title: Fluorescence confocal microscopy and image analysis of bladder cancer using 5-aminolevulinic acid.
abstract: 5-aminolevulinic acid mediated changes in tissue specific fluorescence were studied in bladder cancer. Bladders of normal patients and also patients diagnosed with cancer were instilled with 5-aminolevulinic acid and the resultant protoporphyrin IX mediated fluorescence intensity was imaged and quantified with confocal laser microscopy and fluorescence image analysis. Urothelial tumour cells were observed to fluoresce more intensely than normal urothelial cells. Submucosa and muscle tissues exhibited minimal fluorescence compared to urothelial cells of malignant origin and also normal urothelial cells. Degree of fluorescence intensity was in the order of malignant urothelium > normal urothelium > normal submucosa > normal muscles. Fluorescence intensity was also found to increase with duration of ALA instillation. Grade 3 malignant cells produced more fluorescence compared to grade 2 and grade 1. Similarly, T1 transitional cell carcinoma (TCC) showed increased fluorescence intensity than that of Ta TCC. Also, tumour blood vessels fluoresced more intensely compared to blood vessels found in normal bladder tissue. Tissue specific ALA mediated PpIX micro fluorescence can be used as a diagnostic technique for early detection of neoplasms and confocal laser microscopy and fluorescence image analysis are advantageous diagnostic tools for the photodynamic diagnosis of bladder neoplasms in vivo.
authors.affiliation: Division of Medical Sciences, National Cancer Centre, Singapore 169610. dmsmcd@nccs.com.sg
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
authors.forename: Weber
authors.initials: W
authors.lastname: Lau
authors.forename: Vanaja
authors.initials: V
authors.lastname: Manivasager
authors.forename: Tan Puay
authors.initials: TP
authors.lastname: Hoon
authors.forename: Cheng
authors.initials: C
authors.lastname: Christopher
mesh_terms: D000283:Administration, Intravesical; D000622:Aminolevulinic Acid / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry / Q000175:diagnosis / Q000648:ultrastructure*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000175:diagnosis / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008027:Light; D018613:Microscopy, Confocal / Q000379:methods*; D008856:Microscopy, Fluorescence / Q000379:methods*; D009092:Mucous Membrane / Q000187:drug effects / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000187:drug effects / Q000648:ultrastructure; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000032:analysis* / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000648:ultrastructure*; D019459:Urothelium / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX