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Biomedical subjects

S Svanberg

Publications and source records attributed to S Svanberg.

At least 19 recordsLinked to original sources

Time-resolved laser spectroscopy of multiply ionized atoms: natural radiative lifetimes in Ce IV.

Radiative lifetimes have been measured for two excited levels of Ce IV using the time-resolved laser-induced fluorescence technique. Ce3+ ions were produced in a laser-induced plasma. In the measurements, a suitable magnetic field was applied to reduce the recombination between electrons and the ions and thus the background light from the recombination, and special care was exercised to avoid flight-out-of-view effects on the lifetime measurements for the high-velocity ions. The experimental lifetime results, tau = 30(2) ns for the level 49 737 cm(-1) and tau = 30(3) ns for the level 52 226 cm(-1), were compared with relativistic Hartree-Fock calculations (tau = 30.5 and 30.0 ns) indicating a particularly excellent agreement.

Journal Article↗

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↗

Fluorescence diagnostics and kinetic studies in the head and neck region utilizing low-dose delta-aminolevulinic acid sensitization.

Diagnostic measurements and pharmacokinetic studies were performed in 17 patients with various kinds of malignant, premalignant and benign lesions in the head and neck region by means of point monitoring laser-induced fluorescence. For marking different types of tissue, delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used. The ALA-induced PpIX synthesis was monitored at different time intervals after oral administration of ALA in low doses, 5 and 15 mg/kg b.w. Besides the porphyrin-related signal the tissue endogenous fluorescence was also recorded. The fluorescence spectra were evaluated at two different wavelengths corresponding to the specific drug-related fluorescence peak and the endogenous tissue fluorescence emission at 635 and 490 nm, respectively. The evaluated fluorescence data were correlated to the histopathological tissue investigation. A fall-off in the overall fluorescence intensity at 490 nm was obtained for all the malignant and premalignant areas, as well as an increased red fluorescence. A ratio between the red and the blue/green fluorescence intensity was formed for each time interval after the ALA administration. The lower drug dose seems to be sufficient to obtain a useful demarcation ratio between normal and diseased tissue with a very low PpIX fluorescence intensity in the normal tissue. A PpIX fluorescence maximum seems to occur between 3 and 4 h in normal tissues, whereas malignant tumour tissue shows a higher level for a longer period of time.

Administration, Oral↗

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↗

Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source.

PURPOSE: To determine whether intense laser-produced x rays have an increased radiation hazard. MATERIALS AND METHODS: Mammalian cells were exposed to x rays from a laser-produced plasma that produced ultrahigh peak absorbed dose rates, up to a factor of 10(10) higher than those produced by conventional x rays used in imaging. The cell survival was studied as a function of the absorbed dose. The survival of mammalian cells exposed to high peak absorbed dose rates with laser-produced x rays was compared with the survival of cells exposed to standard absorbed dose rates with conventional x-ray sources. Comparative survival studies were performed by using a conventional x-ray tube and a cobalt 60 source. The absorbed doses in the irradiation field were measured with thermoluminescent dosimeters. RESULTS: Cell survival following irradiation by filtered, laser-produced x rays with a high dose rate was not markedly different from the survival following irradiation by conventional sources. There was, however, a notable difference between the survival after exposure to filtered, laser-produced x rays and the survival after exposure to unfiltered laser-produced x rays. CONCLUSION: Exposure to filtered, laser-produced x rays with a high dose rate does not lead to increased harm to mammalian cells exposed in vitro compared with the harm from exposure to x rays from conventional sources, which indicates that the use of high-power laser facilities for medical imaging is justified.

Animals↗

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↗

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↗

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-induced fluorescence studies of normal and malignant tumour tissue of rat following intravenous injection of delta-amino levulinic acid.

BACKGROUND AND OBJECTIVE: Laser-induced fluorescence was studied in normal and tumour tissue of rat after intravenous injection of delta-amino levulinic acid (ALA). The aim of the study was to investigate the protoporphyrin IX accumulation in different tissue types in rat after systemically administered ALA. STUDY DESIGN/MATERIAL AND METHODS: A malignant rat tumour and normal tissue from 13 different organs were investigated in eight rats. The rats were injected with two different ALA doses, 30 and 90 mg/kg b.w., and the investigations were performed at 10, 30 and 240 min after the injection. The fluorescence was recorded utilising an optical fibre based fluorosensor at 405 nm excitation. RESULTS: Fluorescence spectra were recorded in the 400-750 nm wavelength region including the dual-peaked PpIX fluorescence at about 635 and 705 nm, and the tissue autofluorescence peaking at about 500 nm. The maximum tumour build-up of PpIX was achieved already in less than 1 hr after ALA injection. The fluorescence demarcation between tumour and surrounding tissue was a factor of 7-8:1 after 30 min and decreased for longer retention times. The accumulation in 13 different organs was investigated and a particularly high PpIX build-up was found in stomach and intestine. CONCLUSIONS: Fluorescence detection following i.v. injection of ALA provides attractive diagnostics for the experimental tumour used, indicating clinical usefulness.

Aminolevulinic Acid↗

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↗

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.

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↗

Contrast-enhanced radiography by differential absorption, using a laser-produced x-ray source.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility of differential imaging of contrast media, with division of individual pixel values obtained from digital images generated by characteristic radiation from a laser-produced plasma, bridging the K-absorption edge of the contrast agent. METHODS: Laser pulses from an ultrashort-pulse terawatt laser system were focused onto gadolinium and tantalum targets, creating a plasma from which characteristic radiation and Bremsstrahlung was emitted. The elements of the target were selected so the characteristic emission lines of one of the elements were below the K edge of the contrast agent and the emission lines of the other element above. A phantom with gadolinium and other elements in various concentrations was examined. One radiographic exposure was made using a gadolinium target source and a subsequent exposure using a tantalum source. Both images were recorded digitally and the transmission ratios calculated by division of the individual pixel values. RESULTS: When viewed separately, the two images of the test phantom appeared similar. In the differential image, only the gadolinium solutions were bright, reflecting a difference in attenuation between the two exposures. CONCLUSIONS: Element-specific radiographs can be obtained by differential imaging. When fully explored, the technique may allow for contrast-enhanced radiography with increased sensitivity and decreased contrast dose.

Animals↗