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Northeastern University
1.
Gajadeera, Nisal.
Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids.
Degree: MS, Department of Chemistry and Chemical Biology, 2018, Northeastern University
URL: http://hdl.handle.net/2047/D20316349
► Breast cancer is the most common cancer among women, accounting for nearly third of all the diagnosed cancers. According to the American cancer society, over…
(more)
▼ Breast cancer is the most common cancer among women, accounting for nearly third of all the diagnosed cancers. According to the American cancer society, over 41,000 patients died from the disease in 2018. Due to the high importance of the role played by estrogen and progesterone, agents that target the estrogen receptor (ER) and progesterone receptor (PR) play a major role in breast cancer therapy. Therapeutic strategies include the use of selective estrogen receptor modulators, selective estrogen receptor down regulators and aromatase inhibitors. Treatment success of breast cancer therapy is assessed by tumor estrogen receptor status which employs immunohistochemistry among other modalities. Although suitable for assaying ER expression in primary breast tumors, the accuracy of immunohistochemistry is lower in metastases. Fluorescent imaging methods with high ER affinity and selectivity offer the potential for noninvasive, clinical imaging for primary and metastatic tumors. My thesis describes the background, synthesis and in vitro investigations of a series of fluorescently labeled steroids. Chapter 1 of this thesis provides an extensive review of the fluorescently labeled estrogens prepared since 1995 with an emphasis on their synthesis and their efficacy as imaging agents, with our rationale for developing the 'next generation' fluorescent steroidal ER imaging agents. Chapter 2 provides our synthetic approach for the fluorescent steroidal imaging agents and their controls. Our approached utilized the 11β-(4-azidoethoxyphenyl) estradiol scaffold with small, neutral fluorophores appended Sharpless "click" chemistry. Chapter 3 reports in vitro evaluation of our steroidal imaging agents. The results strongly suggest that our steroidal fluorophores show selectivity towards ER. Potential improvements for the steroidal-fluorophore conjugates is also discussed.
Subjects/Keywords: Estrogen receptor; Imaging agent; Chemistry
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APA (6th Edition):
Gajadeera, N. (2018). Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids. (Masters Thesis). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20316349
Chicago Manual of Style (16th Edition):
Gajadeera, Nisal. “Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids.” 2018. Masters Thesis, Northeastern University. Accessed January 22, 2021.
http://hdl.handle.net/2047/D20316349.
MLA Handbook (7th Edition):
Gajadeera, Nisal. “Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids.” 2018. Web. 22 Jan 2021.
Vancouver:
Gajadeera N. Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids. [Internet] [Masters thesis]. Northeastern University; 2018. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/2047/D20316349.
Council of Science Editors:
Gajadeera N. Design, Synthesis And In Vitro Investigations Of Novel Fluorescently Labeled Steroids. [Masters Thesis]. Northeastern University; 2018. Available from: http://hdl.handle.net/2047/D20316349

University of Toronto
2.
Haedicke, Inga Elisabeth.
The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications.
Degree: PhD, 2016, University of Toronto
URL: http://hdl.handle.net/1807/89259
► Among clinical imaging modalities, magnetic resonance imaging (MRI) has several advantages including high spatial resolution, excellent soft tissue contrast and lack of ionizing radiation. To…
(more)
▼ Among clinical imaging modalities, magnetic resonance imaging (MRI) has several advantages including high spatial resolution, excellent soft tissue contrast and lack of ionizing radiation. To improve sensitivity and specificity for disease diagnosis, contrast agents (CAs) are administered. Clinical CAs are primarily Gd-based and are limited by a decrease of relaxivity at high magnetic fields,1 and have been associated with nephrogenic systemic fibrosis (NSF), a severe and debilitating disease.2 Therefore, this thesis explores the development of manganese porphyrins (MnPs) as novel CAs designed for high field MRI applications.
MnPs were chosen because certain MnPs have been shown to exhibit anomalously high T1 relaxivity at high field,3 and are known to form highly stable metal chelates.4 The first section describes the design of a highly efficient Gd-free extracellular fluid CA based on a water-soluble MnP, manganese (III) meso-tetracarboxyl porphyrin (MnTCP), for clinical disease diagnosis (Chapter 2). To the best of our knowledge, MnTCP displays the highest r1 among all known small T1 CAs with molecular weight below 600 Dalton (Da) and was successfully used to detect tumors by dynamic contrast enhanced MRI. More recently, as the field of cell transplantation is rapidly expanding, CAs are needed to label and longitudinally track specific populations of cells in vivo. This led to the design and successful application of a cell-permeable, trappable and esterase-responsive MnP (Chapter 3). Highly efficient MRI labeling of two types of human cells was achieved with a relatively low concentration and short incubation time. The new CA is biocompatible and as far as we know, is the most efficient T1 cell labeling CA available to date. Finally, this thesis focuses on molecular imaging of enzyme activity. The progress towards the design and synthesis of an alkaline phosphatase responsive MnP for MRI and analogous ZnP for fluorescence is described in Chapter 4.
2018-07-08 00:00:00
Advisors/Committee Members: Zhang, Xiao-an, Chemistry.
Subjects/Keywords: Agent; Contrast; Imaging; MRI; Porphyrin; Synthesis; 0485
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APA (6th Edition):
Haedicke, I. E. (2016). The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89259
Chicago Manual of Style (16th Edition):
Haedicke, Inga Elisabeth. “The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications.” 2016. Doctoral Dissertation, University of Toronto. Accessed January 22, 2021.
http://hdl.handle.net/1807/89259.
MLA Handbook (7th Edition):
Haedicke, Inga Elisabeth. “The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications.” 2016. Web. 22 Jan 2021.
Vancouver:
Haedicke IE. The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/1807/89259.
Council of Science Editors:
Haedicke IE. The Development of MnIII-Porphyrins as T1 Contrast Agents for Biomedical Applications. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/89259

Washington University in St. Louis
3.
Maji, Dolonchampa.
Development and applications of novel fluorescent molecular probe strategies.
Degree: PhD, Biomedical Engineering, 2017, Washington University in St. Louis
URL: https://openscholarship.wustl.edu/eng_etds/242
► Optical imaging and spectroscopy technologies offer the ability to provide structural and functional information in a fast, low-cost, ionizing radiation free, highly sensitive and…
(more)
▼ Optical
imaging and spectroscopy technologies offer the ability to provide structural and functional information in a fast, low-cost, ionizing radiation free, highly sensitive and high throughput fashion. The diverse contrast mechanisms and complementary
imaging platforms form the foundation for the application of optical
imaging in pre-clinical studies of pathophysiological development as well as direct clinical application as a tool for diagnosis and therapy. Fluorescence
imaging techniques have been one of the most rapidly adopted methods in biology and biomedicine. Visualization of biological processes and pathologic conditions at the cellular and tissue levels largely relies on the use of exogenous fluorophores or their bioconjugates. Some fluorescent molecular probes provide usable contrast for disease diagnosis due to their responsiveness to interactions with other molecular species and/or immediate microenvironment. As a result, understanding exogenous fluorescent contrast mechanisms will allow the development of efficient strategies for biomedical fluorescence
imaging.
The present work focuses on exploring novel fluorescent molecular probe strategies for
imaging cancer and cardiovascular diseases. We have developed a platform for synthesizing activatable fluorescent molecular probes using the fluorescence quenching properties of copper (II) ions. We used these activatable probes for rapid
imaging of cancerous tissue in vivo in mice. While developing these molecular probes, we discovered an unexpected molecular interaction that yields stable dimeric molecules. This finding can potentially enable the development of new molecular entities for modifying the signaling properties of fluorescent dyes to minimize background fluorescence.
Although planar fluorescence
imaging methods using exogenous molecular probes provide rapid information about molecular processes in vivo, extraction of depth information require complex data acquisition and image analysis methods. By designing a dual emission fluorescent probe incorporating two spectrally different fluorophore systems, we developed a method to successfully estimate the depth of fluorescent inclusions from planar
imaging data and demonstrated the potential of using this approach to locate a blood vessel and tumorous tissue in mouse in vivo.
An important feature of fluorescence methods is the availability of various techniques that provide complementary information. Combining the fluorescence intensity and lifetime properties of a biologically targeted near infrared fluorescent probe, we demonstrate an effective way to distinguish specific from nonspecific uptake mechanisms in cancer cells, an approach that can be translated in vivo. Alternatively, dynamic fluorescence
imaging technique expands the scope of applications to include detection and estimation of the size of circulating cancer cells and clusters. The approach developed in this work could allow longitudinal monitoring of these cells, which are implicated in cancer metastases. …
Advisors/Committee Members: Samuel Achilefu, Mark Anastasio, Gregory M. Lanza, Srikanth Singamaneni, Lihong V. Wang.
Subjects/Keywords: contrast agent; fluorescence; optical imaging; Biomedical
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Maji, D. (2017). Development and applications of novel fluorescent molecular probe strategies. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/eng_etds/242
Chicago Manual of Style (16th Edition):
Maji, Dolonchampa. “Development and applications of novel fluorescent molecular probe strategies.” 2017. Doctoral Dissertation, Washington University in St. Louis. Accessed January 22, 2021.
https://openscholarship.wustl.edu/eng_etds/242.
MLA Handbook (7th Edition):
Maji, Dolonchampa. “Development and applications of novel fluorescent molecular probe strategies.” 2017. Web. 22 Jan 2021.
Vancouver:
Maji D. Development and applications of novel fluorescent molecular probe strategies. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2017. [cited 2021 Jan 22].
Available from: https://openscholarship.wustl.edu/eng_etds/242.
Council of Science Editors:
Maji D. Development and applications of novel fluorescent molecular probe strategies. [Doctoral Dissertation]. Washington University in St. Louis; 2017. Available from: https://openscholarship.wustl.edu/eng_etds/242

University of Arizona
4.
Hingorani, Dina Vinoo.
Developing Responsive MRI Contrast Agents to Study Tumor Biology
.
Degree: 2014, University of Arizona
URL: http://hdl.handle.net/10150/333481
► Enzymes are important biomarkers for determining tumor growth and progression. We have developed two molecules to image enzyme response by catalyCEST MRI. This technology allows…
(more)
▼ Enzymes are important biomarkers for determining tumor growth and progression. We have developed two molecules to image enzyme response by catalyCEST MRI. This technology allows for non-invasive detection of enzymes. A background of importance of measuring enzyme activity and MRI agents developed for this purpose have been covered in Chapter 1. We have synthesized a responsive paramagnetic Chemical Exchange Saturation Transfer (CEST)
agent, called Tm-DO3A-cadaverine. This contrast agents has been successfully cross-linked to the protein albumin by the enzyme transglutaminase leading to the appearance of CEST at -9.2 ppm. The enzyme catalysis has been validated by measuring chemical exchange rates. We have shown that the position of the CEST peak is influenced by the conformation of the molecule depending on the neighboring amino acids to glutamine. This is the first example to show the appearance of CEST due to formation of a covalent bond. We have also synthesized a diamagnetic CEST
agent with a large chemical shift dispersion to detect cathespin B activity. Upon enzyme mediated cleavage of PheArgSal, the aryl amide CEST peak at 5.3 ppm disappears. Taking a ratio of the CEST effects from salicylic acid at 9.5 ppm and aryl amide at 5.3 ppm we can detect enzyme activity. The salicylic acid moiety also undergoes some slow response due to enzyme action, as evident by the disappearance of CEST at 9.5 ppm. However, this proof of concept study is the first example of a DIACEST
agent designed to measure enzyme activity using a ratio of two CEST effects from the same substrate. The last chapter highlights suggests improvements to the catalyCEST research. The appendix shows the use of bulk magnetic susceptibility measurements by NMR to determine bio-distribution of lanthanides in ex-vivo tissue.
Advisors/Committee Members: Pagel, Mark D (advisor), Pagel, Mark D. (committeemember), Glass, Richard S. (committeemember), Mash, Jr., Eugene A. (committeemember).
Subjects/Keywords: Contrast agent;
Enzymes;
Imaging;
Chemistry;
CEST MRI
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hingorani, D. V. (2014). Developing Responsive MRI Contrast Agents to Study Tumor Biology
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/333481
Chicago Manual of Style (16th Edition):
Hingorani, Dina Vinoo. “Developing Responsive MRI Contrast Agents to Study Tumor Biology
.” 2014. Doctoral Dissertation, University of Arizona. Accessed January 22, 2021.
http://hdl.handle.net/10150/333481.
MLA Handbook (7th Edition):
Hingorani, Dina Vinoo. “Developing Responsive MRI Contrast Agents to Study Tumor Biology
.” 2014. Web. 22 Jan 2021.
Vancouver:
Hingorani DV. Developing Responsive MRI Contrast Agents to Study Tumor Biology
. [Internet] [Doctoral dissertation]. University of Arizona; 2014. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10150/333481.
Council of Science Editors:
Hingorani DV. Developing Responsive MRI Contrast Agents to Study Tumor Biology
. [Doctoral Dissertation]. University of Arizona; 2014. Available from: http://hdl.handle.net/10150/333481

University of Cambridge
5.
Weber, Judith.
Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress.
Degree: PhD, 2019, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/294385
► An early and precise diagnosis of disease is a crucial requirement for fast and targeted therapy in the era of precision medicine. Most diseases possess…
(more)
▼ An early and precise diagnosis of disease is a crucial requirement for fast and targeted therapy in the era of precision medicine. Most diseases possess molecular alterations in their early stages, which precede noticeable morphological changes. One important molecular change that contributes to dysfunction in a wide range of pathologies, including cancer and neurological disorders, is an increase in levels of reactive oxygen species (ROS) and associated oxidative damage. Our understanding of how ROS influence disease biology is currently limited by our inability to perform sensitive and specific assessment of ROS levels with high spatial and temporal resolution in living systems.
The goal of the research described in this thesis was to overcome the challenge of assessing ROS during disease development in cancer and neurodegenerative disease through the design, synthesis and validation of two classes of novel bifunctional, ROS-sensitive contrast agents.
To shed light on the complex redox biology in cancer, the new method of photoacoustic imaging was exploited. A novel activatable, targeted near infrared cyanine dye is reported that enables specific detection of pathological levels of hydrogen peroxide, a major and abundant ROS in living organisms. This approach uses photoacoustic and fluorescence imaging in cancerous tissue to evaluate the performance of the new probe under in vitro and in vivo conditions.
In neurodegeneration, there exists a bidirectional interaction between oxidative stress and protein aggregates. To scrutinise this relationship, both bulk and single-molecule fluorescence imaging methods were used to assess the capability of novel bifunctional fluorescence dyes to localise the presence of the two putative disease-causing species, ROS and protein aggregates, simultaneously under in vitro conditions.
The data shown here provides a promising foundation for the systematic design of contrast agents based on small molecule dyes, that possess ideal optical and biological characteristics to study oxidative stress in a broad range of pathological applications with high temporal and spatial resolution.
Subjects/Keywords: contrast agent; oxidative stress; photoacoustic imaging; fluorescence imaging/microscopy; amyloid aggregates
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Weber, J. (2019). Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/294385
Chicago Manual of Style (16th Edition):
Weber, Judith. “Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 22, 2021.
https://www.repository.cam.ac.uk/handle/1810/294385.
MLA Handbook (7th Edition):
Weber, Judith. “Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress.” 2019. Web. 22 Jan 2021.
Vancouver:
Weber J. Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 22].
Available from: https://www.repository.cam.ac.uk/handle/1810/294385.
Council of Science Editors:
Weber J. Development of Novel Molecular Imaging Contrast Agents for Detection of Oxidative Stress. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/294385

University of Cambridge
6.
Weber, Judith.
Development of novel molecular imaging contrast agents for detection of oxidative stress.
Degree: PhD, 2019, University of Cambridge
URL: https://doi.org/10.17863/CAM.41484
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782916
► An early and precise diagnosis of disease is a crucial requirement for fast and targeted therapy in the era of precision medicine. Most diseases possess…
(more)
▼ An early and precise diagnosis of disease is a crucial requirement for fast and targeted therapy in the era of precision medicine. Most diseases possess molecular alterations in their early stages, which precede noticeable morphological changes. One important molecular change that contributes to dysfunction in a wide range of pathologies, including cancer and neurological disorders, is an increase in levels of reactive oxygen species (ROS) and associated oxidative damage. Our understanding of how ROS influence disease biology is currently limited by our inability to perform sensitive and specific assessment of ROS levels with high spatial and temporal resolution in living systems. The goal of the research described in this thesis was to overcome the challenge of assessing ROS during disease development in cancer and neurodegenerative disease through the design, synthesis and validation of two classes of novel bifunctional, ROS-sensitive contrast agents. To shed light on the complex redox biology in cancer, the new method of photoacoustic imaging was exploited. A novel activatable, targeted near infrared cyanine dye is reported that enables specific detection of pathological levels of hydrogen peroxide, a major and abundant ROS in living organisms. This approach uses photoacoustic and fluorescence imaging in cancerous tissue to evaluate the performance of the new probe under in vitro and in vivo conditions. In neurodegeneration, there exists a bidirectional interaction between oxidative stress and protein aggregates. To scrutinise this relationship, both bulk and single-molecule fluorescence imaging methods were used to assess the capability of novel bifunctional fluorescence dyes to localise the presence of the two putative disease-causing species, ROS and protein aggregates, simultaneously under in vitro conditions. The data shown here provides a promising foundation for the systematic design of contrast agents based on small molecule dyes, that possess ideal optical and biological characteristics to study oxidative stress in a broad range of pathological applications with high temporal and spatial resolution.
Subjects/Keywords: contrast agent; oxidative stress; photoacoustic imaging; fluorescence imaging/microscopy; amyloid aggregates
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Weber, J. (2019). Development of novel molecular imaging contrast agents for detection of oxidative stress. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.41484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782916
Chicago Manual of Style (16th Edition):
Weber, Judith. “Development of novel molecular imaging contrast agents for detection of oxidative stress.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 22, 2021.
https://doi.org/10.17863/CAM.41484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782916.
MLA Handbook (7th Edition):
Weber, Judith. “Development of novel molecular imaging contrast agents for detection of oxidative stress.” 2019. Web. 22 Jan 2021.
Vancouver:
Weber J. Development of novel molecular imaging contrast agents for detection of oxidative stress. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 22].
Available from: https://doi.org/10.17863/CAM.41484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782916.
Council of Science Editors:
Weber J. Development of novel molecular imaging contrast agents for detection of oxidative stress. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.41484 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.782916

University of Texas – Austin
7.
Wilson, Katheryne Elizabeth.
Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets.
Degree: PhD, Biomedical Engineering, 2012, University of Texas – Austin
URL: http://hdl.handle.net/2152/ETD-UT-2012-05-5386
► The recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging…
(more)
▼ The recent increase in survival rates of most cancers is due to early detection greatly aided by medical
imaging modalities. Combined ultrasound and photoacoustic
imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast
agent for combined ultrasound and photoacoustic
imaging named Photoacoustic nanoDroplets. This
agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases.
Advisors/Committee Members: Emelianov, Stanislav Y. (advisor), Fowlkes, Brian (committee member), Hamilton, Mark (committee member), Sokolov, Konstantin (committee member), Williams, Robert (committee member).
Subjects/Keywords: Ultrasound imaging; Photoacoustic imaging; Contrast agent; Perfluorocarbon; Droplets; Nanoparticles; Dual modality
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wilson, K. E. (2012). Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/ETD-UT-2012-05-5386
Chicago Manual of Style (16th Edition):
Wilson, Katheryne Elizabeth. “Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets.” 2012. Doctoral Dissertation, University of Texas – Austin. Accessed January 22, 2021.
http://hdl.handle.net/2152/ETD-UT-2012-05-5386.
MLA Handbook (7th Edition):
Wilson, Katheryne Elizabeth. “Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets.” 2012. Web. 22 Jan 2021.
Vancouver:
Wilson KE. Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2012. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/2152/ETD-UT-2012-05-5386.
Council of Science Editors:
Wilson KE. Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets. [Doctoral Dissertation]. University of Texas – Austin; 2012. Available from: http://hdl.handle.net/2152/ETD-UT-2012-05-5386

University of Minnesota
8.
Du, Juan.
Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents.
Degree: PhD, Electrical/Computer Engineering, 2016, University of Minnesota
URL: http://hdl.handle.net/11299/183381
► Tissue perfusion is an important indicator of the health and vitality of organs such as liver and kidney. Imaging tissue perfusion has significant clinical applications…
(more)
▼ Tissue perfusion is an important indicator of the health and vitality of organs such as liver and kidney. Imaging tissue perfusion has significant clinical applications such as myocardial infarction. Contrast-enhanced ultrasound (CEUS) has been clinically used in imaging myocardial perfusion since the 1990s. It was realized, however, that standard B-mode imaging did not have the specificity required to image tissue perfusion in other clinical applications, e.g. tumor perfusion. Microbubble ultrasound contrast agents (UCA) composed of an elastic shell and inert gas content are able to generate nonlinear harmonics. Therefore, nonlinear methods such as harmonic, subharmonic and multipulse imaging were proposed to improve the sensitivity and specificity of perfusion imaging. In this dissertation, a novel method to image the nonlinear response of UCA is investigated by extracting the signal using an adaptive third-order Volterra filter (TVF). Unlike harmonic and sub-harmonic imaging methods, the TVF separates the linear, quadratic and cubic components from the beamformed pulse-echo data to capture polynomial nonlinearities throughout the system bandwidth. This allows for imaging using broadband pulse transmission to preserve the axial resolution and the signal to noise ratio (SNR). In addition, the quadratic and cubic kernels of the TVF inherently suppress additive Gaussian noise, which lowers the noise floor and improves the detection of UCA activity in low-perfusion regions. Results from in vitro and in vivo imaging experiments have demonstrated the significance of the advantage of the post-beamforming VF in imaging UCA activity. Under microflow conditions (as in blood microcirculation), the echogenicity of the UCA microbubbles exhibit temporal dynamics different from the surrounding tissue. For example, the temporal variance of the echogenicity in the presence of UCA is typically higher than that of the same tissue in the absence of UCA. We introduced the temporal perfusion index (TPI) to capture UCA dynamic activity under microflow conditions. The TPI is a spatial measurement that rewards temporal variance at a given image pixel and penalizes the average image intensity over a small spatial mask. An appropriate selection of dynamic range reduces the sensitivity of the TPI to noise and improves the specificity to temporal contrast variations. This approach for finding the "threshold dynamic range" is extended to account for the breathing motion when the method is applied to in vivo data. The VF and TPI methods were applied to a variety of data sets collected from in vitro and in vivo imaging targets. These include micro channels embedded in tissue-mimicking phantoms, subcutaneous tumors in vivo and brain tissue in vivo with and without UCA. The results clearly demonstrate the advantages of the proposed methods in imaging UCA activity under microflow conditions and show the way towards quantitative noninvasive perfusion imaging using pulse-echo ultrasound.
Subjects/Keywords: Dynamic imaging; Nonlinear filtering; Quantitative perfusion imaging; Tissue perfusion; Ultrasound contrast agent
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Du, J. (2016). Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/183381
Chicago Manual of Style (16th Edition):
Du, Juan. “Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents.” 2016. Doctoral Dissertation, University of Minnesota. Accessed January 22, 2021.
http://hdl.handle.net/11299/183381.
MLA Handbook (7th Edition):
Du, Juan. “Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents.” 2016. Web. 22 Jan 2021.
Vancouver:
Du J. Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents. [Internet] [Doctoral dissertation]. University of Minnesota; 2016. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/11299/183381.
Council of Science Editors:
Du J. Dynamic Imaging of Tissue Perfusion Using Ultrasound Contrast Agents. [Doctoral Dissertation]. University of Minnesota; 2016. Available from: http://hdl.handle.net/11299/183381

Kansas State University
9.
Marasini, Ramesh.
Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy.
Degree: PhD, Department of
Chemistry, 2020, Kansas State University
URL: http://hdl.handle.net/2097/40868
► Small molecule anticancer drugs are the first-line therapy used in clinical cancer management which has shown success in the killing of rapidly dividing cancer cells.…
(more)
▼ Small molecule anticancer drugs are the first-line
therapy used in clinical cancer management which has shown success
in the killing of rapidly dividing cancer cells. However,
nonspecific distribution of these small molecular therapeutics has
adverse side effects reducing the quality of life. Therefore, in
the past few decades, massive interest and investment have been
given in cancer nanomedicine with the hope to reduce
drug-associated toxicity by targeting cancer cells in a
heterogeneous tumor environment. Nanomedicine is the
drug-containing nanostructured construct with a large
surface-to-volume ratio, which has plenty of room to load drugs and
other necessary constituents to design it as target-specific.
Towards the endeavor of precise anticancer drug delivery to tumors,
significant efforts have been given to obtain an optimized
nanocarrier system to co-operate or bypass biological barriers
further advancing the therapeutic and diagnostic efficiency of
drugs. The main objective of this dissertation is to explore the
different strategies of nanomaterials for drug delivery via
light-triggered and magnet sensitive design considerations
discussed in chapter 1. The synthesized nanomaterials were
extensively studied and evaluated for their chemistry and
biological functions for in vitro cancer therapy and in vivo
diagnosis. In chapter 2, we developed the optimum surfactant
packing strategy for light-responsive gold nanoparticles (NPs) for
photothermal therapy (PTT) of melanoma. Results showed that 5 kDa
polyethylene glycol (PEG) coated gold nanorod provided the highest
colloidal stability and maximum photothermal efficiency compared to
the low (2 kDa) and high mass of PEG (10 kDa) used when treated
with near-infrared (NIR) laser. Taking one step further, in chapter
3, we encapsulated NIR light-responsive indocyanine class of dye
(IR-820) into polymeric NPs for the PTT of breast cancer. The
optical properties of dye were preserved to obtain better
photothermal efficiency than free IR-820 at an equivalent
concentration of dye after laser treatment. Moreover, the molecular
mechanism of PTT revealed that the dye loaded NPs inducedcell death
primarily through apoptosis, a preferred cell-death pathway over
necrosis. In chapter 4, we designed peptide conjugated
lipid-polymer NPs for p32 targeted drug delivery and tracked NIR
dye-labeled NPs in vivo using an optical
imaging system. The
targeted NPs were accumulated 2-fold higher than non-targeted
counterparts in the murine osteosarcoma model suggesting the
diagnostic potential of targeted NPs. In chapter 5, we developed
magnet responsive iron chelated paramagnetic polymeric NPs with
high colloidal stability and longitudinal relaxivity of 10.5
mM-1s-1 as compared to the Magnevist® 3.98 mM-1s-1 (a clinical
gadolinium contrast
agent) and enhanced contrast efficacy in vivo
at clinical magnetic resonance
imaging (3 T) system showing its
promise as a blood pool contrast
agent in disease detection. The
nanoconstructs described herein addresses the current limitations
of conventional…
Advisors/Committee Members: Santosh Aryal.
Subjects/Keywords: Nanomedicine;
Photothermal Therapy; Magnetic
Resonance Imaging;
Fluorescence Imaging; Cancer
theranostics; Iron-based
T1 contrast agent
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Chicago ·
MLA ·
Vancouver ·
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APA (6th Edition):
Marasini, R. (2020). Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/40868
Chicago Manual of Style (16th Edition):
Marasini, Ramesh. “Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy.” 2020. Doctoral Dissertation, Kansas State University. Accessed January 22, 2021.
http://hdl.handle.net/2097/40868.
MLA Handbook (7th Edition):
Marasini, Ramesh. “Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy.” 2020. Web. 22 Jan 2021.
Vancouver:
Marasini R. Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy. [Internet] [Doctoral dissertation]. Kansas State University; 2020. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/2097/40868.
Council of Science Editors:
Marasini R. Design
strategies and application of stimuli-responsive nanoparticles for
cancer diagnosis and therapy. [Doctoral Dissertation]. Kansas State University; 2020. Available from: http://hdl.handle.net/2097/40868
10.
Qutaish, Mohammed Q.
CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS.
Degree: PhD, Biomedical Engineering, 2014, Case Western Reserve University School of Graduate Studies
URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1404998136
► The goal of this work is to create a platform methodology consisting of cryo-imaging experimental methods and specialized image analysis software to provide unique 3D,…
(more)
▼ The goal of this work is to create a platform
methodology consisting of cryo-
imaging experimental methods and
specialized image analysis software to provide unique 3D,
quantitative characterization of tumor models, including spread via
dispersal and metastasis, and assessment of
imaging agent targeting
to dispersed tumor cell and metastatic tumor. Analyses used
microscopic, 3D cryo-
imaging which has the sensitivity to detect
fluorescently labeled single cells over large volumes of tissues.
Specifically, tumor cell dispersal in Glioblastoma multioforme
(GBM) and micrometastases in breast cancer mouse models were
detected, quantified, and visualized. Targeting of the
fluorescently labeled SBK2 peptide to GBM dispersing cells, and
CREKA peptide multiplexed Gd-MR probe to breast cancer metastases,
were analyzed. For GBM tumor cell dispersal analyses in
cryo-images, algorithms were developed to detect blood vessels,
dispersing tumor cells, white matter tract and main tumor mass, as
well as measure cell dispersal distance. Multiple GBM cell lines
were characterized to find those that showed high dispersive
patterns similar to the human disease. Software was created to
assess how far from the main tumor mass, SBK2 efficiently labeled
dispersing cells. Results showed that LN-229 and CNS-1 cell lines
are highly dispersive, and cells mainly dispersed along blood
vessels and white matter tract. Dispersal distance was as far as
562µm in LN-229 and >3mm in CNS-1. Fluorescently labeled SBK2
peptide labeled more than 99% of dispersing cells, and as far as
3.5 mm. For breast cancer metastasis analyses, software was created
to quantify number and size of metastases using cryo-
imaging
volumes. Multimodality 3D deformable image registration was
employed to register MRI and cryo-
imaging volume. This enabled the
validation of CREKA peptide targeting in MRI using the high
resolution cryo volumes, and provided information about limitation
and efficiency of the developed MRI
agent. The 4T1 cell line was
used to create a metastatic breast cancer model. Results showed an
average of 156 metastases in cryo-volumes ranging in size of
0.1–8mm in diameter. Metastases were mainly found in lungs, liver,
bones and adrenal gland. Rose criterion showed >73% of
micrometastases in lungs were labeled by the MRI CREKA. Results
were shown visually and quantitatively. Analysis methods and
software demonstrated in the thesis should be applicable to a wide
range of studies of cancer,
imaging agents and
theranostics.
Advisors/Committee Members: Wilson, David (Advisor).
Subjects/Keywords: Biomedical Engineering; Cryo imaging; Glioblastoma multiforme; imaging agent; cell dispersal; metastatic tumor; image registration
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Qutaish, M. Q. (2014). CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1404998136
Chicago Manual of Style (16th Edition):
Qutaish, Mohammed Q. “CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS.” 2014. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed January 22, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=case1404998136.
MLA Handbook (7th Edition):
Qutaish, Mohammed Q. “CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS.” 2014. Web. 22 Jan 2021.
Vancouver:
Qutaish MQ. CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2014. [cited 2021 Jan 22].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1404998136.
Council of Science Editors:
Qutaish MQ. CRYO-IMAGING ASSESSMENT OF IMAGING AGENT TARGETING TO
DISPERSING AND METASTATIC TUMOR CELLS. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1404998136

University of California – Berkeley
11.
Ramirez, Richard Matthew.
Xenon Host-Guest Interactions for Applications in NMR and MRI.
Degree: Chemistry, 2013, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/5z2691dn
► The ability to detect the presence of specific analytes, whether in vivo or in heterogeneous solutions in vitro, is important for biomedical research as well…
(more)
▼ The ability to detect the presence of specific analytes, whether in vivo or in heterogeneous solutions in vitro, is important for biomedical research as well as chemical sensing devices. These applications demand sensitive detection in order to report on small quantities of the material of interest. For many diseases such as cancer, early detection of the important biomarkers when they exist at very low concentrations improves patient prognosis.NMR is noninvasive and does not require ionizing radiation, making it ideal for passive monitoring, and compatible with biological systems. It can be used to gain spectroscopic information, or alternatively to map the spatial distribution of a signal of interest, as is done with water protons in a 1H MRI experiment. The intrinsic sensitivity of NMR is low, however, due to low polarization which means that only ten protons out of a million are actually contributing to the observed signal. This is acceptable in an ordinary clinical MRI scan, where the in vivo concentration of protons is high ([H2O] $sim; 55 M), but severely limits its utility for low detection applications. Although contrast agents and methods have been successfully developed to address this problem they still lack the sensitivity to compete with nuclear medicine radioactive tracers which can be detected at sub-nanomolar concentrations—concentrations which better reflect the detection thresholds necessary for applications such as biomarker screening.This work considers the use of dissolved 129Xe gas as the imaging medium, rather than water protons. 129Xe can be “hyperpolarized” to increase its NMR signal by greater than 10,000-fold, resulting in signals comparable to that of water from considerably smaller concentrations (e.g. millimolar). Since xenon, a noble gas, cannot easily be functionalized for targeted applications, agents that interact with both xenon and a target are required. These hosts provide a unique environment for xenon such that a unique signature arises in the 129Xe NMR spectrum. This text describes the development, characterization, and application of xenon hosts with a sharp focus on creating new agents with improved sensitivity over state-of-the-art. Three different host platforms are presented. The first system builds upon a decade of previous work using the cage-like molecule cryptophane-A as the xenon host. Here, an agent composed of several hundred cryptophane-A molecules covalently attached to an M13 bacteriophage was synthesized and detected at sub-picomolar concentrations. The second system utilized emulsified, nanometer-sized perfluorocarbon-in-water droplets as the xenon host. This platform benefits from increased xenon payload and faster dynamics as opposed to cryptophane-based agents. Although a similar detection threshold was achieved for these nanoemulsion droplets, the time required for their detection was reduced by about 75%, and their…
Subjects/Keywords: Physical chemistry; contrast agent; hyperpolarized; molecular imaging; MRI; NMR; Xenon
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Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ramirez, R. M. (2013). Xenon Host-Guest Interactions for Applications in NMR and MRI. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/5z2691dn
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ramirez, Richard Matthew. “Xenon Host-Guest Interactions for Applications in NMR and MRI.” 2013. Thesis, University of California – Berkeley. Accessed January 22, 2021.
http://www.escholarship.org/uc/item/5z2691dn.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ramirez, Richard Matthew. “Xenon Host-Guest Interactions for Applications in NMR and MRI.” 2013. Web. 22 Jan 2021.
Vancouver:
Ramirez RM. Xenon Host-Guest Interactions for Applications in NMR and MRI. [Internet] [Thesis]. University of California – Berkeley; 2013. [cited 2021 Jan 22].
Available from: http://www.escholarship.org/uc/item/5z2691dn.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ramirez RM. Xenon Host-Guest Interactions for Applications in NMR and MRI. [Thesis]. University of California – Berkeley; 2013. Available from: http://www.escholarship.org/uc/item/5z2691dn
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto
12.
Qiu, Yi.
Synthesis and Characterization of EGFR-Targeted Immunoporphysomes.
Degree: 2018, University of Toronto
URL: http://hdl.handle.net/1807/89548
► Many nanosized drug delivery systems rely on the phenomena of enhanced permeability and retention (EPR) effect for their accumulation at the tumor site. However, recent…
(more)
▼ Many nanosized drug delivery systems rely on the phenomena of enhanced permeability and retention (EPR) effect for their accumulation at the tumor site. However, recent clinical data suggest that passive accumulation of nanomedicines observed in animal models does not always translate to patients, because the tumor biology in humans is much more complex and heterogeneous. By contrast, active targeting strategies, which involve modifying the surface of nanoparticles with targeting ligands, can theoretically reduce off-target effects and increase tumor accumulation. In this study, cetuximab was conjugated to the surface of porphysomes, which is a liposome-like nanovesicle self-assembled from porphyrin lipids. This nanoparticle exhibits structurally dependent properties that enable fluorescence imaging, photothermal therapy, and photodynamic therapy applications. By functionalizing porphysomes with targeting ligands, the particles will be actively taken up by the target cells, thereby improving the efficacy of the payload.
M.Sc.
Advisors/Committee Members: Zheng, Gang, Pharmaceutical Sciences.
Subjects/Keywords: cetuximab; EGFR; multimodal imaging agent; nanoparticle; porphyrins; porphysomes; 0572
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Qiu, Y. (2018). Synthesis and Characterization of EGFR-Targeted Immunoporphysomes. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/89548
Chicago Manual of Style (16th Edition):
Qiu, Yi. “Synthesis and Characterization of EGFR-Targeted Immunoporphysomes.” 2018. Masters Thesis, University of Toronto. Accessed January 22, 2021.
http://hdl.handle.net/1807/89548.
MLA Handbook (7th Edition):
Qiu, Yi. “Synthesis and Characterization of EGFR-Targeted Immunoporphysomes.” 2018. Web. 22 Jan 2021.
Vancouver:
Qiu Y. Synthesis and Characterization of EGFR-Targeted Immunoporphysomes. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/1807/89548.
Council of Science Editors:
Qiu Y. Synthesis and Characterization of EGFR-Targeted Immunoporphysomes. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89548

University of Toronto
13.
Leung, Andrew.
Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting.
Degree: 2018, University of Toronto
URL: http://hdl.handle.net/1807/91492
► When evaluating regional health performance in a multi-facility setting, patient behaviour must be accounted for with services where facility choice is available. This paper describes…
(more)
▼ When evaluating regional health performance in a multi-facility setting, patient behaviour must be accounted for with services where facility choice is available. This paper describes the development of an agent-based simulation model designed to evaluate policy scenarios which incorporates facility choice, patient behaviour and operational constraints in the diagnostic imaging setting, specifically in MRI. The model is validated by retrospectively simulating the performance of the region for a year and comparing the results with actual performance. Using the model, theoretical results are confirmed where additional facility choice leads to more equitable but higher waiting times. We demonstrate how the model can be used by policy makers to evaluate various planning scenarios by expanding capacity at selected sites and show that the benefits of additional capacity is not limited to the expanding sites.
M.A.S.
Advisors/Committee Members: Carter, Michael, Mechanical and Industrial Engineering.
Subjects/Keywords: Agent based simulation; Diagnostic imaging; Patient behaviour; 0769
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Leung, A. (2018). Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/91492
Chicago Manual of Style (16th Edition):
Leung, Andrew. “Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting.” 2018. Masters Thesis, University of Toronto. Accessed January 22, 2021.
http://hdl.handle.net/1807/91492.
MLA Handbook (7th Edition):
Leung, Andrew. “Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting.” 2018. Web. 22 Jan 2021.
Vancouver:
Leung A. Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/1807/91492.
Council of Science Editors:
Leung A. Generic Policy Evaluation Model In a Multi-Facility Diagnostic Imaging Setting. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/91492

University of Arizona
14.
Kombala Nanayakkara Thambiliyagodage, Chathuri Jeewanthi.
Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
.
Degree: 2020, University of Arizona
URL: http://hdl.handle.net/10150/642025
► The extracellular tumor microenvironments of many solid tumors have high acidosis and high protease activity. The detection of tumor acidosis and protease activity can potentially…
(more)
▼ The extracellular tumor microenvironments of many solid tumors have high acidosis and high protease activity. The detection of tumor acidosis and protease activity can potentially impact the cancer diagnosis. Noninvasive
imaging methods have previously been developed that measure extracellular pH or can detect enzyme activity using Chemical Exchange Saturation Transfer Magnetic Resonance
Imaging (CEST MRI). CEST MRI is an inherently insensitive MRI modality which requires a high concentration of small molecule
agent to be delivered to the tumor. Therefore, nanosized molecules have received increased attention to be used in CEST
imaging to improve the sensitivity.
Herein, we developed a nanoscale CEST
agent that can measure pH using acidoCEST MRI, which may decrease the requirement for high delivery concentrations of
agent. We also developed a monomer
agent for comparison to the polymer. After optimizing CEST experimental conditions, we determined that the polymer
agent could be used during acidoCEST MRI studies at 125-fold and 488-fold lower concentration than the monomer
agent and iopamidol, respectively. In vivo acidoCEST MRI studies using the three agents were performed to study a xenograft MDA-MB-231 model of mammary carcinoma. The tumor pHe measurements were 6.33 ± 0.12, 6.70 ± 0.15, and 6.85 ± 0.15 units with iopamidol, the monomer
agent and polymer
agent, respectively. The higher pHe measurements with the new agents was attributed to the concentration dependence of these agents. This study demonstrated that nanoscale agents have merit for CEST MRI studies, but consideration should be given to the dependence of CEST contrast on the concentration of these agents.
We also investigated the development and application of a single hybrid CEST
agent that can simultaneously measure pH and evaluate protease activity using a combination of dual-power acidoCEST MRI and catalyCEST MRI. Simultaneously assessing both characteristics may improve diagnostic evaluations of aggressive tumors and the effects of anti-cancer treatments. Our
agent showed CEST signals at 9.2 ppm from a salicylic acid moiety and at 5.0 ppm from an aryl amide. The CEST signal at 9.2 ppm could be measured after selective saturation was applied at 1 and 4 T, and these measurements could be used with a ratiometric analysis to determine pH. The CEST signal at 5.0 ppm from the aryl amide disappeared after the
agent was treated with cathepsin-B, while the CEST signal at 9.2 ppm remained, indicating that the
agent could detect protease activity through amide bond clevage. Michaelis-Menton kinetics studies with catalyCEST MRI demonstrated that the binding affinity (as shown with the Michaelis constant KM), the catalytic turnover rate (kcat), and catalytic efficiency (kcat/kM), were each higher for cathepsin B at lower pH. The kcat rates measured with catalyCEST MRI were lower than the comparable rates measured with LC-MS, which reflected a limitation of inherently noisy and relatively insensitive CEST MRI analyses. Although this level of precision limited…
Advisors/Committee Members: Mash, Eugene A (advisor), Pagel, Mark D. (committeemember), Charest, Pascale G. (committeemember), Kuo, Philip H. (committeemember).
Subjects/Keywords: CEST;
Contrast agent;
Enzyme activity;
Magnetic resonance imaging;
pH;
Polymer
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kombala Nanayakkara Thambiliyagodage, C. J. (2020). Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/642025
Chicago Manual of Style (16th Edition):
Kombala Nanayakkara Thambiliyagodage, Chathuri Jeewanthi. “Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
.” 2020. Doctoral Dissertation, University of Arizona. Accessed January 22, 2021.
http://hdl.handle.net/10150/642025.
MLA Handbook (7th Edition):
Kombala Nanayakkara Thambiliyagodage, Chathuri Jeewanthi. “Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
.” 2020. Web. 22 Jan 2021.
Vancouver:
Kombala Nanayakkara Thambiliyagodage CJ. Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
. [Internet] [Doctoral dissertation]. University of Arizona; 2020. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10150/642025.
Council of Science Editors:
Kombala Nanayakkara Thambiliyagodage CJ. Development and Application of CEST MRI Contrast Agents that Evaluate Tumor Acidosis and Enzyme Activity
. [Doctoral Dissertation]. University of Arizona; 2020. Available from: http://hdl.handle.net/10150/642025

Wayne State University
15.
Vithanarachchi, Sashiprabha Manjari.
Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging.
Degree: PhD, Chemistry, 2014, Wayne State University
URL: https://digitalcommons.wayne.edu/oa_dissertations/932
► The focus of the research described in this thesis is the study of chemistry relevant to target-specific contrast agents for magnetic resonance imaging (MRI).…
(more)
▼ The focus of the research described in this thesis is the study of chemistry relevant to target-specific contrast agents for magnetic resonance
imaging (MRI). MRI is a widely used technique in diagnostic medicine and biomedical research to obtain anatomical and physiological details of soft tissues. Contrast agents are used to enhance the contrast of MR images by causing changes to the chemical environment of water molecules. Clinically approved GdIII-containing contrast agents for MRI are non-specific, and consequently, have limited utility. Target-specific contrast agents represent one way to circumvent this limitation. In the research described in this thesis, myelin and Β-amyloid aggregates were selected as targets because they are important in diagnosing neurological diseases. The myelin-targeted complexes were designed to mimic the structural features of a known myelin-specific histology stain, and ex vivo mouse-brain staining method was developed to test these complexes. Ex vivo staining studies (optical, MRI, and mass spectrometry
imaging) demonstrated the ability of these complexes to interact with the myelinated regions in mouse brain tissue. Additionally, a Β-amyloid-targeted
agent was synthesized by conjugating a GdIII-containing complex to curcumin. The binding ability of this complex with in vitro Β-amyloid peptide aggregates was studied using relaxation time and fluorescence measurements. This dissertation presents the synthesis, characterization, and in vitro and ex vivo
imaging of these complexes. The studies using these paramagnetic metal complexes have the potential to enable a reliable method to observe structural changes in the brain.
Advisors/Committee Members: Matthew J. Allen.
Subjects/Keywords: beta-amyloid; contrast agent; gadolinium; Magnetic resonance imaging; multimodal; myelin; Chemistry
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APA ·
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MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vithanarachchi, S. M. (2014). Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging. (Doctoral Dissertation). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_dissertations/932
Chicago Manual of Style (16th Edition):
Vithanarachchi, Sashiprabha Manjari. “Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging.” 2014. Doctoral Dissertation, Wayne State University. Accessed January 22, 2021.
https://digitalcommons.wayne.edu/oa_dissertations/932.
MLA Handbook (7th Edition):
Vithanarachchi, Sashiprabha Manjari. “Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging.” 2014. Web. 22 Jan 2021.
Vancouver:
Vithanarachchi SM. Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging. [Internet] [Doctoral dissertation]. Wayne State University; 2014. [cited 2021 Jan 22].
Available from: https://digitalcommons.wayne.edu/oa_dissertations/932.
Council of Science Editors:
Vithanarachchi SM. Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging. [Doctoral Dissertation]. Wayne State University; 2014. Available from: https://digitalcommons.wayne.edu/oa_dissertations/932

University of Leicester
16.
Khalil, Mofid Nasef.
The assessment of myocardial perfusion using a new scanning agent.
Degree: PhD, 1987, University of Leicester
URL: http://hdl.handle.net/2381/34121
Subjects/Keywords: 610; Myocardial imaging agent
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khalil, M. N. (1987). The assessment of myocardial perfusion using a new scanning agent. (Doctoral Dissertation). University of Leicester. Retrieved from http://hdl.handle.net/2381/34121
Chicago Manual of Style (16th Edition):
Khalil, Mofid Nasef. “The assessment of myocardial perfusion using a new scanning agent.” 1987. Doctoral Dissertation, University of Leicester. Accessed January 22, 2021.
http://hdl.handle.net/2381/34121.
MLA Handbook (7th Edition):
Khalil, Mofid Nasef. “The assessment of myocardial perfusion using a new scanning agent.” 1987. Web. 22 Jan 2021.
Vancouver:
Khalil MN. The assessment of myocardial perfusion using a new scanning agent. [Internet] [Doctoral dissertation]. University of Leicester; 1987. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/2381/34121.
Council of Science Editors:
Khalil MN. The assessment of myocardial perfusion using a new scanning agent. [Doctoral Dissertation]. University of Leicester; 1987. Available from: http://hdl.handle.net/2381/34121

University of Arizona
17.
Goldsher, Anetta Victoria.
Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
.
Degree: 2017, University of Arizona
URL: http://hdl.handle.net/10150/625887
► Detection of enzyme activity has gained popularity in molecular imaging because increased activity of enzymes such as urokinase plasminogen activator (uPA) can serve as biomarkers…
(more)
▼ Detection of enzyme activity has gained popularity in molecular
imaging because increased activity of enzymes such as urokinase plasminogen activator (uPA) can serve as biomarkers and assist in cancer diagnosis. Chemical exchange saturation transfer (CEST) Magnetic Resonance
Imaging (MRI) is a non-invasive technique that can be utilized to detect enzyme activity; however, CEST MRI is not the only technique that can assess enzyme activity. Chapter 1 provides an overview of various
imaging modalities that have been used to detect enzyme activity in vivo. Advances made in probe-design are discussed, in addition to advantages and disadvantages of each technique. Chapter 2 focuses on detection of uPA activity in a pancreatic cancer tumor model using a catalyCEST MRI contrast
agent. Chapter 2 also discusses the importance of uPA in tumor biology, addresses the synthesis of the contrast
agent, and evaluates the results of in vivo detection and ex vivo validation of uPA activity in response to therapy of pancreatic tumor models of Capan-2. The in vivo and ex vivo results showed no significant difference in uPA activity between chemotherapy-treated and non-treated mice. Additionally, no significant difference was observed between before and after chemotherapy-treated groups. Chapter 3 addresses some of the limitations of the study detailed in Chapter 2 and proposes improvements.
Advisors/Committee Members: Pagel, Mark D (advisor), Jewett, John C (advisor), Pagel, Mark D. (committeemember), Jewett, John C. (committeemember), Baker, Amanda F. (committeemember).
Subjects/Keywords: CEST;
contrast agent;
molecular imaging;
MRI;
pancretic cancer;
uPA
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APA (6th Edition):
Goldsher, A. V. (2017). Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
. (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/625887
Chicago Manual of Style (16th Edition):
Goldsher, Anetta Victoria. “Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
.” 2017. Masters Thesis, University of Arizona. Accessed January 22, 2021.
http://hdl.handle.net/10150/625887.
MLA Handbook (7th Edition):
Goldsher, Anetta Victoria. “Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
.” 2017. Web. 22 Jan 2021.
Vancouver:
Goldsher AV. Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
. [Internet] [Masters thesis]. University of Arizona; 2017. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10150/625887.
Council of Science Editors:
Goldsher AV. Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI
. [Masters Thesis]. University of Arizona; 2017. Available from: http://hdl.handle.net/10150/625887

Virginia Tech
18.
Pen, Olga Vladimirovna.
Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations.
Degree: MS, Biomedical Engineering, 2016, Virginia Tech
URL: http://hdl.handle.net/10919/78149
► The author discusses the difficulties that arise with the determination of the concentration of the iodinated contrast agents in the blood stream via the traditional…
(more)
▼ The author discusses the difficulties that arise with the determination of the concentration of the iodinated contrast agents in the blood stream via the traditional gray-scale computer tomography and searches for the new
imaging modalities that would provide for better sensitivity. The topic of the energy-discriminative color CT is discussed as a potential solution and its suitability is evaluated by performing the experiments on the contrast materials phantom and the phantom containing the iohexol solutions of varying concentrations on the original CT system assembled by the author. A method of the effective atomic number mapping is discussed as a viable alternative to the traditional attenuation-based tomography. The dependency of the effective atomic number of the compound on the energy of the x-ray beam is a phenomenon well recorded in the literature, yet no formal study exists to correctly predict the effective atomic number for a given compound. An extensive physical model is developed based on the previously presented models and adaptations unique to the task in order to determine the effective atomic numbers for exact energies experimentally. The method is tested on different materials. The resultant effective atomic numbers for the water, oil, and iohexol-water solutions of varying concentrations are presented in the study. The effects of the k-edge on both the linear attenuation curve and the effective atomic number curve are discussed. The possible future venues of the research are presented in the final part of the thesis.
Advisors/Committee Members: Cao, Guohua (committeechair), Bourland, J. Daniel (committee member), LaConte, Stephen M. (committee member).
Subjects/Keywords: effective atomic number; color CT; x-ray imaging; iodine contrast agent
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Pen, O. V. (2016). Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/78149
Chicago Manual of Style (16th Edition):
Pen, Olga Vladimirovna. “Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations.” 2016. Masters Thesis, Virginia Tech. Accessed January 22, 2021.
http://hdl.handle.net/10919/78149.
MLA Handbook (7th Edition):
Pen, Olga Vladimirovna. “Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations.” 2016. Web. 22 Jan 2021.
Vancouver:
Pen OV. Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations. [Internet] [Masters thesis]. Virginia Tech; 2016. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10919/78149.
Council of Science Editors:
Pen OV. Calculation of the effective atomic number for the iodine contrast agent of the varying concentrations. [Masters Thesis]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/78149

University of Louisville
19.
Wang, Jianting, 1983-.
Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging.
Degree: PhD, 2011, University of Louisville
URL: 10.18297/etd/1512
;
https://ir.library.louisville.edu/etd/1512
► Gold nanoparticles (GNPs) have shown beneficial properties for biomedical use, e.g., their non-toxic nature and surface properties for easy modification. Upon receiving light, they generate…
(more)
▼ Gold nanoparticles (GNPs) have shown beneficial properties for biomedical use, e.g., their non-toxic nature and surface properties for easy modification. Upon receiving light, they generate a strong surface plasmon field, which can alter the fluorescence of fluorophores. The level and type of the fluorescence alteration depend on the GNP size and shape, excitation (Ex)/emission (Em) wavelengths and quantum yield of the fluorophore, as well as the distance between the fluorophore and GNP. In this dissertation, the effect of the properties listed above on the fluorescence output was theoretically analyzed for the fluorophores frequently used in biomedical studies. For fluorescence quenching, fluorophores with the Em wavelength near the GNP plasmon resonance peak (520 nm) are better suited. As the Em wavelength increases, a shorter distance is required for achieving the same level of quenching. A bigger GNP requires shorter distance for quenching. To obtain fluorescence enhancement, the Em wavelength of the fluorophore needs to be longer than the GNP plasmon resonance peak (e.g., > 650 nm). The fluorophore with lower intrinsic quantum yield tends to be enhanced more. The GNP needs to be sufficiently large (> 5 nm), and a bigger GNP provides a higher maximum enhancement. Utilizing the quenching/enhancement ability of GNPs, a near-infrared (NIR) contrast
agent that emits fluorescence at a higher level only at the particular cancer site was developed. Cypate, a safe NIR fluorophore, was selected as the fluorophore because NIR penetrates deeper into tissue and because Cypate is non-toxic. Cypate was conjugated to a GNP via two spacers. One is short for the quenching and with a substrate for a breast cancer-specific enzyme, urokinase-type plasminogen activator (uPA). The other is a long, biocompatible polymer chain for fluorescence enhancement. The fluorescence of the contrast
agent was quenched by GNP by 93%. In the presence of uPA, the short spacer was cleaved and the remaining long spacer enhanced fluorescence 1.8 times. The study results are beneficial for developing efficacious optical contrast agents. This novel contrast
agent can detect and diagnose breast cancer with high specificity and sensitivity, as FRET or molecular beacon but with a higher sensitivity and without the restriction of using DNA/RNA segments.
Advisors/Committee Members: Kang, Kyung A..
Subjects/Keywords: Optical contrast agent; Bioimaging; Gold nanoparticle; Biosensing; Fluorescence manipulation; Molecular imaging
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Export
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APA (6th Edition):
Wang, Jianting, 1. (2011). Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging. (Doctoral Dissertation). University of Louisville. Retrieved from 10.18297/etd/1512 ; https://ir.library.louisville.edu/etd/1512
Chicago Manual of Style (16th Edition):
Wang, Jianting, 1983-. “Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging.” 2011. Doctoral Dissertation, University of Louisville. Accessed January 22, 2021.
10.18297/etd/1512 ; https://ir.library.louisville.edu/etd/1512.
MLA Handbook (7th Edition):
Wang, Jianting, 1983-. “Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging.” 2011. Web. 22 Jan 2021.
Vancouver:
Wang, Jianting 1. Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging. [Internet] [Doctoral dissertation]. University of Louisville; 2011. [cited 2021 Jan 22].
Available from: 10.18297/etd/1512 ; https://ir.library.louisville.edu/etd/1512.
Council of Science Editors:
Wang, Jianting 1. Theoretical and experimental studies on manipulation of fluorescence by gold nanoparticle : application for molecular imaging. [Doctoral Dissertation]. University of Louisville; 2011. Available from: 10.18297/etd/1512 ; https://ir.library.louisville.edu/etd/1512

Virginia Tech
20.
Ye, Youqing.
Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents.
Degree: MS, Chemistry, 2014, Virginia Tech
URL: http://hdl.handle.net/10919/47781
► Gadolinium endohedral metallofullerenes (EMFs) have shown the potential to become next generation magnetic resonance imaging (MRI) contrast agents due to their significantly improved efficiency and…
(more)
▼ Gadolinium endohedral metallofullerenes (EMFs) have shown the potential to become next generation magnetic resonance
imaging (MRI) contrast agents due to their significantly improved efficiency and safety, as well as multi-day body retention which allows for a longer surgery and observation compared to current contrast agents. In Chapter 1, I have reviewed the development of gadolinium EMF based MRI contrast agents. In Chapter 2, I have described my study of
[email protected] and
[email protected] metallofullerenols as next generation MRI contrast agents. The metallofullerenols are synthesized and characterized utilizing UV-vis, IR, X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS). In addition, relaxivity data were obtained for the two metallofullerenes, and the results showed that
[email protected] metallofullerenol had enhanced relaxivity compared to
[email protected] metallofullerenol. This result is consistent with the observation of magnetic resonance images of the samples at different concentrations. The enhanced relaxivity was attributed to the special "egg shape" of the
[email protected] cage. In Chapter 3, I have described the relaxivity study of
[email protected] (without functionalization) in oleic acid, which could be used as an MRI contrast
agent for more hydrophobic bioenvironments. The results show that
[email protected] has a reasonable relaxation effect (relaxivity ~10 mM-1S-1 at 1.4 T) in oleic acid and could be a viable contrast
agent even without functionalization. In Chapter 4, I have discussed the outlook of gadolinium EMF-based MRI contrast agents and suggested several directions for future work.
Advisors/Committee Members: Dorn, Harry C. (committeechair), Gibson, Harry W. (committee member), LaConte, Leslie E. W. (committee member).
Subjects/Keywords: Endohedral Metallofullerene; Trimetallic Nitride Template; Magnetic Resonance Imaging; Relaxivity; Contrast Agent
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ye, Y. (2014). Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/47781
Chicago Manual of Style (16th Edition):
Ye, Youqing. “Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents.” 2014. Masters Thesis, Virginia Tech. Accessed January 22, 2021.
http://hdl.handle.net/10919/47781.
MLA Handbook (7th Edition):
Ye, Youqing. “Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents.” 2014. Web. 22 Jan 2021.
Vancouver:
Ye Y. Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents. [Internet] [Masters thesis]. Virginia Tech; 2014. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10919/47781.
Council of Science Editors:
Ye Y. Gadolinium Endohedral Metallofullerenes for Future Magnetic Resonance Imaging Contrast Agents. [Masters Thesis]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/47781
21.
Aired-Selmani, Leila.
Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents.
Degree: Docteur es, Sciences de la Vie et de la Santé, 2013, Université François-Rabelais de Tours
URL: http://www.theses.fr/2013TOUR3301
► Depuis leur introduction, les agents de contraste ont révolutionné l'imagerie échographique. Ils sont composés de microbulles gazeuses, qui injectés par voie intraveineuse dans le sang,…
(more)
▼ Depuis leur introduction, les agents de contraste ont révolutionné l'imagerie échographique. Ils sont composés de microbulles gazeuses, qui injectés par voie intraveineuse dans le sang, ils améliorent l'image échographique. Une autre application pour laquelle les caractéristiques physiques des agents de contraste sont exploitées est l'imagerie ciblée. Une approche basée sur l'utilisation de ligands intégrés à la paroi des microbulles, celles-ci adhérent aux facteurs de surfaces moléculaires surexprimés par les cellules endothéliales qui tapissent la paroi interne des vaisseaux sanguins. Pour pouvoir distinguer ces microbulles de celles qui circulent librement, elles doivent réfléchir un signal acoustique suffisamment intense. Cependant, le faible taux d'adhérence des microbulles engendre une réduction du signal acoustique. Pour résoudre ce problème, il est important de déterminer l'effet des parois sur leurs dynamiques acoustiques. Dans cette thèse, nous avons étudié l’effet des parois élastiques sur le comportement dynamique des microbulles constituant les agents de contraste. Dans un premier temps, un modèle théorique représentant une paroi avec une épaisseur finie a été développé. Il a été démontré que l’amplitude de l’écho rétrodiffusé par une microbulle proche d’une paroi avec une épaisseur finie est inférieure à celui d’une microbulle se trouvant dans un fluide infini. D'autres parts, pour représenter la paroi d’un vaisseau sanguin, les propriétés mécaniques de la paroi élastique ont été intégrées au modèle. Il a été observé que la fréquence de résonance d’une microbulle proche d’une paroi est supérieure à celle dans un fluide infini. Par la suite, nous avons étudié l’effet de trois types de parois sur le comportement d’une microbulle parmi lesquelles la paroi d'OptiCell communément utilisée en expérimentations ultrasonores. Les résultats ont montré que la microbulle proche de la paroi d’OptiCell diffuse un écho supérieur à celui de la microbulle éloignée de la paroi, lorsque la fréquence d’excitation est au-dessus de sa fréquence de résonance. Nous avons constaté aussi que les petites bulles sont plus sensibles à la proximité de la paroi. Par la suite, nous avons développé un modèle décrivant une microbulle attachée à une paroi élastique. Nous avons montré que le contact direct de la bulle avec la paroi induit une diminution de l'écho par rapport à la même bulle dans un liquide infini. Le contact direct de la bulle avec la paroi engendre une augmentation de la fréquence de résonance part rapport à une bulle sans contact direct. Enfin, une étude expérimentale a montré l'avantage de l'imagerie sous-harmonique pour différencier les microbulles attachées des microbulles libres.
Since they were introducted, contrast agents have revolutionized the ultrasound imaging. They are composed of tiny gaseous microbubbles and when injected intravenously into the blood, they improve the ultrasound image. Targeted imaging is another application based on the physical characteristics of contrast agents. This approach is based…
Advisors/Committee Members: Bouakaz, Ayache (thesis director).
Subjects/Keywords: Agent de contraste; Ultrasons; Microbulle; Imagerie ciblée; Paroi élastique; Sous-harmonique; Contrast agent; Ultrasound; Microbubble; Targeted imaging; Elastic wall; Subharmonic
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Aired-Selmani, L. (2013). Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2013TOUR3301
Chicago Manual of Style (16th Edition):
Aired-Selmani, Leila. “Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents.” 2013. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 22, 2021.
http://www.theses.fr/2013TOUR3301.
MLA Handbook (7th Edition):
Aired-Selmani, Leila. “Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents.” 2013. Web. 22 Jan 2021.
Vancouver:
Aired-Selmani L. Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2013. [cited 2021 Jan 22].
Available from: http://www.theses.fr/2013TOUR3301.
Council of Science Editors:
Aired-Selmani L. Caractérisations théoriques et expérimentales d'agents de contraste ultrasonore ciblés : Theorical and experimental characteristics of ultrasound targeted contrast agents. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2013. Available from: http://www.theses.fr/2013TOUR3301
22.
Yong-Sang, Jennyfer.
Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available.
Degree: Docteur es, Chimie organique, 2017, Université de la Réunion
URL: http://www.theses.fr/2017LARE0062
► Les maladies cardiovasculaires représentent la première cause de mortalité et de morbidité dans le monde. L’athérosclérose est à l’origine de 50 % des décès dans…
(more)
▼ Les maladies cardiovasculaires représentent la première cause de mortalité et de morbidité dans le monde. L’athérosclérose est à l’origine de 50 % des décès dans les pays industrialisés. Cette pathologie multifactorielle est caractérisée par l’accumulation de lipides dans la paroi des artères formant une plaque d’athérome. Les manifestations cliniques dues à la rupture de cette plaque dépendent du territoire vasculaire touché, allant de l’accident vasculaire cérébral ischémique à l’infarctus du myocarde. Pour pallier ce problème majeur de santé publique dont la prévalence est deux fois supérieure à l’Île de La Réunion par rapport à la Métropole, nous proposons de développer de nouveaux outils de diagnostic par l’imagerie utilisant la tomographie par émission de positon (TEP). À ce jour, aucun outil ne permet la détection précoce de ces plaques d’athérome. Nous avons choisi de marquer deux types de lipoprotéines (HDL et LDL) pour imager ces plaques. Elles possèdent toutes les deux des rôles opposés mais ont en commun un tropisme avéré pour la plaque d’athérome. Nos travaux ont permis la synthèse puis le radiomarquage d’un nouvel agent chélatant PCTA du Gallium 68 couplé à un biovecteur phospholipidique, la 1,2-distéaroyl-sn-glycéro-3-phosphoéthanolamine (DSPE), qui a ensuite été insérée au niveau de la couche lipidique des lipoprotéines afin d’étudier sa biodistribution dans des modèles in vivo murin et ex vivo humain d’athérosclérose.
Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Atherosclerosis accounts for 50% of deaths in industrialized countries. This multifactorial pathology is characterized by the accumulation of lipids within the arterial wall forming an atheromatous plaque. Clinical manifestations due to plaque rupture depend on the affected vascular territory, ranging from ischemic stroke to myocardial infarction. In order to overcome this major public health problem, which is twice more prevalent in Reunion Island relative to Mainland France, we aimed at developing new diagnostic tools using tomography by positron emission (PET) imaging. To date, no specific tool allows the early detection of atheromatous plaques. We chose to label two types of lipoproteins (HDLs and LDLs) in order to image these plaques. They both have opposite roles but have in common a proven tropism for atheromatous plaque. Our work allowed the synthesis and the radiolabelling of a new Gallium 68 PCTA chelating agent coupled to the phospholipid biovector, 1,2-distearoyl-sn-glycero-3phosphoethanolamine (DSPE), which was then inserted in the lipid layer of lipoproteins in order to study its biodistribution in mouse in vivo and in human ex vivo models of atherosclerosis.
Advisors/Committee Members: Meilhac, Olivier (thesis director), Ferroud, Clotilde (thesis director).
Subjects/Keywords: Agent chélatant; Imagerie TEP; Lipoprotéines; Athérosclérose; Synthèse organique; Chelating agent; PET imaging; Lipoproteins; Atherosclerosis; Organic synthesis
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yong-Sang, J. (2017). Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available. (Doctoral Dissertation). Université de la Réunion. Retrieved from http://www.theses.fr/2017LARE0062
Chicago Manual of Style (16th Edition):
Yong-Sang, Jennyfer. “Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available.” 2017. Doctoral Dissertation, Université de la Réunion. Accessed January 22, 2021.
http://www.theses.fr/2017LARE0062.
MLA Handbook (7th Edition):
Yong-Sang, Jennyfer. “Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available.” 2017. Web. 22 Jan 2021.
Vancouver:
Yong-Sang J. Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available. [Internet] [Doctoral dissertation]. Université de la Réunion; 2017. [cited 2021 Jan 22].
Available from: http://www.theses.fr/2017LARE0062.
Council of Science Editors:
Yong-Sang J. Synthèse de nouveaux agents chélatants PCTA du 68Ga - Application au marquage de lipoprotéines pour l’imagerie TEP de la plaque d’athérosclérose : No English title available. [Doctoral Dissertation]. Université de la Réunion; 2017. Available from: http://www.theses.fr/2017LARE0062
23.
Moreau, Mathieu.
Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes.
Degree: Docteur es, Chimie - physique, 2012, Université de Bourgogne
URL: http://www.theses.fr/2012DIJOS016
► Ce travail de thèse réalisé à l’Institut de Chimie Moléculaire de l’Université de Bourgogne porte dans un premier temps sur la synthèse d’agents chélatants bifonctionnels…
(more)
▼ Ce travail de thèse réalisé à l’Institut de Chimie Moléculaire de l’Université de Bourgogne porte dans un premier temps sur la synthèse d’agents chélatants bifonctionnels adaptés à la chélation de radiométaux trivalents, notamment l’indium-111. La plus grande partie de ce travail a ensuite consisté à réaliser le greffage d’un agent chélatant bifonctionnel dérivé du DOTA sur différents anticorps ou fragments d’anticorps monoclonaux : le trastuzumab (anti HER2, traitement de cancers du sein), le cétuximab (anti EGFR, traitement de nombreux cancers, dont le cancer colorectal) et l’abciximab (antiagrégant plaquettaire). Une attention particulière a été apportée à la caractérisation des différents immunoconjugués. La dernière étape de ce travail de thèse porte sur le radiomarquage à l’indium-111 de deux immunoconjugués préparés : le trastuzumab et le cétuximab. Ces étapes de radiomarquage nous ont permis de déterminer la fraction immunoréactive et l’affinité de chaque radiotraceur. Nous avons ainsi pu étudier la biodistribution in vivo de ces radiotraceurs chez la souris par imagerie SPECT-CT. Nous avons également développé une méthode de greffage originale pour le marquage d’un fragment d’anticorps de type Fab, l’abciximab, dans le but de suivre la biodistribution de cet antiagrégant plaquettaire. Enfin, nous avons également validé le concept d’imagerie multimodale à travers le greffage et le radiomarquage d’un agent bimodal pour l’imagerie optique et la SPECT sur des lipopolysaccharides bactériens. Les travaux réalisés nous ont permis d’acquérir un savoir faire en matière de greffage d’anticorps et de radiomarquage. Les résultats obtenus permettent d’envisager le greffage d’autres anticorps ou biomolécules, ainsi que l’utilisation d’autres radionucléides pour l’imagerie PET ou la radioimmunothérapie
This work conducted at the “Institut de Chimie Moléculaire de l’Université de Bourgogne” carries at first on the synthesis of bifunctional chelating agents suitable for the chelation of trivalent radiometals, including indium-111. The greater part of this work was then dedicated to the grafting of a DOTA derivative bifunctional chelating agent on different antibodies or fragments of monoclonal antibodies: trastuzumab (anti-HER2 treatment of breast cancer), cetuximab (anti EGFR, treatment of many cancers, including colorectal cancer) and abciximab (antiplatelet). Particular attention was paid to the characterization of various immunoconjugates. The critical step of this thesis consisted in the indium-111 radiolabeling of two previously prepared immunoconjugates: trastuzumab and cetuximab. These steps of radiolabelling allowed us to determine the immunoreactive fraction and affinity of each radiotracer. Thus, we were able to study the in vivo biodistribution of the radiotracers in tumour-bearing mice by SPECT-CT. We also developed an original method for the labeling of a Fab antibody fragment in order to monitor the biodistribution of the antiplatelet agent (abciximab). Finally, we also validated the concept of multimodal…
Advisors/Committee Members: Denat, Franck (thesis director), Brunotte, François (thesis director).
Subjects/Keywords: Polyazacycloalcanes; Imagerie préclinique; Agent multimodal; Imagerie moléculaire; Radiochimie; SPECT-CT; PET; Polyazacycloalkanes; Preclinical imaging; Multimodal agent; Molecular imaging; Radiochemistry; SPECT-CT; PET; 541.38; 616
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moreau, M. (2012). Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes. (Doctoral Dissertation). Université de Bourgogne. Retrieved from http://www.theses.fr/2012DIJOS016
Chicago Manual of Style (16th Edition):
Moreau, Mathieu. “Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes.” 2012. Doctoral Dissertation, Université de Bourgogne. Accessed January 22, 2021.
http://www.theses.fr/2012DIJOS016.
MLA Handbook (7th Edition):
Moreau, Mathieu. “Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes.” 2012. Web. 22 Jan 2021.
Vancouver:
Moreau M. Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes. [Internet] [Doctoral dissertation]. Université de Bourgogne; 2012. [cited 2021 Jan 22].
Available from: http://www.theses.fr/2012DIJOS016.
Council of Science Editors:
Moreau M. Marquage de molécules biologiques par des complexes de radiométaux à base de polyamines macrocycliques : Radiolabeling of biological vectors by polyazamacrocyclic complexes. [Doctoral Dissertation]. Université de Bourgogne; 2012. Available from: http://www.theses.fr/2012DIJOS016
24.
Iqbal, Muhammad.
Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy.
Degree: Docteur es, Pharmacotechnie, 2015, Université Claude Bernard – Lyon I
URL: http://www.theses.fr/2015LYO10227
► L'objectif de cette étude était de préparer et de caractériser les particules submicroniques multifonctionnelles utilisables simultanément pour le diagnostic et le traitement de plusieurs maladies…
(more)
▼ L'objectif de cette étude était de préparer et de caractériser les particules submicroniques multifonctionnelles utilisables simultanément pour le diagnostic et le traitement de plusieurs maladies mortelles telles que le cancer. Pour ce faire, une étude systématique a été réalisée afin de comprendre les mécanismes impliqués et d'optimiser les paramètres du procédé de double émulsion-évaporation de solvant pour la préparation de ces particules. Pour l’imagerie in vitro, des nanoparticules polymériques fluorescentes (FluoSpheres®) ont été encapsulées dans une matrice polycaprolactone dégradable en utilisant le procédé de l’émulsion double-évaporation de solvant. Pour l’imagerie invivo, des nanoparticules d'or colloïdal ont été préparées et encapsulées via le même procédé et parfaitement caractérisées. Enfin, pour application theranostic, les nanoparticules d'or (comme agent de contraste) et un actif moléculaire (hydrophile Nefopam et hydrophobe benzoate de benzyle) ont été encapsulés simultanément dans des particules de polycaprolactone. Ces particules multifonctionnelles ont été caractérisées et évaluées in vitro comme model de pénétration cutané
The objective of this study was to prepare and characterize multifunctional submicron particles that can be used for diagnosis and therapy of several fatal diseases including cancer (i.e theranostic). For this purpose, a systematic study was performed in order to optimize the process parameters for preparation of polymeric particle that can be used as a platform for effective delivery of drugs and imaging labels. The imaging agent (FluoSpheres®) was encapsulated via double emulsion solvent evaporation technique to be used fluorescent contrast agent and their in vitro evaluation was performed. Then, gold nanoparticles were prepared by using NaBH4 reduction method, characterized and encapsulated by polycaprolactone polymer for in vitro applications. Finally, the gold nanoparticle were loaded into polycaprolactone particle along with a hydrophilic drug (Nefopam) and a hydrophobic drug (benzyl benzoate) simultaneously. The prepared particles were then characterized physicochemically and in vitro skin penetration study was performed
Advisors/Committee Members: Fessi, Hatem (thesis director), Elaissari, Abdelhamid (thesis director).
Subjects/Keywords: Encapsulation; Les particules submicroniques; Imaging; Théranostic; Double émulsion; Les nanoparticules d'or; Agent de contraste; Encapsulation; Submicron particles; Imaging; Theranostic; Double emulsion; Gold nanoparticles; Contrast agent; 540
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Iqbal, M. (2015). Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2015LYO10227
Chicago Manual of Style (16th Edition):
Iqbal, Muhammad. “Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy.” 2015. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 22, 2021.
http://www.theses.fr/2015LYO10227.
MLA Handbook (7th Edition):
Iqbal, Muhammad. “Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy.” 2015. Web. 22 Jan 2021.
Vancouver:
Iqbal M. Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2015. [cited 2021 Jan 22].
Available from: http://www.theses.fr/2015LYO10227.
Council of Science Editors:
Iqbal M. Préparation de particules submicroniques pour applications théranostiques : imagerie et thérapie : Preparation of submicron particles for theranostic applications : imaging and therapy. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2015. Available from: http://www.theses.fr/2015LYO10227

Université Paris-Sud – Paris XI
25.
Gargam, Nicolas.
Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits.
Degree: Docteur es, Physique, 2012, Université Paris-Sud – Paris XI
URL: http://www.theses.fr/2012PA112118
► Dans la foulée des avancées en médecine nucléaire, l’imagerie moléculaire par résonance magnétique a pris son essor ces dernières années car elle constitue un enjeu…
(more)
▼ Dans la foulée des avancées en médecine nucléaire, l’imagerie moléculaire par résonance magnétique a pris son essor ces dernières années car elle constitue un enjeu contemporain en vue d’améliorer le diagnostic et le suivi thérapeutique de pathologies comme le cancer ou la maladie d’Alzheimer. Cependant, cette technique d’imagerie médicale souffre à la fois de la petite quantité de récepteurs disponibles in vivo et de la faible sensibilité de l’IRM pour la détection d’agents de contraste exogènes. De ce fait, la littérature montre un intérêt croissant pour le développement de nouveaux agents de contraste pouvant porter plusieurs milliers de contrastophores et de nouvelles techniques sont nécessaires pour évaluer l’efficacité de ces derniers. Ainsi, lorsqu’un agent de contraste fonctionnalisé est injecté in vivo, ce dernier va subir de nombreux processus biochimiques (extravasation, fixation spécifique sur les récepteurs, internalisation dans les cellules…) qui peuvent rendre les mécanismes de prise de contraste difficile à appréhender. De ce fait, nous avons développé une nouvelle méthode in vitro d’observation cellulaire permettant de caractériser les agents de contraste par IRM en modélisant expérimentalement certains des mécanismes ayant lieu in vivo, tout en s’affranchissant des problèmes liées à l’expérimentation sur petit animal (résolution, Rapport signal sur bruit, reproductibilité inter-animale,…). Notre approche a reposé sur la conception d’un dispositif de microhistologie par IRM qui permet de détecter une monocouche de cellules d’une dizaine de microns d’épaisseur dans un environnement microfluidique. Après avoir totalement caractérisé notre méthode avec des cellules ayant internalisé un agent de contraste commercial (Dotarem), nous l’avons utilisé pour évaluer la capture dynamique d’un nouvel agent de contraste développé à Guerbet : une émulsion paramagnétique fonctionnalisée avec des peptides RGD destinée à l’imagerie de l’angiogénèse tumorale. Dans un canal microfluidique, nous avons préparé une monocouche confluente de cellules endothéliales et appliqué un flux d’agent de contraste au-dessus de ces dernières. Par IRM, nous avons pu réaliser un suivi dynamique de la capture de l’agent de contraste par les récepteurs membranaires des cellules. En plus de démontrer la spécificité de l’agent de contraste comme le font les méthodes traditionnelles, notre technique nous a permis d’évaluer les constante cinétiques d’association et de dissociation et la constante d’affinité de l’agent de contraste pour les récepteurs dans des conditions physiologiques proches de celles existant in vivo, notamment en termes de disposition des cellules et de la vitesse et de la concentration de l’agent de contraste.
Following the recent advances in nuclear medicine, magnetic resonance imaging has rapidly become an emerging technique for molecular imaging since it constitutes a contemporary issue for the improvement of the diagnosis and the post-treatment follow-up of pathologies such as cancer and Alzheimer’s disease.…
Advisors/Committee Members: Darrasse, Luc (thesis director).
Subjects/Keywords: IRM; Imagerie Moléculaire; Agents de contraste; Gadolinium; Imagerie cellulaire; Angiogénèse; MRI; Molecular Imaging; Contrast agent; Gadolinium; Cell imaging; Angiogenesis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gargam, N. (2012). Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2012PA112118
Chicago Manual of Style (16th Edition):
Gargam, Nicolas. “Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits.” 2012. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed January 22, 2021.
http://www.theses.fr/2012PA112118.
MLA Handbook (7th Edition):
Gargam, Nicolas. “Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits.” 2012. Web. 22 Jan 2021.
Vancouver:
Gargam N. Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2012. [cited 2021 Jan 22].
Available from: http://www.theses.fr/2012PA112118.
Council of Science Editors:
Gargam N. Banc microfluidique d’histologie IRM pour la modélisation in vitro du marquage moléculaire : effet du choix du marqueur et du champ magnétique sur les seuils de détection : Microfluidic bench for histological MRI to model in vitro molecular imaging : effect of the choice of the contrast agent and the magnetic field on the detection limits. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2012. Available from: http://www.theses.fr/2012PA112118

University of Western Ontario
26.
Snir, Jonatan.
The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease.
Degree: 2015, University of Western Ontario
URL: https://ir.lib.uwo.ca/etd/3437
► Background: Currently there is no widely accepted test to diagnose AD. The involvement of the lysosomal system in Alzheimer’s disease (AD) progression provides an opportunity…
(more)
▼ Background: Currently there is no widely accepted test to diagnose AD. The involvement of the lysosomal system in Alzheimer’s disease (AD) progression provides an opportunity to develop associated biomarkers. The lysosomal enzyme Cathepsin D (CatD) has been shown to be over-expressed in the AD brain before clinical onset. We have developed a dual modality contrast agent (CA) to detect CatD activity which consists of an HIV-1 Tat Cell Penetrating Peptide (CPP) conjugated to a CatD cleavage sequence and two imaging moieties consisting of a fluorescently- tagged probe and a DOTA cage for chelating Gallium-68. The purpose of this work was to validate CatD as an AD biomarker across multiple AD disease models and to test our novel CA in-vivo by means of optical near infra-red (NIR) fluorescence imaging and positron emission tomography (PET). Methods: Three transgenic (Tg) mouse AD model strains were tested for CatD expression by Western blot and immunohistochemistry analysis. The chosen mouse line (5XFAD) and controls were imaged at 5 and 12 months of age using an eXplore Optix scanner (GE Healthcare, Milwaukee, WI, USA). Next, mice at 2, 6 and 9 months of age were tested using an Inveon microPET system (Siemens Medical Solutions, Knoxville TN, USA) using a 68Ga-labeled CatD targeted CA. Results: All 3 AD mice demonstrated an elevation of CatD expression in parallel with AD pathology. The 5XFAD had the highest levels of CatD, making it the best mouse model to study CatD upregulation. The rate of the NIR CatD Targeted CA washout was significantly slower in the 5XFAD mice (p
Subjects/Keywords: Alzheimer’s disease; Cathepsin D; Optical Imaging; Positron Emission Tomography; contrast agent; Magnetic Resonance Imaging.; Medical Biophysics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Snir, J. (2015). The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3437
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Snir, Jonatan. “The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease.” 2015. Thesis, University of Western Ontario. Accessed January 22, 2021.
https://ir.lib.uwo.ca/etd/3437.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Snir, Jonatan. “The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease.” 2015. Web. 22 Jan 2021.
Vancouver:
Snir J. The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Jan 22].
Available from: https://ir.lib.uwo.ca/etd/3437.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Snir J. The Development and Validation of a Molecular Imaging Probe Targeted to Cathepsin D for the In-vivo Detection of Alzheimer Disease. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/3437
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Florida
27.
Al-Marzooq, Fatimah Yousef.
Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties.
Degree: MS, Chemistry, 2014, University of Florida
URL: https://ufdc.ufl.edu/UFE0047226
In this thesis, two sets of experiments will be discussed: synthesizing a T1 contrast agent as nanosize particles and in bulk.
Advisors/Committee Members: TALHAM,DANIEL R (committee chair), TOTH,ANNA F (committee member).
Subjects/Keywords: Gadolinium; Imaging; Ions; Ligands; Magnetic resonance imaging; Nanoparticles; Phosphates; Protons; Signals; Solar X rays; agent – contrast – gadolinium – mri
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Al-Marzooq, F. Y. (2014). Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties. (Masters Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0047226
Chicago Manual of Style (16th Edition):
Al-Marzooq, Fatimah Yousef. “Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties.” 2014. Masters Thesis, University of Florida. Accessed January 22, 2021.
https://ufdc.ufl.edu/UFE0047226.
MLA Handbook (7th Edition):
Al-Marzooq, Fatimah Yousef. “Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties.” 2014. Web. 22 Jan 2021.
Vancouver:
Al-Marzooq FY. Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties. [Internet] [Masters thesis]. University of Florida; 2014. [cited 2021 Jan 22].
Available from: https://ufdc.ufl.edu/UFE0047226.
Council of Science Editors:
Al-Marzooq FY. Synthesis of Gadolinium Phosphonate (Gd-Hedp) as a New MRI Contrast Agent and Measurement of Its Relaxivity Resonance Properties. [Masters Thesis]. University of Florida; 2014. Available from: https://ufdc.ufl.edu/UFE0047226

University of Toronto
28.
Cheng, Weiran.
Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.
Degree: PhD, 2016, University of Toronto
URL: http://hdl.handle.net/1807/81016
► Magnetic Resonance Imaging (MRI) provides detailed anatomical information and has become indispensable for a wide range of medical applications. To further broaden our diagnostic capabilities,…
(more)
▼ Magnetic Resonance Imaging (MRI) provides detailed anatomical information and has become indispensable for a wide range of medical applications. To further broaden our diagnostic capabilities, about 40% of clinical MRI scans are performed with the administration of MRI contrast agents (CAs). There are, however, two major limitations to the current clinical CAs which are mainly small Gd-based chelates. 1) They exhibit low relaxivities at high magnetic fields, requiring high dose in modern clinical MRI scanners and 2) the release and accumulation of Gd ions in vivo is correlated with Nephrogenic Systemic Fibrosis (NSF) in some patients with renal dysfunction. These challenges motivate us to develop a new class of CAs using more biocompatible metal species. Paramagnetic Mn-porphyrin (MnP) was the building block of choice as it is stable and exhibits high relaxivities at high fields. This thesis focuses on the development of MnP MRI CAs for blood pool and targeted imaging purposes. In Chapter 2, a water-soluble MnP dimer, MnP2 was designed as a high-relaxivity T1 agent. Preliminary in vivo study of MnP2 showed prolonged blood circulation, desirable for MR angiography (MRA). In Chapter 3, MnP2 was systematically evaluated as a BPA in vitro and in vivo. Using different spectroscopic methods, MnP2 was found to form a tight and non-covalent interaction with HSA. Via a competitive binding study using ligands with known HSA binding site, results suggest MnP2 to be bound in subdomain IB. In Chapter 4, a second generation dimer, m-MnP2 was developed. m-MnP2 exhibited slightly lower relaxivity than MnP2, likely due to its smaller size. The relaxivity of m-MnP2 did not increase upon binding to HSA and is similar to that of the MnP2â HSA complex. This suggests that both CAs are potential BPAs and that the tumbling rate may be excessively slow. (Chapter 5) Towards the goal of active targeted imaging, a versatile covalent protein tagging MnPNCS was synthesized. Successful tagging of multiple MnPs onto HSA was demonstrated and the resulting MnPâ HSA exhibited excellent blood pool properties. Overall, through rational design, the highly sensitive MnPs have shown promise as the next generation Gd-free MRI CAs.
2017-12-30 00:00:00
Advisors/Committee Members: Zhang, Xiao-an, Chemistry.
Subjects/Keywords: Blood Pool Agent; Contrast Agents; Human Serum Albumin; Magnetic Resonance Imaging; Mn Porphyrin; Targeted Imaging; 0485
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cheng, W. (2016). Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/81016
Chicago Manual of Style (16th Edition):
Cheng, Weiran. “Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.” 2016. Doctoral Dissertation, University of Toronto. Accessed January 22, 2021.
http://hdl.handle.net/1807/81016.
MLA Handbook (7th Edition):
Cheng, Weiran. “Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.” 2016. Web. 22 Jan 2021.
Vancouver:
Cheng W. Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/1807/81016.
Council of Science Editors:
Cheng W. Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/81016

University of Toronto
29.
Cheng, Weiran.
Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.
Degree: PhD, 2016, University of Toronto
URL: http://hdl.handle.net/1807/81015
► Magnetic Resonance Imaging (MRI) provides detailed anatomical information and has become indispensable for a wide range of medical applications. To further broaden our diagnostic capabilities,…
(more)
▼ Magnetic Resonance Imaging (MRI) provides detailed anatomical information and has become indispensable for a wide range of medical applications. To further broaden our diagnostic capabilities, about 40% of clinical MRI scans are performed with the administration of MRI contrast agents (CAs). There are, however, two major limitations to the current clinical CAs which are mainly small Gd-based chelates. 1) They exhibit low relaxivities at high magnetic fields, requiring high dose in modern clinical MRI scanners and 2) the release and accumulation of Gd ions in vivo is correlated with Nephrogenic Systemic Fibrosis (NSF) in some patients with renal dysfunction. These challenges motivate us to develop a new class of CAs using more biocompatible metal species. Paramagnetic Mn-porphyrin (MnP) was the building block of choice as it is stable and exhibits high relaxivities at high fields. This thesis focuses on the development of MnP MRI CAs for blood pool and targeted imaging purposes. In Chapter 2, a water-soluble MnP dimer, MnP2 was designed as a high-relaxivity T1 agent. Preliminary in vivo study of MnP2 showed prolonged blood circulation, desirable for MR angiography (MRA). In Chapter 3, MnP2 was systematically evaluated as a BPA in vitro and in vivo. Using different spectroscopic methods, MnP2 was found to form a tight and non-covalent interaction with HSA. Via a competitive binding study using ligands with known HSA binding site, results suggest MnP2 to be bound in subdomain IB. In Chapter 4, a second generation dimer, m-MnP2 was developed. m-MnP2 exhibited slightly lower relaxivity than MnP2, likely due to its smaller size. The relaxivity of m-MnP2 did not increase upon binding to HSA and is similar to that of the MnP2â HSA complex. This suggests that both CAs are potential BPAs and that the tumbling rate may be excessively slow. (Chapter 5) Towards the goal of active targeted imaging, a versatile covalent protein tagging MnPNCS was synthesized. Successful tagging of multiple MnPs onto HSA was demonstrated and the resulting MnPâ HSA exhibited excellent blood pool properties. Overall, through rational design, the highly sensitive MnPs have shown promise as the next generation Gd-free MRI CAs.
2017-12-30 00:00:00
Advisors/Committee Members: Zhang, Xiao-an, Chemistry.
Subjects/Keywords: Blood Pool Agent; Contrast Agents; Human Serum Albumin; Magnetic Resonance Imaging; Mn Porphyrin; Targeted Imaging; 0485
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cheng, W. (2016). Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/81015
Chicago Manual of Style (16th Edition):
Cheng, Weiran. “Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.” 2016. Doctoral Dissertation, University of Toronto. Accessed January 22, 2021.
http://hdl.handle.net/1807/81015.
MLA Handbook (7th Edition):
Cheng, Weiran. “Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging.” 2016. Web. 22 Jan 2021.
Vancouver:
Cheng W. Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/1807/81015.
Council of Science Editors:
Cheng W. Development of Mn(III) Porphyrins as High Relaxivity MRI Contrast Agents for Blood Pool and Targeted Imaging. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/81015

Duke University
30.
Hofmann, Christina Lehmkuhl.
Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
.
Degree: 2015, Duke University
URL: http://hdl.handle.net/10161/9843
► There is a critical need to target tumor hypoxia as patients with hypoxic tumors have worse prognosis due to aggressive phenotypes and resistance to…
(more)
▼ There is a critical need to target tumor hypoxia as patients with hypoxic tumors have worse prognosis due to aggressive phenotypes and resistance to radiotherapy and chemotherapy. The overall goal of this work is to improve response to conventional cancer therapies by targeting tumor hypoxia. This has been carried out and evaluated through the use of polymersome-encapsulated myoglobin (PEMs) with the hypothesis that O2-releasing PEMs will increase tumor oxygenation, and thereby improve response to radiotherapy. Mb was chosen as an O2 carrying protein to deliver to tumors because it has a strong association to O2, providing a mechanism to deliver O2 only within the hypoxic regions of the tumor. Mb was loaded within nanoscale polymeric vesicles that were expected to accumulate within solid tumors due to the enhanced permeability and retention (EPR) effect. This hypothesis has been tested through the following aims: 1. Develop NIR
imaging techniques for studying the biodistribution and pharmacokinetics of polymersomes 2. Establish the effects of Mb-containing polymersomes on tumor physiology 3. Modify tumor growth through delivery of Mb polymersomes in combination with a cytotoxic therapy specific to aerobic tumors These aims have been evaluated through numerous in vivo studies. First, polymersomes of various polymer formulations and diameters ranging from 110-550 nm were prepared with a near-infrared (NIR) -emissive fluorophore. Using live animal fluorescence
imaging, I was able to study the biodistribution of the polymersomes following i.v. administration, demonstrating significant polymersome accumulation in orthotopic 4T1 mammary carcinomas. In addition, a novel method for measuring pharmacokinetics was developed, using serial small volume blood draws from individual mice. The plasma fluorescence in microcapillary tubes was used to quantify polymersome concentrations, demonstrating long circulation half-lives that varied from 6-23 h. Toxicity of various polymersome formulations were also studied in vitro and in vivo, revealing negligible toxicities. For the second aim, PEMs were administered i.v. in tumor-bearing mice. Unexpectedly, we observed a dramatic gross tumor effect within hours of treatment in both orthotopic 4T1 tumors and flank Renca renal cell carcinomas. Histological analysis revealed endothelial cell apoptosis as early as 1 h following treatment, with scattered tumor cell death throughout the tumor by 4 h. Hematoxylin and eosin staining showed significant necrosis 24 h following PEM treatment. Vascular effects and polymersome distribution were studied in 4T1 window chamber tumors. Following i.v. treatment with PEMs, intravital microscopy was used to image polymersome fluorescence, brightfield transmission was imaged for vessel morphology and blood flow, and a tunable filter was used for determining hemoglobin (Hb) oxygen saturation. Tumor hemorrhaging was observed within hours of PEM treatment, which was not seen with empty polymersomes. This was consistent with the…
Advisors/Committee Members: Dewhirst, Mark W (advisor).
Subjects/Keywords: Biomedical engineering;
Medical imaging and radiology;
Oncology;
myoglobin;
near-infrared imaging;
polymersome;
radiation;
tumor;
vascular disrupting agent
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APA (6th Edition):
Hofmann, C. L. (2015). Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/9843
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hofmann, Christina Lehmkuhl. “Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
.” 2015. Thesis, Duke University. Accessed January 22, 2021.
http://hdl.handle.net/10161/9843.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hofmann, Christina Lehmkuhl. “Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
.” 2015. Web. 22 Jan 2021.
Vancouver:
Hofmann CL. Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
. [Internet] [Thesis]. Duke University; 2015. [cited 2021 Jan 22].
Available from: http://hdl.handle.net/10161/9843.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hofmann CL. Delivery of Myoglobin Polymersomes Results in Tumor Hemorrhagic Necrosis and Enhanced Radiation Response
. [Thesis]. Duke University; 2015. Available from: http://hdl.handle.net/10161/9843
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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