Development of a non-contact fluorescence tomography system with appropriate reconstruction techniques [Elektronische Ressource] / presented by Ralf B. Schulz

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• Publié par: ruprecht-karls-universitat_heidelberg
• Publié le: 01 janvier 2006
• Nombre de lectures: 163
• Langue: Deutsch
• Poids de l'ouvrage: 29 Mo

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Dissertation
submittedtothe
CombinedFacultiesfortheNaturalSciencesandforMathematics
oftheRuperto Carola UniversityofHeidelberg,Germany
forthedegreeof
DoctorofNaturalSciences
presentedby
Dipl. Inform. Med.: RalfB.Schulz
bornin: Munich,Germany
thOralexamination: July,19 ,2006Developmentofa
Non ContactFluorescenceTomographySystem
withAppropriateReconstructionTechniques
Referees: Prof. Dr. Dr. WolfhardSemmler
Prof. Dr. FredHamprechtZusammenfassung
Molekulare Bildgebung ist ein aktuelles Forschungsgebiet, das auf der Kombina
tionhochspezifischerKontrastmittelmitpassendenBildgebungstechnikenberuht.
SiebeschäftigtsichhauptsächlichmitderErprobungneuartigerPharmazeutikaan
kleinen Tieren und ermöglicht die tägliche Beobachtung des Therapiefortschritts
am lebenden Tier. Unter den verfügbaren Bildgebungsmodalitäten erfreuen sich
fluoreszenzbasierte Techniken großer Beliebtheit, da zugehörige Experimente ein-
fachdurchzuführenundzahlreicheKontrastmittelfürdenexperimentellenEinsatz
verfügbar sind. Da Licht im biologischen Gewebe stark gestreut wird, sind aufge
nommeneBilderderFluoreszenzjedochstarkvonderenGewebetiefeabhängig,so
dassBildernichtuntereinanderverglichenwerdenkönnen. Diefluoreszenzbasierte
Tomographie (FMT) verspricht diesen Nachteil zu beheben, da sie als quantitative
BildgebungstechnikdieKonzentrationsbestimmungvonFluorochromeninvivoer-
laubt. Üblicherweise verwenden FMT-Geräte Lichtleiter als Detektoren, die am zu
bildgebenden Tier befestigt werden. Neuerdings wurden jedoch berührungsfreie
Methodenentwickelt, beidenenvoneinerCCD KameraaufgenommeneBilderals
Projektionsdatenverwendetwerden. EinehierinpräsentierteStudiezumVergleich
von lichtleiterbasierter und berührungsfreier Bildgebung zeigt zum ersten Mal zu
verlässig die überlegenen Eigenschaften der berührungsfreien Technik. Auf diesen
Erkenntnissenaufbauendwurdeeinneuartiges,berührungsfreiarbeitendesTomo
graphiesystem für kleine Tiere entwickelt. An Phantomen wie auch anhand einer
TierstudiewerdendieFähigkeitendesGeräteszurRekonstruktionfluoreszierender
QuellenindiffusenMediengezeigt.Abstract
Molecular Imaging is a highly topical research field based on the combination of
highly selective markers and appropriate imaging devices. It is mainly concerned
with studying the effects of prototype drugs in small animals, following day by day
theevolutionofthediseaseinvivo. Amongsttheimagingtechniquesavailable,flu
orescence based imaging is very popular due to the simplicity of the experimental
systemsandthewidespreadavailabilityofsuitableprobes. Ashoweverlightisheav
ily scattered in tissue, fluorescence images depend heavily on the inclusion depth
so that different images cannotbe compared. Fluorescence mediatedtomography
(FMT) as presented herein is hoped to overcome these shortcomings by provid
ing a quantitative means of estimating fluorochrome concentrations in vivo. Usu
ally, FMT systems rely on detector readings obtained through light guiding fibers
mounted in contact to the imaged animals. Recently, non contact methods have
beenproposed,allowingCCD cameraimagestobeusedasprojectiondata. Herein,
astudyispresentedcomparingfiber basedandnon contactimagingmethodsand
reliableindicatesforthefirsttimethesuperiorityofnon-contacttechniques. Based
on these findings, a novel non-contact tomography system for small animals was
developed. Inphantomsaswellasinananimalstudythecapabilitiesofthesystem
toreconstructfluorescentsourcesinturbidmediaaredemonstrated.Tomyparents
andallthecountlesspeople
whohaveaccompaniedmeonthislongjourney
WhenIcanlookLifeintheeyes,
Growncalmandverycoldlywise,
LifewillhavegivenmetheTruth,
Andtakeninexchange—myyouth.
SaraTeasdaleAcknowledgments
MANY are those who helped me in working on the experiments or results pre
sentedinthisthesis;mayitbewithnewideas,mayitbewithexperimentalsupport,
mechanicallypreparingsystemparts,orwithfoodandlove,oreventravelgrants.
Firstofall,mydeepestthanksgotomyadvisers,Prof. Dr. Dr. WolfhardSemm
ler from the German Cancer Research Center (dkfz) and Prof. Dr. Fred Hamprecht
from the physics faculty of the university of Heidelberg for accepting me as their
PhD student, for enabling the creationofthiswork, andfor givingme thefreedom
toproceedinanywaypossiblewithouttoomanyboundconstraints. Itwasagreat
pleasuretoworkinthegroupofDr. JörgPetertogetherwithDr. OliverNix,Wolfram
Stiller,andDanielUnholtz.Forexperimentalsupportwhenlivinganimalswerecon-
cerned,IhavetoacknowledgethehelpandexpertiseofDr. FabianKießlingandDr.
ManfredJugold.
I got addicted to the field of biomedical optics while preparing my diploma
thesisattheCenterforMolecularImagingResearchinBoston,MA,USA,underProf.
VasilisNtziachristos,Dr. JorgeRipoll,andProf. RalphWeissleder,whomIalsoowea
heartfeltthank youforagreattimeinBoston,andthemanydoorsthisstayopened
formeaftermyreturntoGermany.
All computations on finite element meshes were performed using the great
DEAL.II library developed by Dr. Wolfgang Bangerth, Dr. Guido Kanschat, and Dr.
RalfRannacher[21]. Thislibrarynotonlyisverywellwrittenandfast,itisalsofreely
availableandsupportinmostcasesisimmediateandhelpful.
WithoutHeinrichRühle,VolkerStamm,DietbertBucher,WolfgangStroh,and
the other staff from the mechanics workshop at dkfz, the experimental setups pre
sented herein could not have been set up, manufactured, or improved in such ex
cellentqualityandprecision. JürgenVierling,ThomasVogt,andtheotherstafffrom
theelectronicsworkshopatdkfzhelpedincreatingthenecessarycontrolelectronics
for the tomographic scanner. Gernot Echner and Clemens Lang prepared the first
CADdrawingsoftheanimalscanner’simagingchamber.
Then there is the laboratory of Prof. Rinaldo Cubeddu, where I not only had
the opportunity during a couple of weeks to learn a lot about how good research
9should be performed, but also met an abundance of helpful and knowledgeable
people, whom I now consider good friends, namely Prof. Dr. Cosimo D’Andrea,
Prof. Dr. Gianluca Valentini, Dr. Daniela Comelli, Prof. Dr. Paola Taroni, Prof. Dr.
Alessandro Toricelli, Dr. Andrea Bassi, and—last but not least—the man who built
numerous apparatus and made nearly everything possible by his machining skills,
LucianoPallaro. TheworkIwasabletoperformintheirlabispresentedinchapter
4.
FurtherthanksandacknowledgmentshavetogotomyChinesefriendsfrom
HuazhongUniversityofScienceandTechnologyinWuhan,P.R.China,whomIhad
theopportunitytoworkwithforacoupleofweeks. NamelyIhavetothankProf. Dr.
Qingming Luo, the head of the lab, for inviting me to Wuhan, and Shangbin Chen
forlettingmeparticipateinhisexperimentalwork.
Last but not least, I am very grateful for very helpful and friendly support by
Sabine Fritz in all aspects of the logistics concerned in performing PhD research.
Also,manythanksgotoherhusband,RolandFritz,forsupportinLatinandancient
Greek.
ThisthesiswasinpartsupportedbyaPhDscholarshipoftheGermanCancer
Research Center (dkfz), by the EU Laserlab Network under contract RII3 CT 2003
506350 (collaboration with the Politecnico di Milano, Italy), the Boehringer Ingel
heimFoundationwhichallowedmetostayforfiveweeksattheKeyLaboratoryfor
BiomedicalPhotonicsinWuhan,P.R.China,andSiemensPreclinicalSolutions(for-
merlyCTIimaging)whoawardedmewitha500$travelgranttoattendthe2005IEEE
MedicalImagingConferenceinFajardo,PuertoRico.
AThe document was typeset in LT X using Adobe’s Utopia font and the textE
managing IDE T XnicCenter, a very useful piece of freeware that can be obtainedE
fromthedevelopers’webpageathttp://www.toolscenter.org.
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