Cancer is the leading cause of death worldwide and one third of its burden can be decreased with early detection. Surface enhanced Raman spectroscopic (SERS) based imaging is a promising new technique for non-invasive detection of tumours due to its ultra-sensitivity and multiplexing capabilities. For in vivo SERS molecular imaging, a biocompatible, robust and targeted nanoparticle is required to attain high sensitivity and specificity. In this thesis, a SERS capable gold nanoparticle was rationally designed by encapsulation with a phospholipid bilayer which conferred biocompatibility, colloidal stability and versatility to changing surface chemistry. Moreover, validation of this SERS probe with a specific targeting ligand for carcinoma cells was studied through the targeting of a commonly overexpressed cancer receptor, epidermal growth factor receptor. Using this phospholipid design, optimizations with differing chemistries, targeting ligand or modifications for additional functionalities can be achieved for further development as a viable in vivo molecular imaging tool.

Cancer is the leading cause of death worldwide and one third of its burden can be decreased with early detection. Surface enhanced Raman spectroscopic (SERS) based imaging is a promising new technique for non-invasive detection of tumours due to its ultra-sensitivity and multiplexing capabilities. For in vivo SERS molecular imaging, a biocompatible, robust and targeted nanoparticle is required to attain high sensitivity and specificity. In this thesis, a SERS capable gold nanoparticle was rationally designed by encapsulation with a phospholipid bilayer which conferred biocompatibility, colloidal stability and versatility to changing surface chemistry. Moreover, validation of this SERS probe with a specific targeting ligand for carcinoma cells was studied through the targeting of a commonly overexpressed cancer receptor, epidermal growth factor receptor. Using this phospholipid design, optimizations with differing chemistries, targeting ligand or modifications for additional functionalities can be achieved for further development as a viable in vivo molecular imaging tool.

Thesis (MSc (Radiography))--Cape Peninsula University of Technology, 2019 / INTRODUCTION: The Breast Imaging Reporting and Data System (BI-RADS) was developed by the American College of Radiology (ACR). The BI-RADS is an internationally accepted method of assessing and reporting on mammograms and breast ultrasound images. The BI-RADS consists of a lexicon (descriptors) and assessment categories. The ACR aimed to standardise mammography reporting and placing the findings in the appropriate assessment category. The aim of this study was to establish the accuracy of the BI-RADS assessment categories for mammography and breast ultrasound images in women diagnosed with breast cancer. METHOD: Data were retrieved from 77 patients who were diagnosed with breast cancer from 1 January 2013 to 31 December 2014. Seven did not meet the inclusion criteria and were excluded. The study sample size was 70 (n=70) patients. All mammography reports included a BI-RADS assessment category of all patients diagnosed with breast cancer within the study period. These reports were analysed and compared with histopathology results. The BI-RADS assessment category and descriptors were collected from the mammogram reports; the histopathology report indicated the type of breast cancer. All reports were obtained from the patients' folders at the research site. In addition, questionnaires were distributed among radiologists to assess whether their experience and training had an influence on the accuracy of reporting in the BI-RADS assessment categories. Descriptive and inferential statistical analysis was used for data analysis. RESULTS: The most common malignancy diagnosed was invasive ductal carcinoma with a total of 70% (n=54), followed by ductal carcinoma in situ with 10.4% (n=8) and invasive lobular carcinoma with 9.1% (n=7). The histology results confirmed breast cancer for all BI-RADS 4 and 5 assessment categories. The mammogram was able to detect 93.5% of abnormalities and breast ultrasound 84.4% of abnormalities in this study sample. Breast ultrasound was used as an adjunct to mammography and hence an overall combined diagnostic rate was 100%. Mammography descriptors: The more common malignancy findings were spiculated mass margin, 35.1% (n=27). Ultrasound descriptors: The more common malignancy findings were hypoechoic echo pattern, 55.8% (n=43). There was no significant association (p=0.152) between the radiologists' years of experience and BI-RADS 3, 4 and 5 assessment category reporting. Of the 15 responses, 67% agreed that the BI-RADS standardises breast imaging reporting and reduces confusion, 33% agreed that the BI-RADS allows better communication between radiologists and referring physicians, and 40% agreed that the BI-RADS clarifies further management for patients by helping to stratify risk management. CONCLUSION: The outcome of this study indicated that the use of BI-RADS assessment categories is useful for predicting the likelihood of malignancy when used correctly. The outcome of BI-RADS 4 and BI-RADS 5 had a positive predictive value of 100%, which corresponded well with histology results. The descriptor findings suggested that spiculated mass margins, irregular-shaped masses, hypoechoic echo pattern and posterior shadowing were high predictors of malignancy and warranted a placement in the BI-RADS 5 assessment category.

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During a clinical breast exam, a doctor palpates the breast and uses factors such as estimated size and stiffness of subcutaneous inclusions to determine whether they may be malignant tumors. The Tactile Imaging System (TIS) under development at the Control, Sensing, Networking and Perception Laboratory (CSNAP) is an effort to provide accurate and consistent characterization of inclusions. The sensing principle of the TIS is based on Total Internal Reflection (TIR) of light in a Polydimethylsiloxane (PDMS) optical waveguide positioned in front of a digital camera. When the PDMS is pressed against an object of greater stiffness it deforms, causing some light to escape the waveguide and be sensed by the camera. An algorithm maps the light pattern caused by the deformation and the force applied during the image acquisition to estimate the size, depth and stiffness of the inclusion based on a kernel model. The Third Generation Experimental TIS (TIS 3E) is an effort to improve the performance, repeatability, and usability of the system. Performance is increased through a new graphical user interface (GUI) allowing fine tuning of camera parameters, and interchangeable sensing probes for varying PDMS waveguides. Repeatability is improved with a digitally controlled lighting system, hardware triggered force sensing, and an online PDMS lighting and condition monitoring system, lowering the overall measurement error of the system. Usability is improved by a new chassis, reducing the device size and weight by 50 percent. Accuracy of the TIS 3E is comparable to the maximum accuracy TIS 1E, and exceeded the minimum accuracy of the TIS 1E. The measurement frequency was also increased from 10Hz to 50Hz. The TIS 3E will provide an accurate, consistent data acquisition platform for future Tactile Imaging Research efforts. / Electrical and Computer Engineering

Le cancer est un problème de santé publique dans le monde entier et d'importantes ressources en soins de santé sont dépensées pour le diagnostic. Plus précoce sera le dépistage des tumeurs, meilleures sont les chances de rémission sans rechute. Les techniques d'imagerie permettent de suivre l’évolution du traitement et de réorienter la stratégie en cas d’échec. En combinaison avec des agents de contraste ciblés, les modalités d'imagerie permettent même de sonder les structures à l’échelle moléculaires ce qui pourrait laisser envisager un traitement personnalisé du cancer [1, 2]. L’imagerie par résonance magnétique (IRM) et l’échographie sont deux techniques complémentaires et non invasives qui permettent la détection de plusieurs cancers (sein, colon, cerveau ...). L'échographie est rentable, portable et fournit, en temps reel, des informations anatomiques. L'IRM profite d’une pénétration profonde dans les tissus mous, d’un contraste élevé et d’une meilleure sensibilité que l’échographie [3]. Néanmoins, l'utilisation de ces techniques en combinaison avec des agents de contraste est difficile, surtout parce que la concentration locale atteint dans la tumeur est souvent inférieure à la plage de sensibilité de détection [4]. Au cours des 20 dernières années, les agents de contraste multifonctionnels ont été construits sur mesure pour atteindre une accumulation préférentielle dans les tissus malades [5]. Dans cette étude, des stratégies de ciblage passif et actif de la tumeur ont été envisagées pour renforcer la concentration locale de nanocapsules polymère, contenant un noyau liquide de bromure de perfluorooctyle (PFOB). L’approche de ciblage passif est basée sur l’effet de pénétration et la rétention accrue (EPR). Les nanocapsules doivent avoir un diamètre inférieur à 400nm une demi-vie plasmatique prolongée. L’approche de ciblage actif est basée sur la reconnaissance spécifique d’un ligand pour une cible biologique surexprimée par la tumeur ou la néovascularisation. Pour le ciblage passif, les nanocapsules ont été préparées avec PLGA-b-PEG par un procédé d'émulsion-évaporation. La morphologie cœur-couronne a été confirmée par RMN du Fluor et cryo microscopie électronique. La surface des nanocapsules est densément couverte par des chaînes de PEG qui adoptent une conformation en brosse, telle qu'évaluée par XPS et diffusion des neutrons aux petits angles. La furtivité des nanocapsules a été démontrée in vitro par des mesures d'activation du complément et in vivo par une étude cinétique de la capture hépatique, réalisée après l'administration intraveineuse de nanocapsules chez la souris nude. L'imagerie des tumeurs, par IRM du Fluor, a révélé que seulement 1% de la dose injectée a été accumulée dans le tissu malade. Par échographie aucun réhaussement du contraste n’a été observé. Ainsi, une autre approche de ciblage a été nécessaire afin d’augmenter l’accumulation des nanocapsules au sein de la tumeur. Les nanocapsules ont été fonctionnalisées avec un peptide RGD (Arginine-Glycine-Acide aspartique afin de cibler les intégrines avß3, qui sont des protéines transmembranaires surexprimées par les néovaisseaux. Deux stratégies, appelées bottom-up et top-down, ont été élaborées pour mener à une décoration satisfaisante du peptide à la surface des nanocapsules. L'efficacité du couplage a été mesurée par RMN du proton. La morphologie des nanocapsules a été étudiée par CryoTEM. / Cancer is a worldwide public health concern and significant health care resources are spent on diagnosis. The sooner the tumor detection, the better the chance of remission without relapse. Furthermore, imaging modalities facilitate the treatment monitoring and feedback, and support decision making to change the strategy when the treatment fails. When used in combination with targeted contrast agents, imaging modalities even enable to probe molecular structures on specific cells opening the doors to personalized cancer therapy [1, 2]. Ultrasonography and Magnetic Resonance Imaging (MRI) are two complementary and non invasive imaging modalities, which allow the detection of a broad range of cancers (breast, colon, brain…). Ultrasonography is cost-effective, portable and provides real-time anatomical information. MRI imparts deep penetration into soft tissues with high contrast and better sensitivity [3]. Nevertheless the use of these techniques in combination with contrast agents is challenging, mostly because the local concentration reached in the tumor is often below the sensitivity detection range [4]. In the last 20 years, multifunctional contrast agents were custom-built to achieve preferential accumulation in the diseased tissue [5]. In this study, passive and active tumor targeting strategies were considered to enhance the local concentration of polymeric nanocapsules, containing a liquid core of perfluorooctyl bromide (PFOB). The passive tumor targeting approach is based on the enhanced permeation and retention (EPR) effect. The related nanocapsules require to be small enough (< 400nm) and have extended plasmatic half life. The active tumor targeting approach is based on the specific receptor-ligand recognition.For passive tumor targeting, the nanocapsules were prepared with PLGA-b-PEG by an emulsion-evaporation process. The core shell morphology was confirmed by cryoTEM and 19F NMR. The surface of nanocapsules was densely covered by PEG chains with brush conformation, as assessed by XPS and Small Angle Neutrons Scattering. The related stealthiness of nanocapsules was evidenced in vitro by complement activation measurements and in vivo by a kinetic study of the mice liver uptake, performed after intravenous administration of nanocapsules. The tumor imaging, by 19F MRI, revealed that only 1% of the injected dose was accumulated in the diseased tissue whereas, by ultrasonography no contrast enhancement was observed. Thus, another targeting approach was required to increase nanocapsule distribution within the tumor. Nanocapsules were functionalized with an Arginine-Glycine-Aspartic acid (RGD) peptide to target the αvβ3 integrins, which are overexpressed proteins on neovessels. Two strategies, called bottom-up and top-down, were designed to achieve satisfying peptide decoration on nanocapsule surface. The coupling efficiency was measured by 1H NMR. The nanocapsule morphology was studied by CryoTEM.

Thesis (D.Tech.: Radiography)-Dept. of Radiography, Durban Institute of Technology, 2006 xxiii, 166 leaves / The purpose of this study was to evaluate 99mTc- methoxyisobutylisonitrile (MIBI) imaging, in terms of sensitivity and specificity, for non invasively detecting extracutaneous involvement of Kaposi’s sarcoma (KS) and for differentiating pulmonary infection from malignancy in acquired immunodeficiency syndrome (AIDS) patients before and after treatment. Current investigations are invasive.