Developing novel polymer architectures for applications In magnetic resonance imaging and self-assembly

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (pages 48-49).Macromolecular scaffolds for drug delivery, self-assembly, and imaging applications have attracted significant attention over the last several decades. As polymerization techniques become more sophisticated, it becomes possible to create polymeric architectures with increasing control over structure, molecular weight, and mass dispersity. Herein, ring-opening metathesis polymerization (ROMP) is paired with highly efficient synthetic methods to create functional bottle-brush polymers for MRI imaging and self-assembly applications. In this "graft-through" approach, bivalent macromonomers bearing a terminal exo-norbornene group were synthesized and polymerized to yield bottle-brush polymers with controlled molar masses and low dispersities. This approach is first utilized in the development of organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). These ORCAs are composed of macromonomers bearing long polyethylene glycol chains and sterically hindered bis(spirocyclohexyl) nitroxide free radicals. This approach enables facile tuning of nitroxide loading percentages and molecular size. Bottle-brush ORCAs displayed high r₁ and r₂ relaxivities suggesting that they have potential for further in vivo MRI studies. Next, bottle-brush copolymers composed of multiple polymeric domains are synthesized by ROMP. We propose that these multi-block bottle-brush polymers will self-assemble into interesting solution and bulk architectures. Several approaches to synthesizing tetrablock bottle-brush polymers were explored by combining "graft-through" and "graft-from" polymerization methods.by Jessica R. McCombs.S.M

Effects of Instrument Handle Design on Dental Hygienists\u27 Forearm Muscle Activity During Scaling

Purpose: The purpose of this study was to determine the effects of 4 different commercially available instrument handle designs (A. 16 grams and 12.7 mm diameter, B. 23 grams and 11.1 mm diameter, C. 21 grams and 7.9 mm diameter and D. 18 grams and 6.35 mm diameter) on the muscle activity of four forearm muscles during a simulated scaling experience. Methods: A convenience sample of 27 (n=27) dental hygienists used a Columbia 13/14 curet with four different instrument handles to scale artificial calculus from typodont teeth. Each participant\u27s muscle activity was measured using surface electromyography (sEMG). Results: Similar muscle activity was generated when scaling with instruments at 16, 18, and 21 grams with varying diameter handles. Instrument B generated significantly more muscle activity when compared to each of the other instrument handle designs (p=0.001, p=0.002, p=0.039). The lower left quadrant displayed significantly less muscle activity during scaling than the upper and lower right quadrants (p=0.026, p=0.000), although no significant interaction effect was found with instruments within quadrants. Most participants (62.96%) preferred instrument A, which was rated more comfortable based on weight when compared to the other instruments tested. Conclusions: Instrument handle design has an effect on forearm muscle activity when scaling in a simulated environment. The heaviest instrument with a relatively large diameter (B 11.1 mm and 23 g) generated significantly more overall mean muscle activity compared to the other three instruments. Similar amounts of muscle activity were produced by instruments weighing between 16 and 21 g. Participants\u27 instrument preferences were more affected by handle diameter than weight. Results support the need for further research to determine the impact of these findings on muscle load related to risk of musculoskeletal disorders in a real-world setting

Redox-responsive branched-bottlebrush polymers for \u3ci\u3ein vivo\u3c/i\u3e MRI and fluorescence imaging

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging

Redox-responsive branched-bottlebrush polymers for \u3ci\u3ein vivo\u3c/i\u3e MRI and fluorescence imaging

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging

Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ​ascorbate or ​ascorbate/​glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ​ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging.Massachusetts Institute of Technology. Department of ChemistryMassachusetts Institute of Technology. Research Support CommitteeLincoln LaboratoryNational Institutes of Health (U.S.) (NIBIB 1R21EB018529-01A1)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32EB017614-01)United States. Dept. of Defense. Ovarian Cancer Research Program (Teal Innovator Award)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

Directed conservation of the world's reef sharks and rays

Many shark populations are in decline around the world, with severe ecological and economic consequences. Fisheries management and marine protected areas (MPAs) have both been heralded as solutions. However, the effectiveness of MPAs alone is questionable, particularly for globally threatened sharks and rays (‘elasmobranchs’), with little known about how fisheries management and MPAs interact to conserve these species. Here we use a dedicated global survey of coral reef elasmobranchs to assess 66 fully protected areas embedded within a range of fisheries management regimes across 36 countries. We show that conservation benefits were primarily for reef-associated sharks, which were twice as abundant in fully protected areas compared with areas open to fishing. Conservation benefits were greatest in large protected areas that incorporate distinct reefs. However, the same benefits were not evident for rays or wide-ranging sharks that are both economically and ecologically important while also threatened with extinction. We show that conservation benefits from fully protected areas are close to doubled when embedded within areas of effective fisheries management, highlighting the importance of a mixed management approach of both effective fisheries management and well-designed fully protected areas to conserve tropical elasmobranch assemblages globally

Widespread diversity deficits of coral reef sharks and rays

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities