RESUMO
: Local drug delivery aims to minimize systemic toxicity by preventing off-target effects; however, injection parameters influencing depot formation of injectable gels have yet to be thoroughly studied. We explored the effects of needle characteristics, injection depth, rate, volume, and polymer concentration on gel ethanol distribution in both tissue and phantoms. METHODS: The polymer ethyl cellulose (EC) was added to ethanol to form an injectable gel to ablate cervical precancer and cancer. Tissue mimicking phantoms composed of 1% agarose dissolved in deionized water were used to establish overall trends between various injection parameters and the resulting gel distribution. Additional experiments were performed in excised swine cervices with a CT-imageable injectate formulation, which enabled visualization of the distribution without tissue sectioning. RESULTS: Needle type and injection rate had minimal impact on gel distribution, while needle depths ≥13 mm yielded significantly larger distributions. Needle gauge and EC concentration impacted injection pressure with maximum gel distribution achieved when the pressure was 70-250 kPa. Injection volumes ≤3 mL of 6% ECethanol minimized fluid leakage away from the injection site. Results guided the development of a speculum-compatible handheld injector to deliver gel ethanol into the cervix. CONCLUSION: Needle depth, gauge, and polymer concentration are critical to consider when delivering injectable gels. SIGNIFICANCE: This study addressed key questions related to the impact of injection-based parameters on gel distribution at a scale relevant to human applications including: 1) how best to deliver EC-ethanol into the cervix and 2) general insights about injection protocols relevant to the delivery of injectable gels in tissue.
RESUMO
Current therapies for treating cervical dysplasia are often inaccessible in low and middle-income countries (LMICs), highlighting the need for novel low-cost therapies that can be delivered at the point of care. Ethanol ablation is a low-cost therapy designed to treat locoregional cancers, which we augmented into an ethyl cellulose (EC)-ethanol gel formulation to enhance its efficacy. Here, we evaluated whether EC-ethanol ablation is able to safely achieve an ablation zone comparable to thermocoagulation, a commonly used therapy for cervical dysplasia. The study was performed in 20 female Yorkshire pigs treated with either a single 500 µL injection of EC-ethanol into the 12 o'clock position of the cervix or a single application of thermocoagulation at 100 °C for 20 s. The average temperature, heart rate, respiratory rate, and blood oxygen remained within normal ranges throughout the EC-ethanol procedure and were similar to the thermocoagulation group. No major side effects were observed. The reproductive tracts were excised after 24 h to examine ablation zones. Comparable depths of necrosis were seen for EC-ethanol (18.6 ± 1.6 mm) and thermocoagulation (19.7 ± 4.1 mm). The volumes of necrosis induced by a single injection of EC-ethanol (626.2 ± 122.8 µL) were comparable to the necrotic volumes induced by thermocoagulation in the top half of the cervices (664.6 ± 168.5 µL). This suggests that two EC-ethanol injections could be performed (e.g., at the 12 and 6 o'clock positions) to achieve comparable total necrotic volumes to thermocoagulation and safely and effectively treat women with cervical dysplasia in LMICs. This is the first study to systematically evaluate EC-ethanol ablation in a large animal model and compare its safety and efficacy to thermocoagulation, a commonly used ablative therapy for cervical dysplasia.
RESUMO
PURPOSE: To introduce a novel methodology for developing anthropomorphic breast phantoms for use in X-ray-based imaging modalities. METHODS: "Hyperization" is a quasi-stippling mapping operation in which regions of varying grayscale values in a 2D image are transformed into regions of varying holes on a surface. The holes can be cut or engraved on the sheet of paper using a high-resolution laser cutter/engraver. In hyperization, the main parameters are the size and the distance between the holes. Here, we introduce the concept and chronicle the development and characterization of a proof-of-concept prototype. In this study, we hypothesized that a resulting "Hyperia" phantom would be a realistic representative of a patient's breast tissue: it would exhibit similar X-ray properties and show textural complexities. We used breast computed tomography (bCT) images of real patients as the input models. Using a previously developed segmentation method, the input CT images were segmented into different tissue classes (skin, adipose, and fibroglandular). The segmented images were then "Hyperized". A series of Monte Carlo simulations were conducted to find the optimal hyperization parameters. Different laser cutter/engraver systems and substrate materials were explored to find a viable option for developing an entire Hyperia breast phantom. The resulting phantom was imaged on a prototype breast CT system, and the resulting images were evaluated based on physical properties and similarity to the original patient data. RESULTS: The simulation results indicate close similarities - both in the distribution of different tissue types and the resulting CT numbers - between the patient bCT image and the bCT of the Hyperia phantom, regardless of the breast size and density: the Pearson correlation coefficient (ρ) ranged from 0.88 in a BIRADS A breast to 0.94 in BIRADS C and D breasts (ρ of 1.00 suggests perfect structural similarity), and the volumetric mean squared error ranged from 0.0033 (in BIRADS D breast) to 0.0059 (in BIRADS A), suggesting good agreement between the resulting CT numbers. For fabricating the slices, the office paper was found to be an optimal substrate material, with the Hyperization parameters of (α, ß) = (0.200 mm, 0.400 mm). CONCLUSION: A novel phantom can be used for X-ray-based breast cancer imaging systems. The main advantage is that only one material is used for creating a contrast between different tissue types in an image.