Medical imaging based on radioactive tracers exposes the patient to radiation. For this reason, a phantom is preferably used for non-clinical studies such as routine quality assurance and research. The aim of this project was to design, build and test a multi-compartment phantom to be used in dynamic SPECT/CT, PET/CT and PET/MRI studies. By treating each compartment as a biological system and plotting activity distribution, desired characteristics of the phantom can be obtained. A software program was created to simulate compartment activity distribution for different input parameters. Such parameters include number of compartments, administered activity, flow rates between compartments and compartment volume. Based on the simulation, the phantom was designed to meet the desired characteristics. Due to the outbreak of the SARS-CoV-2 virus, no phantom could be built nor tested. Consequently, leading the project to create a foundation that facilitates future building of the phantom. / Medicinsk avbildning med radioaktiva spårämnen utsätter patienter för en stråldos. Av detta skäl används företrädesvis en fantom för icke-kliniska studier såsom rutinmässig kvalitetssäkring och forskning. Syftet med detta projekt var att designa, bygga och testa ett flerkammarfantom som ska användas i dynamiska SPECT/CT, PET/CT och PET/MRI studier. Genom att behandla varje kammare som ett biologiskt system och plotta aktivitetsfördelning kan önskade egenskaper hos fantomen erhållas. Ett program skapades för att simulera aktivitetsdistributionen i flerkammarfantomer för olika in parametrar så som antal kammare, administrerad aktivitet, flöden mellan kammare och kammarvolym. Baserat på simuleringen utformades fantomen för att uppfylla de önskade egenskaperna. På grund av utbrottet av SARS-CoV-2 viruset kunde ingen fantom byggas eller testas. Följaktligen leddes projektet till att skapa en grund som underlättar framtida byggande av fantomen.

Thesis (MSc (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2010. / ENGLISH SUMMARY: Introduction: Bone scintigraphy is used extensively in evaluating metastatic disease. There are currently no clear recommendations for the use of SPECT/CT in metastatic bone disease. Existing procedural guidelines from the Society of Nuclear Medicine (SNM) for SPECT/CT do not provide specific indications for use of SPECT/CT in bone scintigraphy, and there are currently no other guidelines for the use of SPECT/CT in bone scintigraphy that the author is aware of. The aim of this study was to investigate the additional value of SPECT/CT, and to identify the clinical indications for which SPECT/CT is most useful in patients with suspected bone metastases. Subjects and Methods: Forty-two patients with equivocal lesions on planar scintigraphy were prospectively recruited and planar imaging, SPECT, and SPECT/CT done on all patients. On reading of SPECT and then SPECT/CT, patients and individual lesions were classified as malignant, benign or equivocal. Radiological studies and available clinical information were also used during reading of scans. Review of clinical information, radiological studies and/or follow-up bone scans were used as gold standard. The results of the SPECT and SPECT/CT were compared in terms of proportion of equivocal findings and accuracy. Results: Forty-two patients with 189 skeletal lesions were examined. There was a diverse variety of primary tumours, although the majority had breast (n=22) or prostate cancer (n=8). Overall, SPECT/CT resulted in a significant reduction in the proportion of equivocal findings on both a patient-wise (p=0.0015) and lesion-wise basis (p<0.0001). The overall accuracy of SPECT/CT was significantly higher than that of SPECT on both a patient-wise (p=0.0026) and lesion-wise basis (p<0.0001). Generally SPECT/CT decreased the proportion of equivocal findings and increased the accuracy independent of the presence of bone pain, type of primary tumour, or skeletal region involved. SPECT/CT did not significantly improve the diagnostic confidence of readers in equivocal lumbar lesions although accuracy was significantly improved in this region. Conclusion: SPECT/CT performs significantly better than SPECT alone for the interpretation of equivocal planar lesions. There is no evidence that the benefit of SPECT/CT is dependent on the type of primary tumour or the presence of bone pain. Where resources are limited, SPECT/CT is indicated only in those patients in whom correct classification of the lesions in question is expected to alter the patient’s management. SPECT/CT images should be interpreted with the aid of a diagnostic radiologist or nuclear medicine physicians should acquire sufficient experience in Computed Tomographic image interpretation in order to optimise diagnostic benefit from SPECT/CT. / AFRIKAANSE OPSOMMING: Inleiding: Beenflikkergrafie word wyd vir die evaluering van metastatiese siekte gebruik. Daar bestaan tans geen duidelike aanbevelings vir die gebruik van Enkelfotonemissie rekenaartomografie gekombineer met rekenaartomografie (EFERT/RT, Engels SPECT/CT) in metastatiese beensiekte nie. Bestaande riglyne van die Amerikaanse Society of Nuclear Medicine (SNM) vir EFERT/RT gee nie spesifieke indikasies vir die gebruik van EFERT/RT in beenflikkergrafie nie, en daar is tans geen ander riglyne waarvan die outeur bewus is nie. Die doel van hierdie studie was om die bykomende waarde van EFERT/RT te ondersoek, en om dié kliniese indikasies waar EFERT/RT in pasiënte met vermoedelike beenmetastases mees nuttig sal wees, te identifiseer. Pasiënte en Metodes: Twee en veertig pasiënte met twyfelagtige letsels op planare skeletflikkergrafie is prospektief geselekteer en planare beelding, EFERT en EFERT/RT is op alle pasiënte gedoen. Tydens beoordeling van EFERT en daarna EFERT/RT beelde is pasiënte en individuele letsels as maligne, benigne of twyfelagtig geklassifiseer. Radiologiese studies en beskikbare kliniese inligting is ook tydens interpretasie van flikkergramme gebruik. Kliniese inligting, radiologiese studies en/of opvolg beenflikkergramme is as goue standaard gebruik. Die resultate van EFERT en EFERT/RT is ten opsigte van die aantal twyfelagtige bevindings en akkuraatheid vergelyk. Resultate: Twee en veertig pasiënte met 189 skeletale letsels is ondersoek. Daar was ‘n verskeidenheid van primêre tumore, maar die meerderheid van pasiënte het borsvi (n=22) of prostaatkanker (n=8) gehad. Die gebruik van EFERT/RT het gelei tot ‘n betekenisvolle afname in die aantal twyfelagtige bevindings, beide op ‘n pasiënt- en ‘n letselbasis (p=0.0015 en p<0.0001 onderskeidelik). Die algehele akkuraatheid van EFERT/RT was betekenisvol hoër as die van EFERT alleen, beide op pasiënt- en op letselbasis (p=0.0026 en p<0.0001 onderskeidelik). Oor die algemeen het EFERT/RT die aantal twyfelagtige letsels verminder en die akkuraatheid verhoog, ongeag die teenwoordigheid van beenpyn, die tipe primêre tumor of die area van die skelet wat betrokke was. In twyfelagtige lumbale letsels het EFERT/RT nie die diagnostiese vertroue van beoordelaars van flikkergramme verhoog nie, alhoewel die akkuraatheid vir hierdie gebied wel betekenisvol toegeneem het. Gevolgtrekking: EFERT/RT vaar betekenisvol beter as EFERT in die beoordeling van twyfelagtige letsels op planare beenflikkergramme. Daar is geen bewys dat die voordeel van EFERT/RT afhanklik is van die tipe primêre tumor of die teenwoordigheid van beenpyn nie. Waar hulpbronne beperk is, is EFERT/RT slegs aangedui in dié pasiënte waar verwag word dat korrekte klassifikasie van die betrokke letsel behandeling sal beïnvloed. EFERT/RT beelde behoort met die hulp van ‘n diagnostiese radioloog beoordeel te word, of kerngeneeskundiges moet genoegsame ondervinding in die interpretasie van rekenaartomografiebeelde hê om die diagnostiese voordeel van EFERT/RT optimaal te kan benut.

"Patient motion, which causes artifacts in reconstructed images, can be a serious problem in Single Photon Emission Computed Tomography (SPECT) imaging. If patient motion can be detected and quantified, the reconstruction algorithm can compensate for the motion. A real-time multi-threaded Visual Tracking System (VTS) using optical cameras, which will be suitable for deployment in clinical trials, is under development. The VTS tracks patients using multiple video images and image processing techniques, calculating patient motion in three-dimensional space. This research aimed to develop and implement an algorithm for feature matching and stereo location computation using multiple cameras. Feature matching is done based on the epipolar geometry constraints for a pair of images and extended to the multiple view case with an iterative algorithm. Stereo locations of the matches are then computed using sum of squared distances from the projected 3D lines in SPECT coordinates as the error metric. This information from the VTS, when coupled with motion assessment from the emission data itself, can provide a robust compensation for patient motion as part of reconstruction."

Bakgrund: Kranskärlssjukdom (CAD) är en hjärtsjukdom som kan diagnostiseras med icke-invasiva metoder, såsom myocardial perfusion imaging med single-photon emission computed tomography (SPECT), och genom invasiva metoder, såsom invasiv koronarangiografi (ICA). ICA är den golden standardmetod för att diagnostisera CAD. Men å andra sidan är ICA mer kostsam än SPECT och kan orsaka många komplikationer. Metoder och resultat: det är en retrospektiv kohortstudie. Studien analyserade 62 patienter som har genomgått både SPECT och ICA under 2018 vid Universitetssjukhuset Örebro (USÖ). Av dessa 62 utförde 56 patienter SPECT först. Analyseringen gjordes för att undersöka hur väl resultatet av ICA-sjukdomsdetektering och lokalisering kunde bestämmas av SPECT. Aktiv CAD definierades som närvaron av en behandling-krävande signifikant stenos vid ICA. SPECT-resultaten visade att 91% av fallen var patologiska och 9% var icke-patologiska. Sensitivitet, specificitet och noggrannhet för SPECT för detektering av aktiv CAD var 89%, 7% respektive 47% vid referens till ICA. Medan positiva prediktiva värden (PV +) och negativa prediktiva värden (PV-) var 48% respektive 40%. SPECT sensitivitet för lokalisering av defekter i referens till ICA var 35% för LAD-defekter, 68% för LCX-defekter och 92% för RCA-defekter. Slutsats: Resultatet skilde sig från den ursprungliga hypotesen. SPECT anses fortfarande vara effektiv för att identifiera patienter med aktiv CAD. Därför kan SPECT användas som initial undersökningsmetod för utvärdering av CAD hos patienter med låg till måttlig risk. SPECT var inte optimalt för att lokalisera defekterna.

Orientador: Marcelo Zanchetta do Nascimento / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia da Informação, 2011

Bien que les mécanismes moléculaires précis à l’origine de la neurodégénérescence dopaminergique ne soient pas encore totalement connus, un ensemble de preuves épidémiologiques, cliniques et expérimentales indiquent que la neuroinflammation peut avoir un rôle important dans la pathogenèse de la MP. L’étude des liens spatio-temporels entre la neuroinflammation et la neurodégénérescence au cours de la MP pourrait améliorer la compréhension du mécanisme physiopathologique et aussi l'accessibilité à un diagnostic précoce et/ou à de nouvelles approches thérapeutiques anti-inflammatoires. Le développement actuel des méthodes non invasives d'imagerie moléculaire permettant la surveillance directe du processus de neuroinflammation devrait être utile à cet effet. La cible moléculaire de choix dans ce domaine est la protéine de 18 kDa translocateur (TSPO), biomarqueur sensible associée à la neuroinflammation, qui est surexprimé dans les microglies activées. Dans le travail présenté ici nous avons réalisé l'évaluation longitudinale des deux mécanismes physiopathologiques en parallèle avec les modifications de la fonction dopaminergique à plusieurs points au cours du temps après lésion à la 6-OHDA chez le rat, modèle qui imite un stade précoce de la MP. Après l'administration unilatérale, intra-striatale de la 6-OHDA, nous avons quantifié l'évolution temporelle de la TSPO, de l’immunoréactivité TH et du DAT dans le striatum et la SNC de 3 à 56 jours post-lésion (jpl). L’augmentation de la liaison des ligands de la TSPO utilisés, c-à-d [3H]-PK11195 et [125I]-CLINDE, a été observée dans le striatum lésé à 3, 7 et 14 jpl, suivie d'un retour progressif à un niveau basal à 56 jpl. Le profil de liaison dans la SNC a montré une augmentation progressive de la fixation qui débute à 3 jpl, avec un pic à 14 jpl, et diminue progressivement jusqu'à ce que 56 jpl. Dans ce modèle de rongeur de la MP, les processus neuroinflammatoire et neurodégénératif surviennent de façon concomitante. La présence transitoire de l'activation microgliale pourrait être impliquée dans l’apparition et l'installation durable de la perte neuronale dopaminergique. Cette étude confirme donc le lien entre la neuroinflammation et de la neurodégénérescence et met aussi l'accent sur l'intérêt du CLINDE comme traceur potentiel de la neuroinflammation in-vivo en fournissant des informations précieuses pour le diagnostic précoce et le suivi longitudinal de la progression de la maladie, avec des applications potentielles chez l'homme. En effet, la détection précoce de la neuroinflammation, de façon antérieure à une perte neuronale cliniquement significative, pourrait devenir un enjeu majeur dans la prise en charge pré-symptomatique de la MP. Dans ce sens, nous mettons en évidence l’existence d'une fenêtre thérapeutique, survenant juste après la lésion, qui peut être proposé pour l'introduction de traitements anti-inflammatoires qui viseraient à ralentir le processus neurodégénératif. La poursuite de l’exploration des relations entre la neuroinflammation et la neurodégénéréscence in-vivo dans le même modèle animal avec la méthode d’imagerie micro-TEP, transposable à l’homme, en utilisant en parallèle le [18F]-DPA714 pour la TSPO et le [18F]-LBT999 pour le DAT est en cours. / Although the precise molecular mechanisms causing the dopaminergic neurodegeneration are still not totally understood, a body of epidemiological, clinical and experimental evidence indicates that neuroinflammation may have an important role in the pathogenesis of PD. Study of spatio-temporal links between neuroinflammation and neurodegeneration during the course of PD would improve understanding of the physiopathological mechanism and also accessibility to early diagnosis and/or new antiinflammatory therapeutic approaches. The current development of non-invasive molecular imaging methods allowing direct monitoring of the neuroinflammation process should be valuable for this purpose. The molecular target of choice in this field is the 18 kDa translocator protein (TSPO), a sensitive biomarker associated with neuroinflammation, which is over-expressed in activated microglia. In the study presented here we achieved the longitudinal evaluation of both physiopayhological mechanisms in parallel with the modifications of dopaminergic function at several time-points after 6-OHDA lesion in the rat that mimics an early stage of PD. After unilateral intra-striatal 6-OHDA administration, we quantified the temporal evolution of the TSPO, TH immunoreactivity and DAT in the striatum and the SNc from 3 to 56 days post-lesion (dpl). Increased binding of TSPO ligands used, i.e. [3H]PK11195 and [125I]CLINDE, was observed in the lesioned striatum at 3, 7 and 14 dpl, followed by a progressive return to the basal level at 56 dpl. The binding profile in the SNc showed progressive binding beginning at 3 dpl, peaking at 14 dpl, and progressively decreasing until 56 dpl. In this rodent model of PD, the neuroinflammatory and neurodegenerative processes occurred concomitantly. The transitory occurrence of microglial activation could be involved in the advent and the lasting installation of dopaminergic neuron loss. This study supports the link between neuroinflammation and neurodegeneration and emphasizes the interest of CLINDE as potent in vivo tracer of neuroinflammation by providing valuable information for early diagnosis and longitudinal follow-up of disease progression, with potential applications to human patients. Indeed, early detection of neuroinflammation, prior to a clinically significant loss of neurons, could become a major issue in the management of pre-symptomatic PD. To support this idea, we demonstrate the existence of a therapeutic window, occurring just after the lesion, which may be proposed for the introduction of anti-inflammatory treatments that aimed to slow the neurodegenerative process. Further exploration of the relationship between neuroinflammation and neurodegeneration in vivo in the same animal model with the method of micro-PET imaging, transposable to humans, using in parallel the [18F]-DPA714 for TSPO and [18F]-LBT999 for DAT is pending.

<p>The fuel assemblies used at the Swedish nuclear power plants contain typically between 100 and 300 fuel rods. An experimental technique has been demanded for determining the relative activities of specific isotopes in individual fuel rods without dismantling the assemblies. The purpose is to validate production codes, which requires an experimental relative accuracy of <2 % (1 σ).</p><p>Therefore, a new, non-destructive tomographic measurement technique for irradiated nuclear fuel assemblies has been developed. The technique includes two main steps: (1) the gamma-ray flux distribution around the assembly is recorded, and (2) the interior gamma-ray source distribution in the assembly is reconstructed. The use of detailed gamma-ray transport calculations in the reconstruction procedure enables accurate determination of the relative rod-by-rod source distribution.</p><p>To investigate the accuracy achievable, laboratory equipment has been constructed, including a fuel model with a well-known distribution of ¹³⁷Cs. Furthermore, an instrument has been constructed and built for in-pool measurements on irradiated fuel assemblies at nuclear power plants.</p><p>Using the laboratory equipment, a relative accuracy of 1.2 % was obtained (1 σ). The measurements on irradiated fuel resulted in a repeatability of 0.8 %, showing the accuracy that can be achieved using this instrument. The agreement between rod-by-rod data obtained in calculations using the POLCA–7 production code and measured data was 3.1 % (1 σ).</p><p>Additionally, there is a safeguards interest in the tomographic technique for verifying that no fissile material has been diverted from fuel assemblies, i.e. that no fuel rods have been removed or replaced. The applicability has been demonstrated in a measurement on a spent fuel assembly. Furthermore, detection of both the removal of a rod as well as the replacement with a non-active rod has been investigated in detail and quantitatively established using the laboratory equipment.</p>

The fuel assemblies used at the Swedish nuclear power plants contain typically between 100 and 300 fuel rods. An experimental technique has been demanded for determining the relative activities of specific isotopes in individual fuel rods without dismantling the assemblies. The purpose is to validate production codes, which requires an experimental relative accuracy of &lt;2 % (1 σ). Therefore, a new, non-destructive tomographic measurement technique for irradiated nuclear fuel assemblies has been developed. The technique includes two main steps: (1) the gamma-ray flux distribution around the assembly is recorded, and (2) the interior gamma-ray source distribution in the assembly is reconstructed. The use of detailed gamma-ray transport calculations in the reconstruction procedure enables accurate determination of the relative rod-by-rod source distribution. To investigate the accuracy achievable, laboratory equipment has been constructed, including a fuel model with a well-known distribution of 137Cs. Furthermore, an instrument has been constructed and built for in-pool measurements on irradiated fuel assemblies at nuclear power plants. Using the laboratory equipment, a relative accuracy of 1.2 % was obtained (1 σ). The measurements on irradiated fuel resulted in a repeatability of 0.8 %, showing the accuracy that can be achieved using this instrument. The agreement between rod-by-rod data obtained in calculations using the POLCA–7 production code and measured data was 3.1 % (1 σ). Additionally, there is a safeguards interest in the tomographic technique for verifying that no fissile material has been diverted from fuel assemblies, i.e. that no fuel rods have been removed or replaced. The applicability has been demonstrated in a measurement on a spent fuel assembly. Furthermore, detection of both the removal of a rod as well as the replacement with a non-active rod has been investigated in detail and quantitatively established using the laboratory equipment.

The aim of this doctoral thesis was to study neuropsychological function in relation to structural and functional brain changes in Alzheimer´s disease (AD). In the first study relations between hippocampal volume, neuropsychological function and limbic-hypothalamic-pituitary-adrenal (LHPA) axis disturbances in AD were investigated with magnetic resonance imaging (MRI). Reduced hippocampal CA1 volume and suppressed cortisol levels in combination, best predicted the variation in neuropsychological performance. The conclusion was that reduced hippocampal volume and LHPA axis disturbances are associated to level of cognitive function in AD. The second study focused on whether patients with early AD showed an altered regional cerebral blood flow (rCBF) pattern compared to control persons, correlation between performance on memory tests and rCBF in sub-lobar volumes of the brain were investigated. The rCBF was measured with single photon emission computed tomography (SPECT). AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus compared to controls. The diagnostic sensitivity and specificity for AD was high in temporoparietal regions. AD-patients had significantly lower performance on semantic and, in particular, episodic memory-tests compared to the controls, and their performance on several episodic tests correlated with rCBF in parietal and temporal regions including left hippocampus, which suggest that abnormalities in the rCBF pattern underlie impaired episodic memory functioning in AD. The conclusion was that an observer-independent analyzing method for SPECT with sub-lobar volumes VOI´s is promising in the diagnosis of AD. In a third study possible differences in memory-related functional brain activation between persons with high versus low risk for AD were examined with functional magnetic resonance imaging (fMRI). The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences. During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal and hippocampal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. The conclusion was that patterns of prefrontal brain activity related to episodic memory differed between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease. In a final study SPECT was used to map patterns of rCBF in an activated state (an episodic encoding task) and in a rest condition in persons with mild AD and in healthy elderly control persons. A reduction of rCBF in temporoparietal regions that was more pronounced in mild AD in the activated encoding task was observed. The conclusion was that there are rCBF differences between mild AD patients and healthy controls in temporoparietal regions, and the temporoparietal reduction is more pronounced during activation than during rest which might be important in the early diagnosis of AD. Taken together, these findings show that level of neuropsychological function, notably episodic memory, can be systematically related to functional disturbances in the LHPA axis and to the function of temporoparietal and prefrontal brain regions in AD patients. These changes are detectable in patients with risk for AD and in an early phase of AD which suggests that the obtained results might be important for early diagnosis of AD.

Background: Single photon emission computed tomography (SPECT) with dopamine transporter (DAT) and dopamine D2 receptor (D2R) ligands can visualise the integrity of the nigrostriatal dopamine system. Parkinson’s disease (PD) and the atypical parkinsonian diseases (APD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), have similar symptoms and dopamine depletion, but differ in pharmacological response and prognosis. Clinical differentiation between PD and APD is often difficult in the early stages. The aims of the thesis were to evaluate the differential diagnostic and prognostic value of SPECT in early PD, MSA and PSP, to map the pattern of progression with dopamine SPECT, and map the pattern of dopamine SPECT in non-affected elderly volunteers with a prospective approach. Also, we evaluated the methodological aspects of dopamine SPECT with respect to image evaluation tools, reconstruction parameters and gamma cameras. Methods: 172 patients, included in an on-going clinical prospective study on idiopathic parkinsonism, participated in the SPECT study. Also, 31 age-matched healthy controls (HC) were followed within this study. SPECT was done with 123I-FP-Cit (DAT SPECT) and 123I-IBZM (D2R SPECT). Regions of interest (ROI) were used as a standard method for semi-quantitative image analysis. Results: SPECT uptake ratios from different gamma cameras could be equalised through correction equations derived from images of a brain-like phantom, provided that attenuation correction was applied. The ROI method had high reproducibility. SPECT uptake  in HC, measured with the ROI method and a volume based (VOI) method rendered similar trends, but gender and age differences in SPECT uptake were more marked with the VOI method, and less pronounced in DAT SPECT compared to D2R SPECT with both methods. The DAT SPECT uptake was significantly reduced in very early disease stage of PD and APD compared to HC. DATSPECT uptake was more reduced in PD with postural and gait disturbance (PIGD) compared to tremor-dominant PD. Decline in DAT SPECT uptake during the first year was more pronounced in PD and PSP compared to HC. D2R SPECT uptake overlapped between untreated PD and APD. After initiated treatment, the D2R SPECT uptake was significantly higher in MSA patients compared to PD, PSP and HC. Decline in D2R SPECT uptake during the first year was not significantly different between patients or compared to HC. Conclusions: 123I-FP-Cit SPECT is a valuable and sensitive method to detect early stage idiopathic parkinsonism. A different level of uptake between PIGD-PD compared to TD-PD indicates a prognostic potential. It is not possible to differ between PD, MSA and PSP in early stage with 123I-FP-Cit SPECT and no differential diagnostic value was found using 123I-IBZM SPECT in the early, untreated stage of PD, MSA and PSP. A different pattern of uptake of this ligand in MSA compared to PD and PSP during the first years of L-dopa treatment may, however, indicate a diagnostic value during the follow-up period.