"Patient motion is a significant cause of artifacts in SPECT imaging. It is important to be able to detect when a patient undergoing SPECT imaging is stationary, and when significant motion has occurred, in order to selectively apply motion compensation. In our system, optical cameras observe reflective markers on the patient. Subsequent image processing determines the marker positions relative to the SPECT system, calculating patient motion. We use this information to decide how to aggregate detected gamma rays (events) into projection images (frames) for tomographic reconstruction. For the most part, patients are stationary, and all events acquired at a single detector angle are treated as a single frame. When a patient moves, it becomes necessary to split a frame into subframes during each of which the patient is stationary. This thesis presents a method for splitting frames based on hypothesis testing. Two competing hypotheses and probability model are designed. Whether to split frames is based on a Bayesian recursive estimation of the likelihood function. The estimation procedure lends itself to an efficient iterative implementation. We show that the frame splitting algorithm performance is good for a sample SNR. Different motion simulation cases are presented to verify the algorithm performance. This work is expected to improve the accuracy of motion compensation in clinical diagnoses."

Early research into the stable hydrogen isotopic compositions (δD) of petroleum involved bulk deuterium/hydrogen (D/H) measurements which, while providing some useful information, had to contend with the analysis of complex mixtures of hydrocarbons, and alteration resulting from the rapid exchange of nitrogen-, oxygen- and sulphur-bound hydrogen. The use of gas chromatography-isotope ratio mass spectrometry (GC-irMS) overcomes these problems by allowing the analysis of individual compounds containing only the most isotopically conservative aliphatic carbon-bound (C-bound) hydrogen. This project investigates the geochemical utility and reliability of compound-specific δD values, with the aim to better understand and exploit this analytical capability. To demonstrate the source diagnostic potential of compound-specific δD values, normal and branched alkanes extracted from series of immature bog-head coals (torbanites) were analysed. The torbanites contain immature organic matter predominantly from a single, freshwater algal source, i.e. Botryococcus braunii (B. braunii). The δD values of n-alkanes reflect the climate regime at the time of deposition of the torbanites, and vary mainly in response to the δD values of the source meteoric waters in their depositional environments. n-Alkanes from torbanites deposited at high latitude in a glacial climate are depleted in D by up to 70% relative to those from a torbanite deposited at low latitude under a tropical climate regime. Torbanites deposited in a mid-latitude region under cool-temperate conditions contain n-alkanes with δD values falling in between those of n-alkanes from tropical and glacial torbanites. / The δD values of the n-alkanes also reflect their multiple source inputs. For example, a saw-toothed profile of n-alkane δD values in Australian torbanites is attributed to a dual-source system: a predominant B. braunii input, with a minor terrestrial plant input to odd-carbon-numbered n-alkanes in the range n-C20 [subscript] to n-C29 [subscript]. The δD values of n-alkanes and isoprenoids (pristane and phytane) differ significantly in two Permian torbanites from Australia, thought to be reflective of the offset between the δD values of their precursors in extant organisms. The torbanite data indicate that a biological δD signal has been preserved for at least 260–280 million years, extending the utility of δD values for palaeoclimate studies. To elucidate the effect of sedimentary processes on the δD values of petroleum hydrocarbons, three sedimentary sequences have been studied. These comprise one from the Perth Basin (Western Australia) and two from the Vulcan Sub-basin (northern Australia) covering a wide range of maturities, i.e. 0.53–1.6% vitrinite reflectance (Ro). The δD values of n-alkanes extracted from immature-early mature sediments (marine shales/siltstones and mudstones) are consistent with that expected of marine-derived n-alkyl lipids. The hydrocarbons become enriched in D with increasing maturity. The large (ca. 115%) biologically-derived offset between the δD values of n-alkanes and acyclic isoprenoids from immature sediments gradually decreases with increasing maturity, as the isoprenoids become enriched in D more rapidly than the n-alkanes. The D-enrichment in isoprenoids correlates strongly with Ro and traditional molecular maturity parameters. / This suggests that H/D exchange during maturation occurs via a mechanism involving carbocation-like intermediates, which proceeds more rapidly with compounds containing tertiary carbon centres. Significant epimerisation of pristane and phytane coincides with their D-enrichment, suggesting that hydrogen exchange occurs at their tertiary carbons. A mechanism is proposed which can account for both H/D exchange and the epimerisation of pristane and phytane in the sedimentary environment. Pristane and phytane extracted from a post-mature sediment from the Paqualin-1 sequence are significantly enriched in D (ca. 40%) relative to the n-alkanes, indicating that D-enrichment persists at very high maturity, and is more pronounced for the regular isoprenoids than the n-alkanes. This supports the notion that H/D exchange causes the observed shift in δD values, rather than free-radical hydrogen transfer. The differences between the δD values of pristane and phytane show opposite trends in the Perth Basin and Vulcan Sub-basin sediments. In the Perth Basin, phytane is enriched in D relative to pristane, likely due to a dominant algal source. In the Vulcan Sub-basin, pristane is enriched in D relative to phytane, and thus is attributed to a lower relative input of algal organic matter. The variance of the δD values of pristane and phytane is generally consistent throughout the maturity range and provides evidence that pristane and phytane exchange hydrogen at similar rates. δD analysis of crude oils and condensates reservoired in the Perth Basin and Vulcan Sub-basin has been carried out to evaluate potential applications in oil-source correlation. / The n-alkanes from crude oils and condensates are often more enriched in D than n-alkanes extracted from their supposed source rocks, and the oils also show relatively small differences between the δD values of n-alkanes and isoprenoids. These results suggest significant H/D exchange has occurred, implying that the liquids were generated from mature source rocks. A Perth Basin crude oil (Gage Roads-1) thought to be derived from a lacustrine/terrestrial source contains hydrocarbons that are significantly depleted in D relative to Perth Basin oils derived from a marine source, attributed to variability in the isotopic composition of marine and terrestrial source waters. δD values of n-alkanes from Vulcan Sub-basin crude oils and condensates are largely consistent with their prior classification into two groups: Group A, having a marine source affinity; and Group B, having a terrigenous source affinity. Some oils and condensates are suggested to be mixtures of Group A and Group B hydrocarbons, or Group A hydrocarbons and other as yet unknown sources. An exception is a former Group A oil (Tenacious-1) containing n-alkanes that are enriched in D relative to those from other Group A oils and condensates, attributed to mixing with another source of more mature hydrocarbons. The n-alkane δD profile appears to be indicative of source and sedimentary processes. One Perth Basin crude oil (Dongara-14) contains lower-molecular-weight n-alkanes that are depleted in D relative to higher-molecular-weight n-alkanes, attributed to a mixed marine/terrestrial source. / Group A crude oils and condensates from the Vulcan Sub-basin display a ‘bowl-shaped’ profile of n-alkane δD values. An upward inflection in the n-alkane δD profile from n-C11 [subscript] to n-C15 [subscript] is suggested to represent the addition of D-enriched lower-molecular-weight n-alkanes from a more mature wet gas/condensate to an initial charge of lower maturity oil. Ultimately, this project has demonstrated that the δD values of individual petroleum hydrocarbons can be used to elucidate the nature of source organic matter and depositional environments. The preservation potential of lipid δD values is greater than previously thought, although it is clear that H/D exchange accompanying maturation can have a significant effect on the δD values of certain hydrocarbons. Thus, great care must be taken when interpreting δD values of individual hydrocarbons, particularly those derived from sediments of high thermal maturity.

Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that can develop following exposure to a traumatic event involving actual or threatened death or serious injury. Responses include intense fear, helplessness or horror. Symptoms are characterised into clusters, described as re-experiencing, avoidance, and arousal. These symptoms, which are also evident in other conditions, have been associated with dysfunctions in the central acetylcholinergic system. Benefits from administering acetylcholinesterase inhibitors (AChEI) to people suffering these symptoms have been demonstrated. Donepezil hydrochloride, a reversible inhibitor of the enzyme acetylcholinesterase, is used in the treatment of conditions with difficulties in cognitive function, but has not been used in PTSD. The aim of this thesis was to determine (1) whether there was a difference in the ACh system in people with PTSD and (2) whether administration of an AChEI would change the symtomatology. IDEX (I¹ ² ³ iododexetimide) has been useful in imaging muscarinic-ACh receptors using Single Photon Emission Computerised Tomography (SPECT) and was utilised to investigate whether cholinergic activity in PTSD is altered. One hundred and sixty eight potential subjects were screened and eleven PTSD subjects were enrolled in the IDEX SPECT study. Three healthy non-PTSD control subjects also completed the study. Due to technical complications only the data obtained from eight PTSD and two control subjects was available for analysis. Imaging data for 2 further healthy non-PTSD control subjects were obtained from another study. Sixteen subjects were enrolled in the donepezil open label study (assessed at baseline, Week 2, 6 and 10). Nine PTSD subjects completed the 10-week trial and seven withdrew prematurely (at or after Week 2) due to side effects or a worsening of PTSD symptoms. For the IDEX SPECT study, a voxel-by-voxel statistical analysis of the PTSD subject group versus the control group showed both areas of reduced and increased IDEX uptake. Significant clusters in the PTSD group with a reduced IDEX uptake centred around the bilateral hippocampus, left insula and right precuneus, while increased IDEX uptake appeared in the caudate head. For the donepezil study, in the per-protocol analysis (including only the 9 subjects that completed the protocol), all psychological assessments revealed a difference between the totals obtained at the Week 10 visit compared to those at the Baseline visit and the improvement was in the order of 51%. The intention-to-treat analysis (including all 16 subjects), a repeated measures Analysis of Variance (ANOVA) with a mixed models approach showed that all psychological measures demonstrated statistically significant benefits of the treatment. All subjects who completed the protocol recounted considerable improvement in their overall PTSD symptom profile, which covered symptoms in each of the three clusters. The results of the IDEX SPECT study suggest that alterations in ACh binding in PTSD are evident and may begin to explain a part of the altered cognitive symptomatology apparent in this condition. The pilot open label donepezil trial provided some preliminary evidence that treatment with an AChEI can lessen the intrusions and distress associated with traumatic memories in people with PTSD. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1374974 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Medicine, 2009

<p><strong>Objectives</strong></p><p>The aim of this study was to compare left ventricular ejection fraction (LVEF) results derived from gated single photon emission computed tomography (SPECT) using Cedars-Sinai quantitative gated SPECT (QGS) processing software with results from 2D echocardiography, both obtained in routine clinical diagnostic use.</p><p> </p><p><strong>Methods</strong></p><p>Data from previously performed tests were obtained from 73 patients who had undergone both 2D echocardiography and gated SPECT within a time span of 6 months and had not had significant events that could influence LVEF. LVEF from 2D echocardiography was reassessed to obtain discrete values and then the data was compared using Bland-Altman analysis.</p><p> </p><p><strong>Results</strong></p><p>The correlation between the tests was shown to be good, but precision lacked. Bland-Altman analysis showed a bias of -0.8 percentage points when gated SPECT compared to mean values and 2 standard deviations (SD) ranged from -20.2 to 18.6.</p><p> </p><p><strong>Conclusions</strong></p><p>LVEF values from the two methods can differ quite a bit and comparisons between them should be done with great caution.</p> / <p><strong>Syfte</strong></p><p>Syftet med studien var att jämföra hur bra ultraljud av hjärta och isotopundersökning av hjärta stämmer överens när det gäller att visa hjärtats pumpförmåga.</p><p> </p><p><strong>Metod</strong></p><p>Data från tidigare utförda undersökningar av 73 patienter jämfördes. Patienter som hade gjort båda undersökningarna inom 6 månader och under perioden mellan undersökningarna inte hade haft hjärtinfarkt eller någon annan händelse som kan påverka hjärtats pumpförmåga valdes till studien.</p><p> </p><p><strong>Resultat</strong></p><p>Utslaget över hela studiepopulationen stämde resultaten från de båda undersökningarna bra överens. Jämförde man däremot resultaten från de båda undersökningarna med varandra patient för patient förekom mycket stora variationer.</p><p> </p><p><strong>Slutsats</strong></p><p>Resultaten angående hjärtats pumpförmåga kan skilja sig mycket från varandra. Jämförelser av värden från dessa två metoder bör därför göras med väldigt stor försiktighet.</p>

La nanomédecine est un secteur d'activité en plein essor depuis le développement des liposomes, nanovecteurs permettant d'encapsuler des molécules hydrosolubles ou amphiphiles pour la délivrance de médicament. Les nouveaux agents thérapeutiques synthétisés étant de plus en plus lipophiles, le développement de nouveaux vecteurs nanoparticulaires permettant leur transport constitue aujourd'hui un enjeu majeur. Les lipidots, nanoparticules lipidiques solides biocompatibles de 50 nm de diamètre, composées d'un mélange d'huile, de cire et de lécithine stabilisées par une couronne de surfactants pegylés, permettent de transporter des composés hautement hydrophobes en leur cœur. Des agents nucléaires pour la tomographie à émission monophotonique et des agents de fluorescence ont pu y être encapsulés pour l'évaluation de la biodistribution de ces nanoparticules chez la souris saine ainsi que dans différents modèles tumoraux. Un peptide de ciblage, le cRGD a également été greffé à la surface des lipidots afin d'adresser préférentiellement, dans les 3 premières heures après injection, les nanoparticules vers les tumeurs surexprimant les intégrines αvβ3. Une biodistribution particulière des lipidots dans les organes stéroïdiens (surrénales, ovaires) a été observée avec une localisation spécifique dans les zones synthétisant les hormones stéroïdiennes (le corps jaune pour les ovaires, la zone corticale pour les surrénales). Cette affinité unique a été mise à projet pour cibler des tumeurs hormono-dépendantes, ainsi que pour encapsuler des hormones ovariennes pour le traitement hormonal substitutif ou le contrôle de la procréation.

In single photon emission computed tomography (SPECT) one is interested in reconstructing the activity distribution f of some radiopharmaceutical. The data gathered suffer from attenuation due to the tissue density µ. Each imaged slice incorporates noisy sample values of the nonlinear attenuated Radon transform (formular at this place in the original abstract) Traditional theory for SPECT reconstruction treats µ as a known parameter. In practical applications, however, µ is not known, but either crudely estimated, determined in costly additional measurements or plainly neglected. We demonstrate that an approximation of both f and µ from SPECT data alone is feasible, leading to quantitatively more accurate SPECT images. The result is based on nonlinear Tikhonov regularization techniques for parameter estimation problems in differential equations combined with Gauss-Newton-CG minimization.

Peritoneal carcinomatosis (PC) is traditionally regarded as a terminal stage of disease with a poor prognosis and systemic chemotherapy is regarded as palliative treatment. In order to improve survival and even to achieve cure for selected patients with PC, cytoreductive surgery and intraperitoneal che-motherapy have been advocated. Despite complete macroscopic removal of tumour, residual microscopic malignant cells might result in recurrence. Intraperitoneal chemotherapy aims to kill residual malignant cells and thereby needs to be distributed in the entire peritoneal cavity. This aggres-sive combined loco-regional treatment has a high risk of morbidity and mor-tality. Whether the increased risks are acceptable to improve survival re-quires investigation and the impact of loco-regional treatment of PC on health-related quality of life (HRQL) needs to bee explored The overall aim of this thesis was to analyse the impact of cytoreductive surgery and intraperitoneal chemotherapy on patients with peritoneal carci-nomatosis. A significant survival improvement (median 32 months) was seen in 18 patients with PC of colorectal origin subjected to loco-regional treatment, in comparison to matched controls treated with systemic chemotherapy (me-dian survival 14 months, Paper I). The results of single-photon emission computer-tomography (SPECT) in 51 patients were correlated to the number of intraperitoneal chemotherapy courses that could be performed without further surgery (Paper II). Postoperative 30-days morbidity and 90-days mortality was investigated in 123 PC-patients after loco-regional treatment. Severe adverse events occurred in 51 (41%) patients. Five patients (4%) had treatment-related mortality. Stoma formation, duration of surgery, periopera-tive blood loss, and extent of PC was associated with morbidity (Paper III). HRQL was investigated in 64 patients. HRQL was negatively affected at 3 months but a partial recovery was seen at 8 months. 30-day morbidity did not have any impact on HRQL at 8 months (Paper IV). This treatment there fore appears justified despite considerable toxicity in view of possible life prolongation.

Objectives The aim of this study was to compare left ventricular ejection fraction (LVEF) results derived from gated single photon emission computed tomography (SPECT) using Cedars-Sinai quantitative gated SPECT (QGS) processing software with results from 2D echocardiography, both obtained in routine clinical diagnostic use.   Methods Data from previously performed tests were obtained from 73 patients who had undergone both 2D echocardiography and gated SPECT within a time span of 6 months and had not had significant events that could influence LVEF. LVEF from 2D echocardiography was reassessed to obtain discrete values and then the data was compared using Bland-Altman analysis.   Results The correlation between the tests was shown to be good, but precision lacked. Bland-Altman analysis showed a bias of -0.8 percentage points when gated SPECT compared to mean values and 2 standard deviations (SD) ranged from -20.2 to 18.6.   Conclusions LVEF values from the two methods can differ quite a bit and comparisons between them should be done with great caution. / Syfte Syftet med studien var att jämföra hur bra ultraljud av hjärta och isotopundersökning av hjärta stämmer överens när det gäller att visa hjärtats pumpförmåga.   Metod Data från tidigare utförda undersökningar av 73 patienter jämfördes. Patienter som hade gjort båda undersökningarna inom 6 månader och under perioden mellan undersökningarna inte hade haft hjärtinfarkt eller någon annan händelse som kan påverka hjärtats pumpförmåga valdes till studien.   Resultat Utslaget över hela studiepopulationen stämde resultaten från de båda undersökningarna bra överens. Jämförde man däremot resultaten från de båda undersökningarna med varandra patient för patient förekom mycket stora variationer.   Slutsats Resultaten angående hjärtats pumpförmåga kan skilja sig mycket från varandra. Jämförelser av värden från dessa två metoder bör därför göras med väldigt stor försiktighet.

Affibody molecules have lately shown great potential as tools for in vivo molecular imaging. These small, 3-helical bundles, with their highly stable protein scaffold, are well suited for the often harsh conditions of radiolabeling. Their small size allows for rapid clearance from the blood circulation which permits the collection of images already within hours after injection. This thesis includes four papers aimed at engineering different variants of a HER2-binding Affibody molecule to enable effective  and  flexible  radiolabeling  and  enhancing  the  molecular  imaging  in  terms  of  imaging contrast and resolution. In paper I an Affibody molecule was engineered to function as a multifunctional platform for site-specific labeling with different nuclides for radionuclide imaging. This was done using only natural amino  acids,  thereby  allowing  for  both  synthetic  and  recombinant  production.  By  grafting  the amino acid sequence -GSECG to the C-terminal of our model-protein, a HER2-binding Affibody molecule, we enabled site specific labeling with both trivalent radiometals and with  99m Tc. Maleim-ide-DOTA was conjugated to the cysteine residue for labeling with  111 In, while the peptide sequence was able to chelate  99m Tc directly. This approach can also be used for site-specific labeling with other probes available for thiol-chemistry, and is applicable also to other protein scaffolds. In paper II we investigated the impact of size and affinity of radiolabeled Affibody molecules on tumor targeting and image contrast. Two HER2-targeting Affibody molecules, a two-helix (~5 kDa) and a three-helix (~7 kDa) counterpart, were synthetically produced, labeled with  111 In via chelation by  DOTA  and  directly  compared  in  terms  of  biodistribution  and  targeting  properties.  Results showed  that  the  smaller  variant  can  provide  higher  contrast  images,  at  the  cost  of  lower  tumor uptake,  in  high-expressing  HER2-tumors.  However,  neither  the  tumor  uptake  nor  the  contrast of the two-helix variant is sufficient to compete with the three-helix molecule in tumors with low expression of HER2. In paper III and IV we were aiming to find methods to improve the labeling of Affibody molecules with  18 F for PET imaging. Current methods are either complex, time-consuming or generate heavily lipophilic conjugates. This results in low yields of radiolabeled tracer, low specific activity left for imaging, undesirable biodistribution or a combination thereof. In paper III we demonstrate a swift and efficient 2-step, 1-pot method for labeling HER2-binding Affibody molecules by the formation of aluminum  18 F-fluoride (Al 18 F) and its chelation by NOTA, all in 30 min. The results show that the  18 F-NOTA-approach is a very promising method of labeling Affibody molecules with  18 F and further investigation of this scheme is highly motivated. In the last paper we pursued the possibility of decreasing the high kidney retention that is common among small radiotracers with residual-izing radiometabolites. In this work  18 F-4-fluorobenzaldehyde (FBA) was conjugated to a synthetic HER2-targeting Affibody molecule via oxime ligation. However, to avoid elevated liver retention, as seen in previous studies with this kind of label, a hydrophilic triglutamyl spacer between the aminooxy moiety and the N-terminal was introduced. A comparison of the two constructs (with and without the triglutamyl spacer) showed a clear reduction of retention in both kidney and liver in NMRI mice at 2 h p.i. when the spacer was included. In the light of these promising results, further studies including tumor-bearing mice, are in preparation. / <p>QC 20130203</p>

En el contexto de la técnica de SPECT, la simulación Monte Carlo es una herramienta que permite profundizar en el fundamento físico de la formación de la imagen, evaluando diversos aspectos que serían muy difíciles de medir experimentalmente. Monte Carlo es un método estadístico que parte del seguimiento de partículas, generadas aleatoriamente, en una distribución tridimensional. Este seguimiento se hace incluyendo toda la física implicada, modelizada con unas funciones de probabilidad para las diferentes interacciones posibles. Este método se utiliza en diversas especialidades relacionadas con la interacción radiación ionizante-materia como son la medicina nuclear, radioterapia, dosimetría y protección radiológica.Esta herramienta se empleará en dos aplicaciones: 1) Cuantificación de estudios de SPECT de neurotransmisión y 2) Localización del foco epileptógeno en el contexto de la epilepsia farmacorresistente.A) Cuantificación de estudios de SPECT de neurotransmisión:El estudio de los sistemas de neurotransmisión cerebral tiene una gran importancia en el diagnóstico de enfermedades neurológicas y psiquiátricas. En concreto, la disfunción del sistema dopaminérgico presináptico está relacionado con la Enfermedad de Parkinson. La valoración visual es a menudo suficiente para valorar las imágenes del transportador de dopamina (DAT), pero una cuantificación de las imágenes permitiría hacerla menos dependiente del observador. Los valores cuantitativos están afectados por la degradación de las imágenes debido a los efectos asociados a la interacción radiación-materia, a los efectos relacionados con la respuesta del sistema colimador/detector y al efecto de volumen parcial. Para alcanzar la cuantificación exacta de estas imágenes es necesario desarrollar algoritmos de reconstrucción y métodos de corrección de cada uno de los efectos degradantes que afectan a la técnica de SPECT. Para evaluar la fiabilidad y la exactitud de los algoritmos de reconstrucción y de los métodos de cuantificación se puede hacer uso de las técnicas de simulación Monte Carlo. Por medio de la simulación de maniquíes numérico se puede evaluar la exactitud de un método de cuantificación comparando los valores teóricos (del maniquí) con los valores calculados (en la imagen reconstruida).B) Localización del foco epileptógeno:Las crisis epilépticas parciales se caracterizan por presentar un origen focal y porque tienen una elevada farmacorresistencia, por lo que se plantea la búsqueda de otras alternativas terapéuticas. Una posibilidad es el tratamiento quirúrgico extrayendo el foco sin que se produzcan déficits neurológicos significativos. Por este motivo la detección y correcta localización del foco es fundamental para valorara la posibilidad de cirugía en estos pacientes. El método SISCOM permite localizar el foco mediante el registro de dos estudios de SPECT (ictal e interictal) para detectar los cambios de perfusión y esta información funcional registrarla con la imagen de resonancia magnética, que aporta el detalle estructural y así permite localización del foco detectado. La evaluación cuantitativa de los algoritmos de registro empleados en la técnica requiere el conocimiento de una transformación geométrica de referencia. Para obtener esta transformación algunos estudios emplean marcadores externos, otros marcos estereotácticos o el cálculo de la transformación geométrica a partir de los resultados de registros intermedios. Una manera de conseguir este gold standard es por medio de la simulación realista de datos de SPECT.