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Biomedical subjects

S Andersson-Engels

Publications and source records attributed to S Andersson-Engels.

At least 19 recordsLinked to original sources

Multivariate analysis of laryngeal fluorescence spectra recorded in vivo.

BACKGROUND AND OBJECTIVE: The potential of using various multivariate analysis methods for classification of fluorescence spectra acquired in vivo from laryngeal tissues in Patients was investigated. STUDY DESIGN/MATERIALS AND METHODS: Autofluorescence spectra were measured on 29 normal tissue sites and 25 laryngeal lesions using 337-nm excitation. Four different multivariate analysis schemes were applied. Laryngeal fluorescence spectra from patients who had been administered delta-aminolevulinic acid (ALA) were obtained using 405-nm excitation and were classified using partial least squares discriminant analysis (PLS-DA). RESULTS: For autofluorescence spectra, logistic regression based on principal component analysis (PCA) or PLS, or PLS-DA all resulted in sensitivities and specificities around 90% for lesion vs. normal. Using ALA and 405-nm excitation gave a sensitivity of 100% and a specificity of 69%. CONCLUSION: Multivariate analysis of fluorescence spectra could allow classification of laryngeal lesions in vivo with high sensitivity and specificity. PLS performs at least as well as PCA, and PLS-DA performs as well as logistic regression techniques on these data.

Adult↗

Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial.

BACKGROUND: A previously reported randomized clinical trial showed treatment of Bowen's disease using photodynamic therapy (PDT) with topically applied delta-aminolaevulinic acid (ALA) to be at least as effective as cryosurgery and to be associated with fewer adverse effects. OBJECTIVES: To compare ALA-PDT and cryotherapy in the treatment of histopathologically verified basal cell carcinomas (BCCs) in a non-blinded, prospective phase III clinical trial. METHODS: One lesion from each of 88 patients was included. The BCCs were divided into superficial and nodular lesions. The follow-up period was restricted to 1 year with close follow-up for the first 3 months. Efficacy was assessed as the recurrence rate 12 months after the first treatment session, verified by histopathology. Tolerability was evaluated as the time of healing, pain and discomfort during and after the treatment, and final cosmetic outcome. RESULTS: Histopathologically verified recurrence rates in the two groups were statistically comparable and were 25% (11 of 44) for ALA-PDT and 15% (six of 39) for cryosurgery. However, clinical recurrence rates were only 5% (two of 44) for PDT and 13% (five of 39) for cryosurgery. Additional treatments, usually one, had to be performed in 30% of the lesions in the PDT group. The healing time was considerably shorter and the cosmetic outcome significantly better with PDT. Pain and discomfort during the treatment session and in the following week were low, and were equivalent with the two treatment modalities. CONCLUSIONS: In terms of efficacy, ALA-PDT is comparable with cryosurgery as a treatment modality for BCCs. Retreatments are more often required with PDT than with cryosurgery. This can easily be performed due to the shorter healing time, less scarring and better cosmetic outcome that follows ALA-PDT.

Adult↗

Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin.

BACKGROUND AND OBJECTIVE: Fluorescence techniques can provide powerful noninvasive means for medical diagnosis, based on the detection of either endogenous or exogenous fluorophores. The fluorescence of delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has already shown promise for the diagnosis of tumors. The aim of the study was to investigate the localization of skin tumors after the topical application of ALA, by detecting the PpIX fluorescence either in the spectral or in the time domain. STUDY DESIGN/MATERIALS N AND METHODS: Two fluorescence imaging systems were used to identify basal cell carcinomas of the skin in humans, after topical application of 20% ALA ointment. Both systems rely on the comparison between the exogenous and the endogenous fluorescence, performed either in the spectral domain or in the time domain. The first system works by using three images acquired through different spectral filters, whereas the second one measures the spatial map of the average fluorescence lifetime of the sample. RESULTS: A clear demarcation of skin malignancies was successfully performed in vivo noninvasively with both fluorescence imaging systems. CONCLUSION: The two complementary approaches considered in the present study show promise for skin tumor detection and delineation based on specific fluorescence features.

Adult↗

Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas.

Laser-induced fluorescence (LIF) investigations have been performed in connection with photodynamic therapy (PDT) of basal cell carcinomas and adjacent normal skin following topical application of 5-aminolaevulinic acid (ALA) in order to study the kinetics of the protoporphyrin IX (PpIX) build-up. Five superficial and 10 nodular lesions in 15 patients are included in the study. Fluorescence measurements are performed prior to the application of ALA, 2, 4 and 6 h post ALA application, immediately post PDT (60 J cm-2 at 635 nm), and 2 h after the treatment. Hence, the build-up, photobleaching and re-accumulation of PpIX can be followed. Superficial lesions show a maximum PpIX fluorescence 6 h post ALA application, whereas the intensity is already the highest 2-4 h after the application in nodular lesions. Immediately post PDT, the fluorescence contribution at 670 nm from the photoproducts is about 2% of the pre-PDT PpIX fluorescence at 635 nm. Two hours after the treatment, a uniform distribution of PpIX is found in the lesion and surrounding normal tissue. During the whole procedure, the autofluorescence of the lesions and the normal skin does not vary significantly from the values recorded before the application of ALA.

Administration, Topical↗

Photodynamic therapy utilising topical delta-aminolevulinic acid in non-melanoma skin malignancies of the eyelid and the periocular skin.

PURPOSE: Photodynamic therapy utilising delta-aminolevulinic acid-induced protoporphyrin IX photosensitisation, was evaluated as a treatment modality for nonmelanoma skin malignancies of the eyelids and the periocular skin. METHODS: Photodynamic therapy with laser light at 635 nm was performed in 13 patients with 19 basal cell carcinomas and one patient with 3 cutaneous T-cell lymphoma lesions. A topical application regimen was used and in median 3 treatment sessions were given to each lesion. RESULTS: A visually judged complete response was achieved in 42% (8/19) of the basal cell carcinomas and in 100% of the T-cell lymphoma lesions (3/3). Partial tumour response was seen in 42% (8/19) and no response in 16% (3/19) of the basal cell carcinomas. The median follow-up time was 12 months. No, or very little scarring and loss of cilia were induced by the treatment. CONCLUSION: Photodynamic therapy with delta-aminolevulinic acid can eradicate eye-close non-melanoma skin malignancies without compromising the function of the eyelids. Further development of the method is needed to reach the same cure rates as those of the conventional treatment modalities.

Administration, Topical↗

Clinical spectral characterisation of colonic mucosal lesions using autofluorescence and delta aminolevulinic acid sensitisation.

BACKGROUND AND AIMS: Laser induced fluorescence (LIF) from colonic mucosa was measured in vivo with and without delta aminolevulinic acid (ALA) in an attempt to differentiate between neoplasia and non-neoplasia in real time during colonoscopy. METHODS: Spectra from 32 adenomas, 68 normal sites, and 14 hyperplastic polyps in 41 patients were obtained with a point monitoring system. Twenty one of the patients had been given a low dose of ALA as a photosensitiser before the examination. Light of 337, 405, or 436 nm wavelength was used as excitation. Stepwise multivariate linear regression analysis was performed. RESULTS: With 337 nm excitation, 100% sensitivity and 96% specificity was obtained between normal mucosa and adenomas. Seventy seven per cent of the hyperplastic polyps were classified as non-neoplastic. When exciting with 405 and 436 nm, the possibility of distinguishing different types of tissue was considerably better in the ALA patients than in the non-ALA patients. CONCLUSIONS: The in vivo point measurements imply that a good discrimination between normal tissue and adenomatous polyps can be obtained using the LIF technique. Excitation at 337 nm and at 405 nm or 436 nm using ALA gives good results. LIF also shows potential for distinguishing adenomatous from hyperplastic polyps. The number of detection wavelengths could be reduced if chosen properly.

Adenoma↗

Laser-based spectroscopic methods in tissue characterization.

Laser-based spectroscopic techniques were developed for tumor tissue characterization utilizing different tumor-localizing substances. In particular, sensitization with the heme precursor delta-amino levulinic acid (ALA) administered topically, orally or intravenously was used for the induction of protoporphyrin IX (PpIX). The autofluorescence as well as the PpIX-related fluorescence signals were monitored, and tumor demarcation functions were calculated for different human malignant tumors, such as tumors in the urinary bladder and the prostatic gland, in the head and neck region, in the breast and in the gastrointestinal tract. In the gastrointestinal tract, colon tumors were examined as well as tumors and dysplastic lesions in the esophagus, where patients with Barrett's esophagus were examined. Time-integrated laser-induced fluorescence measurements utilizing a point monitoring fluorosensor and a multicolor fluorescence imaging system were performed in vivo in patients in different clinical specialities.

Fluorescence↗

Optimizing transurethral microwave thermotherapy: a model for studying power, blood flow, temperature variations and tissue destruction.

OBJECTIVE: To examine the role of microwave power and blood flow on temperature variations and tissue destruction in the prostate, using a theoretical model of transurethral microwave thermotherapy (TUMT), and thus compare fixed-energy TUMT with no intraprostatic temperature monitoring (constant microwave power applied over a fixed period) with 'feedback' TUMT in which the microwave power is adjusted according to the monitored intraprostatic temperature. MATERIALS AND METHODS: The temperature distribution in the prostate was modelled for a typical TUMT catheter at various blood flow rates. The volume of tissue destroyed was simultaneously calculated from cell survival data after thermal exposure. The calculated quantity of tissue destroyed at the different microwave power levels and blood flow rates was used to describe qualitatively the simulated treatments. RESULTS: Treatment monitoring and consistency were better during feedback TUMT than fixed-energy TUMT, in that the former compensated for variations in blood flow rate. The modelled values agreed with observations during real TUMT. CONCLUSIONS: Blood flow rate is a key factor in the outcome of TUMT. Only by measuring intraprostatic temperature is it possible to compensate for the large variations in prostatic blood flow and obtain consistent treatment results. Repeated interruptions prompted by high rectal temperatures should be minimized and preferably avoided, as the quantity of tissue destroyed is then greatly reduced, and in extreme cases the treatment is totally ineffective.

Blood Flow Velocity↗

Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.

PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.

Adult↗

Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat.

Interstitial laser-induced thermotherapy (ILT) destroys tumors thermally. ILT was performed for treatment of liver tumors in rats to investigate the effect of hepatic inflow occlusion on temperature distribution and lesion size. Tumors were irradiated for 20 min with near-infrared light from a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. The laser light at a power of 1.5 W was delivered through a plane-cut optical fiber, the tip of which was placed in the tumor. Rats in group I received ILT without interruption of hepatic blood flow. Those in group II received ILT during hepatic inflow occlusion. Liver temperatures were measured during treatment. After 3 days the animals were sacrificed and the size of the lesions was measured. Occlusion of the hepatic inflow during ILT increased the maximum lesion diameter, as measured at the liver surface, by 47%. Linear interpolation between the temperatures measured at 6 and 12 mm distance from the fiber tip revealed that the temperature at the necrotic border just before the end of treatment was approximately 45 degrees C in both the occluded and nonoccluded groups, indicating that the hepatic inflow occlusion caused no increase in tissue thermal sensitivity. This study shows that occlusion of the hepatic inflow during interstitial laser-induced thermotherapy causes a significant increase in lesion size, which could have implications for the treatment of hepatic tumors.

Animals↗

Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues.

Laser-induced fluorescence (LIF) for in vivo point monitoring and fluorescence microscopy incorporating a CCD camera were used to study the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in tumours. Fluorescence in a chemically-induced adenocarcinoma in the liver of rats and in an aggressive basal cell carcinoma in a patient were studied after intravenous injection of ALA at a dose of 30 mg/kg body weight. The LIF technique demonstrated slightly more ALA-induced PpIX fluorescence in the tumour than in the surrounding normal liver and abdominal muscle of rats. The visible parts of the human basal cell carcinoma exhibited strong ALA-induced fluorescence, while this fluorescence was much weaker in the necrotic areas of the tumour and in the surrounding normal skin.

Adenocarcinoma↗

Tumour vessel damage resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy.

This study examined tumour vessel injury resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy (PDT) in the treatment of rat liver tumours by means of scanning electron microscopy. A total of 18 Wistar rats were divided into three groups. Group I (six animals) underwent hyperthermia for 15 min (15-min hyperthermia). Group II (six animals) underwent hyperthermia for 30 min (30-min hyperthermia). Group III (six animals) received the combined treatment of PDT and 30-min hyperthermia. For PDT, delta-amino laevulinic acid at a dose of 60 mg/kg of body weight was intravenously administered 60 min before irradiation at 635 nm. The morphological results indicated that 15-min hyperthermia gave rise to an increase in permeability of the vessels in the treated tumour. Thirty-min hyperthermia caused extreme oedema of vascular endothelial cells and restrictive openings of tumour branch vessels. The combined therapy of PDT and hyperthermia destroyed tumour vasculature. Large breaks of the inner wall of the treated tumour vessels were deeply involved in the basement membrane of the vessel. The results indicate that there may be a close link between inhibition of tumour growth and degree of damage to tumour vessels.

Animals↗

Laser Doppler perfusion imaging: new technique for determination of perfusion and reperfusion of splanchnic organs and tumor tissue.

BACKGROUND AND OBJECTIVE: Several investigations indicated that laser Doppler flowmetry on the liver surface reflects relative changes of the total liver blood flow. In this study, Laser Doppler Perfusion Imaging (LDI), monitoring the surface only, was used for measurements of tissue perfusion of normal and/or impaired liver, pancreas, spleen, stomach and intestines, and the blood flow of hepatic tumors in rats. STUDY DESIGN/MATERIALS AND METHODS: Eighty Wistar/Furth rats were divided into five groups. Group I served as controls. Groups II and III underwent ischemic injury of the liver and intestine with or without the administration of WEB2170, a platelet-activating factor receptor antagonist. Laser-induced photodynamic therapy (PDT) utilizing delta-amino levulinic acid sensitization was performed in Groups IV and V. RESULTS: Normal pancreas and intestine had a high LDI perfusion value and the liver and stomach exhibited a medium perfusion value whereas the perfusion value from the spleen was low. WEB2170 improved the reperfusion of the postischemic liver and intestine. An immediate decrease in surface blood flow of hepatic tissue treated by laser-induced PDT and a decreased blood flow in large tumors were observed. CONCLUSION: LDI is a useful technique for the measurement of tissue perfusion of various splanchnic organs or tumor tissues.

Aminolevulinic Acid↗

Near infrared diffuse reflection and laser-induced fluorescence spectroscopy for myocardial tissue characterisation.

In order to evaluate the potential of cardiovascular tissue characterisation using near-infrared (NIR) spectroscopy, spectra in a previously unexplored wavelength region 0.8-2.3 micron were recorded from various pig heart tissue samples in vitro: normal myocardium (with and without endo/epicardium), aorta, fatty and fibrous heart tissue. The spectra were analysed with principal component analysis (PCA), revealing several spectroscopically characteristic features enabling tissue classification. Several of the identified spectral features could be attributed to specific tissue constituents by comparing the tissue signals with spectra obtained from water, elastin, collagen and cholesterol as well as with published data. The results obtained with the NIR spectroscopy technique in terms of its potential to classify different tissue types were compared with those from laser-induced fluorescence (LIF) using 337 nm excitation. LIF and NIR spectroscopy can in combination with PCA be used to discriminate between all previously mentioned tissue groups, apart from fatty versus fibrous tissue (LIF) and aorta versus fibrous tissue (NIR), respectively. The NIR analysis was improved by focusing the PCA to the wavelength segment 2.0-2.3 microns, resulting in successful spectral characterisation of all cardiovascular tissue groups.

Animals↗

Time-resolved white light transillumination for optical imaging.

PURPOSE: To describe a new breast-imaging method with the potential of multi-spectral optical transillumination based on a time-resolved technique. MATERIAL AND METHODS: A breast phantom was irradiated with ultra-short laser pulses of white light generated by self-phase modulation of an incident high-power laser pulse in water. Time-resolved detection of the transmitted light was performed. Contrast resolution was studied using different absorbers located inside the breast phantom. RESULTS AND CONCLUSION: The results showed that simultaneous, multi-spectral transillumination is possible. The technique can also be used for measurements of optical properties in tissue.

Breast↗

In vivo fluorescence imaging for tissue diagnostics.

Non-invasive fluorescence imaging has the potential to provide in vivo diagnostic information for many clinical specialties. Techniques have been developed over the years for simple ocular observations following UV excitation to sophisticated spectroscopic imaging using advanced equipment. Much of the impetus for research on fluorescence imaging for tissue diagnostics has come from parallel developments in photodynamic therapy of malignant lesions with fluorescent photosensitizers. However, the fluorescence of endogenous molecules (tissue autofluorescence) also plays an important role in most applications. In this paper, the possibilities of imaging tissues using fluorescence spectroscopy as a mean of tissue characterization are discussed. The various imaging techniques for extracting diagnostic information suggested in the literature are reviewed. The development of exogenous fluorophores for this purpose is also presented. Finally, the present status of clinical evaluation and future directions are discussed.

Diagnostic Imaging↗

Changes in optical properties of human whole blood in vitro due to slow heating.

Optical properties of human whole blood were investigated in vitro at 633 nm using a double integrating sphere set-up. The blood flow was maintained at a constant rate through a flow cell while continuously heating the blood at 0.2-1.1 degrees C/min from approximately 25 to 55 degrees C in a heat exchanger. A small, but rather abrupt decrease in the scattering asymmetry factor (g-factor) of 1.7 +/- 0.6% and a similar increase in the scattering coefficient of 2.9 +/- 0.6% were observed at approximately 45-46 degrees C yielding an increase in the reduced scattering coefficient of 40 +/- 10%. Furthermore, a continuous, manifest increase in the absorption coefficient was seen with increasing temperature, on average 80 +/- 70% from 25 to 50 degrees C. The effect of the heating on the blood cells was also studied under a white-light transmission microscope. A sudden change in the shape of the red blood cells, from discshaped to spherical, was observed at approximately the same temperature at which the distinct changes in g-factor and scattering coefficient were observed, i.e. at 45-46 degrees C. The results indicate that this shape transformation could explain the sudden change in scattering properties.

Blood Physiological Phenomena↗

Tissue temperature control using a water-cooled applicator: implications for transurethral laser-induced thermotherapy of benign prostatic hyperplasia.

A prototype to a water-cooled applicator to be used in transurethral laser-induced thermotherapy of benign prostatic hyperplasia was developed. The flexible applicator was made of Teflon tubes except for the distal outer part which was made of glass, providing a transparent medium for laser radiation and enabling efficient cooling of the surrounding tissue. For heating, laser light from a Nd:YAG laser emitting at 1064 nm, which was coupled into an optical fiber with an institutionally made diffusing tip, was used. Cooling was performed by flushing water through the applicator. By using a mathematical model it was possible to connect the temperature rise of the water in the applicator to the maximum tissue temperature. Tissue light absorption was calculated using Monte Carlo simulations and the heat conduction equation was solved numerically using a finite-difference technique. Experiments on porcine liver in vitro showed that the maximum tissue temperature could be estimated with an average accuracy of 0.4 degree C by measuring the difference in outlet and inlet applicator water temperature and using the thermal model. The results presented suggest that the described method for temperature control can be used during laser prostatectomy to maximize the lesion size while preventing carbonization.

Animals↗