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Optical spectroscopy and fluorescence imaging for cancer diagnostics

Svenmarker, Pontus LU (2012)
Abstract (Swedish)
Popular Abstract in Swedish

Denna avhandling beskriver olika optiska metoder för att diagnostisera cancer.En sådan metod är optisk spektroskopi (att med hjälp av ljus bestämma fysiska och kemiska egenskaper hos ett prov) som har används för att undersöka cancer i ögat. Avhandlingen omfattar vidare studier av optiska kontrastmedel tillverkade

av nanokristaller (nano = en miljarddels meter), vilkas innehåll av sällsynta jordartsmetaller ger unika optiska egenskaper. Dessa kontrastmedel är i huvudsak ämnade för forskningsmodeller.



Nästan alla olika ögoncancersjukdomar kan idag diagnostiseras med hjälp av standardiserade undersökningsmetoder som ögonspegling, ultraljud, kärlavbildning och... (More)
Popular Abstract in Swedish

Denna avhandling beskriver olika optiska metoder för att diagnostisera cancer.En sådan metod är optisk spektroskopi (att med hjälp av ljus bestämma fysiska och kemiska egenskaper hos ett prov) som har används för att undersöka cancer i ögat. Avhandlingen omfattar vidare studier av optiska kontrastmedel tillverkade

av nanokristaller (nano = en miljarddels meter), vilkas innehåll av sällsynta jordartsmetaller ger unika optiska egenskaper. Dessa kontrastmedel är i huvudsak ämnade för forskningsmodeller.



Nästan alla olika ögoncancersjukdomar kan idag diagnostiseras med hjälp av standardiserade undersökningsmetoder som ögonspegling, ultraljud, kärlavbildning och magnetröntgen. Ögoncancer kan trots tillgång till dagens hjälpmedel ibland vara svår att diagnostisera. Som ett komplement till befintliga metoder har vi undersökt möjligheten att använda optisk spektroskopi för diagnos. Metoden är speciellt känslig för att kvantifiera innehållet av olika ämnen i mänsklig vävnad, som vatten och melanin och kan även tillämpas t.ex. för att mäta blodvärde och syremättnad. Synligt och nära-infrarött ljus kan belysa vävnad på flera centimeters djup, vilket kan användas för att söka ytligt liggande tumörer.

I en serie experiment på grisögon har vi säkerställt att optisk spektroskopi kan med gott resultat kvantifiera mängden melanin och mängden blod i tumörliknande fantomer placerade i ögats åderhinnan. Vi har även kunnat visa att denna undersökning inte skadar ögat eller ger upphov till ökat ögontryck. Vidare har enuklerade ögon från människa med känd melanomdiagnos studerats. Optisk spektroskopi visade härvid relativt god träffsäkerhet i att mäta graden av pigmentering i melanomen. Sammanfattningsvis: optisk spektroskopi erbjuder ett gott komplement till nuvarande diagnosmetoder för ögoncancersjukdomar.



Optiska kontrastmedel inom forskning är ett starkt växande fält. En av anledningarna är att optiska markörer kan emitera upp till en miljard fotoner per sekund per markör. Detta är en mycket hög aktivitet jämfört med mer traditionella nukleära markörer. Därutöver kan optiska markörer tillverkas av proteiner. Detta möjliggör fundamentala biologiska studier av genuttryck. På

senare tid har nanomaterial med en storlek betydligt mindre än enstaka celler specialkonstruerats med unika optiska egenskaper. Vi har i en rad experiment studerat hur nanokristaller innehållande sällsynta jordartsmetaller kan utnyttjas som optiska markörer. Vi har funnit följande fördelar: 1) dess optiska signatur kan enkelt skiljas från den annars snarlika signaturen hos normal vävnad. Denna särskiljning är svår att uppnå med traditionella optiska markörer. 2) nanokristaller är stabila och faller inte sönder vid hög ljusintensitet. Detta är ett vanligt förekommande hos organiska markörer. 3) nanokristaller möjliggör avbildning med högre upplösning. 4) nanokristaller avger ljus med specifika färger. Sammanfattningsvis: nanokristaller innehållande sällsynta jordartmetaller uppvisar unika egenskaper vilket gör dem attraktiva som optiska markörer. (Less)
Abstract
This work presents optical methods for diagnosing cancer. A complementary method for diagnosing eye cancer was investigated using a technique developed within this work named transscleral optical spectroscopy (TOS). Furthermore, nano-sized crystals doped with lanthanides were exploited as probes for fluorescence imaging

with direct applications to preclinical cancer research.



Almost all intraocular malignancies can today be correctly diagnosed using techniques like ophthalmoscopy, ultrasonography and fluorescein angiography. Even with the rich flora of tools available, some tumors present non-typical behaviors and are difficult to diagnose. As a complementary diagnostic method, TOS was developed, which exploits... (More)
This work presents optical methods for diagnosing cancer. A complementary method for diagnosing eye cancer was investigated using a technique developed within this work named transscleral optical spectroscopy (TOS). Furthermore, nano-sized crystals doped with lanthanides were exploited as probes for fluorescence imaging

with direct applications to preclinical cancer research.



Almost all intraocular malignancies can today be correctly diagnosed using techniques like ophthalmoscopy, ultrasonography and fluorescein angiography. Even with the rich flora of tools available, some tumors present non-typical behaviors and are difficult to diagnose. As a complementary diagnostic method, TOS was developed, which exploits the natural optical contrast in tissue for diagnosis. The method is particularly sensitive in identifying physiological changes characteristic of tumors, i.e. tissue hemoglobin (total, oxy- , and deoxy- forms), oxygen saturation, blood volume fraction, water content, melanin content and cellular structure. In a series of experiments on porcine eyes, TOS was successful in quantifying the blood and melanin content of tumor phantoms placed in the choroid. It was also showed that TOS measurements did not cause any visible damage to the sclera, resulted in a significant temperature rise, or led to an unacceptable intra ocular pressure elevation. In further experiments on enucleated human eyes with a predetermined melanoma diagnosis, TOS measurements were found to correlated well with the degree of pigmentation in the melanoma. To summarize, TOS offers a tool to probe the physiology of intraocular tumor, which can be used in a complementary diagnosis.



Fluorescence imaging is a versatile tool for studying biology on the nanometer to centimeter length-scale through labeling tissue with fluorescent probes to induce the desired contrast. In this work, upconverting nanoparticles (UPNs) were evaluated as fluorescent probes for deep tissue fluorescence imaging. Efficient upconversion was achieved using a NaYF4 host co-doped with Yb3+ and Tm3+ or Er3+ ions. In comparison to traditional fluorescent probes, UPNs were found to have the follow benefits: 1) they allow autofluorescence insensitive imaging through anti-Stokes shifted 2) they show no signs of photo-damage even at high intensities. 3) for deep tissue imaging, they provide higher resolution images. 4) they emit multiple line emissions with large Stoke shifts. To summarize, UPNs hold unique optical properties which make them attractive as fluorescent probes. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr Dehghani, Hamid, The University of Birmingham, United Kingdom
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Biomedical optics, Diffuse-reflection spectroscopy, Upconverting nanoparticles, Inverse problem, Fluorescence, Tomography, Imaging, Scattering media, Photon migration, Fysicumarkivet A:2012:Svenmarker
pages
201 pages
defense location
Lecture hall B, Fysicum, Professorsgatan 1, Lund University Faculty of Engineering
defense date
2012-04-20 10:15
ISSN
0281-2762
language
English
LU publication?
yes
id
ea66e005-9748-42b1-b6a8-07384f935cae (old id 2427920)
date added to LUP
2012-03-29 13:30:32
date last changed
2016-09-19 08:45:00
@phdthesis{ea66e005-9748-42b1-b6a8-07384f935cae,
  abstract     = {This work presents optical methods for diagnosing cancer. A complementary method for diagnosing eye cancer was investigated using a technique developed within this work named transscleral optical spectroscopy (TOS). Furthermore, nano-sized crystals doped with lanthanides were exploited as probes for fluorescence imaging<br/><br>
with direct applications to preclinical cancer research.<br/><br>
<br/><br>
Almost all intraocular malignancies can today be correctly diagnosed using techniques like ophthalmoscopy, ultrasonography and fluorescein angiography. Even with the rich flora of tools available, some tumors present non-typical behaviors and are difficult to diagnose. As a complementary diagnostic method, TOS was developed, which exploits the natural optical contrast in tissue for diagnosis. The method is particularly sensitive in identifying physiological changes characteristic of tumors, i.e. tissue hemoglobin (total, oxy- , and deoxy- forms), oxygen saturation, blood volume fraction, water content, melanin content and cellular structure. In a series of experiments on porcine eyes, TOS was successful in quantifying the blood and melanin content of tumor phantoms placed in the choroid. It was also showed that TOS measurements did not cause any visible damage to the sclera, resulted in a significant temperature rise, or led to an unacceptable intra ocular pressure elevation. In further experiments on enucleated human eyes with a predetermined melanoma diagnosis, TOS measurements were found to correlated well with the degree of pigmentation in the melanoma. To summarize, TOS offers a tool to probe the physiology of intraocular tumor, which can be used in a complementary diagnosis.<br/><br>
<br/><br>
Fluorescence imaging is a versatile tool for studying biology on the nanometer to centimeter length-scale through labeling tissue with fluorescent probes to induce the desired contrast. In this work, upconverting nanoparticles (UPNs) were evaluated as fluorescent probes for deep tissue fluorescence imaging. Efficient upconversion was achieved using a NaYF4 host co-doped with Yb3+ and Tm3+ or Er3+ ions. In comparison to traditional fluorescent probes, UPNs were found to have the follow benefits: 1) they allow autofluorescence insensitive imaging through anti-Stokes shifted 2) they show no signs of photo-damage even at high intensities. 3) for deep tissue imaging, they provide higher resolution images. 4) they emit multiple line emissions with large Stoke shifts. To summarize, UPNs hold unique optical properties which make them attractive as fluorescent probes.},
  author       = {Svenmarker, Pontus},
  issn         = {0281-2762},
  keyword      = {Biomedical optics,Diffuse-reflection spectroscopy,Upconverting nanoparticles,Inverse problem,Fluorescence,Tomography,Imaging,Scattering media,Photon migration,Fysicumarkivet A:2012:Svenmarker},
  language     = {eng},
  pages        = {201},
  school       = {Lund University},
  title        = {Optical spectroscopy and fluorescence imaging for cancer diagnostics},
  year         = {2012},
}