In Vivo Diagnostic Imaging Using Micro-CT: Sequential and Comparative Evaluation of Rodent Models for Hepatic/Brain Ischemia and Stroke

BACKGROUND: There is an increasing need for animal disease models for pathophysiological research and efficient drug screening. However, one of the technical barriers to the effective use of the models is the difficulty of non-invasive and sequential monitoring of the same animals. Micro-CT is a powerful tool for serial diagnostic imaging of animal models. However, soft tissue contrast resolution, particularly in the brain, is insufficient for detailed analysis, unlike the current applications of CT in the clinical arena. We address the soft tissue contrast resolution issue in this report. METHODOLOGY: We performed contrast-enhanced CT (CECT) on mouse models of experimental cerebral infarction and hepatic ischemia. Pathological changes in each lesion were quantified for two weeks by measuring the lesion volume or the ratio of high attenuation area (%HAA), indicative of increased vascular permeability. We also compared brain images of stroke rats and ischemic mice acquired with micro-CT to those acquired with 11.7-T micro-MRI. Histopathological analysis was performed to confirm the diagnosis by CECT. PRINCIPAL FINDINGS: In the models of cerebral infarction, vascular permeability was increased from three days through one week after surgical initiation, which was also confirmed by Evans blue dye leakage. Measurement of volume and %HAA of the liver lesions demonstrated differences in the recovery process between mice with distinct genetic backgrounds. Comparison of CT and MR images acquired from the same stroke rats or ischemic mice indicated that accuracy of volumetric measurement, as well as spatial and contrast resolutions of CT images, was comparable to that obtained with MRI. The imaging results were also consistent with the histological data. CONCLUSIONS: This study demonstrates that the CECT scanning method is useful in rodents for both quantitative and qualitative evaluations of pathologic lesions in tissues/organs including the brain, and is also suitable for longitudinal observation of the same animals

Themes that Determine Quality of Life in Patients with Peripheral Arterial Disease: A Systematic Review

© 2018 Springer International Publishing AG, part of Springer Nature Objectives: The aim of this study was to identify domains that determine quality of life in patients with peripheral arterial disease and find the patient-reported outcome measures that can examine the identified themes. Methods: A systematic review of all the main six databases was undertaken to identify primary qualitative studies reporting on the health and/or quality of life of patients with peripheral arterial disease. The quality of studies was assessed using the Critical Appraisal Skills Program criteria. Findings from the included studies were analysed using framework analysis methodology. The identified themes were mapped against the items/domains of validated patient-reported outcome measures used in patients with peripheral arterial disease. Results: The systematic review identified eight papers that fulfilled the inclusion criteria. The included papers reported the views of 186 patients with peripheral arterial disease including patients with intermittent claudication, critical ischaemia and amputation secondary to peripheral arterial disease. The overall quality of the included studies was good based on Critical Appraisal Skills Program criteria. Framework analysis identified 35 themes that were divided into six main groups: symptoms, impact on physical functioning, impact on social functioning, psychological impact, financial impact and process of care. The best-fit generic and disease-specific patient-reported outcome measures were the Nottingham Health Profile and the Vascular Quality of Life Questionnaire, respectively. None of the patient-reported outcome measures covered all the themes important to patients with peripheral arterial disease. Discussion: The findings from the review identified the important domains that affect patients living with peripheral arterial disease. None of the current generic and disease-specific patient-reported outcome measures provide a comprehensive measure for all themes that impact the daily living of patients with peripheral arterial disease

Novel Virus-Like Particle Vaccine Encoding the Circumsporozoite Protein of Plasmodium falciparum Is Immunogenic and Induces Functional Antibody Responses in Mice

RTS,S is the leading malaria vaccine in development, but has demonstrated only moderate protective efficacy in clinical trials. RTS,S is a virus-like particle (VLP) that uses the human hepatitis B virus as scaffold to display the malaria sporozoite antigen, circumsporozoite protein (CSP). Particle formation requires four-fold excess scaffold antigen, and as a result, CSP represents only a small portion of the final vaccine construct. Alternative VLP or nanoparticle platforms that reduce the amount of scaffold antigen and increase the amount of the target CSP antigen present in particles may enhance vaccine immunogenicity and efficacy. Here, we describe the production and characterization of a novel VLP that uses the small surface antigen (dS) of duck hepatitis B virus to display CSP. The CSP-dS fusion protein successfully formed VLPs without the need for excess scaffold antigen, and thus CSP represented a larger portion of the vaccine construct. CSP-dS formed large particles approximately 31-74 nm in size and were confirmed to display CSP on the surface. CSP-dS VLPs were highly immunogenic in mice and induced antibodies to multiple regions of CSP, even when administered at a lower vaccine dosage. Vaccine-induced antibodies demonstrated relevant functional activities, including Fc-dependent interactions with complement and Fcγ-receptors, previously identified as important in malaria immunity. Further, vaccine-induced antibodies had similar properties (epitope-specificity and avidity) to monoclonal antibodies that are protective in mouse models. Our novel platform to produce VLPs without excess scaffold protein has wide implications for the future development of vaccines for malaria and other infectious diseases