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Sökning: WFRF:(Bendsöe Niels)

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2.
  • Andersson-Engels, Stefan, et al. (författare)
  • Integrated system for interstitial photodynamic therapy
  • 2003
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 5142, s. 42-49
  • Konferensbidrag (refereegranskat)abstract
    • A novel photodynamic therapy system based on interstitial illumination using multiple fibres is under development. The aim with this system is to enable treatment of large tumour volumes and also to utilise real-time measurements to allow on-line dosimetry. Important dosimetric parameters to measure are light fluence rate, sensitizer fluorescence intensity and local blood oxygenation. A construction which allows all functions to be readily performed with a single system is presented. We believe that interstitial PDT utilising this technique may be attractive in many clinical situations.
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3.
  • Andersson-Engels, Stefan, et al. (författare)
  • Integrated system for interstitial photodynamic therapy
  • 2002
  • Ingår i: Advanced Optical Devices, Technologies, and Medical Applications. - : SPIE. - 0277-786X .- 1996-756X. ; 5123, s. 293-302
  • Konferensbidrag (refereegranskat)abstract
    • To develop PDT beyond treatment of thin superficial tumours, to also be an efficient treatment alternative for deeply located and/or thick tumours, a system based on interstitial illumination using multiple fibres has been developed. Conditions that could benefit from such a treatment modality are for instance malignant brain tumours and tumours in the oral cavity. In interstitial PDT one needs to use multiple fibres for light delivery in order to allow treatments of tumours larger than a few millimetres in diameter. Our system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a custom-made dosimetry programme. The concept is then to use these fibres not only for delivering the treatment light but also to measure parameters of interest for the treatment outcome. The fluence rate of the light emitted by each fibre is measured at the positions of the other fibre tips. From these results the light dose at all positions could be recalculated. Changes in optical properties as well as bleaching and concentration of the photosensitizer during the treatment could be monitored and compensated for in the dosimetry. Tumours have been treated both in experimental studies and in patients with thick superficial Basal Cell Carcinomas. Almost all treated skin lesions responded with complete response.
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4.
  • Bendsöe, Niels (författare)
  • Characterization of a new amino acid transport system in human epidermal Langerhans cells
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Based on the discovery of a new amino acid transport system in Langerhans cells (LC), various aspects concerning the L-dopa uptake mechanism into human epidermal LC and the energy metabolism of epidermis have been examined and subsequently characterised. The system lacks any characteristics of other described amino acid transport systems in other cell types. The Falck/Hillarp histofluorescence method was used, studying uptake in individual LC in situ in their microenvironment. For the first time, experiments showed that, despite the formal presence of mitochondria, the human epidermis is capable of an aerobic lactate production, probably dependent on a disturbed Pasteur effect. It was also proved that human epidermis has a lower energy charge value than other body cells, apart from smooth muscle cells. Increased lactate production in epidermis, which can be inhibited by iodoacetate, implies an increased intracellular proton production. The energetics of the L-dopa transport into LC is probably a countertransport (antiport) of protons due to aerobic production of lactate. Further experiments showed that L-dopa can be dislocated out of LC by certain amino acids on the outside of the cells, either acting in a trans-stimulatory fashion or by exchanging with intracellular L-dopa, getting “useful” amino acids into the cells. This, now extracellular L-dopa, can begin a new in- and out-transport cycle. Using a H+,K+-ATPase-inhibitor (omeprazole and some analogues), experiments showed that most of these inhibit the L-dopa transport into LC, probably not caused by affecting a thiol group essential for this transport. The actual mechanism is unknown.
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6.
  • Bendsöe, Niels, et al. (författare)
  • Inflammatory reactions from organic pigments in red tattoos
  • 1991
  • Ingår i: Acta Dermato-Venereologica. - 1651-2057. ; 71:1, s. 70-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Two different red pigments used for tattooing were found to give rise to inflammatory reactions in the skin. No inorganic component was found in the pigments. NMR and MS analyses elucidated the molecular structures of two different organic compounds. A bright red pigment was found to be an aromatic azo-derivative, and a red-violet pigment was found to be linear quinacridone. A strong exposure to UV-light was reported in most cases prior to the onset of the inflammation.
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7.
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8.
  • Brydegaard, Mikkel, et al. (författare)
  • Complete parameterization of temporally and spectrally resolved laser induced fluorescence data with applications in bio-photonics
  • 2015
  • Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439. ; 142, s. 95-106
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a set of spectrally and temporally resolved clinical fluorescence data-with two separate excitation wavelengths-that was recorded in vivo. We demonstrate that data in the spectral and temporal domains are in certain ways coupled and provide a method for integrated and effective parameterization of spectrally and temporally resolved fluorescence (i.e., time-resolved emission spectra). This parameterization is based on linear algebra, matrix formulation and system identification. We demonstrate how to empirically extract single exponentially decaying components and provide rectified emission spectra without prior knowledge. We investigate the potential for improved cancer diagnostics according to the reduced parameters along the various domains. In this case, in terms of cancer diagnostics, we were unable to identify any benefits of simultaneously measuring both the temporal and spectral properties of the observed fluorescence. However, we note that this may be explained by an important experimental bias present in many studies of optical cancer diagnostics, namely, that, in general, suspected lesions always differ visually from the neighboring healthy tissue. (C) 2015 Elsevier B.V. All rights reserved.
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9.
  • Cheng, Haynes P. H., et al. (författare)
  • Autofluorescence of pigmented skin lesions using a pulsed UV laser
  • 2010
  • Ingår i: Proceedings of SPIE. - : SPIE. ; 7715, s. 1-77151
  • Konferensbidrag (refereegranskat)abstract
    • We report preliminary clinical results of autofluorescence imaging of malignant and benign skin lesions, using pulsed 355 nm laser excitation with synchronized detection. The novel synchronized detection system allows high signal-tonoise ratio to be achieved in the resulting autofluorescence signal, which may in turn produce high contrast images that improve diagnosis, even in the presence of ambient room light. The synchronized set-up utilizes a compact, diode pumped, pulsed UV laser at 355 nm which is coupled to a CCD camera and a liquid crystal tunable filter. The excitation and image capture is sampled at 5 kHz and the resulting autofluorescence is captured with the liquid crystal filter cycling through seven wavelengths between 420 nm and 580 nm. The clinical study targets pigmented skin lesions and evaluates the prospects of using autofluorescence as a possible means in differentiating malignant and benign skin tumors. Up to now, sixteen patients have participated in the clinical study. The autofluorescence images, averaged over the exposure time of one second, will be presented along with histopathological results. Initial survey of the images show good contrast and diagnostic results show promising agreement based on the histopathological results.
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10.
  • Enejder, Annika M K, et al. (författare)
  • Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic- and cryo therapy employing laser-Doppler imaging
  • 2000
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 80:1, s. 19-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Superficial blood perfusion mas monitored using laser-Doppler perfusion imaging in connection with a phase LII clinical trial comparing photodynamic therapy, utilizing topically applied aminoleuvlinic acid, with cryotherapy of basal cell, carcinomas. A total of 526 images mere recorded before and immediately after the treatment and during the follow-up period. Before treatment, the lesions exhibited a blood perfusion 3+/-2 times that in normal tissue. Both treatment modalities induced an increased blood perfusion inside the lesions, which slowly approached normal values in conjunction with successful treatments. The blood perfusion in successfully treated lesions approached normal values 2 months after photodynamic therapy, and about 1 year after cryotherapy, The tissue perfusion in recurrent lesions did not decrease to normal values after the treatment, suggesting that the laser-Doppler perfusion imaging technique can be used to follow the healing process and discover possible persistent tumour growth.
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12.
  • Falck, Bengt, et al. (författare)
  • New mechanism for amino acid influx into human epidermal Langerhans cells: L-dopa/proton counter-transport system.
  • 2003
  • Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 12:5, s. 602-609
  • Tidskriftsartikel (refereegranskat)abstract
    • We have characterized a stereospecific transport mechanism for L-dopa into human epidermal Langerhans cells (LCs). It is different from any other amino acid transport system. It is highly concentrative, largely pH-independent, and independent of exogenous Na+, glucose and oxygen, and fuelled by a renewable intracellular energy source inhibited by iodoacetate but not by arsenate. We propose that the mechanism is a unidirectional L-dopa/proton counter-transport system. We have recently demonstrated anaerobic glycolysis in human epidermis, which substantiates the need of proton pumps for resident LCs. The findings prompt a re-evaluation of the profound changes LCs undergo when exposed to oxygen in aerobic culture. L-dopa is not metabolized by LCs but can rapidly be dislocated to the intercellular space by certain extracellular amino acids, i.e. LCs can profit by L-dopa in a dualistic way, altogether a remarkable biological phenomenon.
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13.
  • Jensen, LK, et al. (författare)
  • Optical coherence tomography in clinical examination of non-pigmented skin malignancies
  • 2003
  • Ingår i: OPTICAL COHERENCE TOMOGRAPHY AND COHERENCE TECHNIQUES. - : SPIE. - 0277-786X .- 1996-756X. - 0819450103 ; 5140, s. 160-160
  • Konferensbidrag (refereegranskat)abstract
    • Optical coherence tomography (OCT) images of basal cell carcinomas (BCCs) have been acquired using a compact handheld probe with an integrated video camera allowing the OCT images to be correlated to a skin surface image. In general the healthy tissue of the skin has an obvious stratified structure, whereas the cancerous tissue shows a more homogenous structure. Thus it was demonstrated that it is possible to distinguish BCCs from healthy tissue by means of OCT. Furthermore different histological types of BCC were identified. Comparison of OCT images taken prior to and immediately after photodynamic therapy clearly shows the tissue response to the treatment, and indicates local oedema in the treated area.
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14.
  • Johansson, Ann, et al. (författare)
  • Fluorescence and absorption assessment of a lipid mTHPC formulation following topical application in a non-melanotic skin tumor model.
  • 2007
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 12:3, s. 034026-034026
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the benefits of topical sensitizer administration have been confirmed for photodynamic therapy (PDT) ALA-induced, protoporphyrin IX is the only sensitizer clinically used with this administration route. Unfortunately, ALA-PDT results in poor treatment response for thicker lesions. Here, selectivity and depth distribution of the highly potent sensitizer meso-tetra(hydroxyphenyl)chlorin (mTHPC), supplied in a novel liposome formulation was investigated following topical administration for 4 and 6 h in a murine skin tumor model. Extraction data indicated an average [standard deviation (SD)] mTHPC concentration within lesions of 6.0(+/- 3.1) ng/mg tissue with no significant difference (p<0.05) between 4- and 6-h application times and undetectable levels of generalized photosensitivity. Absorption spectroscopy and chemical extraction both indicated a significant selectivity between lesion and normal surrounding skin at 4 and 6 h, whereas the more sensitive fluorescence imaging setup revealed significant selectivity only for the 4-h application time. Absorption data showed a significant correlation with extraction, whereas the results from the fluorescence imaging setup did not correlate with the other methods. Our results indicate that this sensitizer formulation and administration path could be interesting for topical mTHPC-PDT, decreasing the effects of extended skin photosensitivity associated with systemic mTHPC administration. (C) 2007 Society of Photo-Optical instrumentation Engineers.
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15.
  • Johansson, Ann, et al. (författare)
  • In vivo measurement of parameters of dosimetric importance during interstitial photodynamic therapy of thick skin tumors
  • 2006
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • A system for interstitial photodynamic therapy is used in the treatment of thick skin tumors. The system allows simultaneous measurements of light fluence rate, sensitizer fluorescence, and tissue oxygen saturation by using the same fibers as for therapeutic light delivery. Results from ten tumor treatments using delta-aminolevulinic acid (ALA)-induced protoporphyrin IX show a significant, treatment-induced increase in tissue absorption at the therapeutic wavelength, and rapid sensitizer photobleaching. The changes in oxy- and deoxyhemoglobin content are monitored by means of near-infrared spectroscopy, revealing a varying tissue oxygenation and significant changes in blood volume during treatment. These changes are consistent with the temporal profiles of the light fluence rate at the therapeutic wavelength actually measured. We therefore propose the observed absorption increase to be due to treatment-induced deoxygenation in combination with changes in blood concentration within the treated volume. A higher rate of initial photobleaching is found to correlate with a less pronounced increase in tissue absorption. Based on the measured signals, we propose how real-time treatment supervision and feedback can be implemented. Simultaneous study of the fluence rate, sensitizer fluorescence, and local tissue oxygen saturation level may contribute to the understanding of the threshold dose for photodynamic therapy. (c) 2006 Society of Photo-Optical Instrumentation Engineers.
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16.
  • Johansson, Ann, et al. (författare)
  • Influence of treatment-induced changes in tussue absorption on treatment volume during interstitial photodynamic therapy
  • 2006
  • Ingår i: Medical Laser Application. - : Elsevier BV. - 1615-1615. ; 21, s. 261-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Interstitial photodynamic therapy on thick skin lesions has been shown to induce changes in tissue light transmission as a direct consequence of variations in total blood volume and oxygen saturation. A finite element method was used in order to simulate the fluence rate distribution and total light dose throughout the target tissue for two cases. The first case constitutes a pre-treatment model where the tissue optical properties are assumed constant during the entire treatment. The second situation takes into account observed changes in tissue light transmission, small deviations in fiber insertion depth and a few cases of almost complete loss of source fiber output power possibly as a result of blood accumulation in front of the fiber tip. The pre- and post-treatment models from six clinical treatments are compared in terms of simulated treatment volumes. We conclude that real-time monitoring of the delivered fluence is necessary in order to ascertain a pre-determined light dose to the target tissue. Finally, we speculate on how to also include the sensitizer fluorescence level and tissue oxygenation in the real-time treatment feedback.
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17.
  • Johansson, Ann, et al. (författare)
  • Interstitial photodynamic therapy for primary prostate cancer incorporating realtime treatment dosimetry
  • 2007
  • Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1042-4687 .- 1605-7422. ; 6427, s. 4270-4270
  • Konferensbidrag (refereegranskat)abstract
    • Photodynamic therapy (PDT) for the treatment of prostate cancer has been demonstrated to be a safe treatment option capable of inducing tissue necrosis and decrease in prostate specific antigen (PSA). Research groups report on large variations in treatment response, possibly due to biological variations in tissue composition and shortterm response to the therapeutic irradiation. Within our group, an instrument for interstitial PDT on prostate tissue that incorporates realtime treatment feedback is being developed. The treatment protocol consists of two parts. The first part incorporates the pre-treatment plan with ultrasound investigations, providing the geometry for the prostate gland and surrounding risk organs, an iterative random-search algorithm to determine near-optimal fiber positions within the reconstructed geometry and a Block-Cimmino optimization algorithm for predicting individual fiber irradiation times. During the second part, the therapeutic light delivery is combined with measurements of the light transmission signals between the optical fibers, thus monitoring the tissue effective attenuation coefficient by means of spatially resolved spectroscopy. These data are then used as input for repeated runs of the Block-Cimmino optimization algorithm. Thus, the irradiation times for individual fibers are updated throughout the treatment in order to compensate for the influence of changes in tissue composition on the light distribution at the therapeutic wavelength.
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18.
  • Johansson, Ann, et al. (författare)
  • mTHPC pharmacokinetics following topical administration
  • 2006
  • Ingår i: Optical Diagnostics and Sensing VI. - : SPIE. - 1996-756X .- 0277-786X. ; 6094, s. 940-940
  • Konferensbidrag (refereegranskat)abstract
    • Measurements of concentration of sensitizers for photodynamic therapy can provide important information in the dosimetry planning and can also give input to the optimal time for treatment. There has been skepticism towards fluorescence techniques for this purpose, as the signal depends on the fluorescence yield and optical properties of the tissue. Absorption based techniques, lack on the other hand, often the sensitivity required for many sensitizers with relative weak absorption in a wavelength region where hemoglobin absorption is dominant. A direct comparison between absorption and fluorescence techniques for measuring mTHPC concentration after topical application on hairless SKH-1 mice bearing skin carcinomas has been performed. 20 μl/cm2 of m-THPC thermogel (0.5 mg m-THPC/ml) were applied on normal and tumor area and the concentration of mTHPC was measured at 4 and 6 hours after drug application by two methods: 1. A fluorescence imaging system capturing images at two wavelengths (500 and 650 nm) following 405 nm excitation. Signals from different regions of interest were averaged and the intensity ratio at 650 to 500 was calculated. 2. A diffuse reflectance spectroscopy system with a fiber separation of 2 mm, providing the absorbance at 652 nm. Both systems provided consistent results related to the photosensitizer concentration. The methods show a remarkable difference in the concentration of photosensitizer in normal skin and tumor. No significant difference in mTHPC concentration in tumor could be observed between the 4 and 6h groups after drug application.
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19.
  • Johansson, Ann, et al. (författare)
  • System for integrated interstitial photodynamic therapy and dosimetric monitoring
  • 2005
  • Ingår i: Proceedings of the SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 5689:1, s. 130-140
  • Konferensbidrag (refereegranskat)abstract
    • Photodynamic therapy for the treatment of cancer relies on the presence of light, sensitizer and oxygen. By monitoring these three parameters during the treatment a better understanding and treatment control could possibly be achieved. Here we present data from in vivo treatments of solid skin tumors using an instrument for interstitial photodynamic therapy with integrated dosimetric monitoring. By using intra-tumoral ALA-administration and interstitial light delivery solid tumors are targeted. The same fibers are used for measuring the fluence rate at the treatment wavelength, the sensitizer fluorescence and the local blood oxygen saturation during the treatment. The data presented is based on 10 treatments in 8 patients with thick basal cell carcinomas. The fluence rate measurements at 635 nm indicate a major treatment induced absorption increase, leading to a limited light penetration at the treatment wavelength. This leads to a far from optimal treatment since the absorption increase prevents peripheral tumor regions from being fully treated. An interactive treatment has been implemented assisting the physician in delivering the correct light dose. The absorption increase can be compensated for by either prolonging the treatment time or increasing the output power of each individual treatment fiber. The other parameters of importance, i.e. the sensitizer fluorescence at 705 nm and the local blood oxygen saturation, are monitored in order to get an estimate of the amount of photobleaching and oxygen consumption. Based on the oxygen saturation signal, a fractionized irradiation can be introduced in order to allow for a re-oxygenation of the tissue
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23.
  • Pålsson, Sara, et al. (författare)
  • Methods for detailed histopathological investigation and localization of biopsies from cervix uteri to improve the interpretation of auto fluorescence data
  • 2006
  • Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 321-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Fluorescence spectroscopy is one of many optical methods that are potentially clinically useful for noninvasive detection and characterization of disorders on the cervical part of uterus, including precancerous lesions. The cervix uteri exhibits a biologically complex tissue and the morphology of a biopsy is generally not homogenous. The standard histopathological protocol accounts only for the most severe condition found within the biopsy and no information is given on other constituents potentially influencing the recorded fluorescence spectra. Spectra are usually correlated, using multivariate techniques, to the histopathological diagnosis of the biopsies. Since the probe volume of fluorescence spectroscopy is considerably smaller than the extension of the biopsy, this can cause problems in the search for correlation between the fluorescence signals and the pathological structures. In addition, the orientation and location of the biopsies are normally not recorded. We now report on the first detailed histopathological protocol where numerous tissue parameters, such as thickness and type of the epithelium and the number of blood vessels, glands, and inflammatory cells, are tabulated and the orientation and location of the biopsy are recorded as precisely as possible. Hopefully, the use of this protocol together with sophisticated mathematical methods will increase the probability to classify cervical disorders of the uterus, including precancerous lesions, with high sensitivity and specificity.
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24.
  • Ronquist, G, et al. (författare)
  • Human epidermal energy metabolism is functionally anaerobic
  • 2003
  • Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 12:5, s. 572-579
  • Tidskriftsartikel (refereegranskat)abstract
    • We have reported that epidermal Langerhans cells possess an H+-extruding mechanism signalling their existence in an anaerobic environment. This study highlights the energy metabolism of human epidermis. In their habitual state the keratinocytes contain more lactate than do most other cell types. Their lactate production in vitro is vigorous and independent of oxygen and most of it is released to the medium. Autoincubation of the epidermis under starved conditions resulted in a 30% increase of lactate, indicating ongoing glycogenolysis. Iodoacetate inhibited lactate production by > 90%. Energy charge values were low, approximately 0.82, and comparable with those previously reported for smooth muscle. Moreover, the overwhelming majority of the keratinocytic mitochondria had an appearance markedly deviating from those in the Langerhans cells, melanocytes and fibroblasts, and, above all, were characterized by an enormous reduction of the inner membrane. This structure is in all probability incompatible with an effective oxidative metabolism of glucose. We conclude that epidermal energy metabolism is predominantly anaerobic in spite of the formal presence of mitochondria. The high production of lactate obviously demands extracellular transport pathways for rapid elimination of this organic acid. An extracellular space complying with such a demand emerges on electron microscopy when an isotonic glutaraldehyde-based fixative is used. The prevailing view regarding the size of the extracellular space is based on the common use of hypotonic fixatives, such as Karnovski's fixative, which causes gross cellular swelling and concomitant near total elimination of the extracellular space, leaving interstices with a diameter significantly smaller than that allowing fluid flow.
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25.
  • Soto Thompson, Marcelo, et al. (författare)
  • Clinical system for interstitial photodynamic therapy with combined on-line dosimetry measurements
  • 2005
  • Ingår i: Applied Optics. - 2155-3165. ; 44:19, s. 4023-4031
  • Tidskriftsartikel (refereegranskat)abstract
    • A system for interstitial photodynamic therapy with delta-aminolaevulinic acid and multiple optical fibers has been developed. The system enables photodynamic treatment of large embedded tumor volumes and utilizes real-time measurements to allow on-line dosimetry. Important parameters such as light fluence rate, sensitizer fluorescence intensity, and changes in local blood oxygen saturation are measured with the same fibers that deliver the therapeutic light. Data from the first clinical treatments on nodular basal cell carcinomas indicate a major treatment-induced light absorption increase, rapid sensitizer photo-bleaching, and a relatively constant global tissue oxygen saturation level during the treatment.
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26.
  • Soto Thompson, Marcelo, et al. (författare)
  • Photodynamic therapy and diagnostic measurements of basal cell carcinomas using esterified and non-esterified delta-aminolevulinic acid
  • 2001
  • Ingår i: Journal of Porphyrins and Phthalocyanines. - 1099-1409. ; 5:2, s. 147-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Various optical techniques were used to investigate relevant parameters involved in photodynamic therapy (PDT) of human basal cell carcinomas (BCCs). The aim of the study was to compare the diagnostic and therapeutic outcome when using topically applied methyl-esterified delta -aminolevulinic acid (ALA-ME) and delta -aminolevulinic acid (ALA). A total of 35 pathologically verified BCCs in 14 patients were investigated. A diode laser. emitting continuous light at 633 nm, was used to induce PDT. The diagnostic measurements were performed before, during, and after PDT. Laser-induced fluorescence (LIF) was used to monitor the build-up of the ALA/ALA-ME-induced protoporphyrin IX (PpIX), The superficial tissue perfusion was measured with laser-Doppler perfusion imaging (LDPI) and the temperature of the lesion and the surrounding tissue was imaged with an IR-camera. A clear demarcation between the lesion and the normal skin was detected with LIF before the treatment for both PpIX precursors. The fluorescence measurements suggest that PpIX builds up to a higher degree and more selectively in the tumour following ALA-ME as compared to ALA. The LDPI measurements indicate a local transient restriction in blood perfusion immediately post-PDT. The measurement with the IR-camera revealed a temperature rise of about 1-2 degreesC during the treatment.
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27.
  • Soto Thompson, Marcelo, et al. (författare)
  • Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery
  • 2006
  • Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 411-424
  • Tidskriftsartikel (refereegranskat)abstract
    • To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.
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28.
  • Sterenborg, Henricus J. C. M., et al. (författare)
  • Clinical Biophotonics
  • 2011
  • Ingår i: Journal of Biophotonics. - : Wiley. - 1864-063X. ; 4:10, s. 665-666
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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29.
  • Svanberg, Katarina, et al. (författare)
  • Photodynamic therapy: superficial and interstitial illumination.
  • 2010
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Photodynamic therapy (PDT) is reviewed using the treatment of skin tumors as an example of superficial lesions and prostate cancer as an example of deep-lying lesions requiring interstitial intervention. These two applications are among the most commonly studied in oncological PDT, and illustrate well the different challenges facing the two modalities of PDT-superficial and interstitial. They thus serve as good examples to illustrate the entire field of PDT in oncology. PDT is discussed based on the Lund University group's over 20 yr of experience in the field. In particular, the interplay between optical diagnostics and dosimetry and the delivery of the therapeutic light dose are highlighted. An interactive multiple-fiber interstitial procedure to deliver the required therapeutic dose based on the assessment of light fluence rate and sensitizer concentration and oxygen level throughout the tumor is presented.
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30.
  • Svensson, Jenny, et al. (författare)
  • Multispectral fluorescence imaging for tumor detection and molecular biology
  • 2006
  • Ingår i: 2006 IEEE LEOS Annual Meeting Conference. - 0780395557 ; , s. 227-228
  • Konferensbidrag (refereegranskat)abstract
    • The use of a multispectral imaging system provides possibilities to map all information encoded in the spectral fingerprint of an exogenous or endogenous chromophore in biological media. The spectral information has been used to demarcate the spatial extent of superficial skin tumours. Monitoring the fluorescence emitted from the photosensitizer over time yield information about the photodynamic treatment progression. The multispectral approach will also enable depth estimation of a lesion and thus allow quantitative measurements of a fluorophore as shown by the results presented
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31.
  • Svensson, Jenny, et al. (författare)
  • Pharmacokinetic study of a systemically administered novel liposomal Temoporfin formulation in an animal tumor model
  • 2007
  • Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE. - 1605-7422 .- 1042-4687. ; 6427, s. 4270-4270
  • Konferensbidrag (refereegranskat)abstract
    • Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (international generic name Temoporfin) is a potent photosensitizer used for photodynamic therapy (PDT). In this study the pharmacokinetics of a systemically administered novel lipid formulation of Temoporfin in a murine tumor model has been investigated. Fluorescence spectroscopy measurements were performed at several time intervals following drug administration, yielding information on the Temoporfin concentration within excised internal organs as a function of time after injection. Both point-monitoring and imaging setups were used. The acquired fluorescence data were correlated to the concentration of Temoporfin obtained with High Performance Liquid Chromatography (HPLC). There was a significant correlation between the fluorescence methods and HPLC for most organs investigated. The pharmacokinetics of this new liposomal formulation of Temoporfin exhibited a rather flat temporal profile in the time interval 2-8 hours in this study.
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32.
  • Thompson, Alex, et al. (författare)
  • Hyperspectral fluorescence lifetime fibre probe spectroscopy for use in the study and diagnosis of osteoarthritis and skin cancer
  • 2011
  • Ingår i: Optical Biopsy IX. - : SPIE. - 1605-7422. - 9780819484321 ; 7895
  • Konferensbidrag (refereegranskat)abstract
    • We present the application of two fibre-optic-coupled time-resolved spectrofluorometers and a compact steady-state diffuse reflected light/fluorescence spectrometer to in vivo and ex vivo studies of skin cancer and osteoarthritis. In a clinical study of skin cancer, 27 lesions on 25 patients were investigated in vivo before surgical excision of the region measured. Preliminary analysis reveals a statistically significant decrease in the autofluorescence lifetime of basal cell carcinomas compared to neighbouring healthy tissue. A study of autofluorescence signals associated with the onset of osteoarthritis indicates autofluorescence lifetime changes associated with collagen degradation.
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33.
  • Thompson, Alex J., et al. (författare)
  • In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas
  • 2012
  • Ingår i: Journal of Biophotonics. - : Wiley. - 1864-063X. ; 5:3, s. 240-254
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • We present a clinical investigation of diffuse reflectance and time-resolved autofluorescence spectra of skin cancer with an emphasis on basal cell carcinoma. A total of 25 patients were measured using a compact steady-state diffuse reflectance/fluorescence spectrometer and a fibre-optic-coupled multispectral time-resolved spectrofluorometer. Measurements were performed in vivo prior to surgical excision of the investigated region. Singular value decomposition was used to reduce the dimensionality of steady state diffuse reflectance and fluorescence spectra. Linear discriminant analysis was then applied to the measurements of basal cell carcinomas (BCCs) and used to predict the tissue disease state with a leave-one-out methodology. This approach was able to correctly diagnose 87% of the BCCs. With 445 nm excitation a decrease in the spectrally averaged fluorescence lifetime was observed between normal tissue and BCC lesions with a mean value of 886 ps. Furthermore, the fluorescence lifetime for BCCs was lower than that of the surrounding healthy tissue in all cases and statistical analysis of the data revealed that this decrease was significant (p = 0.002). (C) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
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34.
  • Thomsen, J, et al. (författare)
  • Optical Doppler tomography for monitoring vascularization during photodynamic therapy of skin cancer lesions
  • 2008
  • Ingår i: BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE. - : SPIE. - 1996-756X .- 0277-786X. - 9780819471895 ; 6991
  • Konferensbidrag (refereegranskat)abstract
    • We investigate vascular changes during Photodynamic therapy (PDT) of skin tumors using optical Doppler tomography (ODT). The effect of vascular shut down on tumor destruction is currently not known, and to optimize treatment it is relevant to investigate this issue further. Optical Doppler tomography is capable of measuring blood flow in biological tissue down to 1-2 mm with sub-mm/s velocity sensitivity and micrometer spatial resolution making it suitable for blood flow measurements in the skin. We demonstrate the ability of detecting blood flow in the human skin using non-interstitial ODT to preserve the non-invasiveness. In general a very limited blood flow activity was observed in normal skin and around skin tumors making monitoring of changes difficult. We suggest solutions to a number of practical issues such as sampling errors and natural fluctuations in flow activity for future work.
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35.
  • Vogler, Nadine, et al. (författare)
  • Multimodal imaging to study the morphochemistry of basal cell carcinoma
  • 2010
  • Ingår i: Journal of Biophotonics. - : Wiley. - 1864-063X. ; 3:10-11, s. 728-736
  • Tidskriftsartikel (refereegranskat)abstract
    • Basal cell carcinoma is the most abundant malignant neoplasm in humans, the pathology of which is characterized by an abnormal proliferation of basal cells. Basal cell carcinoma can show a variety of different morphologies, which are based on different cellular biology. Furthermore, the carcinoma often grows invisibly to the eye imbedded in the surrounding skin. Therefore, in some cases its clinical detection is challenging. Thus, our work aims at establishing an unsupervised tissue classification method based on multimodal imaging and the application of chemometrics to discriminate basal cell carcinoma from non-diseased tissue. A case study applying multimodal imaging to ex-vivo sections of basal cell carcinoma is presented. In doing so, we apply a combination of various linear and non-linear imaging modalities, i.e. fluorescence, Raman and second-harmonic generation microscopy, to study the morphochemistry of basal cell carcinoma. The joint information content obtained by such multimodal approach in studying various aspects of the malignant tissue alterations associated with basal cell carcinoma is discussed. [GRAPHICS] Multimodal imaging combining coherent anti-Stokes Raman scattering, second-harmonic generation and two-photo fluorescence is combined with Raman spectroscopy to investigate the morphochemistry of human basal cell carcinoma.
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36.
  • Wang, I., et al. (författare)
  • Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial
  • 2001
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 144:4, s. 832-840
  • Tidskriftsartikel (refereegranskat)abstract
    • 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, ISLA-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.
  •  
37.
  • Xie, Haiyan, et al. (författare)
  • Design and validation of a fiber optic point probe instrument for therapy guidance and monitoring
  • 2014
  • Ingår i: Journal of Biomedical Optics. - 1083-3668. ; 19:7, s. 11-071408
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in Undetermined ABSTRACT. Optical techniques for tissue diagnostics currently are experiencing tremendous growth in biomedical applications, mainly due to their noninvasive, inexpensive, and real-time functionality. Here, we demonstrate a hand-held fiber optic probe instrument based on fluorescence/reflectance spectroscopy for precise tumor delineation. It is mainly aimed for brain tumor resection guidance with clinical adaptation to minimize the disruption of the standard surgical workflow and is meant as a complement to the state-of-the-art fluorescence surgical microscopy technique. Multiple light sources with fast pulse modulation and detection enable precise quantification of protoporphyrin IX (PpIX), tissue optical properties, and ambient light suppression. Laboratory measurements show the system is insensitive to strong ambient light. Validation measurements of tissue phantoms using nonlinear least squares support vector machines (LS-SVM) regression analysis demonstrate an error of <5% for PpIX concentration ranging from 400 to 1000 nM, even in the presence of large variations in phantom optical properties. The mean error is 3% for reduced scattering coefficient and 5% for blood concentration. Diagnostic precision of 100% was obtained by LS-SVM classification for in vivo skin tumors with topically applied 5-aminolevulinic acid during photodynamic therapy. The probe could easily be generalized to other tissue types and fluorophores for therapy guidance and monitoring.
  •  
38.
  • Xie, Haiyan, et al. (författare)
  • Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations.
  • 2011
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate quantification of photosensitizers is in many cases a critical issue in photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging has attracted particular interest for quantification in pre-clinical research. However, due to the absorption of excitation and emission light by turbid media, such as biological tissue, the detected fluorescence signal does not have a simple and unique dependence on the fluorophore concentration for different tissues, but depends in a complex way on other parameters as well. For this reason, little has been done on drug quantification in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law. This method shows that the corrected fluorescence intensity is almost proportional to the absolute fluorophore concentration. The results on controllable tissue phantoms and murine tissues are presented and show good correlations between the evaluated fluorescence intensities after the light-absorption correction and absolute fluorophore concentrations. These results suggest that the technique potentially provides the means to quantify the fluorophore concentration from fluorescence images.
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39.
  • Xie, Haiyan, et al. (författare)
  • Pharmacokinetic and biodistribution study following systemic administration of Fospeg - a Pegylated liposomal mTHPC formulation in a murine model
  • 2015
  • Ingår i: Journal of Biophotonics. - : Wiley. - 1864-063X. ; 8:1-2, s. 142-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in Undetermined Fospeg® is a newly developed photosensitizer formulation based on meso-tetra(hydroxyphenyl)chlorin (mTHPC), with hydrophilic liposomes to carry the hydrophobic photosensitizer to the target tissue. In this study the pharmacokinetics and biodistribution of Fospeg® were investigated by high performance liquid chromatography at various times (0.5-18 hours) following systemic i.v. administration. As a model an experimental HT29 colon tumor in NMRI nu/nu mice was employed. Our study indicates a higher plasma peak concentration, a longer circulation time and a better tumor-to-skin ratio than those of Foslip®, another liposomal mTHPC formulation. Data from ex vivo tissue fluorescence and reflectance imaging exhibit good correlation with chemical extraction. Our results have shown that optical imaging provides the potential for fluorophore quantification in biological tissues. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
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