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Optical spectroscopy in biomedicine - detection of embedded inclusions and in vivo pharmacokinetics

Svensson, Jenny LU (2007) In Lund Reports in Atomic Physics LRAP-374.
Abstract (Swedish)
Popular Abstract in Swedish

Denna avhandling beskriver hur fluorescens kan användas inom biomedicinområdet. Fluorescens är ett fenomen, som uppstår när molekyler absorberar inkommande ljus och sedan återutsänder ljus som har längre våglängd än det inkommande ljuset, och därför lägre energi, då en del av det absorberade ljuset omvandlats till värme i det omkringliggande mediet. I mänsklig vävnad finns flera olika molekyler, så kallade fluoroforer, som kan absorbera ljus och skapa fluorescens.



Arbetet som denna avhandling bygger på kan delas in i tre delar, där varje del innefattar mätning och analys av fluorescensljus som genererats.



Den första delen behandlar möjligheten att bestämma... (More)
Popular Abstract in Swedish

Denna avhandling beskriver hur fluorescens kan användas inom biomedicinområdet. Fluorescens är ett fenomen, som uppstår när molekyler absorberar inkommande ljus och sedan återutsänder ljus som har längre våglängd än det inkommande ljuset, och därför lägre energi, då en del av det absorberade ljuset omvandlats till värme i det omkringliggande mediet. I mänsklig vävnad finns flera olika molekyler, så kallade fluoroforer, som kan absorbera ljus och skapa fluorescens.



Arbetet som denna avhandling bygger på kan delas in i tre delar, där varje del innefattar mätning och analys av fluorescensljus som genererats.



Den första delen behandlar möjligheten att bestämma djupet av ett fluorescerande objekt som befinner sig någonstans under ytan i ett spridande material. Fluorescensljuset, som sänds ut från det fluorescerande objektet, kommer att dämpas medan det färdas från objektet till ytan, där ljuset kan detekteras. Dämpningen uppkommer då vävnaden både sprider och absorberar ljus. Fluorescensen vid olika våglängder kommer att dämpas olika mycket då både spridning och absorption är våglängdsberoende. Denna skillnad kommer att bli mer påtaglig ju längre väg ljuset färdas i vävnaden. En kvot mellan intensiteterna vid två olika detekterade våglängder kan därmed ge information om djupet av det fluorescerande objektet. Detta har studerats både med simuleringar och experiment med så kallade vävnadsfantomer, vilka uppvisar optiska egenskaper liknande mänsklig vävnad. Det senaste arbetet inom detta området beskriver hur denna djupinformation kan utnyttjas för att kunna rekonstruera ett fluorescerande objekt från tomografiska mätningar.



Fotodynamisk tumörterapi är en metod för lokal behandling av tumörer. Ljus, syre och en kemisk substans, som ackumuleras i högre grad i tumör jämfört med frisk vävnad, är de tre komponenter som krävs för själva behandlingen. Inom det andra stora projektet i denna avhandling har farmakokinetiska mätningar av substansen Temoporfin utförts, d.v.s. monitorering av hur mycket det finns av substansen i tumör respektive frisk vävnad vid olika tidpunkter efter att substansen tillförts. Dessa försök har utförts i djurmodell både då substansen applicerats på huden och också via injicering i blodet. En uppskattning av mängden substans i olika vävnader har utförts med fluorescensspektroskopi och dessa värden har sedan jämförts med den koncentration som uppmätts via kemisk extraktion av substansen i vävnaden. Resultaten visar att det finns en selektivitet av substansen i tumör jämfört med normal vävnad vilket är positivt för att kunna behandla tumörer och spara normal vävnad. Fluorescensmätningar har också utförts under behandling av patienter, då med ytlig applicering av Temoporfin.



Den sista delen av avhandlingen beskriver en optisk metod för att mäta temperatur. Det finns vissa kristaller vars fluorescens ändrar karaktär med temperaturen. Om en liten bit av en sådan kristall limmas fast på en fiberspets, är det sedan möjligt att studera temperaturen i just den punkt där fibern är placerad genom att mäta kristallens fluorescensljus. Under en 10 minuter lång belysning med laserljus via fibern med kristallen placerad på mänsklig hud, kunde en temperaturökning under de första minuterna monitoreras. Tekniken testades också interstitiellt i kött, varvid en temperaturökning under hela belysningen uppmättes eftersom inget blodflöde fanns som kunde kyla ner vävnaden. (Less)
Abstract
The main theme of this thesis is the use of fluorescence spectroscopy in biomedicine. The work presented in the thesis can be divided into three areas of applications.



The first area involves the use of fluorescence to find the location of a deeply situated fluorophore within turbid media. Fluorescence emitted from the fluorophore will be attenuated when propagating through the medium, due to the optical properties of the surroundings. The fluorescence light will be more attenuated at some wavelengths as the tissue optical properties are wavelength-dependent, and this difference will be more pronounced the longer the light travels. An intensity ratio of fluorescence at two selected wavelengths can therefore provide... (More)
The main theme of this thesis is the use of fluorescence spectroscopy in biomedicine. The work presented in the thesis can be divided into three areas of applications.



The first area involves the use of fluorescence to find the location of a deeply situated fluorophore within turbid media. Fluorescence emitted from the fluorophore will be attenuated when propagating through the medium, due to the optical properties of the surroundings. The fluorescence light will be more attenuated at some wavelengths as the tissue optical properties are wavelength-dependent, and this difference will be more pronounced the longer the light travels. An intensity ratio of fluorescence at two selected wavelengths can therefore provide information about the depth of the inclusion. This has been investigated with both simulations and experiments with tissue phantoms. A further step has been to incorporate this depth-dependent ratio into a reconstruction algorithm used in fluorescence tomography.



Photodynamic therapy (PDT) is a local treatment modality of tumors, requiring light, oxygen and an administered photosensitizer, which preferably accumulates in tumor tissue. The second main area in this thesis has been the study of the pharmacokinetics of a liposomal formulation of the photosensitizer Temoporfin in different animal tumor models. Fluorescence measurements have been performed in order to estimate the quantity of photosensitizer within tumor and normal tissues following either topical or systemical administration of the drug. These quantities were compared to the drug concentrations obtained with chemical extraction. Time intervals of 2-8 hours between administration and measurements were investigated. Absorption spectroscopy was also performed when using topical application of the drug, yielding a good correlation of photosensitizer concentration compared to extraction data. Tumor selectivity of this liposomal Temoporfin formulation was shown at these short time intervals. Fluorescence measurements have also been performed in a first clinical PDT trial using topical application of this new formulation.



The final application utilizing fluorescence was to measure temperature optically. Certain crystals change their fluorescence spectrum when the temperature is altered. By attaching a crystal to a fiber tip, the temperature can be monitored at the position of the fiber. An intensity ratio of detected fluorescence in two wavelength bands can provide an estimate of the temperature. The temperature was monitored during a 10 minutes long light illumination on skin of a volunteer, indicating a temperature increase. The technique was also tested interstitially in meat, showing a temperature increase during the entire illumination as no perfusion was present, which normally stabilizes the temperature. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Assistant Professor Georgakoudi, Irene, Biomedical Engineering Department, Tufts University, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
temperature, Atomic and molecular physics, Atom- och molekylärfysik, photosensitizer, photodynamic therapy, fluorescence spectroscopy, multispectral imaging
in
Lund Reports in Atomic Physics
volume
LRAP-374
pages
188 pages
publisher
Atomic Physics, Department of Physics, Lund University
defense location
Room B, Department of Physics, Professorsgatan 1, Lund University Faculty of Engineering
defense date
2007-05-11 10:15
ISSN
0281-2762
ISBN
978-91-628-7128-4
language
English
LU publication?
yes
id
4290e36d-add8-4c8e-9ed6-3c74f589d00f (old id 548465)
date added to LUP
2007-10-01 15:43:39
date last changed
2016-09-19 08:44:58
@phdthesis{4290e36d-add8-4c8e-9ed6-3c74f589d00f,
  abstract     = {The main theme of this thesis is the use of fluorescence spectroscopy in biomedicine. The work presented in the thesis can be divided into three areas of applications.<br/><br>
<br/><br>
The first area involves the use of fluorescence to find the location of a deeply situated fluorophore within turbid media. Fluorescence emitted from the fluorophore will be attenuated when propagating through the medium, due to the optical properties of the surroundings. The fluorescence light will be more attenuated at some wavelengths as the tissue optical properties are wavelength-dependent, and this difference will be more pronounced the longer the light travels. An intensity ratio of fluorescence at two selected wavelengths can therefore provide information about the depth of the inclusion. This has been investigated with both simulations and experiments with tissue phantoms. A further step has been to incorporate this depth-dependent ratio into a reconstruction algorithm used in fluorescence tomography.<br/><br>
<br/><br>
Photodynamic therapy (PDT) is a local treatment modality of tumors, requiring light, oxygen and an administered photosensitizer, which preferably accumulates in tumor tissue. The second main area in this thesis has been the study of the pharmacokinetics of a liposomal formulation of the photosensitizer Temoporfin in different animal tumor models. Fluorescence measurements have been performed in order to estimate the quantity of photosensitizer within tumor and normal tissues following either topical or systemical administration of the drug. These quantities were compared to the drug concentrations obtained with chemical extraction. Time intervals of 2-8 hours between administration and measurements were investigated. Absorption spectroscopy was also performed when using topical application of the drug, yielding a good correlation of photosensitizer concentration compared to extraction data. Tumor selectivity of this liposomal Temoporfin formulation was shown at these short time intervals. Fluorescence measurements have also been performed in a first clinical PDT trial using topical application of this new formulation.<br/><br>
<br/><br>
The final application utilizing fluorescence was to measure temperature optically. Certain crystals change their fluorescence spectrum when the temperature is altered. By attaching a crystal to a fiber tip, the temperature can be monitored at the position of the fiber. An intensity ratio of detected fluorescence in two wavelength bands can provide an estimate of the temperature. The temperature was monitored during a 10 minutes long light illumination on skin of a volunteer, indicating a temperature increase. The technique was also tested interstitially in meat, showing a temperature increase during the entire illumination as no perfusion was present, which normally stabilizes the temperature.},
  author       = {Svensson, Jenny},
  isbn         = {978-91-628-7128-4},
  issn         = {0281-2762},
  keyword      = {temperature,Atomic and molecular physics,Atom- och molekylärfysik,photosensitizer,photodynamic therapy,fluorescence spectroscopy,multispectral imaging},
  language     = {eng},
  pages        = {188},
  publisher    = {Atomic Physics, Department of Physics, Lund University},
  school       = {Lund University},
  series       = {Lund Reports in Atomic Physics},
  title        = {Optical spectroscopy in biomedicine - detection of embedded inclusions and in vivo pharmacokinetics},
  volume       = {LRAP-374},
  year         = {2007},
}