Stem cell therapy is emerging as a possible method for treating many diseases and disorders, such as cardiovascular disease. In particular, stem cells may be able to revive the dead tissue caused by acute myocardial infarction (heart attack). Adipose-derived stem cells were labelled with 18F-fluorodeoxyglucose (FDG) and superparamagnetic iron oxide (SPIO) particles, for imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), respectively, and injected into several rats following induced myocardial infarction. Stem cell retention in the heart was investigated following three injection sites; two within the heart (intramyocardial and left intraventricular), and one easily accessible vein (tail vein). The PET and MR images were registered and the initial distributions analyzed using region of interest (ROI) analysis, to determine which injection method would result in the highest stem cell retention in the infarcted heart. The ROI results determined that the intramyocardial injection had the highest % injected dose (%ID) in the heart with 14 +/- 4%, followed by left intraventricular and tail vein with %IDs of 3.6 +/- 0.8% and 1.2 +/- 0.6%, respectively. The results indicate that stem cell delivery via intramyocardial injection should be utilized for optimal retention in the heart.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.

No description available.

Positron emission tomography (PET) employs short half-life positron emitting isotopes, typically ¹⁸F, for in vivo measurement of physiological processes. Easy access to structurally diverse radiolabelled probes would accelerate the rapid progress of PET imaging but, to date, radiochemistry is still limited by cost and efficiency. Nucleophilic fluorination with ¹⁸F-fluoride is the preferred “non-carrier-added” methodology in the synthesis of ¹⁸F-labelled pharmaceuticals because it leads to radiotracers with a high specific activity, a key feature allowing for investigations to be performed in sub-toxic doses. Chapter 1 serves as an introduction on radiochemistry, especially focussing on current radiosynthetic methods for the synthesis of ¹⁸F-labelled aromatics. Aromatic compounds without electron-withdrawing groups are notoriously difficult to label with ¹⁸F-fluoride. In this thesis, we present two novel methodologies to deliver ¹⁸F-labelled aromatic compounds from nucleophilic 18F-fluoride. Chapter 2 details the experimental efforts towards “Convergent Radiosynthesis” (Scheme 1). We proposed a convergent synthetic tactic that allows for simultaneous reaction between three or more substrates, including an ¹⁸F-labelled building block. This chemistry has been validated by the radiosynthesis of various structural scaffolds which are not responsive to direct nucleophilic fluorination. Chapter 3 presents our research into “Oxidative Nucleophilic ¹⁸F-Fluorination” (Scheme 2). We proposed that electron-rich aromatics, such as phenols, which are not responsive to nucleophilic fluorination may undergo umpolung reactivity under oxidative conditions. This “umpolung strategy” allows for the direct transformation from ¹⁸F-fluoride to 4-[¹⁸F]fluorophenol. Potentially, this established oxidative fluorination strategy could be adapted to the radiosynthesis of radiotracers containing a 4-fluorophenol sub-motif, such as 6-fluoro-meta-tyrosine. An appropriate precursor has been validated for the prospective radiosynthesis of 6-[18F]fluoro-meta-tyrosine.

This dissertation aims to investigate two different applications in optics using maximum-likelihood (ML) estimation. The first application of ML estimation is used in optical metrology. For this application, an innovative iterative search method called the synthetic phase-shifting (SPS) algorithm is proposed. This search algorithm is used for estimation of a wavefront that is described by a finite set of Zernike Fringe (ZF) polynomials. In this work, we estimate the ZF coefficient, or parameter values of the wavefront using a single interferogram obtained from a point-diffraction interferometer (PDI). In order to find the estimates, we first calculate the squared-difference between the measured and simulated interferograms. Under certain assumptions, this squared-difference image can be treated as an interferogram showing the phase difference between the true wavefront deviation and simulated wavefront deviation. The wavefront deviation is defined as the difference between the reference and the test wavefronts. We calculate the phase difference using a traditional phase-shifting technique without physical phase-shifters. We present a detailed forward model for the PDI interferogram, including the effect of the nite size of a detector pixel. The algorithm was validated with computational studies and its performance and constraints are discussed. A prototype PDI was built and the algorithm was also experimentally validated. A large wavefront deviation was successfully estimated without using null optics or physical phase-shifters. The experimental result shows that the proposed algorithm has great potential to provide an accurate tool for non-null testing. The second application of ML estimation is used in nuclear medical imaging. A high-resolution positron tomography scanner called BazookaPET is proposed. We have designed and developed a novel proof-of-concept detector element for a PET system called BazookaPET. In order to complete the PET configuration, at least two detector elements are required to detect positron-electron annihilation events. Each detector element of the BazookaPET has two independent data-acquisition channels. One of the detector channels is a 4 x 4 silicon photomultiplier (SiPM) array referred to as the SiPM-side. The SiPM-side is directly coupled to an optical window of the scintillator with optical grease. The other channel is a CCD-based gamma camera with an imaging intensifier called the Bazooka-side. Instead of coupling by direct contact like the SiPM-side, an F/1.4 lens pair is used for optical coupling. The scintillation light from the opposite optical window to the SiPM-side is imaged by the F/1.4 lens to the Bazooka-side. Using these two separate channels, we can potentially obtain high energy, temporal and spatial resolution data by associating the data outputs via several ML estimation steps. We present the concept of the system and the prototype detector element. In this work, we focus on characterizing individual detector channels, and initial experimental calibration results are shown along with preliminary performance-evaluation results. We also address the limitations and the challenges of associating the outputs of the two detector channels.

No description available.

Masters Research - Master of Philosophy (Physics) / Fluoro-deoxyglucose (FDG) labeled with fluorine-18 is commonly used in positron emission tomography (PET) imaging. PET imaging is a powerful tool used primarily in the diagnosis and management of cancer. The growth of PET has been limited partly by the difficulties associated in producing fluorine-18. This project involves a theoretical investigation of a novel method of producing fluorine-18 utilising proton generation via the 3He(d,p)4He nuclear reaction. Currently the most common method of producing fluorine-18 for PET is with a medical cyclotron that accelerates protons to mega-voltage energies. These protons are then directed onto a target rich in oxygen-18. This initiates the 18O(p,n)18F reaction to produce fluorine-18. The 3He(d,p)4He reaction, utilized for the present study, has a Q-value of 18.35 MeV and this results in protons being produced at energies similar to that produced in a medical cyclotron. This reaction was investigated as an alternative proton source for the 18O(p,n)18F reaction. The expected advantage of this method over the cyclotron is that particles need only be accelerated to keV energies rather than the tens of MeV that a medical cyclotron accelerates protons to. This is expected to significantly reduce the cost and associated size of the system. Two systems based on the 3He(d,p)4He reaction were designed and calculations were performed to determine the respective yields of fluorine-18. The first system involved separate targets for the 3He(d,p)4He and 18O(p,n)18F reactions. Helium-3 ions are initially fired onto a deuterated plastic target. A heavy-water (H2O18) target is placed immediately behind this plastic target to absorb mega-voltage protons produced by the reaction 3He(d,p)4He in the plastic. The second system involved a single, super heavy water (D2O18) target onto which helium-3 is fired so that both the 3He(d,p)4He and 18O(p,n)18F reactions can occur concurrently in the one target. The input parameters of energy and beam current for the helium-3 beam required for the 3He(d,p)4He reaction were selected on the basis of the performance of currently available ion sources and in particular the saddle-field ion source. Practical considerations such as radiation safety, target degradation and lifetime and ultra high vacuum (UHV) issues were also investigated to further determine the feasibility of the two systems. With the beam current and energy at the extreme limits of the saddle-field ion source it was calculated that insufficient fluorine-18 could be produced daily to supply a PET facility with FDG. It was also found that the high helium-3 beam currents and energy required to produce significant amounts of fluorine-18 resulted in prohibitive temperature rises in the targets that would likely result in target vaporization.

Masters Research - Master of Philosophy (Physics) / Fluoro-deoxyglucose (FDG) labeled with fluorine-18 is commonly used in positron emission tomography (PET) imaging. PET imaging is a powerful tool used primarily in the diagnosis and management of cancer. The growth of PET has been limited partly by the difficulties associated in producing fluorine-18. This project involves a theoretical investigation of a novel method of producing fluorine-18 utilising proton generation via the 3He(d,p)4He nuclear reaction. Currently the most common method of producing fluorine-18 for PET is with a medical cyclotron that accelerates protons to mega-voltage energies. These protons are then directed onto a target rich in oxygen-18. This initiates the 18O(p,n)18F reaction to produce fluorine-18. The 3He(d,p)4He reaction, utilized for the present study, has a Q-value of 18.35 MeV and this results in protons being produced at energies similar to that produced in a medical cyclotron. This reaction was investigated as an alternative proton source for the 18O(p,n)18F reaction. The expected advantage of this method over the cyclotron is that particles need only be accelerated to keV energies rather than the tens of MeV that a medical cyclotron accelerates protons to. This is expected to significantly reduce the cost and associated size of the system. Two systems based on the 3He(d,p)4He reaction were designed and calculations were performed to determine the respective yields of fluorine-18. The first system involved separate targets for the 3He(d,p)4He and 18O(p,n)18F reactions. Helium-3 ions are initially fired onto a deuterated plastic target. A heavy-water (H2O18) target is placed immediately behind this plastic target to absorb mega-voltage protons produced by the reaction 3He(d,p)4He in the plastic. The second system involved a single, super heavy water (D2O18) target onto which helium-3 is fired so that both the 3He(d,p)4He and 18O(p,n)18F reactions can occur concurrently in the one target. The input parameters of energy and beam current for the helium-3 beam required for the 3He(d,p)4He reaction were selected on the basis of the performance of currently available ion sources and in particular the saddle-field ion source. Practical considerations such as radiation safety, target degradation and lifetime and ultra high vacuum (UHV) issues were also investigated to further determine the feasibility of the two systems. With the beam current and energy at the extreme limits of the saddle-field ion source it was calculated that insufficient fluorine-18 could be produced daily to supply a PET facility with FDG. It was also found that the high helium-3 beam currents and energy required to produce significant amounts of fluorine-18 resulted in prohibitive temperature rises in the targets that would likely result in target vaporization.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.