Biomedical subjects

R Baumgartner

Publications and source records attributed to R Baumgartner.

At least 19 recordsLinked to original sources

PubMed2007

Influence of secondary infection on amputation in chronic critical limb ischemia.

OBJECTIVES: To evaluate the influence of secondary infection on major amputation in chronic critical leg ischemia (CLI). DESIGN: Prospective, controlled observational study. MATERIALS AND METHODS: Sixty-seven patients with CLI and ischemic lesions participated in the study. Presence of infection was defined by clinical, laboratory and radiological criteria. Patients were categorized as having no local infection, soft tissue infection or osteomyelitis treated without antibiotics, amoxicillin/clavulanacid for 1 month or ciprofloxacin and clindamycin for 3 months, respectively. Clinical outcome was assessed at 2, 6 and 12 months. Study endpoints were major amputation and mortality. Analyses were performed using the Kaplan-Meier method. RESULTS: Forty-seven of 67 patients had a local infection. Major amputation was lower in patients with successful revascularization as compared to patients unsuitable for or with failed (without) revascularization (0% vs 26%, p<0.01). In patients with successful revascularization the probability of complete healing was lower with secondary infection (23% vs 71%, p=0.03). In patients without revascularization complete healing was rare (<10%), but secondary infection did not influenced major amputation, mortality or serious adverse events. CONCLUSION: Secondary infection reduces the likelihood of successful healing following revascularisation of CLI.

Aged↗

PubMed2006

Low frequency of colorectal dysplasia in patients with long-standing inflammatory bowel disease colitis: detection by fluorescence endoscopy.

BACKGROUND AND STUDY AIM: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colonic dysplasias. Dysplastic changes in flat mucosa are likely to be missed by conventional colonoscopy. Endoscopic fluorescence imaging, using 5-aminolevulinic acid (5-ALA) as photosensitizer, has evolved as a new technique to differentiate between normal colonic mucosa and dysplasia. We combined this technique with random biopsies to prospectively evaluate the occurrence of dysplasias in patients with long-standing IBD. PATIENTS AND METHODS: 52 colonoscopies were performed in 42 consecutive patients (n = 28 with ulcerative colitis, n = 11 with Crohn's colitis, n = 3 with indeterminate colitis; mean age 43 years, range 21 - 78) with long-standing IBD colitis (median disease duration 14 years, range 3 - 40). All patients were in clinical remission. Patients were examined using both conventional white light and by fluorescence colonoscopy using oral 5-ALA. Four biopsies were taken every 10 cm from mucosa of normal appearance. In addition, macroscopically suspicious and fluorescence-positive areas were biopsied. RESULTS: A total of 688 biopsies of red-fluorescent (n = 20) and nonfluorescent (n = 662) areas of mucosa were taken. Dysplasia was detected histopathologically in only two of the biopsies. These biopsies were taken from two polypoid lesions which were fluorescence-negative. CONCLUSIONS: The rate of colonic dysplasia in patients with long-standing IBD colitis may be lower than previously reported.

Administration, Oral↗

PubMed2004

5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on the patterns of tumour invasion.

5-ALA-induced protoporphyrin IX (PPIX) fluorescence kinetics was quantified by fluorescence microscopy in three-dimensional organ co-cultures of human bronchial epithelium, which were infiltrated by four different lung tumour cell lines (EPLC-M31, LCLC-103H, NCI-H125 and NCI-H841). Corresponding fluorescence measurements were performed in monolayer cultures of these tumour cell lines and BEAS-2B cells as a model for normal bronchial epithelium by flow cytometry. Significant differences of fluorescence intensities (FI) between the tumours were detected in organ co-cultures as well as in single cell measurements. Relative FI values in organ co-cultures (FI(EPLC-32M1)>FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)) did not correspond to the measurements in single cells (FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)>FI(EPLC-32M1)). Histology of organ co-cultures revealed different patterns of invasion and tumour cell densities depending on the tumour type. After correction of FI in the co-cultures to tumour cell density the correlation coefficient for fluorescence values between both models increased considerably. Thus, additionally to distinctive features of 5-ALA metabolism, patterns of tumour invasion may be a factor determining 5-ALA-induced fluorescence. Considering these results, a pronounced heterogeneity of 5-ALA-induced fluorescence might be expected in different bronchial tumours in vivo. This could interfere with the diagnostic reliability of 5-ALA-induced fluorescence for early tumour detection.

Aminolevulinic Acid↗

PubMed2004

Mapping high-dimensional data onto a relative distance plane--an exact method for visualizing and characterizing high-dimensional patterns.

We introduce a distance (similarity)-based mapping for the visualization of high-dimensional patterns and their relative relationships. The mapping preserves exactly the original distances between points with respect to any two reference patterns in a special two-dimensional coordinate system, the relative distance plane (RDP). As only a single calculation of a distance matrix is required, this method is computationally efficient, an essential requirement for any exploratory data analysis. The data visualization afforded by this representation permits a rapid assessment of class pattern distributions. In particular, we can determine with a simple statistical test whether both training and validation sets of a 2-class, high-dimensional dataset derive from the same class distributions. We can explore any dataset in detail by identifying the subset of reference pairs whose members belong to different classes, cycling through this subset, and for each pair, mapping the remaining patterns. These multiple viewpoints facilitate the identification and confirmation of outliers. We demonstrate the effectiveness of this method on several complex biomedical datasets. Because of its efficiency, effectiveness, and versatility, one may use the RDP representation as an initial, data mining exploration that precedes classification by some classifier. Once final enhancements to the RDP mapping software are completed, we plan to make it freely available to researchers.

Algorithms↗

PubMed2004

Unsupervised feature dimension reduction for classification of MR spectra.

We present an unsupervised feature dimension reduction method for the classification of magnetic resonance spectra. The technique preserves spectral information, important for disease profiling. We propose to use this technique as a preprocessing step for computationally demanding wrapper-based feature subset selection. We show that the classification accuracy on an independent test set can be sustained while achieving considerable feature reduction. Our method is applicable to other classification techniques, such as neural networks, support vector machines, etc.

Candida↗

PubMed2003

Class prediction and discovery using gene microarray and proteomics mass spectroscopy data: curses, caveats, cautions.

MOTIVATION: Two practical realities constrain the analysis of microarray data, mass spectra from proteomics, and biomedical infrared or magnetic resonance spectra. One is the 'curse of dimensionality': the number of features characterizing these data is in the thousands or tens of thousands. The other is the 'curse of dataset sparsity': the number of samples is limited. The consequences of these two curses are far-reaching when such data are used to classify the presence or absence of disease. RESULTS: Using very simple classifiers, we show for several publicly available microarray and proteomics datasets how these curses influence classification outcomes. In particular, even if the sample per feature ratio is increased to the recommended 5-10 by feature extraction/reduction methods, dataset sparsity can render any classification result statistically suspect. In addition, several 'optimal' feature sets are typically identifiable for sparse datasets, all producing perfect classification results, both for the training and independent validation sets. This non-uniqueness leads to interpretational difficulties and casts doubt on the biological relevance of any of these 'optimal' feature sets. We suggest an approach to assess the relative quality of apparently equally good classifiers.

Algorithms↗

PubMed2003

[Precancerous conditions in the urothelium. Early detection and molecular understanding through endoscopic fluorescence diagnosis].

Fluorescence diagnosis after application of 5-aminolevulinic acid (ALA) detects red-fluorescing preneoplastic and neoplastic lesions using light excitation. The principle of the method is the relative tumor-selective accumulation of the metabolite protoporphyrin IX (PPIX), which is built intracellularly out of exogenously applied ALA. The early detection of tumors and especially preneoplasias is an ideal prerequisite for genetic analysis of these lesions. With this approach, methods such as fluorescence in situ hybridization and loss of heterozygosity analysis for deletion mapping as well as gene sequencing data could be compared. New data are presented on deletions, numeric chromosomal aberrations, and oligoclonality of tumors found in about 30% of cases. The phenomenon of tumor-selective fluorescence was further investigated by parallel biochemical analysis, which showed marked differences in heme metabolism. The analysis of gene and protein expression may aid in identifying tumor-specific molecules associated with heme metabolism.

Coloring Agents↗

PubMed2003

Transmeatal cochlear laser (TCL) treatment of cochlear dysfunction: a feasibility study for chronic tinnitus.

Low-level-laser-therapy (LLLT) targeting the inner ear has been discussed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. Former studies demonstrate dose-dependent biological and physiological effects of LLLT such as enhanced recovery of peripheral nerve injuries, which could be of therapeutic interest in cochlear dysfunction. To date, in patients with chronic tinnitus mastoidal and transmeatal irradiation has been performed without systematic dosimetric assessment. However, light-dosimetric studies on human temporal bones demonstrated that controlled application of laserlight to the human cochlea depends on defined radiator position within the external auditory meatus. This feasibility study first presents a laser application system enabling dose-controlled transmeatal cochlear laser-irradiation (TCL), as well as preliminary clinical results in patients with chronic cochlear tinnitus. The novel laser TCL-system, consisting of four diode lasers (lambda=635 nm-830 nm) and a new specific head-set applicator, was developed on the basis of dosimetric data from a former light-dosimetric study. In a preliminary clinical study, the TCL-system was applied to 35 patients with chronic tinnitus and sensorineural hearing loss. The chronic symptoms persisted after standard therapeutic procedures for at least six months, while retrocochlear or middle-ear pathologies have been ruled out. The patients were randomised and received five single diode laser treatments (lambda=635 nm, 7.8 mW cw, n=17 and lambda=830 nm, 20 mW cw, n=18) with a space irradiation of 4 J/cm2 site of maximal cochlear injury. For evaluation of laser-induced effects complete otolaryngologic examinations with audiometry, tinnitus masking and matching, and a tinnitus-self-assessment were performed before, during and after the laser-irradiation. The first clinical use of the TCL-system has been well tolerated without side-effects and produced no observable damage to the external, middle or inner ear. Changes of tinnitus loudness and tinnitus matching have been described. After a follow-up period of six months tinnitus loudness was attenuated in 13 of 35 irradiated patients, while two of 35 patients reported their tinnitus as totally absent. Hearing threshold levels and middle ear function remained unchanged. Further investigations by large double-blind placebo-controlled studies are mandatory for clinical evaluation of the presented TCL-system and its therapeutic effectiveness in acute and chronic cochlear dysfunction.

Chronic Disease↗

PubMed2003

Whole bladder photodynamic therapy with 5-aminolevulinic acid using a white light source.

OBJECTIVES: To determine whether whole bladder photodynamic therapy after intravesical administration of 5-aminolevulinic acid using a white light source would destroy urothelial carcinoma. We sought to define the optimal target group of patients for this therapy. The side effects of treatment were also assessed. METHODS: We performed whole bladder photodynamic therapy with 100 J/cm(2) white light 2 to 4.5 hours after intravesical administration of 17% 5-aminolevulinic acid in 12 patients with recurring, multifocal, Stage pTa, grade I to III, urothelial tumors of the bladder and carcinoma in situ. RESULTS: Immediately after whole bladder irradiation, histologic examination of biopsies taken from flat suspicious lesions showed no viable cells; remnants of malignant cells were found in papillary tumors. Of the 12 patients, 11 returned for follow-up examination. At a median follow-up of 18 months (range 3 to 25), 3 of the 7 patients with carcinoma in situ and 2 of the 4 patients with papillary tumors were free of disease. In all patients, urinary frequency and urgency subsided within 3 weeks. No decreased bladder capacity or systemic side effects were observed. CONCLUSIONS: Our preliminary data show that whole bladder photodynamic therapy with intravesically applied 5-aminolevulinic acid using a white light source is effective in destroying flat malignant lesions of the bladder such as carcinoma in situ. The procedure is easy to perform and is not associated with any major side effects. The findings warrant long-term and multicenter studies.

Administration, Intravesical↗

PubMed2002

[Fluorescence staining of oral and laryngeal cancer after application of 5-aminolevulinic acid].

BACKGROUND: Cancer of the oral cavity, oropharynx and larynx are the most common malignancies in the head and neck region. The prognosis for the patients concerned is highly dependent on an early detection and fast surgical treatment. Fluorescence guided examinations may serve as a possible diagnostic tool for better demarcation and delimitation of head and neck cancer. Therefore, the presented study was aimed at the detection of a selective Protoporphyrin IX (PPIX) accumulation in malignant oral, oropharyngeal and laryngeal lesions following topical and systemic application of 5-aminolevulinic acid (5-ALA). PATIENTS: We investigated 193 patients with suspected lesions in the oral cavity and oropharynx (n = 126) as well as in the larynx (n = 67). The patients received a varying dose (rinsing 200 mg, inhalation 30 mg, 2,5 - 25 mg/kg BW by mouth) of 5-ALA in aqueous solution. Both fluorescence pictures and macroscopic findings under white light were recorded using a target integrating, color CCD camera. Fluorescence contrasts between tumor and normal tissue were registered by an optical multichannel analyser. RESULTS: Our results have shown that after topical and systemic application of 5-ALA, PPIX fluorescence could be identified within the mucosa of the oral cavity, oropharynx and the larynx of all patients with a duration of up to 48 hours after systemic application. Malignant lesions usually showed higher intensities of PPIX-fluorescence than surrounding innocuous mucosa. A maximum fluorescence contrast between normal tissue and neoplastic lesions was observed at 1.5 hours after topical application and 3 hours after systemic application. CONCLUSIONS: It will be the aim of further investigations to verify the optimal time of incubation and dosing of systemical 5-ALA application to enhance fluorescence contrasts and set the basis for fluorescence guided resections.

Administration, Inhalation↗

PubMed2001

Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer.

Photodynamic therapy using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX is a promising tool in bladder-cancer therapy. However, little is known about the cellular mechanisms of phototoxicity. Our aim was to characterize the cellular damage and to optimize differential photodynamic effectiveness between tumor and normal urothelial cells. RT4 tumor and UROtsa normal urothelial cells were used to simulate a papillary bladder tumor in contrast to normal urothelium. Photodynamically induced damage in plasma membrane and mitochondria was monitored by flow cytometry with propidium iodide exclusion and analysis of aggregate formation of the dye JC-1. Cell morphology was investigated by phase-contrast and fluorescence microscopy following acridine orange staining. Long incubation times (3 hr) led to complete RT4 tumor cell kill accompanied by a marked fraction of damaged normal UROtsa cells. Shorter incubation intervals (1 hr) also resulted in complete RT4 tumor cell kill; however, most UROtsa cells retained their cell properties, including intact plasma membrane and active mitochondria as well as intact cellular morphology. Phototoxicity depends not only on cellular sensitizer accumulation but also on intracellular localization. Analysis of phototoxic mechanisms is an important step for planning combination therapy regimens with, e.g., DNA-damaging agents. Further, data indicate that differential phototoxicity in normal and tumorous urothelium can be enhanced using differences in cellular protoporphyrin IX distribution following short 5-ALA incubation times. These data are encouraging for the in vivo situation since short incubation times are a more practical approach for local photodynamic therapy of early tumor stages not only in the bladder but also, e.g., in the gastro-intestinal tract or bronchial mucosa.

Aminolevulinic Acid↗

PubMed2001

Lightdosimetric quantitative analysis of the human petrous bone: experimental study for laser irradiation of the cochlea.

BACKGROUND AND OBJECTIVE: Application of laser irradiation targeting the inner ear has to be investigated for therapeutic effectiveness in cochlear injury and dysfunction. In vitro data demonstrate low-level laser-induced photochemical and photobiologic cell response, depending on cell type and irradiation parameters such as light dose. The aim of the presented study was to determine the light dose received by the cochlear hair cells by using different irradiation modalities for the human petrous bone. STUDY DESIGN/MATERIALS AND METHODS: Lightdosimetric assessment was performed in human cadaver temporal bones (n = 13) after removing the cochlear membranous labyrinth. The external auditory meatus, the tympanic membrane (quadrants), and the mastoid bone were illuminated by a helium-neon laser (lambda = 593 nm) and diode lasers of different wavelengths (lambda = 635, 690, 780, and 830 nm). The spatial distribution of transmitted light in the cochlear windings was measured by means of a retrocochlearly positioned endoscopic CCD camera for image processing and was assigned to acoustic frequencies according to the tonotopic organization of the cochlea. For an estimation of the corresponding space irradiance in an intact cochlea, correction factors have been calculated by a Monte Carlo procedure on the basis of experimentally determined optical properties of skull bone. RESULTS: The transmission of light across the tympanic cavity and the promontory depends strongly on wave-length of the laser and the position of the radiator. Transtympanal irradiation results in spatial intensity variations of a factor 4 to 10 within the cochlear windings. The space irradiance in an intact cochlea is 10 to 20 times the measured irradiance. For an irradiation of the mastoid, the light transmission within the cochlea is 10(3) to 10(5) times smaller compared with an irradiation of the tympanic membrane and is extremely variable for different specimens. CONCLUSION: The strong dependence of the cochlear light distribution on various irradiation parameters demonstrates the impact of preclinical lightdosimetric investigations for effective individual laser irradiation of the human cochlea. Because of the observed spatial intensity variations, the optimal external light dose has to be chosen with regard to the tonotopy of the human cochlea. The obtained results are enabling us to apply defined laser light doses to different cochlear winding areas. Mastoidal irradiation leads to therapeutically insufficient light doses within reasonable treatment times, whereas transmeatal irradiation is recommendable. Further studies are mandatory for development of clinical devices for transmeatal irradiation of the cochlea.

Cadaver↗

PubMed2001

Laser treatment of hyperplastic inferior nasal turbinates: a review.

BACKGROUND AND OBJECTIVE: Since the early 80s various types of lasers have been used for the reduction of hyperplastic inferior nasal turbinates. Up to now many studies have revealed a variety of important information. To summarize these findings and to determine the value of laser treatment of hyperplastic inferior nasal turbinates, a comparative review of the literature was performed. STUDY DESIGN/MATERIALS AND METHODS: The study of the literature revealed that hyperplastic inferior turbinates of more than 2,000 patients have been treated and followed up. Treatment was performed with the CO2 (10,600 nm), diode (805/810/940 nm), Argon-ion (488/514 nm), KTP (532 nm), Nd:YAG (1,064 nm), and Ho:YAG (2,080 nm) laser in more than 20 studies so far. Generally, the authors of the trials used different laser parameters (power, energy) and application modalities (contact, non-contact, interstitial, superficial). To determine the long-term results objective (active anterior rhinomanometry, acoustic rhinometry, mucociliary function tests, allergy tests) as well as subjective parameters (questionnaire) were recorded and evaluated. In some cases morphological changes of the turbinate tissue were studied by light and scanning electron microscopy (SEM). RESULTS: Laser surgery of inferior turbinates can be performed as an outpatient procedure under local anesthesia. Due to a minimally invasive and controllable coagulation and ablation of soft tissue, almost no complications or bleedings were observed during the operation or postoperatively. Depending on the chosen parameters (power, energy) and the application modalities (contact, non-contact, superficial, interstitial) laser treatment of hyperplastic inferior nasal turbinates achieved comparable or better results than most of the conventional techniques for turbinate surgery like conchotomy, electrocautery, cryotherapy, chemical cauterization, and vidian neurectomy. More invasive (radical) operative methods, such as inferior turbinoplasty, submucous turbinectomy, lateral outfracture, partial and total turbinectomy, seemed to be more effective than laser surgery in the long-term. CONCLUSIONS: Laser treatment of hyperplastic inferior nasal turbinates can be considered as a useful, cost-effective, and time-saving procedure for the reduction of hyperplastic inferior nasal turbinates. Short operation time, good results, and minor side effects compared to other surgical methods provide an excellent clinical response of the patients.

Humans↗

PubMed2001

Ranking fMRI time courses by minimum spanning trees: assessing coactivation in fMRI.

In fMRI, time courses with similar temporal "activation" patterns may belong to different brain regions (i.e., these regions are functionally connected, coactivated). A group of time courses (TCs) corresponding to a particular type of temporal activation pattern should be maximally self-consistent (homogeneous). We demonstrate that ordering a group of multidimensional fMRI time courses by a minimum spanning tree (MST) may be used to investigate the temporal homogeneity of a group of TCs. We show the utility of MST ranking for data-driven analysis methods in investigating coactivation in fMRI. MST ranking is equally useful for hypothesis-led methods. Furthermore, MST ranking enables pairwise comparisons of groups/clusters (i.e., any collection of TCs, no matter how derived) of fMRI time courses.

Brain↗

PubMed2001

Endoscopic detection of transitional cell carcinoma with 5-aminolevulinic acid: results of 1012 fluorescence endoscopies.

OBJECTIVES: The initial encouraging results using 5-aminolevulinic acid (5-ALA) induced fluorescence endoscopy (AFE) have promised a procedure with an outstanding sensitivity for the detection of early stage bladder cancer. Summarized here is our clinical experience and data comprising 1012 fluorescence endoscopies. METHODS: Two hours, 30 minutes before endoscopy, 1.5 g 5-ALA dissolved in 50 mL of 5.7% sodium monohydrogen phosphate was instilled in patients intravesically. Before AFE, all patients underwent white light endoscopy, and a bladder washing cytologic specimen was obtained. A special light source provided blue light (375 to 440 nm) for fluorescence excitation. Suspicious sites were identified by their red fluorescence contrasting against backscattered blue light when observed through the long pass filter (445 nm) integrated into the telescope eyepiece. RESULTS: Two thousand four hundred seventy-five specimens were obtained (2.4 biopsies per AFE). In 552 AFEs (54.5%), neoplastic urothelial lesions were detected, in 34.2% only because of their positive fluorescence; 38.7% of these additionally detected neoplastic foci had poorly differentiated histologic features. CONCLUSIONS: AFE has proved to be a clinically feasible procedure with an outstanding detection rate for flat, urothelial, high-risk lesions.

Administration, Intravesical↗

PubMed2001

Autofluorescence imaging to optimize 5-ALA-induced fluorescence endoscopy of bladder carcinoma.

OBJECTIVES: To design an optical system for detecting autofluorescence (AF) of bladder tumors and to determine the success of reducing the false-positive rate of 5-aminolevulinic acid-induced fluorescence endoscopy (AFE). AFE provides significantly higher sensitivity in detecting and localizing bladder carcinoma compared with white light endoscopy. The specificity of AFE is equivalent to white light endoscopy, mostly because of the false-positive fluorescence of chronic cystitis lesions. Laser-induced spectral autofluorescence detection is also an efficient method in the diagnosis of bladder carcinoma. METHODS: Bladder tissue was excited to AF using the D-Light (375 to 440 nm) after regular AFE with detection of fluorescence-positive areas. The optical image was produced using a special RGB camera. Biopsies were taken from AFE-positive areas, the peritumoral edges, and normal bladder mucosa. The AF images of the suspicious areas were compared with the AFE images and the histologic results. RESULTS: A total of 43 biopsies were histologically examined (24 benign and 19 neoplastic). AF imaging showed contrast differences between papillary tumors, flat lesions, and normal mucosa. The combination of AFE with AF raised the specificity of AFE alone from 67% to 88%. CONCLUSIONS: AF imaging is possible. The value of the method in reducing the false-positive rate of the highly sensitive AFE needs to be validated with higher numbers. The combination of AF with AFE had a 20% higher specificity than AFE alone in our study.

Administration, Intravesical↗

PubMed2001

Graphical display of fMRI data: visualizing multidimensional space.

Visualization of multidimensional data is an integral part of computational statistics and exploratory data analysis (EDA). We show how visualization of fMRI time-courses may be used to reveal the fMRI data structure. We consider fMRI time-courses (TCs) as points in multidimensional space. In simulated and in vivo data, we show that minimum spanning tree (MST)-based sequencing of multivariate time-courses, in combination with a homogeneity map visualization, allows for effective and useful graphical display of the groups of coactivated time-courses obtained by temporal clustering. This display may serve as a tool for investigation of brain connectivity. We also suggest a simple overall display of the entire fMRI data set.

Artifacts↗

PubMed2001

Fluorescence staining of oral cancer using a topical application of 5-aminolevulinic acid: fluorescence microscopic studies.

INTRODUCTION: Topical application of 5-aminolevulinic acid (5-ALA) by means of a rinsing solution has been shown to be a promising new procedure in the diagnosis of oral malignancies. However, for assessing the reliability of this method regarding fluorescence-guided tumor resections and photodynamic therapy, further information on the distribution and penetration depth of 5-ALA-induced protoporphyrin IX (PPIX) in the tissue is needed. METHODS: 24 patients suffering from oral cancer were included in this investigation. Biopsies were taken immediately after fluorescence examination and either used as native sections for immediate fluorescence microscopic examination (n = 3) or shock frozen in liquid nitrogen and prepared as frozen sections (n = 46). Fluorescence imaging and digital image processing were utilized in order to determine the presence of PPIX in regions of various histologies as well as the penetration depth of PPIX into solid tumor. RESULTS: PPIX fluorescence in the tissue was limited to the epithelium. Both normal and dysplastic epithelium showed PPIX fluorescence. In the stroma, no PPIX fluorescence was found. In some cases (n = 3/4) invasive carcinomas did not show PPIX fluorescence, while the adjacent or overlying normal epithelium was strongly fluorescent. The penetration depth of PPIX after topical application of 5-ALA was found to be limited to less than 1 mm. CONCLUSION: PPIX fluorescence induced by topical application of 5-ALA can be very useful in the determination of superficial tumor margins. However, due to the limited penetration depth there is a risk of not accurately recognizing the infiltration depth of solid tumors. The aim of further investigations will be to assess the tissue distribution and depth of penetration of PPIX following systemic application of 5-ALA.

Aminolevulinic Acid↗