Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced Protoporphyrin IX for the dectection of neoplastic lesions in the oral cavity

Leunig, Andreas; Rick, K.; Stepp, Herbert; Gutmann, R.; Alwin, Goetz; Baumgartner, Reinhold; Feyh, J.

doi:10.1016/s0002-9610(96)00312-1

Cited by 108 publications

(74 citation statements)

References 15 publications

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“…Addition of exogenous ALA causes a preferential accumulation of protoporphyrin IX ͑PpIX͒ in cancerous cells when compared to normal cells. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][33][34][35][36]39,40 PpIX is naturally produced by all nucleated cells during the heme cycle and meticulously controlled to prevent its natural accumulation. 37 This negative feedback system is thought to be modified in cancerous tissues due to ͑i͒ enzymatic defects that lead to an increase in protoporphyrinogen IX oxidase and/or ͑ii͒ reduced activity of ferrochelatase.…”

Section: Introductionmentioning

confidence: 99%

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

et al. 2010

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Abstract. We describe the potential of 5-aminolevulinic acid ͑ALA͒-induced protoporphyrin IX ͑PpIX͒ fluorescence as a source of contrast for margin detection in commonly diagnosed breast cancer subtypes. Fluorescence intensity of PpIX in untreated and ALA-treated normal mammary epithelial and breast cancer cell lines of varying estrogen receptor expression were quantitatively imaged with confocal microscopy. Percentage change in fluorescence intensity integrated over 610-700 nm ͑attributed to PpIX͒ of posttreated compared to pretreated cells showed statistically significant differences between four breast cancer and two normal mammary epithelial cell lines. However, a direct comparison of post-treatment PpIX fluorescence intensities showed no differences between breast cancer and normal mammary epithelial cell lines due to confounding effects by endogenous fluorescence from flavin adenine dinucleotide ͑FAD͒. Clinically, it is impractical to obtain pre-and post-treatment images. Thus, spectral imaging was demonstrated as a means to remove the effects of endogenous FAD fluorescence allowing for discrimination between posttreatment PpIX fluorescence of four breast cancer and two normal mammary epithelial cell lines. Fluorescence spectral imaging of ALAtreated breast cancer cells showed preferential PpIX accumulation regardless of malignant phenotype and suggests a useful contrast mechanism for discrimination of residual cancer at the surface of breast tumor margins.

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Section: Introductionmentioning

confidence: 99%

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

et al. 2010

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“…Clinical studies with PDD and PDT using ALA were performed for the treatment of neural tumours (Obwegeser et al, 1998), lesions of the oral cavity (Leuing et al, 1996), endoscopical detection of bronchial lesions (Campbell et al, 1996) and detection of carcinoma in situ of the bladder during cystoscopy (Kriegmair et al, 1994). The latter reached a sensitivity of 93%.…”

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confidence: 99%

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Ladner

Steiner²,

Allemann³

et al. 2001

Br J Cancer

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Photodynamic diagnosis is of increasing interest for diagnosis in oncology. It is based on a more intense incorporation of a fluorescent dye in tumours compared to normal tissue. As a feasibility study we investigated the effectiveness of oral application of 5-aminolevulinic acid for photodynamic diagnosis of human primary mammary tumours. The study included 16 patients with palpable breast tumours. Aminolevulinic acid was administered at a concentration of 40 mg kg −1 bodyweight 150–420 min prior to tumourectomy. Intraoperatively blue light (405 nm) was applied to the operation site. Sections of the excised tumour and some lymph nodes were prepared and analysed with a fluorescent microscope. All primary mammary tumour tissues showed significantly higher fluorescence intensity than surrounding normal mammary tissue. Fluorescence of the mammary tumours could also be discriminated macroscopically and intraoperatively. Fluorescence intensity in nonmetastatic lymph node tissue was higher in 2 out of 3 patients than in primary tumour tissue. By photodynamic diagnosis using aminolevulinic acid we were able to reliably distinguish primary mammary tumours from normal mammary tissue microscopically and macroscopically in all our patients. We suggest that photodynamic diagnosis with aminolevulinic acid for breast tumours should be further investigated and developed for intraoperative use and may well be a simple tool for better intraoperative diagnosis and recognition of tumour margins. We hypothesize that lymph node metastasis of breast tumours will not be detectable by this method. © 2001 Cancer Research Campaign http://www.bjcancer.com

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“…The fluorescence intensity in the malignant tissue reaches a maximum between 1 and 2 h after ALA application. 6,17,22,24 Numerous studies have shown that violet laser excitation induces both autofluorescence and ALA-induced fluorescence. 15,16,[18][19][20] The wavelength of the former is in the green-to-red range, whereas that of the latter falls mainly in the red band.…”

Section: Basis and Development Of The Image Processing Methodsmentioning

confidence: 99%

“…However, accurate demarcation of early-stage neoplasia is difficult by visual inspection alone. [5][6][7][8][9] Clinicians can usually identify white oral leukoplakia, red oral erythroplakia, and erythroleukoplakia visually, but they cannot know which specific lesion site contains dysplastic or malignant cells. Thus, demarcation of the tumor borders via simple inspection or other common diagnostic procedures often remains unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

“…Two types of fluorescence indicators have been reported to be valuable: autofluorescence 5,[8][9][10][11][12][13] and protoporphyrin IX (PpIX) fluorescence. 6,[14][15][16][17][18] Previous studies have shown autofluorescence to reduce with oral malignancy; 5,9,10,19,20 however, this change is not easy to discriminate by visual inspection. A study applied classification algorithms to compare various contrast features extracted from multispectral optical images and found that the ratio of red-to-green fluorescence intensity in a 405-nm excited autofluorescence image maximized the image contrast for the differentiation of neoplastic and non-neoplastic tissue.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

2011

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Abstract. Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R/B ratio, and R/G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R/G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced Protoporphyrin IX for the dectection of neoplastic lesions in the oral cavity

Cited by 108 publications

References 15 publications

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

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