Дисертації з теми "Diagnostic imaging"

[Truncated abstract] Hypothesis: There is deficiency in the evidence base and scientific underpinning of existing diagnostic imaging pathways (DIP) for diagnostic endpoints. Objective: a) To carry out systematic review of literature in relation to use of diagnostic imaging tests for diagnosis and investigation of 78 common clinical problems, b) To identify deficiencies and controversies in existing diagnostic imaging pathways, and to develop a new set of consensus based pathways for diagnostic imaging (DIP) supported by evidence as an education and decision support tool for hospital based doctors and general practitioners, c) To carry out a trial dissemination, implementation and evaluation of DIP. Methods: 78 common clinical presentations were chosen for development of DIP. For general practitioners, clinical topics were selected based on the following criteria: common clinical problem, complex in regards to options available for imaging, subject to inappropriate imaging resulting in unnecessary expenditure and /or radiation exposure, and new options for imaging of which general practitioners may not be aware. For hospital based junior doctors and medical students, additional criteria included: acute presentation when immediate access to expert radiological opinion may be lacking and clinical problem for which there is a need for education. Systematic review of the literature in relation to each of the 78 topics was carried out using Ovid, Pubmed and Cochrane Database of Systematic Reviews. ... The electronic environment and the method of delivery provided a satisfactory medium for dissemination. Getting DIP implemented required vigorous effort. Knowledge of diagnostic imaging and requesting behaviour tended to become more aligned with DIP following a period of intensive marketing. Conclusions: Systematic review of literature and input and feedback from various clinicians and radiologists led to the development of 78 consensus based Diagnostic Imaging Pathways supported by evidence. These pathways are a valuable decision support tool and are a definite step towards incorporating evidence based medicine in patient management. The clinical and academic content of DIP is of practical use to a wide range of clinicians in hospital and general practice settings. It is source of high level knowledge; a reference tool for the latest available and most effective imaging test for a particular clinical problem. In addition, it is an educational tool for medical students, junior doctors, medical imaging technologists, and allied health care personnel.

The focus of the project has two aspects associated with tumour imaging. The primary and major focus of my thesis was to assess the potential of a radiolabelled agent, 99mTc-Hynic-Annexin V, for the in vivo imaging of apoptosis after chemotherapy and radiotherapy in nude mice bearing thymoma tumours. The second aspect of the thesis examines the potential of a glucose analog, 99mTclabelled 2-deoxyglucosamine (99mTc—ECDG), to detect tumours based on the increased glucose metabolism of tumours in an attempt to evaluate if it can substitute the PET agent, 18F— labelled fluorodeoxyglucose (lgF-FDG) for tumour detection. Apoptosis is a process whereby damaged cells undergo programmed cell death during which phosphatidylserine (PS) becomes extemalised. Annexin V is shown to have a high affinity for PS and has been demonstrated to bind in apoptotic cells. When radiolabelled, Annexin V acts as an imaging probe to detect apoptosis. Available literature revealed many modalities available for apoptosis detection but most are associated with many pitfalls. However, only nuclear medicine imaging is able to provide a non-invasive tool for the early assessment of apoptosis. Furthermore, 99mTc-Hynic-Annexin V has been the best characterised probe for detecting apoptosis to date. Several studies have reported good correlation of this agent with therapy-induced apoptosis. However none have reported on the comparisons of two modes of cancer treatment (chemotherapy and radiotherapy) in a thymoma mouse model.

There are two Gadolinium-based liver-specific contrast media for Magnetic Resonance Imaging on the market, Gd-BOPTA (MultiHance®, Bracco Imaging, Milan, Italy) and Gd-EOB-DTPA (Primovist®, Bayer Schering Pharma, Berlin, Germany). The aim of this study in two parts was to evaluate the dynamics of biliary, parenchymal and vascular enhancement using these contrast media in healthy subjects. Ten healthy volunteers were examined in a 1.5 T magnetic resonance system using three-dimensional Volumetric Interpolated Breath-Hold (VIBE) sequences for dynamic imaging with both contrast media – at two different occasions – until five hours after injection. The doses given were 0.025 mmol/kg for Gd-EOB-DTPA and 0.1 mmol/kg for Gd-BOPTA. The enhancement over time of the common biliary duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.While Gd-EOB-DTPA gave an earlier and more prolonged enhancement of the biliary duct, Gd-BOPTA achieved higher image contrast for all vessels studied, during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.At the obtained time-points and at the dosage used, the high contrast between the common biliary duct and liver parenchyma had an earlier onset and longer duration for Gd-EOB-DTPA, while Gd-BOPTA achieved higher maximal enhancement of the hepatic artery, portal vein and middle hepatic vein than Gd-EOB-DTPA. Diseases of the liver and biliary system may affect the vasculature, parenchyma, biliary excretion or a combination of these. The clinical context regarding the relative importance of vascular, hepatic parenchymal and biliary processes should determine the choice of contrast media for each patient and examination.

 

The increasing popularity of snakes and lizards as pets has led to an increasing demand of specialised veterinary duties in these animals. Diagnostic imaging is often a fundamental step of the clinical investigation. The interpretation of diagnostic images is complex and requires a broad knowledge of anatomy, physiology and pathology of the species object of the clinical investigation. Moreover, in order to achieve a correct diagnosis, the comparison between normal and abnormal diagnostic images, for all the diagnostic imaging modalities, is mandatory. In this PhD thesis the diagnostic imaging features of some snake and lizard species are described. The aim of all the works presented is to provide some normal atlases matching the normal gross and cross-sectional anatomy with the normal radiographic, ultrasonographic, CT features of some of the most popular pet lizard and snake specie. In Chapter I a review of literature regarding snakes and lizards is presented. The aim of this chapter is to review the most commonly used diagnostic imaging modalities as well as to make an updated collection of the available international references describing the normal and pathological imaging features in snakes and lizards. Most of papers describing radiography, ultrasonography, computed tomography, magnetic resonance imaging and other imaging modalities have been collected in order to overcome the lack of a unique reference regarding diagnostic imaging in snakes and lizards. The scientific aims and the outline of this thesis are presented in Chapter II. The general aim of this PhD thesis is to provide some useful anatomical and diagnostic imaging references in snakes and lizards. The first part of this work (Chapters III and IV) is focused on the description of the normal radiographic and computed tomographic features of the head of some snakes and lizards species. The second part (Chapters V to VII) is focused on the diagnostic imaging of the coelomic cavity; the description of the normal contrast enhanced computed tomographic features of the coelomic cavity of some lizards, the normal ultrasonographic features of the coelomic cavity of some snake species and the normal upper gastro-intestinal examination in the ball python are presented. In Chapter III the normal stratigraphic and cross sectional anatomy is matched with the normal radiographic and computed tomographic features of the head of the Boa constrictor. 4 boa constrictor’s cadavers head where used in this study. Radiographs of the head were taken in LL and DV projections using a high detail screen-film combination. CT scans scans of the head where performed in a CC and a LL direction with a slice thickness of 1,5mm and displayed in a bone window. 2 heads where dissected following a stratigraphic approach and 2 heads frozen for 24h (-20°C) and then sectioned into 3mm slices respecting the imaging protocol. All anatomical structures have been identified and labelled with the aid of available literature in the anatomical images and then matched on the corresponding radiographic and computed tomographic images. Radiographic and CT images provided a high detail for the visualisation of bony structures; soft tissues were not easily identified on radiographic and CT images. In Chapter IV the normal radiographic and contrast enhanced computed tomographic features of the head of the green iguana, common tegu and bearded dragon are described. The study included 4 cadavers for each considered species and 6 adult green iguanas, 4 tegus, 3 bearded dragons. Prior to the beginning of the radiographic and computed tomographic studies 2 cadavers were dissected following a stratigraphic approach and 2 cadavers were cross-sectioned for each species. Anatomical studies were performed following the same approach described in Chapter III. Both the radiographic and the computed tomographic studies were performed only in live animals. Radiographic studies included a LL and a DV projection. Pre- and post- contrast computed tomographic studies of the head were performed in a CC direction. CT images were displayed in both bone and soft tissue windows. Individual anatomical structures were first recognised and labelled on the anatomic images and then matched on radiographs and CT images. Radiographic studies provided a good detail both of the soft tissues (especially in the green iguana) and of the bony structures. CT images provided an excellent detail of the bony structures in all the considered species. The soft tissues were clearly outlined only in the green iguana. In the common tegu and the bearded dragon only the eyes were clearly outlined from the remaining soft tissues. In Chapter V the normal contrast enhanced computed tomographic features of the coelomic cavity of the green iguana, black and white tegu and the bearded dragon are described. 4 cadavers and 4 live animals for each considered species were object of this study. The cadavers were frozen for 24 hours and then cross sectioned at 5mm intervals. The slices have been cleaned with water and photographed on both sides. In order to reduce the duration of the procedure only contrast enhanced CT scans have been performed. The CT scans have been performed in a CC direction. The CT scans have been displayed in a soft tissue and, when appropriate, in a lung window. Individual organs have been recognised and labelled on the anatomical images and then matched on the corresponding CT images. Most of the coelomic organs have been identified in all the considered species. Results provide an atlas of the normal cross sectional and CT features of the coelomic cavity of lizards. In Chapter VI the normal ultrasonographic features of the coelomic cavity of the Boa constrictor, Python molurus, Python curtus and Python regius are described. Moreover, normal reference ultrasonographic measurements of the scent glans, the colonic, gastric and pyloric wall thickness are reported. 46 live snakes (16 Python regius, 10 Python molurus, 12 Python curtus and 8 Boa constrictor) and 23 cadavers (6 Python regius, 4 Python molurus, 10 Python curtus, 3 Boa constrictor) where object of this study. Anatomical studies where performed prior to the beginning of the ultrasonographic studies in order to characterise the normal anatomical features of the above mentioned species. In previous ultrasonographic studies of the coelomic cavity of the Boa constrictor studies a ventral approach on sedated animals was proposed. We have decided to use a lateral approach on unsedated animals. Although, especially in larger animals, the shadowing effect produced by the ribs was evident in some images, most of the coelomic organs (scent glands, hemipenes, cloaca, ureters, colon, small intestine, pylorus, stomach, pancreas, liver, gallbladder and oesophagus) have been recognised. The rate of ultrasonographic recognition of individual organs is reported. Results provide a description of the normal ultrasonographic features of coelomic cavity of boid snakes along with a series of tables matching the gross and cross sectional anatomy with corresponding normal ultrasonographic images. In Chapter VII the technique and the normal features of upper gastro-intestinal examination in ball pythons are described. 10 ball python's cadavers have been dissected and cross sectioned prior to the the beginning of the study in order to characterise the normal features of the intestine in this species.18 healthy ball pythons where object of this study. All animals where not fed for at least 7 days before the beginning of the study. The animals have been divided into three groups (A, B, C). Contrast medium (barium sulphate) at the dose of 25 ml/kg has been administered through an esophageal probe at an increasing concentration (25%, 35% and 45 wt/vol) to three groups. An initial animal (Group A , 25% wt/vol) was used to verify the feasibility and establish a time course for the procedure. Imaging quality was evaluated by 3 investigators who assigned a grading score on the basis of predetermined criteria. Results of present study revealed that the 35% wt/vol concentration of contrast medium provided the best imaging quality. Moreover, three pattern of distribution of the contrast medium in the small intestine, independent from the concentration, have been described.
Negli ultimi anni ofidi e sauri sono diventati sempre più diffusi come animali da compagnia. Questa crescente diffusione ha comportato un aumento della richiesta di servizi veterinari specializzati in questi animali. L’imaging diagnostico spesso è una parte fondamentale dell’indagine clinica. La corretta interpretazione delle immagini diagnostiche implica una conoscenza approfondita dell’anatomia, fisiologia e patologia della specie oggetto dell’indagine clinica. Il confronto tra immagini normali e immagini patologiche spesso è di vitale importanza per una corretta interpretazione delle immagini diagnostiche. Lo scopo di questa tesi di dottorato è quella di fornire degli atlanti che mettano in relazione l’anatomia normale e per sezioni con le corrispondenti immagini radiografiche, tomografiche e ecografiche di alcune delle specie più popolari di ofidi e sauri. Il Capitolo I è riportata una revisione della letteratura corrente sull’imaging in ofidi e sauri. Al momento manca un riferimento univoco su questo argomento e la letteratura presente è spesso frammentaria a volte difficile da reperire. L’obiettivo di questo capitolo, quindi, è quello di fare il punto sullo stato dell’arte della diagnostica per immagini in ofidi e sauri. Molti articoli internazionali riguardanti la radiologia, l’ecografia, la tomografia computerizzata, la risonanza magnetica e altre tecniche di imaging sono stati citati in modo da creare un riferimento utile ai clinici che si occupano di animali esotici. Nel Capitolo II vengono presentati gli obiettivi scientifici e la struttura di questa tesi. L’obiettivo generale è quello di fornire una descrizione dell’anatomia e dell’imaging normale in ofidi e sauri. La prima parte (Capitoli III e IV) è incentrata sul confronto tra la l’anatomia normale e per sezioni della testa alcune specie di ofidi e sauri con i normali aspetti radiografici e tomografici. La seconda parte (Capitoli dal V al VII) è incentrata sull’imaging della cavità celomatica. In questi capitoli sono descritti: gli aspetti normali valutati in tomografia computerizzata della cavità celomatica di alcune specie di sauri, l’ecografia normale in alcune specie di ofidi e il Nel Capitolo III sono descritti i normali aspetti anatomici, radiografici e tomografici della testa del Boa constrictor. Per questo studio sono stati impiegate le teste di 4 cadaveri di Boa constrictor. Utilizzando una combinazione pellicola-casetta ad alta definizione sono state ottenute proiezioni latero-laterali e dorso-ventrali di tutte le teste. L’esame tomografico è stato eseguito in direzione cranio-caudale e latero-laterale con uno spessore di fetta di 1,5mm. Le immagini sono state visualizzate in una finestra da osso. 2 teste sono state dissezionate con un approccio stratigrafico. 2 teste invece sono state congelate per 24 ore a -20°C e poi sezionate in fette di 3mm rispettando il protocollo utilizzato in tomografia computerizzata. Le strutture anatomiche sono state identificate nelle immagini anatomiche e poi accoppiate con le corrispondenti immagini radiografiche e tomografiche. I tessuti ossei sono ben definiti sia nelle immagini radiografiche che tomografiche; i tessuti molli risultano poco definiti in entrambe. Nel Capitolo IV l’anatomia stratigrafica e per sezioni della testa dell’iguana, del tegu e del drago barbuto vengono messi in relazione con il loro normale aspetto radiografico e tomografico. Per realizzare questo studio sono stati usati 4 cadaveri per specie e 6 iguane, 4 tegu e 3 draghi barbuti adulti. Prima di iniziare gli studi di imaging 2 cadaveri per specie sono stati dissezionati con un approccio stratigrafico e 2 sono stati sezionati. Gli studi anatomici sono stati eseguiti con la stessa metodica riportata nel Capitolo III. Gli studi radiografici e tomografici sono stati eseguiti solo sugli animali vivi. Le radiografie sono stata scattate in proiezione latero-laterale e dorso-ventrale. Le scansioni tomografiche sono state effettuate pre e post contrasto scansionando gli animali in direzione cranio-caudale. Le immagini tomografiche sono state quindi visualizzate sia in finestra da tessuti molli che da osso. Le strutture anatomiche sono state individuate prima nelle immagini anatomiche e poi correlate con le corrispondenti immagini radiografiche e tomografiche. Gli studi radiografici hanno permesso di visualizzare in maniera ottimale sia i tessuti duri che i tessuti molli (specialmente nell’iguana). Negli studi tomografici le strutture ossee sono state visualizzate in modo ottimale in tutte le specie. I tessuti molli sono chiaramente delineati solo nell’iguana; nel tegu e nel drago barbuto si riescono a distinguere chiaramente solo gli occhi. Nel Capitolo V i normali aspetti anatomici della cavità celomatica dell’iguana verde, del tegu bianco e nero e del drago barbuto sono messi in relazione con i normali aspetti tomografici di queste specie. Per questo studio sono stati usati 4 cadaveri e 4 animali vivi per specie. I cadaveri sono stati congelati per 24 ore e poi sezionati a intervalli di 5mm. Le fette così ottenute sono state lavate da entrambi i lati e poi fotografate. Per ridurre la durata delle procedure diagnostiche sono state effettuate solo procedure post-contrasto. Le scansioni tomografiche sono state effettuate in direzione cranio-caudale. Le immagini tomografiche sono state visualizzate in finestra da tessuti molli e da polmoni. La maggior parte degli organi celomatici sono stati individuati sia nelle immagini anatomiche che nelle immagini tomografiche. Il risultato di questo lavoro è un atlante degli aspetti anatomici e tomografici normali della cavità celomatica di queste specie di sauri. Nel Capitolo VI vengono descritti gli aspetti ultrasonografici normali della cavità celomatica del Boa constrictor, Python molurus, Python curtus e Python regius. Inoltre vengono fornite le misure ecografiche di riferimento delle scent glands e delle mucose gastica, pilorica e del colon nelle suddette specie. Per questo lavoro sono stati utilizzati 46 serpenti vivi (16 Python regius, 10 Python molurus, 12 Python curtus and 8 Boa constrictor) and 23 cadaveri (6 Python regius, 4 Python molurus, 10 Python curtus, 3 Boa constrictor). Gli studi anatomici sono stati effettuati prima di iniziare gli studi ecografici in modo da caratterizzare i normali aspetti anatomici di queste specie. In un lavoro precedente, nel quale vengono descritti i normali aspetti ecografici del Boa constrictor, viene proposto un approccio ventrale al paziente. In questo studio proponiamo un approccio laterale. In alcune immagini ecografiche i coni d’ombra prodotti dalle coste di questi animali, specialmente nei soggetti di maggiori dimensioni, degradavano leggermente la qualità dell’esame. Nonostante ciò è stato possibile riconoscere la maggior parte degli organi celomatici (scent glands, emipeni, cloaca, ureteri, colon, piccolo e grosso intestino, piloro, stomaco, pancreas, fegato, cistifellea ed esofago). Il numero di animali nei quali i singoli organi sono stati visualizzati è stato riportato. Questo lavoro ha prodotto una descrizione completa degli aspetti ecografici normali in alcune specie di boidi oltre a una serie di tavole che mettono in relazione l’anatomia normale e per sezioni con le corrispondenti immagini ecografiche. Nel Capitolo VII è riportata la tecnica e gli aspetti normali dello studio radiografico dell’esofago, stomaco e piccolo intestino nel Python regius. Per caratterizzare l’aspetto normale del piccolo intestino di questa specie i cadaveri di 10 Python regius sono stati dissezionati prima dei iniziare procedure diagnostiche. Per questo lavoro sono stati utilizzati 18 Python regius. Tutti gli animali utilizzati non sono stati nutriti nella settimana precedente lo studio. Gli animali sono stati divisi in 3 gruppi (A, B, C). Il mezzo di contrasto (bario solfato) è stato somministrato alla dose di 25ml/kg tramite una sonda esofagea a concentrazione crescente (25%, 35%, 45% p/v) nei tre gruppi. Un soggetto appartenente al gruppo A (25% p/v) è stato usato per verificare la fattibilità della procedura e per stabilire una timeline radiografica approssimativa per gli studi successivi. La qualità delle immagini diagnostiche è stata valutata da tre autori in basi a criteri pre-definiti. I risultati di questo studio suggeriscono che la concentrazione ideale di mezzo contrasto per questo tipo di indagine diagnostica è del 35%. Inoltre, sono stati descritti tre pattern di distribuzione del mezzo di contrasto nel piccolo intestino, indipendenti dalla concentrazione.

The current trend in magnetic resonance imaging (MRI) is towards higher external magnetic field strengths (B0) to take advantage of increased sensitivity and signal to noise ratio (SNR). Unfortunately, as (B0) increases the effectiveness (relaxivity) of clinical gadolinium (Gd3+)-based contrast agents (CAs) administered to enhance image contrast is significantly reduced. Excellent soft tissue contrast can be generated with current agents despite their non-optimum relaxivities but necessitates large doses. The limits of detection of a CA at high B0 fields can be lowered by recovering the lost relaxivity and is a pre-requisite to the goal of molecular imaging in which CAs are bound to biomarkers of pathology that exist at very low concentrations. Traditional methods for increasing the detectability of CAs have focused on optimizing critical parameters identified from the Solomon-Bloembergen-Morgan (SBM) theory that affect relaxivity. Gains in relaxivity with these methods to date have been modest and are far from the theoretical maximum possible. Although researchers continue to investigate novel complexes that provide improved relaxivities, any such complex would require a lengthy and costly approval process with the U.S. Food and Drug Administration (FDA). Therefore, a method that affords improved relaxivities of current clinically approved CAs, particularly at high B0 fields, that could be adopted into clinical practice rapidly, is of great interest. Spin locking is a nuclear magnetic resonance (NMR) technique that was introduced for imaging in 1985, but has received very little attention in combination with Gd3+-based CAs. The technique employs a low power long duration radiofrequency (RF) pulse (B1) parallel to the net magnetization in the x,y-plane. This locks the magnetization into lower precessional frequencies around an "effective" field (Beff) that is reduced with respect to B0 but maintains the high field advantages required for imaging. When considered in the rotating frame, longitudinal relaxation of the magnetization against Beff exhibits shorter time constants (T1p) expected at these lower precessional frequencies. This leads to higher relaxivities, which has implications for increasing CA detectability. The experiments described herein show that rotating frame longitudinal relaxivities (r1p) for current clinical Gd3+-based CAs are essentially independent of the strength of the spin lock pulse (yB1) as predicted by theory. This result is important because it allows the value of yB1 to be neglected when comparing r1p of Gd3+-based CAs across several B0 fields. The magnetic field dependence of r1p for all clinical agents showed that relaxivity, lost by moving to higher fields, could be "recovered" and that r1p was sensitive to the rotational correlation time constant (TR) of the agent. Using high molecular weight Nanoassembled capsules (NACs) containing a Gd3+-based CA to probe this finding further, we were able to generate relaxivities at high field up to an order of magnitude greater than clinical agents at current imaging fields. These are beyond anything previously reported, or likely to be, with current techniques. Finally, we demonstrated that by spin locking Mn2+ agents, relaxivities at high field increased by a factor of ~ 30 than without spin locking, due to their larger dependence on scalar coupling. These findings show the potential of spin locking to increase detection limits dramatically at high field and are an exciting development towards the goal of molecular imaging.

An increase in the range and capability of imaging modalities has resulted in greater demands for radiology services. This research investigates how these changes have affected role requirements and role extensions of radiographers and the consequent implications for the educational needs of radiographers. Semi-structured interviews and three successive surveys of NHS radiography managers showed that the adoption and diffusion of extended roles in radiography had increased significantly over a ten year period. Role changes included additions both to the procedures carried out by radiographers, and to the reporting of procedures, e.g. film reporting, once the domain of radiologists, is now undertaken by radiographers in many trusts. Imaging managers’ views on the factors that encouraged or deterred the introduction of extended roles were explored. While many radiographers were keen to adopt new roles, implementation was unlikely without radiological support. Respondents believed the proposed ‘four-tier structure’ would help overcome staffing difficulties, while providing an improved career framework to advance the professional status of radiographers. A key theme was the need for greater clinical knowledge to facilitate transition to advanced practice. Three studies investigated radiography education. The first used a survey to investigate the preparedness for practice of three cohorts of newly qualified radiographers. Graduates recognised the importance of continuing professional development with extended role skills identified as a priority. The second study examined the relationship between contemporary practice and UK undergraduate radiography curricula. Most programmes had responded positively to developing technology. The third study used a survey to investigate the training for extended roles provided by employers. While most provided some training, much was unaccredited, and there was considerable variation in the duration of training for similar roles. The research has documented developments taking place at a time of enormous technological innovation. It provides key data on the changing practice of radiography that will be useful to all stakeholders planning improvements to radiography services. The data lead to a re-definition of practice and recommendations for supporting education and training.

Articular cartilage is a connective tissue, that provides virtually frictionless articulation between bones in a joint. Degenerative joint disease, osteoarthritis (OA), is the most common type of arthritis. During its development, cartilage is progressively lost, decreasing the functional capacity of the joint. Currently it is diagnosed with radiography, which might not show changes in cartilage tissue during the early stages of OA. In radiography, cartilage degeneration might be visible only when OA has progressed to advanced stage. The lack of effective treatment methods for advanced stage of OA has generated interest towards the development of biomarkers for the detection of early OA. Magnetic resonance imaging (MRI), especially relaxation time mapping, is able to provide accurate information on early changes in cartilage structure and is considered to be one of the best candidates for the detection of early OA. Morphological assessment of three-dimensional MRI, on the other hand, can be used as an indicator of the rate of cartilage loss. In this work, OA is reviewed and the current methods for diagnosing OA are studied. Relaxation time mapping and morphological assessment of articular cartilage are current research interests and these methods will also be discussed.

Homozygous α0-thalassemia is a serious autosomal recessive disorder with poor fetal outcome and severe maternal complications. Conventionally, prenatal diagnosis is performed by an invasive test. A non-invasive approach using serial ultrasonography can effectively reduce the need for invasive tests in unaffected pregnancies. For two-dimensional ultrasound prediction, a total of 777 at-risk fetuses were studied from 12 to 20 weeks between 1995 and 2006. At 12–15 weeks’ gestation, the highest sensitivity (98.3%) was achieved by the combination of fetal cardiothoracic ratio (CTR) and/or middle cerebral artery peak systolic velocity (MCA-PSV) at a false-positive rate of 15.8%. At 16–20 weeks’ gestation, the sensitivity of CTR was 100.0%, but the false-positive rate was 5.2%. In contrast, the false-positive rate of MCA-PSV alone was 1.4% and that of the combination of CTR and MCA-PSV was 0%, although their sensitivities were less than 65%. In a cross-sectional retrospective study of 546 samples at-risk and control (268 fetal and 278 neonatal cord blood), the degree of anemia was only mild in 27.5% of the affected fetuses (see chapter 3 for definition of mild anemia). Because MCA-PSV is not very predictive of mild anemia, this may be one of the reasons why MCA-PSV is not very sensitive in predicting an affected pregnancy. A total of 832 at-risk pregnancies were studied using same noninvasive approach at Maternal and Neonatal Hospital of Guangzhou (MNH) and Tsan Yuk Hospital (TYH). The overall sensitivity and specificity of the noninvasive approach was 100% and 95.6% respectively. At MNH, the need for an invasive test was reduced by 78.6%, and all the affected pregnancies were diagnosed before 24 weeks’ gestation. After adequate training and monitoring the quality of the subsequent ultrasound examinations, the results achieved at MNH were comparable to TYH, with at-risk pregnancies including the affected ones being seen at a more advanced gestation at MNH. In a retrospective review of 361 women at risk of carrying an affected fetus, 311 (86.2%) opted for the non-invasive approach using CTR and/or placenta. The cost saving of this non-invasive approach was relatively small (HK$ 2,651) in comparison to the cost of the whole prenatal screening program. On the other hand, the non-invasive approach was more expensive than the direct invasive approach for low MCV couples, as well as couples discordant for α-thalassemia and β-thalassemia. ages. These results support the adoption of non-invasive approach in which routine invasive test or karyotyping is no longer performed. A total of 106 at-risk pregnancies and normal controls were prospectively studied using three-dimensional ultrasonography. Placental volume (PV) at 11-14 weeks, and PV/CRL quotient at 9-14 weeks’ gestation of affected pregnancies were significantly greater than unaffected pregnancies (P<0.05). Using a cut-off point of 1.2ml/mm for PV/CRL quotient to predict an affected pregnancy, the sensitivity, and specificity was 96.2%, and 100.0% respectively.
published_or_final_version
Obstetrics and Gynaecology
Master
Doctor of Medicine

This qualitative study describes how physical therapist experts in musculoskeletal disorders evaluate and interpret imaging studies and how they employ imaging in clinical decision-making. The informants are physical therapists who are certified orthopedic clinical specialists (OCS) and/or fellows of the American Academy of Orthopaedic Manual Physical Therapists (AAOMPT). The study employed web conferencing to display patient cases, record screen-capture videos, and to conduct interviews. Informants were observed and their activity video-captured as they evaluated imaging studies and, afterwards, interviews were employed to explore the processes they utilized to evaluate and interpret the images and to discuss imaging-related clinical decision-making, including possible functional consequences of changes seen in the images, contraindications to treatment, and indications for referral. The interviews were transcribed and analyzed in the tradition of grounded theory. This study found that the informants’ evaluation of imaging studies was contextual and non-systematic, guided by the clinical presentation. The informants used imaging studies to provide a deeper understanding of clinical findings and widen perspectives, arriving at clinical decisions through the synthesis of imaging, clinical findings, and didactic knowledge. They tended to look for imaging evidence of interference with normal motion, rather than evidence of pathology. Overall, the informants expressed conservative views on the use of imaging, noting they would rather use clinical findings and treatment response than imaging findings as a basis for referral to other health care professionals. Using imaging studies to support clinical decision-making can provide physical therapists a wider perspective when planning treatment interventions. By showing physical therapists’ approach to interpreting imaging studies and how this relates to their clinical decision-making, the findings of this study could contribute to discussions of the place of imaging in physical therapist practice, as well as help set objectives for imaging curricula in professional-level and continuing education.

xi, 56 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number.
Image processing is a powerful tool for increasing the reliability and reproducibility of disease diagnostics. In the hands of pathologists, image processing provides quantitative data from histological images which supplement the qualitative data currently used by specialists. This thesis presents a novel method for analyzing digitized images of hematoxylin and eosin (H&E) stained histology slides to detect and quantify inflammatory polymorphonuclear leukocytes to aid in the grading of acute inflammation of the placenta as an example of the use of image processing in aid of diagnostics. Methods presented in this thesis include segmentation, a novel threshold selection technique and shape analysis. The most significant contribution is the automated color threshold selection algorithm for H&E stained histology slides which is the only unsupervised method published to date.
Committee in charge: Dr. John Conery, Chair; Dr. Matthew J. Sottile

Pancreatic ductal adenocarcinoma (PDAC) has the poorest five-year survival rate of any cancer. Currently, there are no effective diagnostics or chemotherapeutics. Surgical resection is the only curative therapy. However, most patients experience recurrence due largely to challenges in assessing tumor margin status in the operating room. Molecular probes that selectively highlight pancreatic cancer tissue, having the potential to improve PDAC margin assessment intraoperatively, are urgently needed. In this work, a series of red and near-infrared fluorescent probes is reported. Two were found to distribute to normal pancreas following systemic administration. One selectively accumulates in genetically modified mouse models of PDAC, providing cancer-specific fluorescence. In contrast to the small molecule probes reported previously, it possesses inherent affinity for PDAC cells and tissue, and thus does not require conjugation to targeting agents. Moreover, the probe exhibits intracellular accumulation and enables visualization of four levels of structure including the whole organ, tissue, individual cells and subcellular organelles. It can thus promote new strategies for precision image-guided surgery, pancreatic cancer detection, the monitoring of therapeutic outcomes and basic research.

This study investigated radiographers' infection control practice within the Diagnostic Imaging Department. The investigation was carried out in three phases. Structured observations were carried out in four hospitals to determine the frequency and identify the situations in which infection control procedures were performed. Bacterial analysis was performed on equipment in one hospital to identify levels of contamination associated with the lack of cleaning witnessed during the observational study. Finally Focus Group discussions were used in two hospitals to establish the opinions and attitudes of radiographers regarding infection control, and to identify factors that prevented as well as those that facilitated these practices. Radiographers' compliance with infection control practice was low. Hand decontamination prior to patient contact was observed on only (n=34) 4% of occasions, and afterwards on (n=145) 17% of occasions. Infection control practice was frequently inappropriate when radiographers were dealing with situations involving immunosuppressed patients, those with open wounds, and in the handling of needles. Equipment was cleaned on only (n=30) 4% of occasions. It was found that 56% of the pieces of equipment were found to have unacceptable levels of bacterial contamination. However, after simple decontamination the measure of bacterial load was significantly reduced. The Focus Group discussions indicated that radiographers had good levels of knowledge regarding infection control, but issues such as lack of time and resources, low perceived risk of infection and the culture of the departments and NHS trusts had a negative effect on compliance rates. For maximum compliance it is thought that a multifaceted intervention should be implemented. The researcher believes the use of Quality Circles would develop a culture that would encourage compliance with infection control protocols. Better compliance with infection control protocols achieved through changes in education, procedures and culture in the Diagnostic Imaging Department are, therefore, vital to protect both patients and staff.

Purpose: Medical imaging systems are used to scan patients to obtain valuable information for diseases diagnosis and assisting treatment. An ideal scanner should be sensitive enough to detect any trace amount of abnormal tissue at its early stage. With the continuous development of high-tech treatment systems such as Tomotherapy (manufactured by Tomo HD), the high-resolution imaging system is favorable to reduce the damage of normal tissue due to the image guidance of Mega-voltage beam before treatment. In this study, a software approach was presented to improve image resolution without hardware upgrade of a scanner. Methodology A programming technique “Super Resolution Technique” was used and demonstrated in an example of CT. It utilized several similar images with known relative shifts between them. (They can be positional or angular shifted and taken at the same time frame as far as possible). Those images are of low resolution and can be reconstructed to form a higher resolution image. A Super Resolution program was written by MATLAB to prove the method. The experiments 1 to 4 were purely computer-based simulations and experiment 5 used a LightSpeed VCT scanner for real scans. For the computer-based experiments, a few low resolution images have been attempted and registration steps were explored for image reconstruction. A resolution target, USAF1951, was called from MATLAB and used to examine the resolving power before and after image processing based on Super Resolution algorithm. Image-image subtraction was used to compare pre-processing and post-processing images. The number of non-zero pixels was used to access the percentage of similarity. For the experiment using LightSpeed VCT scanner, a GE VCT QA phantom was used to test the performance of the technique. Result From the experiments using USAF1951, it was found that: the minimum resolvable line pairs had improved from family -1 element 6 to family 0 element 2 (2 elements improvement) after applying “Super Resolution Technique” as shown in the experiment 1. An xy directional shifting of the pre-processing images resulted in a better reconstructed image than x-axis shifting or y-axis shifting in terms of resolution, shown in the experiment 2. The experiment 3 concluded that the more the pre-processing images, the better the reconstructed image would be. The experiment 4 showed that the shifts of pre-processing images greater than the detector size could still result in a higher resolution image. The experiment 5 revealed that applying “Super Resolution Technique” to a real CT scanner could not give an obvious improvement in resolution, but the image background noise had reduced. Conclusion It was concluded that the “Super Resolution Technique” could improve the image resolution and reduce the background noise at expense of more imaging time and more dose from the additional view. In case of hardware upgrade of imaging device is not practicable, Super Resolution could help improve the image quality.
published_or_final_version
Medical Sciences
Master
Master of Medical Sciences

This dissertation concerns the ability of human observers to perform detection tasks in medical images that contain structured noise. We shall show that physical measures of image quality, such as signal-to-noise ratio (SNR), resolution, modulation transfer function (MTF), and contrast, do not accurately predict how well an observer can detect lesions in an image. We have found that for images with equal pixel SNR, humans can detect a low contrast object more readily in images that have a low-pass noise structure, as opposed to a high-pass noise structure. This finding is important in the comparison of images generated by a classical pinhole imaging system with images generated by a computed tomography imager. We would like to have a figure of merit that accurately predicts a physician's ability to perform perceptual tasks. That is, we want a figure of merit for imaging systems that is more than an evaluation of the physician's performance, measured using human observers and an accepted method such as receiver operating characteristic (ROC) techniques. We want a figure of merit that we can calculate without requiring lengthy observer studies. To perform this calculation, we need a model of the imaging system hardware in cascade with a verified model of the human observer. We have chosen to approach this problem by modelling the human observer as an ideal observer. Our hypothesis is that the human observer acts approximately as an ideal-observer who does not have the ability to prewhiten the noise in an image. Without this ability, the ideal observer's detection performance for even a simple task is degraded substantially in correlated noise. This is just the effect that we have found for human observers. In search of a physiological explanation for a human observer's inability to do prewhitening, we shall investigate the detection capability of the ideal observer when a frequency-selective mechanism is invoked. This mechanism corresponds to the frequency channels known to exist in the human visual system. We shall show that the presence of such a mechanism can explain the degradation of human observer performance in correlated noise.

The aims of this work are:
1. To provide the normal cervical and coelomic radiographic appearance of the Loggerhead sea turtle, in the dorso-ventral view, as well as other useful landmarks, to allow for correlation of shell scutes with internal anatomic structures.
2. To provide the normal radiographic anatomy of the limbs of the Loggerhead sea turtle in combination with data obtained from computed tomography - osteological, gross anatomical and histological data.
3. To describe the normal ultrasonographic appearance of cervical structures and coelomic organs of the Loggerhead sea turtle, and to provide the respective images of frozen cross-sections for anatomical reference.
4. To provide normal computed tomographic images of the vertebral column and coelomic structures of the Loggerhead sea turtle, by establishing reference standards for organ size and position in this species; to provide images of virtual tracheo-bronchoscopy and 3D reconstructions of the respiratory tract and bone structures.
5. To provide the normal magnetic resonance imaging (MRI) appearance of coelomic structures of Loggerhead sea turtles in T1 and T2-weighted scans via comparison with cross-sectional anatomic sections of this species.

This thesis describes a series of investigations into the use of optic nerve head (ONH) imaging in primary open-angle glaucoma (POAG), and its relation to visual function. Accurate diagnosis is a key issue in POAG, particularly the difficult task of separating those with early disease from those healthy individuals who display signs of POAG. The purpose of this work is to improve diagnostic methods in glaucoma through use of ONH imaging and its relationship with visual field (VF) loss. First, the performance of a group of expert clinicians evaluating ONH photographs for glaucomatous damage was investigated. The results showed that even when their assessments are combined discrimination between eyes with and without POAG (based on VF loss) is far from perfect, highlighting the need for improvements in diagnosis. The possibility of combining structural and functional data to aid diagnosis was then considered. This requires VF loss and ONH damage to be strongly topographically related. The strength of this relationship was evaluated in 185 patients with POAG. 10,000 computer-generated maps between the ONH and VF were tested and the topographic relationship measured with each of these was compared to that using a published structure-based map. The weak topographic relationships found suggest that the application of these maps to individual patients is limited with current measures. The next chapter describes how a multispectral imaging (MSI, also called hyperspectral imaging) system was set-up for spatial evaluation of ONH oxygenation using a Beer-Lambert law model. Test-retest repeatability was tested and found to be acceptable for the purposes of the following studies. The MSI system was then used for an investigation of the relationship between ONH oxygenation and VF loss. 33 eyes of 18 patients underwent VF testing, MSI and HRT3 imaging. Superior-inferior asymmetries in VF sensitivity were compared to superior-inferior asymmetries in ONH oxygenation measured by MSI and in neuroretinal rim (NRR) area measured by HRT3. This way we take advantage of the typical progression of POAG and each eye acts as its own reference, negating the effect of a wide normal range and overlap between health and disease. This study found, for the first time, a strong association between ONH oxygenation and VF sensitivity. A re-analysis of the 33 ONH oxygenation maps was then performed to assess oxygenation only in the area of the NRR as defined by the HRT. Superior-inferior asymmetries in NRR oxygenation were then compared to superior-inferior asymmetries in VF loss, and the associations found were similarly strong. This study shows that MSI is capable of detecting areas of NRR deemed healthy tissue by structural imaging techniques, which are in fact poorly oxygenated and associated with VF defects. These findings show that NRR oxygenation measured by MSI is strongly related to VF loss. This important information complements existing technologies and may aid in the future diagnosis and management of patients with POAG.

Cancer is the second leading cause of death in the United States, and its early diagnosis is critical to improving treatment options and patient outcomes. In autofluorescence (AF) imaging, light of controlled wavelengths is projected onto tissue, absorbed by specific molecules, and re-emitted at longer wavelengths. Images of re-emitted light are used together with spectral information to infer tissue functional information and diagnosis. This dissertation describes AF imaging studies of three different organs using data collected from fresh human surgical specimens. In the ovary study, illumination was at 365 nm, and images were captured at 8 emission wavelengths. Measurements from a multispectral imaging system and fiber optic probe were used to map tissue diagnosis at every image pixel. For the colon and pancreas studies, instrumentation was developed extending AF imaging capability to sub-300 nm excitation. Images excited in the deep UV revealed tryptophan and protein content which are believed to change with disease state. Several excitation wavelength bands from 280 nm to 440 nm were investigated. Microscopic AF images collected in the pancreas study included both cultured and primary cells. Several findings are reported. A method of transforming fiber optic probe spectra for direct comparison with imager spectra was devised. Normalization of AF data by green reflectance data was found useful in correcting hemoglobin absorption. Ratio images, both AF and reflectance, were formulated to highlight growths in the colon. Novel tryptophan AF images were found less useful for colon diagnostics than the new ratio techniques. Microscopic tryptophan AF images produce useful visualization of cellular protein content, but their diagnostic value requires further study.

Background: There is little published research on the wide variation of corpus callosum (CC) morphology in children, the assessment of which is made difficult by the complex alteration of its appearance in childhood. Objective: The purpose of our study was to assess the morphology of the CC on mid-sagittal T1- weighted magnetic resonance imaging (MRI) in a large number of children and correlate the findings with demographic and clinical criteria. Materials and methods: We reviewed all brain mid-sagittal T1-weighted MRI’s performed from July to December 2015 and obtained relevant demographic and clinical information from the accompanying report and laboratory system. The CC morphology was analysed by three radiologists and compared using cross tabulation with the chi-square test and ANOVA. Interobserver correlation was assessed using Kappa coefficient of conformance. Results: 257 patients with mean age 72±60 months were included, 142 were male (55%). In abnormal MRI’s the CC was less likely to have an identifiable isthmus and was more likely to be convex, thin and have separation of the fornix insertion (all p<0.01). In young children (< 5 years) the CC was also less likely to have an identifiable isthmus (p=0.01) and was more likely to be convex (p=0.04) but the fornix was more likely to insert normally (p<0.01). Children with tuberous sclerosis had significantly thinner splenia (p=0.02). Conclusion: There is a distinct pathological appearance of the CC. The immature appearance of the corpus callosum can mirror this but is distinguished by normal insertion of the fornix and normal quantitative measurements. Splenial thinning in children with tuberous sclerosis warrants further investigation.

Thesis (Ph. D.)--University of Florida, 1999.
Title from first page of PDF file. Document formatted into pages; contains xiv, 137 p.; also contains graphics. Vita. Includes bibliographical references (p. 129-136).

The shoulder is a complex anatomical structure and imaging plays an important role in the diagnosis and management of shoulder conditions. The complexity of the shoulder’s anatomy has led to the development of multiple radiographic projections and techniques within plain film imaging with each projection intended to demonstrate specific aspects of the anatomy of the shoulder. However, reproducing the required projections can be difficult especially if radiographers are not familiar with the projections and their evaluation criteria. Literature has revealed the importance of a comprehensive knowledge and understanding of anatomy, patient positioning, beam direction and centring point, and evaluation criteria to ensure a quality projection for accurate diagnoses. The aim of the study was to determine the knowledge and understanding of radiographers with regard to the supraspinatus outlet projection (SOP) for shoulder impingement syndrome (SIS) and its evaluation criteria. The inferences derived from the research findings were used to develop guidelines for a structured in-service training programme for practising radiographers to optimise their knowledge and understanding of the supraspinatus outlet projection in shoulder impingement syndrome. The proposed study followed a quantitative approach. Furthermore, a descriptive, exploratory, contextual design was employed. The research population consisted of practising radiographers working in the public and private hospitals of the Nelson Mandela Bay Municipality. The data were collected by means of a structured self-administered questionnaire. The questionnaire comprised of three sections. The first section requested demographic information from the participants. The second section assessed their knowledge and understanding regarding the scapular ‘Y’ and the supraspinatus outlet projections and shoulder impingement syndrome. The third section assessed their knowledge and understanding of anatomy and image evaluation/critiquing. The reliability and validity of the data collection instrument was ensured by conducting a pilot study and comparing the results with those of the main study. In addition, the expertise and guidance of a radiographer experienced in the clinical training of radiographers, the supervisor (who has twenty years’ experience in the teaching of radiographers) and a statistician was obtained. Descriptive and inferential statistical analyses were performed by means of a statistical programme and with the guidance of a statistician. The researcher ensured that the study was conducted in an ethical manner by adhering to the ethical principles of beneficence, justice and respect for persons.

Although current head imaging technologies such as magnetic resonance imaging (MRI) and computed tomography (CT) are capable of providing accurate diagnosis of brain injuries such as stroke and brain tumour, they have several limitations including high cost, long scanning time, bulky and mostly stationary. On the other hand, radar-based microwave imaging technology can offer a low cost, non-invasive and non-ionisation method to complement these existing imaging techniques. Moreover, a compact and wearable device for microwave head imaging is required to facilitate frequent or real-time monitoring of a patient by providing more comfort to the patient. Therefore, a wearable head imaging device would be a significant advantage compared to the existing wideband microwave head sensing devices which typically utilise rigid antenna structure. Furthermore, the wearable device can be integrated into different microwave imaging setups such as real-time wearable head imaging systems, portable systems and conventional stationary imaging tools for use in hospitals and clinics. This thesis presents the design and development of wearable devices utilising flexible antenna arrays and compact radio frequency (RF) switching circuits for wideband microwave head imaging applications. The design and characterisation of sensing antennas using flexible materials for the wearable head imaging device are presented in the first stage of this study. There are two main variations of monopole antennas that have been developed in this research, namely trapezoidal and elliptical configurations. The antennas have been fabricated using different flexible substrate materials such as flexible FR-4, polyethylene terephthalate (PET) and textile. Wideband performances of the antennas have been achieved by optimising their co-planar waveguide feeding line structures. Importantly, the efficiencies of the fabricated antennas have been tested using a realistic human head phantom by evaluating their impedance matching performances when operating in close proximity to the head phantom. The second stage of the study presents the development of wearable antenna arrays using the proposed flexible antennas. The first prototype has been built using an array of 12 flexible antennas and a conformal absorbing material backed with a conductive sheet to suppress the back lobe radiation of the monopole antennas. Additionally, the absorber also acts as a mounting base to hold the antennas where the wearable device can be comfortably worn like a hat during the measurement and monitoring processes. The effect of mutual coupling between adjacent antennas in the array has been investigated and optimised. However, the use of the absorbing material makes the device slightly rigid where it can only be fitted on a specific head size. Thus, a second prototype has been developed by using a head band to realise a stretchable configuration that can be mounted on different sizes of human heads. Furthermore, due to the stretchable characteristic of the prototype, the antennas can be firmly held in their positions when measurements are made. In addition, fully textile based sensing antennas are employed in this prototype making it perfectly suitable for monitoring purposes. Low cost and compact switching circuits to provide switching mechanism for the wearable antenna array are presented in the third stage of this study. The switching circuit is integrated with the antenna array to form a novel wearable microwave head imaging device eliminating the use of external bulky switching network. The switching circuit has been built using off-the-shelf components where it can be controlled wirelessly over Bluetooth connection. Then, a new integrated switching circuit prototype has been fabricated using 6-layer printed circuit board (PCB) technology. For the purpose of impedance matching for the radio-frequency (RF) routing lines on the circuit, a wideband Microstrip-to-Microstrip transition is utilised. The final stage of this study investigates the efficacy and sensitivity of the proposed wearable devices by performing experiments on developed realistic human head phantoms. Initially, a human head phantom has been fabricated using food-based ingredients such as tap water, sugar, salt, and agar. Subsequently, lamb's brains have been used to improve the head phantom employed in the experiments to better mimic the heterogeneous human brain. In terms of imaging process, an interpolation technique developed using experimental data has been proposed to assist the localisation of a haemorrhage stroke location using the confocal delay-and-sum algorithm. This new technique is able to provide sensible accuracy of the location of the blood clot inside the brain. The wearable antenna arrays using flexible antennas and their integrations with compact and low cost switching circuits reported in this thesis make valuable contribution to microwave head imaging field. It is expected that a low-cost, compact and wearable radar-based microwave head imaging can be fully realised in the future for wide range of applications including static scanning setup in hospitals, portable equipment in ambulances and as a standalone wearable head monitoring system for remote and real-time monitoring purposes.

Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2010.
Committee Chair: Nie, Shuming; Committee Member: Bao, Gang; Committee Member: Murthy, Niren; Committee Member: Varma, Vijay; Committee Member: Wang, Zhong Lin. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Electrical parameter profiles of human breast images can be used to simulate and analyze the anticipated effects on tissue from its interaction with electromagnetic fields involved in the cancer treatment exposure. In part, the success of this approach depends on the accuracy and precision in identifying the different tissue types. In this work, we propose two methods of segmenting human breast images with malignant tumors. The first method of algorithmic partitioning of the image involves manual color-edge contouring of the tissues using a cursor and subsequent identification of the tissue types. For the second method, MRI T1 values and thresholds are used to perform segmentation and we investigate the potential of incorporating edge detection. The first method is effective, while the second lacks precision, but eliminates the need of manual contouring. The images are imported as BMP files into SEMCAD, an electromagnetic simulation tool based on finite-difference time-domain method, which recognizes the grouped tissues and creates a model of the image. The model allows the user to easily assign electrical parameter values to the grouped tissues, according to the measured values reported in the literature.

There is increasing interest in the use of small field of view (SFOV) portable gamma cameras in medical imaging. A novel hybrid optical-gamma camera (HGC) has been developed through a collaboration between the Universities of Leicester and Nottingham. This system offers high resolution gamma and optical imaging and shows potential for use at the patient bedside, or in the operating theatre. The aim of this thesis was to translate the HGC technology from in vitro laboratory studies to clinical use in human subjects. Pilot studies were undertaken with the HGC as part of this thesis. Furthermore, efforts have been made to transform the HGC technologies into a new medical device, known as Nebuleye. Initial physical evaluation of the pre-production prototype camera was carried out as part of the device developmental process, highlighting some aspects of the design that require further modification. A complete and rigorous testing scheme to assess the pre-production prototype camera has been developed and successfully implemented. The newly introduced tests enabled the system uniformity, system sensitivity, detector head shielding leakage, optical-gamma image alignment and optical image quality of the hybrid camera to be assessed objectively. This harmonised testing scheme allows characterisation and direct comparison of SFOV gamma cameras. In vitro and in vivo preclinical imaging was undertaken to examine the performance of the SFOV gamma cameras for experimental animal studies. The results of animal study have shown for the first time the feasibility and performance of these SFOV gamma cameras for imaging mice injected with a newly developed 111In labelled hybrid tracer. Further investigations are needed to improve the system resolution and prepare the camera system for combined gamma-near infrared fluorescence imaging in future. A systematic in vitro laboratory assessment method has been established to examine the imaging performance of the SFOV gamma camera in radioguided sentinel lymph node biopsy (SLNB) and radioactive seed localisation procedures for breast cancer surgery. Further preparatory work was undertaken to carry out a pilot clinical trial of the use of the pre-production prototype camera in sentinel node localisation procedures during breast cancer surgery. The clinical study protocol and routine quality control procedures have been established and are suitable for future use. Baseline data on the camera performance assessed using the routine quality control scheme have been obtained. Finally, the capabilities of the SFOV gamma camera were assessed. This has provided baseline data on user feedback and the imaging consequences on operator motion effects, as well as examining the detectability of a range of radionuclides, including 99mTc, 111In, 123I, 125I and 75Se. The first clinical results of the use of the HGC in clinical hybrid optical-gamma imaging in patients administered with 99mTc and 123I labelled radiopharmaceuticals have been reported. This clinical study has demonstrated the feasibility and capability of HGC in various clinical applications performed at the patient bedside, which included patients undergoing bone, thyroid, lacrimal drainage and lymphatic imaging as well as DaTscan studies. In conclusion, the work in this thesis has demonstrated the successful translation of an SFOV hybrid gamma camera for clinical use. This system would be ideally suited for use in the operating theatre for radioguided procedures such as sentinel node detection and tumour localisation. This system also offers potential for use with the new generation of hybrid fluorescent-radionuclide tracers currently under development.

This dissertation presents the characterization and evaluation of a new radiological imaging modality, Toshiba Computed Radiography (TCR) 201. The characteristics of the TCR storage phosphor imaging plates such as energy-dependent x-ray quantum efficiency, stored signal decay, low exposure rate signal build-up, and spontaneous and stimulated gain measures are presented. The TCR 201 system is characterized by the signal transfer curve, the total root-mean-squared (rms) output noise, the signal-to-noise ratio, the modulation transfer function (MTF), its noise power spectrum (NPS), and the detective quantum efficiency (DQE). The system rms noise is photon-limited for exposures less than 1.0 mR, but has contributions from phosphor structure and quantization noise for exposures higher than 1.0 mR. The phosphor's information factor is shown to explain deviations from ideal photon-limited noise for exposures of less than 1.0 mR. The MTF of the system is measured for standard imaging plates, 10% at 2.8 lp/mm, and for high resolution imaging plates, 10% at 4.4 lp/mm. An expression for the NPS is statistically derived, and experimental measurements confirm the expression and show an increase in uncorrelated noise power above 1.0 mR which is consistent with rms measurements. Expressions for the DQE are presented. A psychophysical study is performed to directly compare the TCR to film/screen combinations in imaging low-contrast objects. The results of this study show the TCR provides better images for detectability as a function of exposure. Also, the use of the TCR 201 as a two dimensional dosimeter and in single-shot dual energy subtraction is presented.

As new therapeutic targets and drugs are discovered for B-cell lymphoma and other cancers, companion diagnostics are also needed to determine target engagement, therapeutic efficacy, and patient segmentation for clinical trials. We first employed synthetic chemistry to build a platform for modifying small molecule drugs into imaging probes, using the poly(ADP-ribose) polymerase 1 (PARP1) inhibitor AZD2281 (Olaparib) as a model for technology development. Our results showed that small-molecule companion imaging drugs can be used for fluorescence imaging in cells, as well as for pharmacokinetic studies and positron emission tomography (PET) imaging in vivo, without significantly perturbing their target binding properties or cellular uptake. To apply this approach to B-cell lymphoma drugs currently in clinical trials, we modified an irreversible inhibitor of Bruton's Tyrosine Kinase (BTK), PCI-32765 (Ibrutinib), with the fluorophore Bodipy FL (BFL), and used it for imaging in cells and in a mouse window-chamber xenograft model. The excellent co-localization of our probe (Ibrutinib-BFL) with BTK demonstrated its utility for studying additional BTK inhibitors and as a companion imaging probe. In parallel, we hypothesized that central nervous system (CNS) lymphoma diagnosis from paucicellular cerebrospinal fluid (CSF) samples could be improved with molecular profiling of putative lymphoma cells trapped in a customized microfluidic chip. Following fabrication and characterization of a polydimethylsiloxane (PDMS) diagnostic device containing an array of affinity-free single-cell capture sites, we were able to efficiently recover >90% of lymphocytes, perform immunostaining on chip, and apply an image-processing algorithm to group cells based on their molecular marker expression, such as kappa/lambda light chain restriction. Additionally, in combination with Ibrutinib-BFL or other imaging drugs, we demonstrated the potential for on-chip drug imaging for use in conjunction with drug development. Finally, we applied bioorthogonal conjugation chemistries on cellulose paper for potential applications in lowering the cost of drug screening. We anticipate that these approaches will enable direct, molecular information for personalized treatment decisions in B-cell lymphomas, as well as provide a roadmap for the development of companion diagnostic probes and devices for additional indications.