Use of high frequency jet ventilation as a refinement for imaging macaques with respiratory disease

Sharpe, Sally; Scott, S.; Taylor, Irene; Skinner, Oliver P; Clark, Simon; Smyth, Donna; McIntyre, A. S.; Gleeson, Fergus; Dennis, Mike

doi:10.1177/0023677220913328

Cited by 3 publications

(1 citation statement)

References 3 publications

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“…Respiratory control can be achieved by a breath-hold or via a high frequency jet ventilation technique. 5 Both techniques require the insertion of an endotracheal tube and the need to perform respiratory control with mechanical ventilation. Invasive handlings, although performed routinely, increase the chance of animal handling complications and possible cross-contamination with highly contagious diseases.…”

Section: Introductionmentioning

confidence: 99%

Refined acquisition of high-resolution chest CTs in macaques by free breathing

Tölgyesi¹,

Bakker

Nagy³

et al. 2021

Lab Anim

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The use of medical imaging as a non-invasive or minimally invasive method to assess disease or treatment response continues to grow. A similar trend is observed in pre-clinical research, in general, and more specifically in macaques, enabling longitudinal assessment of disease in individual animals. Computed tomography (CT) is such an imaging technique used to obtain clinically applicable data. To acquire a chest CT using a cone beam tomography system, some kind of respiration control is needed. A commonly used technique for this is endotracheal intubation and mechanical ventilation. However, although routinely performed this can increase the risk of impact on welfare in comparison with non-invasive imaging. Therefore, we studied the option of retrospectively gated CTs: acquiring high resolution chest CTs in freely breathing macaques. For this, we compared 748 CTs obtained during free breathing with 881 CTs obtained with mechanical ventilation in combination with a breath-hold procedure predominantly on the appearance of misregistration artifacts. The scans were obtained during different stages of multiple experimentally induced respiratory diseases. The comparison shows that although there are still streaking artifacts present in the retrospective gated scans, the amount of shading artifacts is reduced to such a level that it possibly dominates underlying lesions, causing misdiagnosis. Our data reveal that the use of retrospective gating in high resolution CTs for macaques can be successfully applied. With the use of this technique, artifacts due to free breathing are reduced to a diagnostically appropriate level. Most importantly, this technique makes chest CTs with this instrumentation a non-invasive modality.

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Section: Introductionmentioning

confidence: 99%

Refined acquisition of high-resolution chest CTs in macaques by free breathing

Tölgyesi¹,

Bakker

Nagy³

et al. 2021

Lab Anim

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Facility design and management. Strategies for high level biocontainment

Dennis,

Charlton,

Elam

et al. 2024

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UK Health Security Agency is required to investigate the pathogenesis of emerging or re-emerging infections and to test novel interventions, such as vaccines and therapeutics against these and other diseases, such as tuberculosis and Ebola, that have a significant impact on human health world-wide. Research into the causative agents (mainly BSL 3 and 4) using a wide range of animal species as pre-clinical models brings a number of challenges in terms of effective biocontainment to address human safety whilst optimising delivery of scientific objectives and the welfare of the animals. Here we describe the strategies used for high containment of species that include mice, ferrets, hamsters, rabbits and macaques that have been infected with high consequence pathogens. To ensure relevance of these models we frequently challenge by the aerosol route and monitor the development of disease and protective or therapeutic efficacy by methodologies similar to those used in the clinic. We have devised methods of sampling that can inform on pathogenesis and immune function that include lung lavage and medical imaging such as computed tomography and positron emission tomography-computed tomography. Imaging assists our assessment of progression to disease whilst providing refinement in application of early humane endpoints. We have developed directional flow containment systems that provide quantifiable operator protection whilst allowing group housing and a wide range of enrichment strategies appropriate for each species. Furthermore, we have demonstrated our improvements in animal welfare through use of a software-based Animal Welfare Assessment Grid that was developed with help of NC3Rs funding and enables us to quantify the lifetime experience of animals.

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Opportunities for Refinement of Non-Human Primate Vaccine Studies

et al. 2021

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Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of precious resources. A key aspect is consideration of the 3Rs principles of replacement, reduction, and refinement. Funders of NHP research are placing increasing emphasis on the 3Rs, helping to ensure such studies are legitimate, ethical, and high-quality. The UK’s National Centre for the 3Rs (NC3Rs) and the Coalition for Epidemic Preparedness Innovations (CEPI) have collaborated on a range of initiatives to support vaccine developers to implement the 3Rs, including hosting an international workshop in 2019. The workshop identified opportunities to refine NHP vaccine studies to minimize harm and improve welfare, which can yield better quality, more reproducible data. Careful animal selection, social housing, extensive environmental enrichment, training for cooperation with husbandry and procedures, provision of supportive care, and implementation of early humane endpoints are features of contemporary good practice that should and can be adopted more widely. The requirement for high-level biocontainment for some pathogens imposes challenges to implementing refinement but these are not insurmountable.

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Use of high frequency jet ventilation as a refinement for imaging macaques with respiratory disease

Cited by 3 publications

References 3 publications

Refined acquisition of high-resolution chest CTs in macaques by free breathing

Refined acquisition of high-resolution chest CTs in macaques by free breathing

Facility design and management. Strategies for high level biocontainment

Opportunities for Refinement of Non-Human Primate Vaccine Studies

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