Background: At the time of endobronchial ultrasound (EBUS) staging, ultrasonographic features can be used to predict mediastinal lymph node (LN) malignancy. Predictive tools have been developed, however they have not gained widespread use due to lack of research demonstrating validity and reliability. We sought to develop a novel predictive tool, the Canada Score, capable of predicting malignancy and potentially guide LN biopsy decision making. Methods: We prospectively analyzed the ultrasonographic features of LNs from patients with NSCLC. Ultrasonographic features were identified by a single experienced endoscopist, this data was used to develop the Canada Score. Pathological specimens were used as the gold standard for determination of malignancy. Videos were then circulated to endoscopists across Canada, who were also asked to identify ultrasonographic features for each LN. Hosmer- Lemeshow test, logistic regression, receiver operator characteristic (ROC) curve, and Gwet’s AC1 analyses were used to test the performance, discriminatory capacity, and inter-rater reliability of the Canada Score. Results: A total of 300 LNs from 140 patients were analyzed by 12 endoscopists across 7 Canadian centres. Backwards elimination was used to create a multivariate model. Hosmer-Lemeshow test and ROC curves indicated the model was well-calibrated (chi2=11.86, p=0.1567) with good discriminatory power (c- statistic= 0.72 ±0.042, 95%CI: 0.64-0.80). Beta-coefficients were used to create a simplified score out of four. Evaluation of the tool showed that LNs scoring 3 or 4 had odds ratios of 15.17 (p<0.0001) and 50.56 (p=0.001), respectively for predicting malignancy. A score of 4/4 was associated with 99.59% specificity and a positive likelihood ratio of 22.78. Inter-rater reliability for a score ≥ 3 was 0.81 ± 0.02 (95%CI: 0.77-0.85). Conclusions: The Canada Score shows excellent performance in identifying malignant LN at the time of EBUS. A cut-off of ≥ 3 has the potential to inform decision-making regarding biopsy or repeat/mediastinoscopy if the initial results are inconclusive. / Thesis / Master of Science (MSc) / During lymph node staging for lung and esophageal cancer, specific features of lymph nodes can be seen. Using diagnostic tools these features can be used to predict whether a lymph node is cancerous or benign. However, many of these diagnostic tools are inaccurate or unreliable. To address this, this thesis aimed to develop a novel diagnostic tool based on lymph node features seen during staging procedures and determine its clinical usefulness and application to the wider lung and esophageal cancer population. This thesis also aimed to use improved methods to develop this diagnostic tool such that patient and clinician experiences would be significantly improved. The results of this thesis may contribute to a reduction in the number of repeat procedures required for patients undergoing staging prior to their treatment for lung and esophageal cancers.

Developing a drug delivery vehicle that can control the release kinetics of a therapeutic drug on demand has great potential to improve health by allowing health care professionals to maintain the drug concentration in its therapeutic window and increase the efficiency at which treatment is administered. On-demand release can be triggered by a range of stimuli including magnetic, radiation, and ultrasound activation. Of the three, ultrasound is the only one indiscriminate of the chemical properties of the material and is the most widely available clinically, which makes it versatile and applicable for many systems. However, existing strategies that use ultrasound as a release stimulus either pop the microcapsules altogether (enabling no subsequent effective control over the kinetics of drug release) or require continuous ultrasonic administration (typically impractical in a clinical setting), both of which are suboptimal. Overcoming at least of these shortcomings would vastly improve on the technology. In this thesis, microcapsules with a complex shell were fabricated using a modified electrohydrodynamic approach named immersion coaxial electrospraying, which allowed for an increased polymer loading in the shell and improved manipulation of microcapsule size. The complex shell structure of the microcapsules incorporated silica microparticles that acted as corks plugging pores between the inside and outside of the microcapsule. The modified microcapsules were shown to release their payload in the presence of a focused ultrasound signal, while uncorked microcapsules do not release. Release kinetics were shown to be adjustable based on the number of corks initially present in the shell of the microcapsule material. Altogether, the cork-shell microcapsules fabricated in this thesis show promise as a tunable on-demand drug delivery vehicle that is able to better control release compared to conventional ultrasound triggered microcapsules. / Thesis / Master of Applied Science (MASc) / This thesis focuses on the fabrication of complex microcapsules that can be deliver therapeutic drugs on-demand using ultrasound waves. These microcapsules are composed of a water-based core and a biologically inert shell into which particles are embedded. Upon the application of ultrasound, these embedded particles (like corks on a bottle) are popped out to release the “corks” from the shell, creating pores from which the drug in the microcapsule core can be released. In the absence of ultrasound signals, the microcapsules do not release any of their contents, making these effective for “on-demand” release. These microcapsules are made using a modified process based on electrospraying which allows very precise control over the microcapsules’ physical properties, incorporating a key modification that overcomes an inherent issue with the general technique. These microcapsules also improve on currently used ultrasound triggered drug delivery systems by requiring shorter periods of ultrasound and/or enabling better control over the dynamics of drug release following the ultrasound pulse.

The ability of Listeria monocytogenes, to attach to various food contact surfaces such as stainless steel, polypropylene, and rubber compounds is well documented. The retention of these or other pathogenic bacteria on food contact surfaces increases the risk of transmission to food products. The objective of this study was to compare several methods for quantitative recovery of Listeria monocytogenes from stainless steel surfaces. A cocktail of four serotypes of Listeria monocytogenes (Scott A (4b)), 1/2b, 3b, and 4b) were mixed in equivalent concentrations and inoculated onto type 304 stainless steel coupons in a 2cm x 2cm area. After a one hour exposure, coupons were sampled by one of the following methods: 1) swabbing using a pre-moistened Dacron swab, 2) rinsing with phosphate buffered saline, 3) direct contact onto a Tryptic Soy Agar containing 0.6% yeast extract (TSA+YE) plate surface for 10 seconds, 4) sonication in an ultrasonic water bath (40 kHz), 5) contact with the bristles of a sonicating brush head for 1 min, and 6) indirect contact (2-4 mm) with the bristles of a sonicating brush head for 1 min. Coupon rinses were plated onto TSA containing 0.6% yeast extract and incubated for 24 hours at 35°C. The three sonication methods yielded higher recovery than the other three methods (p < 0.05). Brushing the coupons with the sonicating brush head yielded a recovery level of 58% and indirect exposure to the sonicating brush head permitted a recovery level of 65% from the initial microbial load. The lowest cell recovery (~20%) was observed with the swab and direct agar contact methods. / Master of Science

There is currently no solution for imaging fibrin-rich adhesions following surgery, yet the condition costs healthcare providers upwards of $2 billion annually. Over the past decade the development of ultrasound contrast agents has seen an increase in commercialization of generic microbubble formulations for standard diagnostic applications such as echocardiography. To enhance diagnostic power, molecularly targeted microbubbles are formulated with the addition of a ligand to the outer shell. The microbubble formulation must be modified so that the contrast agents are stable over time and targeted with the appropriate ligand while maintaining their echogenicity relative to surrounding soft tissue. We used a dual approach to look at microbubbles optically to predict their relative signal enhancement in vivo given their size distribution and concentration. An ImageJ macro script was developed based off BubblesizerJ, a previously developed open-source program. To confirm that modified microbubbles maintain acoustic properties relative to soft tissue, an agarose phantom model was developed that allows for high throughput testing of multiple microbubble formulations. / 2026-09-03T00:00:00Z

<p dir="ltr">High-frequency ultrasound is an excellent non-invasive imaging technique that we utilized in both the quantification of intervertebral disc strain and microrobots for targeted drug delivery systems due to its ability to provide real-time, high-resolution images of soft tissues without the need for invasive procedures. In the intervertebral disc study, it allows us to capture detailed strain measurements across time during dynamic loading, offering insights into tissue deformation under physiological conditions. Similarly, in the microrobot study, high-frequency ultrasound enables precise visualization and tracking of the microrobots within the tissue environment, ensuring accurate navigation and monitoring during targeted drug delivery.</p><p><br></p><p dir="ltr">Understanding the mechanics of intervertebral disc injury and validating computational models requires accurate measurement of internal disc strain. While noninvasive imaging and advanced image processing have enabled strain quantification, these methods often depend on visual markers that may alter tissue behavior. Furthermore, they are typically limited to static testing, which does not fully capture physiological loading conditions. This study aims to utilize high-frequency ultrasound combined with texture correlation techniques to quantify strain within intervertebral discs during dynamic axial loading. This study demonstrates that high-frequency ultrasound is an effective tool for measuring disc strain under dynamic loading conditions.</p><p><br></p><p dir="ltr">Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the digestive tract. Common treatments for IBD, such as oral and injectable medications, are selected based on disease severity but present significant challenges. These include systemic toxicity, non-specific drug targeting, and degradation of the therapeutic agents in the upper gastrointestinal tract, which reduces treatment effectiveness before reaching the colon. The goal of this research is to develop and test microrobots for targeted drug delivery to inflamed regions of the colon in IBD patients. The microrobots are guided by external magnetic torque and aim to overcome the limitations of traditional IBD treatments by delivering smaller, more effective drug payloads directly to the site of inflammation. The study demonstrates that microrobots, guided by magnetic torque, can effectively deliver targeted drug payloads to inflamed regions of the colon. This method allows for a smaller drug payload compared to traditional treatments, offering a more precise and efficient approach for treating IBD.</p>

Background: Achilles tendinopathy is a common and debilitating condition among female ballet dancers due to the large repetitive loading forces placed on their Achilles tendons during rehearsals and performances. Tendon health problems in females are exacerbated by a lack of understanding about how energy availability influences tendons. Ballet dancers, as aesthetic athletes, are vulnerable to low energy availability and can enter a spectrum disorder, relative energy deficiency in sport, that consists of low energy availability (with or without disordered eating), menstrual cycle dysfunction, and low bone mineral density (BMD). Aims: 1) To investigate the relationship between insufficient caloric intake and Achilles tendon health in pre-professional ballet dancers. 2) To evaluate if symptoms of relative energy deficiency in sport such as low BMD and menstrual irregularity can be matched with Achilles tendon structural damage in pre-professional ballet dancers. 3) To analyze if there is a relationship between BMD and nutrition in pre-professional ballet dancers. Methods: 30 pre-professional ballet dancers were recruited. Over the course of a 16-week training and performance period, the dancers underwent four ultrasound imaging sessions and two MRI sessions investigating their Achilles tendons. They also underwent one full body DXA scan and completed four ASA24 dietary recall surveys. The dancers additionally filled out questionnaires describing their menstrual history and current Achilles tendon health. At the end of the study, dancers were organized into calorie sufficiency groups (sufficient or insufficient). Results: Within both calorie groups, the Achilles tendon was significantly thicker at the end of the study as compared to the start of the study (p=.046). Within both calorie groups, echogenicity was significantly higher at the first two ultrasound imaging sessions than it was at the last two (p<.05). Additionally, the calorie sufficient group's tendons had a significantly higher echogenicity than the calorie insufficient group at the first two ultrasound imaging sessions (p<.05). There were significantly more dancers in the calorie insufficient group that experienced changes to their menstrual cycle (p=.007). Conclusion: Participants in the calorie sufficient group had significantly more hyperechoic tendons than those in the calorie insufficient group at the start of the study, and all participants saw a significant drop in tendon echogenicity halfway through the study. The results of this study suggest that a better understanding of how average caloric intake affects tendon health in dancers is necessary in order to help treat and prevent AT injuries in this dance population.

Nanoparticle-based delivery vehicles have received substantial interest in the field of drug delivery particularly pertaining to chemotherapeutics. By virtue of their size, nanoscale drug delivery vehicles overcome many obstacles encountered by traditional systems. Moreover, nanocarriers can be fabricated to be ‘smart’, meaning they can be responsive to internal stimuli relating to the microenvironment of the tumor and/or external stimuli that can be delivered non-invasively from outside of the body. One such external trigger is ultrasound, well-known for its role in biomedical imaging based on its wide availability, non-invasiveness, and safety but increasingly being applied for drug delivery. This thesis proposes solutions to two key challenges associated with locally-targeted polymer-based drug delivery: enhanced tumor accumulation and externally-triggered control over release kinetics. In the former case, brush polymer PLA-PEG analogues are synthesized and explored to correlate how the architecture of these brush blocks affects the resulting self-assembled nanoparticle size, zeta potential, cytotoxicity in vitro, circulation time, and accumulation profiles in vivo. Indeed, brush copolymer analogues allow for copolymerization with additional monomers while conserving ‘stealth properties of linear copolymers, as well as exhibit superior circulation times and longer-term tumor accumulation. In the latter case, a new ultrasound-triggered drug delivery platform is designed consisting of a hollow polymeric shell in which silica “corks” are entrapped; the application of ultrasound can exploit the high difference in the compressibility between the polymeric shell and the silica corks to pop out or otherwise perturb the cork particles, allowing for both on-demand drug release as well as a pulsatile release profiles to be achieved. Overall, by manipulating the surface properties and/or morphologies of polymer-based micro/nanoparticles, the results of this thesis show that key challenges in local drug delivery can be addressed and applied specifically to applications in cancer therapy. / Dissertation / Doctor of Philosophy (PhD) / Drug delivery vehicles attempt to address many of the shortcomings of traditional therapeutics, in particular their low solubility and a lack of tissue targeting, which result in poor efficacy and unwanted side-effects. Polymers specifically have been commonly employed in biomedical applications as there are a wide range of biodegradable polymers that do not cause adverse effects during intended application and can be removed from the body through normal biological function. More recently, more advanced, ‘smart’ materials have been developed that can respond to internal or external stimuli to better address treatment needs. This thesis presents novel polymer-based drug delivery vehicles with new structures useful to passively target particular sites in the body and/or alter drug release profiles, enabling improved drug efficacy and reduced side-effects.

Yes / In recent years, imaging has played an increasing role in the clinical management of patients with rheumatic diseases with respect to aiding diagnosis, guiding therapy and monitoring disease progression. These roles have been underpinned by research which has enhanced our understanding of disease pathogenesis and pathophysiology of rheumatology conditions, in addition to their key role in outcome measurement in clinical trials. However, compared to joints, imaging research of muscles is less established, despite the fact that muscle symptoms are very common and debilitating in many rheumatic diseases. Recently, it has been shown that even though patients with rheumatoid arthritis may achieve clinical remission, defined by asymptomatic joints, many remain affected by lingering constitutional systemic symptoms like fatigue, tiredness, weakness and myalgia, which may be attributed to changes in the muscles. Recent improvements in imaging technology, coupled with an increasing clinical interest, has started to ignite new interest in the area. This perspective discusses the rationale for using imaging, particularly ultrasound and MRI, for investigating muscle pathology involved in common inflammatory rheumatic diseases. The muscles associated with rheumatic diseases can be affected in many ways, including myositis—an inflammatory muscle condition, and myopathy secondary to medications, such as glucocorticoids. In addition to non-invasive visual assessment of muscles in these conditions, novel imaging techniques like shear wave elastography and quantitative MRI can provide further useful information regarding the physiological and biomechanical status of the muscle. / This research is funded by the NIHR infrastructure at Leeds.

The use of brightness mode (B-mode) ultrasound (US), color Doppler (CD), and power Doppler (PD) can all help evaluate and characterize splenic lesions. A relatively new non-Doppler technology used to evaluate vasculature called B-Flow helps overcome certain limitations of CD and PD that affect visualization of blood flow. There are no studies describing the use of B-Flow characterizing splenic lesions in dogs. A total of 97 splenic lesions were evaluated. Splenic lesions that were larger than 2 cm, distorted the splenic capsule, or accompanied free fluid were significantly associated with malignancy. Lesions with tortuous internal vessels on CD or B-Flow were significantly associated with malignancy. Lesions with large internal vessels compared to external vessels on PD and B-Flow were significantly associated with malignancy. In conclusion, these B-mode and vascular characteristics on CD, PD and B-flow may help clinicians prioritize malignant etiologies over benign ones and prompt more aggressive diagnostic recommendations.

Histotripsy is a non-invasive, non-thermal, and non-ionizing therapy that utilizes converging high-pressure ultrasound waves at a focal point to produce cavitation and induce mechanical tissue destruction. Currently, rapid prototyped histotripsy transducers consist of multiple elements and are made using 3D printing methods. Multi-element transducers introduce size constraints and 3D printing has limitations in material choice, cost, and time for larger scale manufacturing. This thesis investigates the development of rapid prototyped single element histotripsy transducers and the use of injection molding for transducer fabrication, utilizing an in-house metal CNC mill for mold manufacturing and a desktop injection molding machine. Nylon 101 and 30% glass-filled nylon were chosen as the plastics to inject as these were found to have the most similar acoustic properties to WaterShed, an ABS-like plastic currently used. Six single-element transducers were constructed with a 2 MHz curved Pz26 piezoceramic disc: two with SLA 3D printed housing, two with SLS 3D printed housing, and two with injection molded housing. Electrical impedance, beam dimensions, focal pressure output, and cavitation were characterized for each element. The results show that rapid prototyped single element transducers can generate enough pressure to perform histotripsy. This marks the development of the first rapid prototyped single element histotripsy transducer and further confirms that injection molding can produce transducers comparable, if not identical or potentially superior, to 3D printed counterparts. Future work aims to further characterize these transducers, explore more material options, and apply injection molding to various transducer designs while optimizing both CNC and injection molding parameters. / Master of Science / Histotripsy is a form of cancer therapy that can non-invasively treat tumors using focused ultrasound waves. Focused ultrasound transducers are used to achieve this and are currently prototyped using 3D printing. However, these methods are limiting in material options and upscale manufacturing. Many of these devices currently used tend to be larger in size, comparable to the size of a mixing bowl, which limits its applications. This thesis investigates the development of single element histotripsy transducers and the use of injection molding for transducer fabrication, using an in-house metal CNC mill for mold manufacturing and desktop injection molding machine. Nylon 101 and 30% glass-filled nylon were chosen as the plastics to inject due to their ideal acoustic properties. Six single-element transducers were constructed: two with SLA 3D printing, two with SLS 3D printing, and two with injection molding. All transducers were tested and compared against each other. The results show that 3D printed single element transducers can perform histotripsy and that injection molding can produce comparable results. Future work should continue to test and characterize these transducers, explore more material options for injection molding, apply injection molding to other transducer designs, and optimize CNC and injection molding parameters.