpose of this investigation was to evaluate the use of compact fluorescence spectroscopy together with the photosensitizer prodrug 5-ALA, in assessing clinically suspicious oral lesions. To that end the followings were assessed: • The fluorescence intensity ratio (FIR) or Red/Green ratio at 635/500nm measurements of normal anatomical sites at ten oral anatomical sites to map and create baseline readings for normal oral mucosal site fluorescence. • The effect of participants’ characteristics on the normal oral mucosal site FIR measurements. • The use the fluorescence intensity ratio (FIR) measurements to determine any differences between the lesion and the normal oral readings and whether the FIR from clinically suspicious oral lesions is associated with the histopathology grade. In addition to the sensitivity and specificity of the technique in assessing clinically suspicious (premalignant) oral lesions for potential malignant change. Prior to the trial commencing, approval were obtained from the Research Ethics Committee (REC), local NHS Research and Development (R&D), and Medicine Healthcare product Regulatory Agency (MHRA) and the University of Dundee Research Innovation Services (RIS). A total of thirty five participants with clinically suspicious oral lesions were recruited in Dundee (Dundee Dental Hospital) and Glasgow (Southern General Hospital). A Photodynamic Detection method using compact fluorescence spectroscopy and 5-ALA mouth rinse was applied. FIR measurements from ten normal anatomical sites were obtained in every patient to study the variation at different normal oral sites and the effect of the participant’s characteristics on these readings.
Supervisor: Ogden, Graham Sponsor: Photodynamic Therapy Centre
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.578784  DOI: Not available
Keywords: Photodynamic detection ; PDD ; Oral lesions
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