| 1. |
- Andersson-Engels, Stefan, et al.
(författare)
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Integrated system for interstitial photodynamic therapy
- 2003
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 5142, s. 42-49
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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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| 2. |
- Andersson-Engels, Stefan, et al.
(författare)
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Integrated system for interstitial photodynamic therapy
- 2002
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Ingår i: Advanced Optical Devices, Technologies, and Medical Applications. - : SPIE. - 0277-786X .- 1996-756X. ; 5123, s. 293-302
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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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| 3. |
- deWeert, Michael J., et al.
(författare)
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Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo
- 2003
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Ingår i: Proceedings of SPIE. - : SPIE. ; 4959, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI®) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology.
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| 4. |
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| 5. |
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| 6. |
- Johansson, Ann, et al.
(författare)
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In vivo measurement of parameters of dosimetric importance during interstitial photodynamic therapy of thick skin tumors
- 2006
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Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 11
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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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| 7. |
- Johansson, Thomas, et al.
(författare)
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Feasibility study of a system for combined light dosimetry and interstitial photodynamic treatment of massive tumors
- 2002
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Ingår i: Applied Optics. - 2155-3165. ; 41:7, s. 1462-1468
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Tidskriftsartikel (refereegranskat)abstract
- A system for the photodynamic laser treatment of massive tumors that employs multiple optical fibers to be inserted into the tumor mass is described. The light flux through the tumor can be assessed by use of the individual fibers both as transmitters and as receivers. With a computer model that describes the diffusive light propagation, optical dosimetry is under development, The system has been tested in an experimental animal tumor model in preparation for clinical work. Currently, delta-aminolevulinic acid is used as a sensitizer, activated by 635-nm radiation from a 2.0-W compact diode laser system. With the availability of future, highly selective drugs absorbing approximately 750 nm, larger tumor volumes should be treatable, and surrounding, sensitive normal tissue should be spared.
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| 8. |
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| 9. |
- Pålsson, Sara, et al.
(författare)
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Methods for detailed histopathological investigation and localization of biopsies from cervix uteri to improve the interpretation of auto fluorescence data
- 2006
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Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 321-340
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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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| 10. |
- Soto Thompson, Marcelo, et al.
(författare)
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Clinical system for interstitial photodynamic therapy with combined on-line dosimetry measurements
- 2005
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Ingår i: Applied Optics. - 2155-3165. ; 44:19, s. 4023-4031
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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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| 11. |
- Soto Thompson, Marcelo, et al.
(författare)
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Photodynamic therapy and diagnostic measurements of basal cell carcinomas using esterified and non-esterified delta-aminolevulinic acid
- 2001
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Ingår i: Journal of Porphyrins and Phthalocyanines. - 1099-1409. ; 5:2, s. 147-147
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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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| 12. |
- Soto Thompson, Marcelo, et al.
(författare)
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Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery
- 2006
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Ingår i: Journal of Environmental Pathology and Toxicology. - 2162-6537. ; 25:1-2, s. 411-424
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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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| 13. |
- Soto Thompson, Marcelo
(författare)
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Photodynamic Therapy utilizing Interstitial Light Delivery Combined with Spectroscopic Methods
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since cancer continues to plague humanity there is large need for development of modalities for both diagnosis and therapy. Most of the currently available methods suffer from serious disadvantages. The treatments, e.g. ionising radiation, chemotherapy, surgery, may themselves induce malignancies or the patient may be physically impaired for a longer period of time. The work presented aims at developing equipment and methods that use light for both detection and treatment of various malignant or pre-malignant conditions. Fundamental knowledge on the interaction between light and tissue is required in order to develop models for the light distribution in tissue. Therefore, basic properties of light-tissue interaction, like refractive index, absorption, scattering, and scattering anisotropy, are introduced. How the physiological status of the tissue affects these properties are discussed. Utilizing the differences in the fluorescence spectra emitted by healthy and malignant tissues, when irradiated with visible light, it is possible to detect and delineate certain lesions. The contrast between diseased and healthy tissue can be further enhanced with the use of a fluorescence tumour marker. The evolution of these tumour markers has been fuelled by the fact that many tumour markers also can be utilized for light therapy. The modality is called photodynamic therapy (PDT) and has now been clinically approved for the treatment of several conditions. The possible indications for this type of treatment are generally limited to thin superficial lesions due to the limited penetration of the light in tissue. The work presented in this thesis mainly relates to overcoming the limited light penetration by leading the light through multiple optical fibres inserted into the tumour. In this way both embedded tumour and/or thick tumours could be an indication for this modality. In addition to that the fibres are used to collect information about relevant parameters of therapeutic interest.
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| 14. |
- Stenberg, M, et al.
(författare)
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Interstitial photodynamic therapy - diagnostic measurements and treatment in rat malignant experimental tumours
- 2000
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Ingår i: OPTICAL BIOPSY AND TISSUE OPTICS. - : SPIE. - 1996-756X .- 0277-786X. - 0819438170 ; 4161:32, s. 151-157
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Konferensbidrag (refereegranskat)abstract
- A recently developed multiple fibre system for treating malignant tumours with interstitial photodynamic therapy was used in studies on rats with colon adenocarcinoma inoculated into the muscles of the hind legs. The animals were intraperitonially administrated delta -aminolevulinic acid (ALA), which is metabolised to protoporphyrin IX (PpIX) in the tissue. The treatment system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a dosimetry programme calculating the optimal fibre position within the tumour as well as the treatment time needed to obtain a given threshold value of the light dose. One aim of the study was to compare the treatment outcome with the modelled dosimetry predictions. Tumour reduction was examined three days post treatment. A volume decrease was found in 85\% of the treated tumours. The mean volume reduction was 44\%, with one tumour completely disappearing. Histopathological examination three days post treatment showed substantial necrotic parts which, however, to a smaller extent were present also for non-treated tumours. These results indicated that the tumours have been under treated and the light dose has to be increased. Measurements of the build-up and photo-induced bleaching of PpIX using laser-induced fluorescence were also performed during the experiments.
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