Browsing by study line "Lääketieteellinen fysiikka ja biofysiikka"
Now showing items 1-16 of 16
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(2022)Acuros XB -annoslaskentamalli on Varianin Eclipse-annossuunnitteluohjelmistoon kehitetty annoslaskenta-algoritmi, joka on tarkoitettu ulkoisen sädehoidon fotoniannoslaskentaan. Sen toiminta perustuu lineaaristen Boltzmannin siirtoyhtälöiden ratkaisemiseen. Acuros XB -algoritmi laskee annoksen kudoksessa, minkä johdosta se pystyy tuottamaan tarkan laskennan myös heterogeenisessa väliaineessa. Algoritmin laskentatarkkuus on verrattavissa Monte Carlo -menetelmän tarkkuuteen, mutta tarvittava laskenta-aika on lyhyempi. Tässä tutkimuksessa konfiguroitiin ja testattiin Acuros XB -algoritmi HUS Syöpäkeskuksen sädehoito-osaston lineaarikiihdyttimille. Lisäksi tutkittiin kahden mittalaitteen, OCTAVIUS Detector 1000 SRS -ionisaatiokammiomatriisin ja SRS MapCHECK -puolijohdeilmaisimen, toimintaa pienillä säteilykentillä eli 2cm x 2cm ja tätä pienemmillä säteilykentillä. Acuros XB -algoritmi konfiguroitiin optimoimalla kolmea parametria: fokuspisteen kokoa, moniliuskarajoittimen dosimetrista aukkoa ja moniliuskarajoittimen läpäisykerrointa. Parametrien optimointi tehtiin vertailemalla mitattuja ja Acuros XB -algoritmilla laskettuja annosjakaumia ja säteilykentän keskiakseliannoksia. Konfigurointiprosessissa huomioitiin erilaiset kenttäkoot ja annossuunnittelutekniikat tutkimalla erikokoisia staattisia säteilykenttiä sekä IMRT (Intensity-Modulated Radiation Therapy)-, VMAT (Volumetric Modulated Arc Therapy)- ja SRS (Stereotactic Radiosurgery)-tekniikoilla toteutettuja kenttäjärjestelyjä. Mittalaitteita vertailtiin tutkimalla kolmen pienen staattisen kentän, kolmen dynaamisen kaarikentän ja kolmen VMAT-tekniikalla toteutetun kenttäjärjestelyn tuottamia annosjakaumia. Acuros XB -algoritmin konfiguroinnin tuloksena HUS Syöpäkeskuksen sädehoito-osaston lineaarikiihdyttimille määritettiin fotonienergiakohtaiset arvot fokuspisteen koolle, moniliuskarajoittimen dosimetriselle aukolle ja moniliuskarajoittimen läpäisykertoimelle, ja algoritmi otettiin kliiniseen käyttöön. Mittalaitteiden vertailun tuloksena havaittiin, että SRS MapCHECK -puolijohdeilmaisin toimi pienillä säteilykentillä paremmin kuin OCTAVIUS Detector 1000 SRS -ionisaatiokammiomatriisi. Mittalaitteiden annosjakaumien analysointiohjelmat kuitenkin käsittelevät mittaustulokset eri tavoin, joten lisätutkimusta voidaan tarvita yksiselitteisen tuloksen saamiseksi.
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(2023)In order to streamline the diagnosis process and increase the accessibility of both magnetic resonance imaging (MRI) and magnetoencephalocraphy (MEG), the department of Neuroscience and Biomedical Engineering at Aalto University is developing a new hybrid MEG--MRI device capable of performing both of these imaging methods. Both methods are measured using an array of Superconducting QUantum Interference Device (SQUID) magnetometers, which are extremely sensitive detectors capable of detecting the small magnetic fields generated by the human brain. However, the changing magnetic fields utilized in the MRI implementation cause eddy currents in the magnetically shielded walls of the MEG--MRI room, causing artefacts in the measured signals. In order to nullify these currents, an additional magnetic field of a specifically designed pulse waveform is fed into the room in a new technique called Dynamical Coupling for Additional dimeNsions (DynaCAN). To help in the development of DynaCAN, a program designed to detect and flag SQUIDs which saturate due to various different reasons, such as the induced eddy current fields, has been created and is presented in this work. This program finds saturated and faulty signals using four different Fault Detection Filters (FDFs) and tests if they are physically consistent with the signals of their neighboring detectors using Consistency Analysis (CA). It was found that the FDFs are able to find unambiguously faulty signals repeatably, while CA was more unreliable and was very susceptible to bad data present in the data set it was analysing.
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(2022)MRS or magnetic resonance spectroscopy is an imagining technique which can be used to gain information about the metabolite concentration within a certain volume of interest. This can be used for example in brain imagining. The brain consists of three main types of tissue: cerebrospinal fluid, white and gray matter. It is important to know the different volume fractions of these tissues as the resolution in MRS is significantly lower than that of magnetic resonance imagining (MRI). The tissues all have different metabolite profiles and in order to get meaningful data the volume fractions need to be taken into account. This information can be gained from the segmentation of an image formed by using MRI. In this work a software tool was created to find these volume fractions with the input of a .rda file that is created by the scanner and Nifti file. The Nifti file is the image formed by using MRI and the .rda file is the manufacturers raw data format for spectroscopy data which has the relevant information about the volumes of interest. The software tool was created using Python and JavaScript programming languages and different functions of FSL. FSL is a comprehensive library of analysis tools used in brain imaging data processing. The steps for the software tool are: determining the coordinates of the volume of interest in FSL voxel coordinates, creating a mask in the correct orientation and location, removing non-brain tissue from the image using FSL’s tool tailored for that purpose (BET), segmenting the image using FSL’s segmenting tool (FAST), registering the mask on the segmented images and calculating the volume fractions. The software tool was tested on imaging data that was obtained at Meilahti Kolmiosairaala for the purpose of the testing. The testing data set included five different spectroscopy volumes from different parts of the brain and a T1 weighted image. The software tool was given the relevant information about the volume of interest in the form of a .rda file and the T1 weighted image in the form of a Nifti file. The software tool then determined the different volume fractions from all of the five volumes of interest. There is variation on the volume fraction of different brain areas within different brains and it is not possible to have an absolute reference value. The results of the test corresponded to the possible volume fractions that can be expected from the volumes in question.
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(2023)Eye plaque radiotherapy is a treatment method of ocular tumors: A sealed radiation source is temporarily placed on the surface of the eye in day surgery. Compared to externally delivered conventional radiation treatments, more precisely targeted brachytherapy allows a higher dose in the target tissue while keeping the dose to healthy tissue relatively low. In Finland, all eye plaque treatments are centralised in Helsinki and brachytherapy of the eye is performed annually on approximately 70 patients. Patient specific anatomy takes into account determination of specific location and shape of the tumor in respect of radio-biologically critical structures of the eye. Until now, this has not been systematically modeled in dose calculation of eye plaque brachytherapy at HUS. The new version of Plaque Simulator, a 3D treatment simulation and modeling package for I-125, Pd-103, Ir-192 and Ru-106 plaque therapy of ocular tumors, enables importation and digitisation of patient imaging data (fundus imaging, CT and MRI) which consequently allows for systematically accurate estimation of dose distribution not only in the tumor but also in surrounding healthy tissues. The aim of this Master’s thesis is to prepare the new version of Plaque Simulator simulation and modeling package for clinical use in patient dose calculation at HUS. A comparison is done between the dose calculation method of the old and the new version of Plaque Simulator, and the dose calculation parameters as well as the plaque modeling parameters are reviewed. The function of the image-based dose calculation method is also tested with an anonymised patient treated for a tumor of a more peculiar shape. The absorbed dose to water on the central axis of the radiation source is measured experimentally for two individual I-125-seed along with Ru-106-CCB-, I-125-CCB-, and two I-125-COB-plaques. Experimental results are compared with the results obtained from Plaque Simulator. Individual I-125-seed is used to calibrate the detector at a distance of 10 mm, yielding to a calibration factor of 0.808. The use of the gold parameter in the dose calculation is justified, and a dosimetry modifier of Plaque Simulator is found to be 1.226 for I-125-plaques. Ru-106-plaque measurements are not calibrated, making them only relative. However, an excellent correspondence is observed between Ru-106-plaque dose calculations in Plaque Simulator and the manufacturer’s certificate. The measurements are normalized to the manufacturer’s certificate with a normalisation factor of 1.117.
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(2024)Monoenergetic neutron reference fields are used in neutron metrology for the calibration of different neutron detectors, including dose rate meters. The International Standardization Organization ISO has composed guidelines and requirements for the production of narrow energy spread neutron fields using a particle accelerator. The objective of this Thesis was to investigate a target material that could be used to produce a monoenergetic neutron field by irradiating it with protons. A broader energy distribution was deemed satisfactory in regard to the initial phase of the station’s development, as significant modifications to the beamline would be necessary to acquire more precise beam current values and to achieve proton energies closer to the reaction threshold energy. The target material was chosen to be lithium fluoride (LiF) based on a literature review and Monte Carlo simulations. The simulations were executed with the proton energy of 2.5 MeV, which is close to the threshold energy of the 7Li(p, n)7Be reaction, and with the fixed energy 10 MeV of the IBA cyclotron used to conduct the experiment. The simulations were executed with the MCNP6 code, and the results were compared to those obtained from equivalent Geant4 simulations. The simulations suggested two wide peaks around 3 MeV and 0.6 MeV at the proton energy of 10 MeV. The irradiation experiment included two phases, one of which entailed the use of a shadow cone to estimate the number of scattered neutrons in the neutron yield. The maximum neutron fluence of (2.62 ± 0.78)∙109 s-1 was measured at the pop-up probe current of (8.3 ± 0.8) µA. Gamma spectrometry was utilized after the experiment to further evaluate the number of 7Li(p,n)7Be reactions taken place in the target by calculating the number of 7Be nuclei in the LiF plate. Altogether, lithium fluoride exhibits promising characteristics as a target material for accelerator-based monoenergetic neutron production, although its application demands further considerations regarding for instance, the decrement of the proton energy and the aiming and measurement of the proton beam. These results contribute to the future development of a neutron irradiation station at the University of Helsinki.
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(2023)Nanodiscs are a synthetic model system for studying the behavior of cell membranes. They are used in experimental biological research to understand structural and functional properties of membrane proteins. Their utility is chiefly due to their water solubility and a relative native lipid environment for membrane proteins compared to other synthetic membrane systems. Though membrane proteins are frequently solubilized and stabilized in a nanodisc environment, the physical conditions that they are exposed to in a nanodisc have not been studied in detail. Additionally, the dynamic behavior of transmembrane proteins in a nanodisc environment has not been characterized with respect to a more typical planar bilayer environment. The results presented in this thesis formulate an answer to these open questions through atomistic molecular dynamics simulations and machine learning methods. Nanodiscs and bilayer systems with identical lipid compositions are systematically studied, and separately, both types of systems with adenosine receptor A2AR to understand the differences between the model systems. The membrane environment in the two systems is characterized by two well understood physical properties: the order parameter, and the diffusion of lipids in the membrane. The results not only affirm previous studies of nanodiscs but also provide novel insights into the membrane environment of the nanodisc systems. Finally, with the help of machine learning methods, the dynamical behaviour of the protein is shown to be significantly altered in the nanodisc system when compared to a planar bilayer environment. Specifically, it is shown that the activation behavior of A2AR is dependent on model system used to reconstitute the protein.
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(2023)Kartiokeilatietokonetomografia eli KKTT on tyypillisimmin käytetty kuvausmodaliteetti kuvantaohjatussa sädehoidossa ja sitä käytetään pääasiassa potilaan asemointiin ja sädehoidon kohdistamiseen. KKTT-kuvantaminen perustuu röntgensäteilyyn ja sen käytön haittapuolena potilas saa ylimääräistä säteilyannosta sekä hoidettavalle alueelle että sitä ympäröiville terveille kudoksille. Eturauhassyöpä on miesten yleisin syöpätyyppi Suomessa ja paikallista eturauhassyöpää voidaan hoitaa esimerkiksi sädehoidolla. Ionisoivan säteilyn käyttö lisää terveiden kudosten syöpäriskiä ja siksi KKTT-kuvantamisen aiheuttaman säteilyannoksen määritys ja optimointi on tärkeää. Tämän työn tarkoituksena on selvittää yhdeksässä suomalaisessa sairaalassa käytettäviä KKTT-kuvantamisen kuvausparametreja ja kuvauskäytäntöjä sekä laskennallisesti määrittää kuvantamisen aiheuttamia potilasannoksia ja optimoinnin vaikutuksia. Laskenta tehdään käyttäen Monte Carlo menetelmään perustuvaa ImpactMC-ohjelmaa, ICRP:n vokselitestikappaletta ja suomalaisten sairaaloiden käyttämiä kuvantamisen parametreja. Tulosten esittämiseen käytetään riskielinten kokonais- ja elinannoksia, isodoosipiirroksia xy- ja xz-tasoissa, riskielinten annostilavuushistogrammeja sekä annosprofiileja xy- ja xz-tasoissa. Tässä työssä lasketut riskielinten elinannokset ovat yhdellä kuvauskerralla noin mGy:n luokkaa ja kokonaissäteilyannokset riippuvat vahvasti kuvausfraktioiden määrästä. Symmetrisen keilan geometriassa säteilyannokset ovat pienempiä kuin epäsymmetrisen keilan geometriassa. Kuvantamisessa käytettävä kuvausalueen pituus, kuvausputken aloituskulma ja kuvausputken kiertosuunta vaikuttavat symmetrisessä geometriassa myös eri riskielimien saamaan säteilyannokseen ja säteilyn jakautumiseen xz-tasossa. Tuloksista havaitaan, että sekä symmetrisen että epäsymmetrisen keilan tapauksissa kuvausparametrien optimointi esimerkiksi putkivirtaa laskemalla pienentää eturauhasen, peräsuolen, reisiluun punaista luuydintä sisältävän osan ja virtsarakon saamaa elinannosta. Kuvausparametrien optimointi pienentää annostasoja myös kaikissa muissa lasketuissa tapauksissa kuten isodoosipiirroksissa ja annosprofiileissa.
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(2024)Monienerginen röntgensäde kokee kovenenemista aineessa. Yleisimmin röntgenpaneelien kalibroinnissa käytetty flat-field (FF)-korjaus on riittämätön säteen kovenemisen aiheuttamien kuvavääristymien korjaamiseen. Signal-to-thickness Calibration (STC)-menetelmässä kuvataan useita paksuuksia väliainetta ja luodaan pikselikohtainen sovitus säteen havaitun intensiteetin ja väliaineen välillä.Tämä sovitus ottaa sekä pikselikohtaiset vaste-erot, että säteen kovenemisen huomioon. Tässä tutkimuksessa arvioitiin STC-menetelmän kykyä parantaa kuvanlaatua verrattuna FF-korjattuun rekonstruktioon käyttäen kliinistä pään alueen kartiokeilatomografialaitetta. Kalibrointimateriaalina toimi akryylimuovi (PMMA). Kuvanlaatua arvioitiin kontrastin, kontrasti-kohina-suhteen, paikallisen kohinan ja cupping-ilmiön voimakkuuden sekä rengaskuvavääristymien arvioinnin avulla. Tutkimus avaa STC-menetelmän toimivuutta eri kudoskohteille hyväksikäyttäen fantomia ja kudosekvivalentteja materiaaleja. Tutkimuksessa tarkasteltiin sekä kovia että pehmeitä kudoksia. Kovina kudoksina käytettiin neljää eri konsentraatiota kalsiumhydroksiapatiittia (CaHA) sekä kolmea konsentraatiota jodia. Pehmeitä kudosekvivalentteja materiaaleja olivat aivot, imusolmukkeet, veri,rasvakudos, maksa, keuhko ja lihas. Fantomina toimi QRM Spectral Phantom II. Kun vertaillaan STC-korjattuja rekonstruktioita FF-korjattuihin, sekä kontrastin että kontrasti-kohina-suhteen havaittiin paranevan noin 27-30% aivo-, imusolmuke- ja lihaskudoksilla. Suurin kasvu tapahtui 80 kV:n putkijännitteellä. Ainoa kudosekvivalentti materiaali, jolle ei havaittu systemaattista kontrastin paranemista oli rasvakudos. Muissa pehmeissä kudoksissa kasvua tapahtui n.5%:sta 20%:iin. Koville kohtioille STC-menetelmän havaittiin myös kohentavan kontrastia n.4% - 9%. Cupping-ilmiön voimakkuuden heikkenemistä havaittiin systemaattisesti kaikilla kuvausparametreilla. Suurin heikkeneminen tapahtui kuitenkin intuitiivisesti matalimmalla putkijännitteellä 80 kV. Rengaskuvavääristymien voimakkuutta arvioitiin subjektiivisesti, eikä niiden havaittu heikkenevän merkittävästi. Tulokset antavat viitteitä kohenneesta pehmeän kudoksen kontrastista, joka on yksi suurimmista rajoittavista tekijöistä kartiokeilatietokonetomografiassa. Kudosten HU-arvoissa päästiin STC-korjatuilla rekonstruktoilla lähemmäksi todellisia kudosten HU-arvoja.
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(2023)Tietokonetomografialla (TT) on ollut jo usean vuosikymmenen ajan tärkeä asema lääketieteellisenä kuvantamismenetelmänä, jolla pystytään tuottamaan tarkkoja leikekuvia kehon rakenteista. TT on historiansa aikana muuttunut ja kehittynyt menetelmänä teknologisten harppausten ansiosta. Kuvauksista on tullut nopeampia ja entistä tarkempia. Kaksoisenergiatietokonetomografia (KETT) on yksi TT-kuvantamisen kehitysaskel, jonka teoreettiset perusteet ovat olleet jo pitkään tiedossa, mutta joka on vasta viime vuosikymmenenä saanut enemmän sovelluskohteita. KETT lisää TT-kuvauksen materiaalierottelukykyä, mikä mahdollistaa tarkemman diagnostiikan ja vähentää jatkotutkimusten tarvetta. Laajempi KETT:n kliininen käyttö vaatii kuitenkin toimintatapojen muutosta ja pysyvän laadunvalvontaprotokollan muodostamista. Tämän maisterintutkielman tarkoituksena oli auttaa laadunvalvonnan kehittämistä HUS:n Diagnostiikkakeskuksessa kartoittamalla KETT-kuvausten toimintaa, kuvausparametrien vaikutusta tuloksiin ja laitekohtaisia eroja. Työhön kuuluvat mittaukset suunniteltiin ja toteutettiin yhdessä HUS:n Diagnostiikkakeskuksen Meilahden Tornisairaalan radiologian yksikön kanssa. Kuvauksissa käytettiin Siemens Healthineersin valmistamia SOMATOM Definition Flash - ja SOMATOM Force -laitteita sekä KETT-kuvantamiseen soveltuvaa testikappaletta. Mittauksissa tutkittiin testikappaleen pystysuuntaisen asettelun vaikutusta kuvauksista saataviin tuloksiin, materiaalien elektronitiheyden ja efektiivisen järjestysluvun määritystarkkuutta, varjoaineena käytetyn jodin pitoisuuden määritystarkkuutta ja kuvauksen annostason merkitystä. Työssä käytetyllä menetelmällä määritettiin testikappaleen materiaalien koostumuksellisia eroja. Tutkimuksen avulla voitiin havaita jodipitoisuuden määrittämisen olevan haasteellisempaa hyvin pienillä alueilla, mutta halkaisijaltaan 5 mm:n kokoisilla alueilla määritystarkkuus oli jo kohtalainen. Potilaan oikeanlaisen keskityksen ja kuvanlaadun havaittiin olevan erityisen tärkeää pehmytkudoksia kuvattaessa. Laitteiden välisten erojen todettiin olevan merkittävämpää eri laitemallien välillä kuin samanmallisten laitteiden välillä. Laadunvalvonnassa tulee ottaa huomioon laitteiden kalibraatio, jotta laitteiden välisiä eroja pystytään vähentämään. Jatkossa mittauksia tulee toteuttaa lisää mittausten välisen toistettavuuden varmistamiseksi.
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Mechanical Modeling of Multi-coil Transducers for Brain Stimulation in High Static Magnetic Fields (2023)Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating cortical neurons in the brain. Combining TMS with functional magnetic resonance imaging (fMRI) shows the effects of TMS through the changes in brain metabolism. This information is necessary for developing new applications of TMS and for improving the efficacy and safety of the existing treatments. The biggest setback in current TMS–fMRI technology arises from the mechanical forces formed on the transducer as the interplay of the magnetic fields from the MRI and the changing current in the coil, leading to breakage of the transducers and additional safety risks. The objective of this Thesis was to assess and compare the mechanical stresses on multi-locus TMS (mTMS) transducers inside a high-field fMRI bore using finite element modeling, and to build and test transducer options based on the simulation results. For a transducer design for rats, six different coil former materials and three mTMS coil combinations were simulated with two commonly used current waveforms. In addition, the effect of the transducer orientation relative to the magnetic field was modeled with a transducer designed for humans. Our results show that the current pulses ran through the coils produce shock waves on the coil formers, leading to regions of maximum stresses that depend on the time instant. The intensity and location of the maximum stresses depends on the current waveform and coil combination used. Based on the results, 30% glass-fiber filled polyamide was found to be the most durable material. This Thesis provides novel insights for more durable TMS coil designs.
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(2022)This thesis examines the optical response of tuneable chiral plasmonic nanostructures in linear cross-polarization. Plasmonic gold-silver nanostructures composed of silver-coated gold nanorods, and dynamic DNA origami are investigated because of their optical properties of interest in the visible light wavelength region, and because of their controllable rotational asymmetry, which results in tuneable chirality in dimer structures. These plasmonic nanostructures present optical properties such as circular dichroism and optical rotatory dispersion. In this thesis we establish the relationship between perceived color, spectrometry, circular dichroism and optical rotatory dispersion of the samples, depending on the chiral geometry of the nanostructures within. The motivation is to predict perceived color from the chiral geometry of the nanostructures, which will enable visual detection for biosensing applications. Circular dichroism and optical rotatory dispersion give us detailed knowledge about the polarization state of a sample, but visible light detection and spectrometer measurements are more accessible and portable methods for characterizing the polarization state of a sample. We achieve color modulation from green to blue with the switching of chiral geometry, under cross-polarized white light. This has potential for biosensing applications, based on the perceived color change depending on the chiral geometry of the sample. The DNA origami structures react to the presence of an analyte by changing their chiral geometry. Possible applications in biosensing of analytes can be made more practical if the orientation of the DNA origami template can be determined from the perceived color or the transmission spectra, rather than from the less accessible circular dichroism or optical rotatory dispersion measurements.
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(2021)Electroencephalography (EEG) is a non-invasive neurophysiological method for evaluating brain activity by measuring electrical potential at the scalp. The electrical potentials originate mainly from postsynaptic cortical currents created by neuronal activity. It is a valuable tool for both research and clinical practice. EEG can be used e.g. to diagnose epilepsy, focal brain disorders, brain death, and coma. Intermittent photic stimulation (IPS) is an important tool in clinical EEG. Healthcare professionals use it to induce epileptic activity in patients to help diagnose their conditions. In these tests, various IPS frequencies are used with eyes-closed, eyes-open, and eye-closure conditions. IPS test is listed in clinical practice guidelines in EEG globally, and it is mainly used to diagnose photosensitive epilepsy, i.e., to detect epilepsy-related abnormal sensitivity to flickering light. Magnetoencephalography (MEG) is a non-invasive neurophysiological method in which minute magnetic fields — produced by the same postsynaptic currents as in EEG — are measured with special superconductive sensors around the head. MEG is a valuable tool for research and clinical practice with increasing world-wide utilization. The main advantages of MEG over EEG are easier source modelling and higher resolution at cortical areas. IPS has not been introduced to MEG since the IPS stimulators used in EEG are not compatible with MEG. IPS in MEG could improve the analysis of IPS and provide better tools for diagnoses. Currently, data analysis of IPS is typically limited to healthcare professionals examining the visualization of the raw data while looking for induced epileptiform activites and lateralizing them. In this thesis, an MEG-compatible IPS stimulator is introduced and alternative ways of analyzing IPS data for both MEG and EEG are showcased. Although analysis methods were applied with decent signal-to-noise ratios, further research is needed—especially to compare responses between patients with epilepsy and healthy subjects.
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(2024)Kuvantamisohjatussa sädehoidossa kohdentamiskuvauksella varmistetaan, että potilaan asettelu vastaa suunnittelukuvausta. Samalla on mahdollista huomioida kasvaimessa ja potilaan anatomiassa tapahtuneet muutokset. Kohdentamiskuvaus parantaa ulkoisen sädehoidon tehokkuutta varmistamalla tarkan hoidon. Kohdentamiskuvauksessa käytetään kV/MV kartiokeilatietokonetomografiaa (KKTT) tai tasoröntgenkuvausta. Usein tapahtuvasta kuvantamisesta aiheutuu ylimääräistä säteilyrasitusta. Kuvantamisesta aiheutuvat annokset kohdistuvat hoidettavan alueen lisäksi myös terveeseen kudokseen. Vaikka kuvantamisesta aiheutuva annos on pieni verrattuna hoidosta aiheutuvaan annokseen se voi muodostaa merkittävän osan kokonaisannoksesta hoidon aikana. Silti kuvantamisannosten optimointi on jäljessä hoidon annosoptimointia. Tässä työssä on pyritty kartoittamaan eurooppalaisten sädehoitoklinikoiden käytäntöjä kohdennuskuvauksessa kyselytutkimuksen avulla. Kyselytutkimuksella kerättyjen lantion ja eturauhasen alueen kV-KKTT protokollien elinannokset riskielimille määritettiin laskennallisesti Monte Carlo -menetelmällä ja ICRP:n vokselipohjaisella laskennallisella ihmismallilla. Elinannosten todettiin vaihtelevan merkittävästi eri protokollien välillä. Eturauhasen annokset ovat väliltä 4 mGy – 63 mGy, ja reisiluuhun kohdistuneet annokset olivat väliltä 1 mGy – 74 mGy. Toisaalta laaja vaihteluväli on linjassa kirjallisuudessa esitettyjen arvojen kanssa. Tutkimuksessa esitellään myös erillinen työ, jossa ICRP:n ihmismallia muokattiin esittämään ylipainoisen potilaan anatomiaa lisäämällä ihon alle rasvakudosta. Elinannosten huomioitiin olevan käänteisesti verrannollisia lisätyn rasvakudoksen määrään lantion alueen ja eturauhasen kuvantamisessa.
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(2024)Positron emission tomography (PET) is a tomographic imaging technique based on the administration of a positron-emitting radionuclide attached to a targeting molecule to monitor diverse biochemical and cellular processes in living subjects by obtaining three-dimensional images of the spatial distribution and concentration of the radionuclide activity. 52Mn is a very promising tool for PET imaging, since it decays by EC, β+ (100%) to 52Cr and has favorable physical characteristics such as a half-life of 5.59 days that allows to study long physiological processes and broadens the possibilities for radiolabeling, and a β+ maximum energy of 575 keV, comparable to that of 18F (640 keV), which enhances image resolution. The aim of this thesis has been to analyze the production of 52Mn via proton irradiation using a small medical cyclotron and to achieve the production and separation of the radionuclide in sufficient quantity to be able to carry out preclinical PET studies. 52Mn is easy to produce via proton irradiation of natural chromium in a low energy range. Chromium has four naturally occurring isotopes, of which 52Cr is the most abundant with 83.8%, therefore, a natural Cr target is the most viable and affordable option to produce 52Mn; although the possible reactions of the other isotopes present have to be considered, since each of the byproducts represents a potential contaminant of the final product; for the scope of this work, the main contaminant is 54Mn (t1/2 = 312.2 d). An irradiation conditions optimization for 52Mn production in the IBA Cyclone 10/5 medical cyclotron at the University of Helsinki was performed by analyzing parameters such as beam current, irradiation time, nuclear cross-section and target mounting configurations. 52Mn was produced via the reaction natCr(p,n)52Mn. The activity produced in the test irradiations performed was extracted by solid phase extraction (SPE) ion exchange chromatography with a load-wash-elute method on Dowex 1X8 anion exchange resin 50-100 mesh, where the final product was obtained in the form of manganese chloride [52Mn]MnCl2. The efficiency of the 52Mn extraction procedure was evaluated according to the percentage of activity recovered after it, which was on average 71.80%. It was confirmed that 54Mn is extracted in a fraction very close (66.37%) to that of 52Mn, at least for the type of SPE that was performed in this work. 52Mn was extracted from the irradiated Cr target in sufficient quantity to be able to perform a radiolabeling test of 1,2-Cyclohexylenedinitrilotetraacetic acid (CDTA). Radiolabel stability assays were done in rat serum and cerebrospinal fluid at physiological conditions, and quality control was performed using radio-TLC and autoradiography. The radiolabeled complex showed excellent radiochemical purity up to 48 hours in both media.
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(2023)In nuclear medicine, radiopharmaceuticals are administered to the patient to diagnose or treat various diseases. The radioactive activity of these radiopharmaceuticals is measured using a radionuclide calibrator. In this study, the response of a radionuclide calibrator in different measurement conditions was studied. Code system PENELOPE (2018) that applies Monte Carlo methods in electron and photon transport simulation was used to investigate the response as a function of photon energy emitted by the source, source location, source volume and source container type. These calculated results were compared to corresponding experimental results. Overall, the computational results conformed well with the experimental results. The computational energy-response followed a similar trend to the efficiency curve extracted from the manual of Capintec CRC-25R radionuclide calibrator. The response of the calibrator to a Tc-99m source as a function of both vertical and horizontal displacement was inspected, and the results indicated a cubic and exponential trend, respectively. In both cases, results present that there is an agreeing optimal depth range (14 - 23 cm) at which the source should be located. Within this range, the variation in response remains below 2 %. Furthermore, the central axis of the chamber was deemed horizontally optimal for measurements. In the radius range 0 - 2.1 cm, experimental results showed an increase of 4 % relative to the centre position. Corresponding calculated results presented an increase of about 3 %. The response as a function of volume and container type was calculated for Tc-99m and I-123 source, respectively. In the case of volume-response, computational results presented a decrease of around 0.5 % for volumes between 2 to 5 ml in a plastic syringe. Experimental methods showed a corresponding decrease no greater than 0.8 %. Measuring response in a 15C transparent glass vial instead of a 3 ml plastic syringe, showcased that the response is only 81 % and 75 % of that in the syringe in simulated and experimental results, respectively.
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(2023)Palmitoylation is an important posttranslational modification, which can change the function of proteins by the addition of fatty acids. In this thesis, I studied how palmitoylation affects the behavior of proteins and their interactions with the membranes. I also investigated the molecular mechanism of acetyl-palmitoyl recruitment by DHHC20, an important step in the palmitoyl transfer reaction. To this end, I used atomistic molecular dynamics simulations, which is a common computational method for studying biomolecules. In the first part of the thesis, I present my simulations and free energy calculations that show that palmitoylation enhances the partitioning of cysteines to the membranes and the spontaneous adsorption of amphipathic helices onto the membrane surface. At high levels, membrane cholesterol negatively impacts both of these properties both in the presence and absence of palmitoylation. However, palmitoylation strongly subdues the negative effect of increasing cholesterol. Moreover, palmitoylation helps proteins to maintain their helical conformation upon membrane binding. Overall, palmitoylation appears to be important for membrane interactions and the structural stability of proteins, especially under conditions of high membrane cholesterol. In the second part of my thesis, I investigated how its ligand, acetylpalmitoyl molecules, enters into the binding site of DHHC20. These simulations revealed that a short amphipathic helix at the gate of the ligand binding may play an important role in ligand recruitment and the overall stability of the enzyme. Moreover, I discovered that the protonation state of the cysteine residues that coordinate zinc cofactors is important for the stability of the zinc ions.
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