Thesis (Ph.D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (November 15, 2006) Vita. Includes bibliographical references.

This dissertation presents the results of an investigation into the performance characteristics of a unique hemispherical SPECT (single-photon emission computed tomography) imaging system capable of producing three-dimensional (3D) tomographic images of the human brain. The system is completely stationary and collects all necessary views of the patient simultaneously, with no system motion. The imager consists of twenty small (10cm x 10cm crystal area), digital gamma cameras arranged in a hemispherical pattern around the patient's head and a hemispherical lead aperture. The hemispherical aperture is positioned between the cameras and the head and contains a large number of pinholes; in this way each camera sees a number of overlapping pinhole projections of the radioactive distribution within the patient's brain. The initial investigation of the performance characteristics of a 3D SPECT system of this design were carried out using a computer simulation in which effects due to radiometry, finite pinhole size, finite detector resolution, photon noise, and object attenuation were included. We used a digital 3D brain phantom as the test object and an iterative search algorithm to perform the reconstructions. The simulations were used to compare the performance of a variety of system configurations. Based upon the results of the simulation study, we constructed a laboratory prototype of the 3D SPECT system, which we used to further characterize the expected performance of a clinical imaging system of the same design. Prior to collecting SPECT data we calibrated the imaging system, which required that we efficiently measure and store the spatially variant system response function. These calibration data were then included in the reconstructions of the SPECT phantoms that we imaged. A number of different SPECT phantoms were imaged to demonstrate the system performance. We measured a reconstructed spatial resolution of 4.8mm full-width at half-maximum and a full-system sensitivity of 36cps/μCi, where both values were measured for a point source in air located at the center of the field of view. We also describe an analysis that we performed to determine the equivalent, non-multiplexed system sensitivity; using this method, we found that the equivalent sensitivity was 79% of the measured value for the system configuration and the particular task that we investigated.

Seizures are thought to arise primarily from the cerebral cortex. However, the propagation and behavioral manifestations of seizures involve a network of both cortical and subcortical structures. The medial thalamus and upper brainstem reticular formation are crucial areas for the maintenance of normal consciousness. Bilateral involvement of these structures may be responsible for loss of consciousness during partial seizures. Therefore, we sought to investigate the role of the medial thalamus and brainstem in seizures. We performed SPECT ictal-interictal difference imaging co-registered with high-resolution MRI scans to localize regions of cerebral blood flow changes in patients undergoing inpatient monitoring for epilepsy. Ictal-interictal SPECT scans from 43 seizures in 40 patients were analyzed. The medial thalami showed SPECT difference imaging changes of >20% in 18 patients. Of patients with medial thalamic changes, the majority (13 of 18) had seizure onset in the temporal lobe, while only 1 had confirmed onset in extratemporal structures, and the remainder were non-localized. In contrast, in the 22 patients without >20% SPECT changes in the medial thalami, 6 had extratemporal onset, 6 had temporal onset, and the remainder were non-localized. In patients with temporal lobe seizures, the side of greater medial thalamic and brainstem reticular formation involvement was strongly related to SPECT injection timing such that there was a sequential pattern of ipsilateral followed by contralateral changes. Brainstem structures showed >20% SPECT changes in 27 of 43 seizures with no clear relation to temporal or extratemporal onset. We conclude that the medial thalamus is preferentially involved in seizures arising from the temporal lobes, possibly reflecting the strong connections between limbic temporal structures and the medial thalamus. Sequential involvement of ipsilateral followed by contralateral structures in the medial thalamus and upper brainstem may explain how seizures produce peri-ictal loss of consciousness despite incomplete involvement of the cerebral cortex.

Thesis (Ph. D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2005" Includes bibliographical references.

The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.

Thesis (MScMedSC (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Single photon emission computed tomography (SPECT) with a superior contrast resolution has been shown to be more sensitive and specific with a lower nondiagnostic rate than planar imaging in many nuclear medicine studies but it is still not being routinely implemented in V/Q studies at many centres including Tygerberg Hospital. There are many studies on V/Q SPECT using Technegas as a ventilation agent but very limited studies available on 81m Kr gas. Aim: To clinically compare conventional planar and SPECT V/Q imaging using 81mKr gas in the diagnosis of pulmonary embolism, with CTPA as the gold standard. Patients and Methods: All patients referred with clinical suspicion of pulmonary embolism were assessed. The inclusion criteria were normal chest radiograph, normal renal function and no contrast allergy. Exclusion criteria were age below 18 years old, pregnancy, abnormal chest radiograph, abnormal serum creatinine/urea levels and unstable patients. A Well’s score was assigned to each enrolled patient. Perfusion scintigraphy was performed after intravenous injection 125 MBq of 99mTc MAA. Ventilation scintigraphy was performed with 81mKr gas. On a dual head camera, SPECT was done before planar acquisition, while perfusion was done before ventilation imaging in the same position. Planar V/Q images consisted of 6 standard views. All V/Q SPECT images were reconstructed using ordered-subset expectation-maximization (OSEM) algorithm and a post-reconstruction 3D Butterworth filters were applied. V/Q Planar and V/Q SPECT images were later evaluated and reviewed separately and reported based on recent EANM guidelines blinded to the CTPA results. All patients underwent multi-slice CTPA examinations on a 40-detector row scanner. The images were later assessed and reported blinded to the V/Q results. Statistical analysis was done using the Fisher exact test for comparison of categorical variables and the one-way ANOVA for continuous variables (p<0.05 was significant). Results: A total of 104 consecutive patients were referred with clinical suspicion of pulmonary embolism. Seventy-nine patients were excluded from this study mostly due to abnormal serum creatinine/urea levels. Only 25 patients were included in this study, with a mean age of 48 ± 19 years, and 64% being females. When compared to CTPA as gold standard, the prevalence of PE was 16% [5% – 37% at 95% CI], sensitivity 75% [21% – 99% at 95% CI], specificity 90% [68% – 98% at 95% CI], positive predictive value 60% [17% – 93% at 95% CI], negative predictive value 95% [73% – 100% at 95% CI] and diagnostic accuracy 88% [69% – 97%at 95% CI] for both V/Q Planar and SPECT. V/Q Planar showed a lower reader confidence i.e. could only clearly resolve 72% of cases compared to V/Q SPECT, which could precisely interpret all cases, showed more and better delineated mismatch vs match and segmental vs non-segmental defects. All patients who were scored as PE unlikely on Wells’ score (4) had PE ruled out on CTPA (p=0.04581) as well as 89% of patients on V/Q SPECT and V/Q Planar. Conclusion: Based on this study, V/Q Planar and V/Q SPECT have a similar diagnostic performance in patients with a normal or near normal chest X-rays. / AFRIKAANSE OPSOMMING: Enkelfoton emissie rekenaartomografie (EFERT) met beter kontrasresolusie is bewys om meer sensitief en spesifiek met ‘n laer nie-diagnostiese opbrengs as planare beelding in verskeie kerngeneeskunde ondersoeke te wees. In Tygerberg Hospitaal, soos in verskeie ander sentra, word dit egter steeds nie roetineweg vir ventilasie-perfusiestudies (V/Q) geïmplementeer nie. Daar is verskeie EFERT V/Q studies met Technegas as ventilasie agens, maar beperkte studies met 81m Kr gas beskikbaar. Doel: Om konvensionele planare en EFERT V/Q beelding vir die diagnose van pulmonale embolisme met mekaar te vergelyk, met rekenaartomografie pulmonale angiografie (RTPA) as goue standaard. Pasiënte en Metodes: Alle pasiënte wat met ‘n kliniese vermoede van pulmonale embolisme verwys is, is geevalueer. Die insluitingskriteria was ’n normale borskas Xstraal, normale nierfunksie en geen kontrasallergie nie. Uitsluitingskriteria was pasiënte jonger as 18 jaar, swanger pasiënte, abnormale borskas X-straal, abnormale serum kreatinien / ureumvlakke en onstabiele pasiënte. ’n Wells telling is vir elke pasiënt wat in die studie ingesluit is, bepaal. Perfusiebeelding is uitgevoer na die intraveneuse toediening van 125 MBq 99mTc MAA. Ventilasiestudies is gedoen met 81mKr gas. Die V/Q EFERT studies is voor die planare beelding met ’n dubbelkop gammakamera uitgevoer. Perfusiebeelding is voor die ventilasie in dieselfde posisie verkry. V/Q planare beelding het bestaan uit 6 standaard beelde. Alle V/Q EFERT is met “ordered-subset expectationmaximization” (OSEM) algoritmes verwerk, en post-rekonstruksie 3D Butterworth filters is toegepas. V/Q planare en V/Q EFERT beelding is later afsonderlik en sonder RTPA inligting volgens onlangse EANM riglyne evalueer en gerapporteer. ‘n Veelsnit RTPA met ‘n 40 snit skandeerder is op alle pasiënte uitgevoer. Die beelde is later beoordeel en gerapporteer sonder inagneming van die V/Q beeldingsresultate Statistiese verwerking is gedoen met die Fisher presisietoets vir vergelyking van kategoriese veranderlikes en die eenrigting ANOVA vir kontinue veranderlikes (p<0.05 is statisties betekenisvol). Resultate: ‘n Totaal van 104 opeenvolgende pasiënte met ‘n kliniese vermoede van pulmonale embolisme is verwys. Nege-en-sewentig pasiënte is uitgesluit, in die meeste gevalle as gevolg van abnormale serum kreatinienvlakke. Slegs 25 pasiënte is ingesluit, met ’n gemiddelde ouderdom van 48 ± 19 jaar, en 64% vroue. In vergelyking met RTPA as goudstandaard, was die prevalensie van PE 16% [5% – 37% met 95% VI], sensitiwiteit 75% [21% – 99% met 95% VI], spesifisiteit 90% [68% – 98% met 95% VI], positiewe voorspellingswaarde 60% [17% – 93% met 95% VI], negatiewe voorspellingswaarde 95% [73% – 100% met 95% VI] en diagnostiese akkuraatheid van 88% [69% – 97% met 95% VI] vir beide planare en EFERT V/Q beelde. V/Q planare beelde het ‘n laer lesersvertroue getoon, nl. dat slegs 72% van gevalle opgelos kon word relatief tot V/Q EFERT beelde, wat in alle gevalle presies geïnterpreteer kon word, met meer en beter omskrewe nie-ooreenstemmende teenoor ooreenstemmende en segmentele teenoor nie-segmentele defekte. In alle pasiënte met ‘n Wells puntetelling van 4 is PE met die RTPA uitgeskakel (p=0.04581), terwyl dit in 89% van pasiënte met V/Q EFERT en planare beelde uitgeskakel is. Gevolgtrekking: Gebaseer op hierdie studie het V/Q planare en EFERT beelding ‘n ooreenstemmende diagnostiese prestasie in pasiënte met ’n normale of naby normale borskas X-straal.

ENGLISH ABSTRACT: Background: The detection of bone infection can be very difficult especially in bone with altered structure due to prior trauma or surgical procedures. Complicated osteomyelitis (COM) is becoming a public health problem especially with the difficult choice between, high cost surgery and prolonged courses of intravenous or oral antibiotic therapy, as well as the social and psychological effect of longterm disease and disability of the patient. The correct localisation of especially bone infection is still a challenge for the clinician. The single photon emission computed tomography/low dose computed tomography (SPECT/CT), by fusing the functional information with the anatomical parts, is a wellestablished tool used in many nuclear medicine studies. This improves the overall quality of the study with more clear answers. The aim of the study was to determine the added value of SPECT/CT in the management of complicated osteomyelitis (COM) in patients with endo-prosthesis, post traumatic osteomyelitis with and without metal implants and diabetic foot. Methods: This was a prospective study, between February 2010 and February 2012. Patients with suspected COM who fulfilled the selection and inclusion criteria were included. All had abnormal three phase bone scan followed by infection imaging with 99mTc labelled white blood cells and 99mTc -colloid if the99mTc labelled white blood cell study was abnormal. 67Ga citrate was used in vertebral involvement. Planar and SPECT/CT images were reviewed for presence of abnormal uptake and for its localization in bone and soft tissue. Scan results were defined as positive or negative. Both planar and SPECT/CT images were compared regarding diagnosis and precise localization of infection. The final diagnosis was obtained from surgical specimen or microbiological culture as well as clinical follow-up of all patients. Results: There were 72 patients, 29 male and 43 female with mean age of 57 yrs [range 27-88].There were 24 patients with prosthesis, 16 with hip prosthesis (PH=16), and 8 with knee prosthesis (PK=8). There were 44 patients with post traumatic osteomyelitis, 26 with metal implants (TOM=26) and 18 without metal implants (TOWM= 18). Four patients had diabetic foot (DF= 4). Infection was diagnosed in 19/72 patients on planar images and in 21/72 on SPECT/CT. Infection was diagnosed in 4 patients with prosthesis, 16 patients with post traumatic injury and one diabetic foot patient. The four patients with prosthesis, SPECT /CT added diagnostic value by excluding osteomyelitis in 3 patients and by defining the exact extent and localizing soft tissue and bone infection (STI/OM) in one patient. In 16 patients with post traumatic OM on planar images, SPECT /CT added diagnostic value, by excluding OM in 4 patients and confirming only STI, better localisation of the uptake in bone and soft tissue in 5 patients, of them 2 patient was negative on planar, and in 7 patients, confirmed and defined the exact extent of both OM and STI. One diabetic foot was positive for STI on the planar, the SPECT/CT added diagnostic value by defining the extent of the infection. In summary the added value of SPECT/CT was: a. Overall infection: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (10%) 2. Better localization in bone and soft tissue: 6 patients (8%) 3. Better delineation of extent of infection: 9 patients (12%) 4. None: 50 patients (70%) b. In positive cases only: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (33%) 2. Better localization in bone and soft tissue: 5 patients (24%) 3. Better delineation of extent of infection: 9 patients (43%) 4. None: 0 patients The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy for infection, on planar was 90%, 100%, 100%, 97%, 97%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. For OM on planar, the sensitivity, specificity , positive predictive value, negative predictive value and accuracy was 100%, 89%, 53%, 100%, 90%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. Conclusion: In complicated osteomyelitis, SPECT/CT is useful in localizing, defining the exact extent of infection where the planar images are abnormal, with no added value if the planar images are negative. We recommend in clinical practice the routine use of hybrid SPECT/CT imaging in complicated osteomyelitis when planar images are abnormal. / AFRIKAANSE OPSOMMING: Agtergrond: Die opspoor van beeninfeksie is veral moeilik in been wat as gevolg van vorige trauma of chirurgiese prosedures misvorm is. Gekompliseerde osteomiëlitis word ‘n gesondheidsprobleem veral as gevolg van die moeilike keuse tussen hoë koste chirurgie en langdurige kursusse binneaarse of orale antibiotika, asook die sosiale en sielkundige gevolge van langstaande siekte en die gestremdheid van die pasiënt. Die korrekte lokalisering van veral beeninfeksie is steeds ‘n uitdaging vir die geneesheer. Enkel foton emissie rekenaartomografie / lae dosis rekenaartomografie (SPECT/CT), die kombinasie van funksionele en anatomiese inligting, is ‘n goed gevestigde metode in baie kerngeneeskunde ondersoeke. Dit verbeter die algemene kwaliteit van die studie met ‘n meer spesifieke antwoord. Die doel van hierdie studie was om die bykomende waarde van SPECT/CT in die hantering van gekompliseerde osteomiëlitis in pasiënte met endo-protese, post traumatise osteomiëlitis met en sonder metaal prosteses asook diabetiese voet te bepaal. Metode: ‘n Prospektiewe studie is tussen Februarie 2010 en Februarie 2012 gedoen. Pasiënte met vermoedelik gekompliseerde osteomiëlitis wat aan die keuse en insluitingskriteria voldoen het, is ingesluit. Almal het abnormale drie-fase beenflikkergramme gehad, gevolg deur infeksiebeelding met 99mTc gemerkte witselle en 99mTc kolloïed indien die 99mTc gemerkte witselstudie abnormaal was. 67Ga sitraat is gebruik wanneer daar werwelaantasting teenwoordig was. Die planare en SPECT/CT beelde is vergelyk ten opsigte van diagnose en presiese lokalisering van die infeksie. Die finale diagnose is met behulp van chirurgiese monsters en mikrobiologiese kweking asook die kliniese opvolg van alle pasiënte bepaal. Resultate: Die studie het 72 pasiënte, 29 mans en 43 vroue, met gemiddelde ouderdom van 57 jaar [27 – 88 ingesluit]. Daar was 24 pasiënte met prosteses, waarvan 16 met heupprosteses (PH= 16) en 8 met knieprosteses (PK= 8). Van die 44 pasiënte met post traumatiese osteomiëlitis, het 26 metaal prosteses (TOM= 26) en 18 geen metaalprosteses gehad nie (TOWM= 18). Vier pasiënte het diabetiese voet gehad (DF= 4). By 19/72 van die pasiënte is infeksie op die planare beelde gediagnoseer en in 21/72 op die SPECT/CT beelde. Die bykomende twee gevalle was 1 met TOM en 1 met TOWM. Infeksie is by 4 pasiënte met prosteses, 16 pasiënte met post traumatiese besering en 1 met diabetiese voet gediagnoseer. In die vier pasiënte met prosteses, het SPECT/CT ‘n diagnostiese bydrae gelewer om osteomiëlitis by 3 van die pasiënte uit te skakel en die presiese omvang en lokalisering van sagte weefsel en beeninfeksie (STI/OM) in een pasiënt te bepaal. In 16 pasiënte met post traumatise osteomiëlitis op die planare beelde, was SPECT/CT van diagnostiese waarde, waar osteomiëlitis in 4 pasiënte uitgesluit is, en slegs STI bevestig is. Beter lokalisering van die opname in been en sagte weefsel was in 5 pasiënte moontlik, van wie 2 op die planare beelde negatief was, en in 7 pasiënte bevestig en die presiese omvang met beide OM en STI gedefinieer is. Een diabetiese voet was positief vir STI op die planare beelde, maar die SPECT/CT het diagnostiese waarde verbeter deur die omvang van die infeksie beter te toon. Ter opsomming, was die waarde van die SPECT/CT: 1. Uitsluiting van osteomiëlitis deur slegs van sagte weefsel aantasting te bevestig: 7 pasiënte 10% 2. Beter lokalisering in been en sagte weefsel: 5 pasiënte 7% 3. Beter definisie van omvang van infeksie: 9 pasiënte 12% 4. Geen bykomende waarde: 51 pasiënte 71% Die algehele sensitiwiteit, spesifisiteit, positiewe voorspellingswaarde, negatiewe voorspellingswaarde en akkuraatheid vir die opspoor van infeksie vir die planare beelde was 90%, 100%, 100%, 97%, 97%, onderskeidelik en vir die SPECT/CT 100%, 100%, 100%, 100% en 100%. Vir osteomiëlitis was sensitiwiteit, spesifisiteit, positiewe voorspellingswaarde, negatiewe voorspellingswaarde en akkuraatheid van planare beelde 100%, 89%, 53%, 100%, 90%, onderskeidelik en die van SPECT/CT 100%, 100%, 100%, 100% , 100%. Gevolgtrekking: SPECT/CT is nuttig in die lokalisering en definiëring van die presiese omvang van die infeksie in gekompliseerde osteomiëlitis in gevalle waar die planare beelde abnormaal is, met geen bykomende waarde wanneer planare beelde negatief is nie. Ons beveel SPECT/CT beelding as roetine in kliniese praktyk aan wanneer planare beelde in gekompliseerde osteomiëlitis abnormaal is.

"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."

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 143-150).

No description available.