Search

Medical imaging is widely used clinically and in research to understand disease progression and monitor responses to therapies. Vascular imaging enables the study of vascular disease and therapy, but exogenous contrast agents are generally needed to distinguish the vasculature from surrounding soft tissues. Lanthanide-based agents are commonly employed in MRI, but are also of growing interest for micro-CT, as the position of their k-edges allows them to provide enhanced contrast and also to be employed in dual-energy micro-CT, a technique that can distinguish contrast-enhanced blood vessels from tissues such as bone. Small molecule Gd 3+ chelates are available, but are excreted too rapidly. At the same time, a lack of rapid clearance from the body for long-circulating agents presents toxicity concerns. To address these challenges, we describe here the use of self-immolative polymers for the development of new degradable chelates that depolymerize completely from end-to-end following the cleavage of a single end-cap from the polymer terminus. We demonstrate that tuning the end-cap allows the rate of depolymerization to be controlled, while tuning the polymer length enables the polymer to exhibit long circulation times in the blood of mice. After successfully providing one hour of blood contrast, depolymerization led to excretion of the resulting small molecule chelates into the bladder. Despite the high doses required for micro-CT, the agents were well tolerated in mice. Thus, these self-immolative polymeric chelates provide a new platform for the development of medical imaging contrast agents. STATEMENT OF SIGNIFICANCE: Vascular imaging is used clinically to diagnose and monitor vascular disease and in research to understand the progression of disease and study responses to new therapies. For techniques such as magnetic resonance imaging and x-ray computed tomography (CT), long circulating contrast agents are needed to differentiate the vasculature from surrounding tissues. However, if these agents are not rapidly excreted from the body, they can lead to toxicity. We present here a new polymeric system that can chelate hundreds of lanthanide ions for imaging contrast and can circulate for one hour in the blood, but then after end-cap cleavage breaks down completely into small molecules for excretion. The successful application of this system in micro-CT in mice is demonstrated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Utilizing existing methods for bias detection in machine learning (ML) models is challenging since each method: 1) explores a different ethical aspect of bias, which may result in contradictory output among the different methods; 2) provides output in a different range/scale and therefore cannot be compared with other methods; and 3) requires different input, thereby requiring a human expert's involvement to adjust each method according to the model examined. In this article, we present BENN, a novel bias estimation method that uses a pretrained unsupervised deep neural network. Given an ML model and data samples, BENN provides a bias estimation for every feature based on the examined model's predictions. We evaluated BENN using three benchmark datasets, one proprietary churn prediction model used by a European telecommunications company, and a synthetic dataset that includes both a biased feature and a fair one. BENN's results were compared with an ensemble of 21 existing bias estimation methods. The evaluation results show that BENN provides bias estimations that are aligned with those of the ensemble while offering significant advantages, including the fact that it is a generic approach (i.e., can be applied to any ML model) and does not require a domain expert.

Vascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder., (© 2021. The Author(s).)

Tracheoesophageal speakers can achieve speech without digital occlusion by using a tracheostoma valve. Laryngectomized patients who are successful with this device can regain considerable freedom. However, little is known about which valve suits the patient best. Valve aerodynamics may give a guideline for its use. Three major tracheostoma valves, each divided into four subtypes, were repeatedly measured in this study. Dynamic pressure and airflow rate signals were sampled through an analog-digital interface into a computer. Considerable aerodynamic differences were observed between the tested valves. The maximum airflow rates, closing pressures, and resistances at low velocities were compared. The presented data may help increase the successful use of tracheostoma valves in tracheoesophageal speakers. Patient factors and additional valve factors should always be taken into account. Further clinical study to validate the clinical relevance of the data is needed.