Novel imaging approaches for small animal models of lung disease (2017 Grover Conference series)

Pinar, Isaac; Jones, Heather D.

doi:10.1177/2045894018762242

Cited by 9 publications

(9 citation statements)

References 75 publications

(94 reference statements)

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“…Moreover, animals can be randomized between treatment groups, thus, reducing experimental bias. [47][48][49] In summary, using imaging techniques and analytical methods, we were able to quantify NM-induced pathological alterations over time in live animals and confirm the ability of anti-TNF-α antibody to blunt lung toxicity. These methods can be applied to other animal models to assess lung injury and fibrosis and to enhance the prediction and potential mitigation of injury with therapeutics.…”

Section: Discussionmentioning

confidence: 61%

Assessment of mustard vesicant lung injury and anti‐TNF‐α efficacy in rodents using live‐animal imaging

Murray

Gow

Venosa

et al. 2020

Annals of the New York Academy of Sciences

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Nitrogen mustard (NM) causes acute lung injury, which progresses to fibrosis. This is associated with a macrophagedominant inflammatory response and the production of proinflammatory/profibrotic mediators, including tumor necrosis factor alpha (TNF-α). Herein, we refined magnetic resonance imaging (MRI) and computed tomography (CT) imaging methodologies to track the progression of NM-induced lung injury in rodents and assess the efficacy of anti-TNF-α antibody in mitigating toxicity. Anti-TNF-α antibody was administered to rats (15 mg/kg, every 8 days, intravenously) beginning 30 min after treatment with phosphate-buffered saline control or NM (0.125 mg/kg, intratracheally). Animals were imaged by MRI and CT prior to exposure and 1-28 days postexposure. Using MRI, we characterized acute lung injury and fibrosis by quantifying high-signal lung volume, which represents edema, inflammation, and tissue consolidation; these pathologies were found to persist for 28 days following NM exposure. CT scans were used to assess structural components of the lung and to register changes in tissue radiodensities. CT scans showed that in control animals, total lung volume increased with time. Treatment of rats with NM caused loss of lung volume; anti-TNF-α antibody mitigated this decrease. These studies demonstrate that MRI and CT can be used to monitor lung disease and the impact of therapeutic intervention.

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Section: Discussionmentioning

confidence: 61%

Assessment of mustard vesicant lung injury and anti‐TNF‐α efficacy in rodents using live‐animal imaging

Murray

Gow

Venosa

et al. 2020

Annals of the New York Academy of Sciences

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“…Recent clinical studies have demonstrated that the PBV serves as prognostic marker for diseases affecting the heart and/or lung, in particular chronic heart failure 3 , systemic sclerosis 4 , and acute pulmonary embolism 5 . For preclinical research in cardiac and pulmonary disease mouse models are widely used 6 , 7 , for which PBV may also serve as an interesting parameter. However, non-invasive measurement of PBV in mice appears to be challenging due to the animals’ small size and high heart rate.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging

Kaul¹,

Mummert²,

Graeser³

et al. 2021

Sci Rep

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This methodical work describes the measurement and calculation of pulmonary blood volume in mice based on two imaging techniques namely by using magnetic particle imaging (MPI) and cardiac magnetic resonance imaging (MRI). Besides its feasibility aspects that may influence quantitative analysis are studied. Eight FVB mice underwent cardiac MRI to determine stroke volumes and anatomic MRI as morphological reference for functional MPI data. Arrival time analyses of boli of 1 µl of 1 M superparamagnetic tracer were performed by MPI. Pulmonary transit time of the bolus was determined by measurements in the right and left ventricles. Pulmonary blood volume was calculated out of stroke volume, pulmonary transit time and RR-interval length including a maximal error analysis. Cardiac stroke volume was 31.7 µl ± 2.3 µl with an ejection fraction of 71% ± 6%. A sharp contrast bolus profile was observed by MPI allowing subdividing the first pass into three distinct phases: tracer arrival in the right ventricle, pulmonary vasculature, and left ventricle. The bolus full width at half maximum was 578 ms ± 144 ms in the right ventricle and 1042 ms ± 150 ms in the left ventricle. Analysis of pulmonary transit time revealed 745 ms ± 81 ms. Mean RR-interval length was 133 ms ± 12 ms. Pulmonary blood volume resulted in 177 µl ± 27 µl with a mean maximal error limit of 27 µl. Non-invasive assessment of the pulmonary blood volume in mice was feasible. This technique can be of specific value for evaluation of pulmonary hemodynamics in mouse models of cardiac dysfunction or pulmonary disease. Pulmonary blood volume can complement cardiac functional parameters as a further hemodynamic parameter.

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“…Small rodent models have become crucial to the research of lung physiology and pathology (Kiessling et al, ; Pinar and Jones, ). Owing to the importance of the pathologic changes in airflow and lung volumes in disease, there is an interest in assessing these functions in experimental models.…”

Section: Introductionmentioning

confidence: 99%

“…Owing to the importance of the pathologic changes in airflow and lung volumes in disease, there is an interest in assessing these functions in experimental models. Because spirometry and tidal volume techniques provide only summary measurements of the entire lungs, there is continued interest in image‐based techniques for assessing regional lung physiology (Pinar and Jones, ) via assessing the physical properties of the lung microstructure under various imposed conditions. The current reference standard for small animal lung imaging remains computed tomography (micro‐CT) (Clark and Badea, ; Badea, ).…”

Section: Introductionmentioning

confidence: 99%

Quantification of image texture in X‐ray phase‐contrast‐enhanced projection images of in vivo mouse lungs observed at varied inflation pressures

et al. 2019

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To date, there are very limited noninvasive, regional assays of in vivo lung microstructure near the alveolar level. It has been suggested that x‐ray phase‐contrast enhanced imaging reveals information about the air volume of the lung; however, the image texture information in these images remains underutilized. Projection images of in vivo mouse lungs were acquired via a tabletop, propagation‐based, X‐ray phase‐contrast imaging system. Anesthetized mice were mechanically ventilated in an upright position. Consistent with previously published studies, a distinct image texture was observed uniquely within lung regions. Lung regions were automatically identified using supervised machine learning applied to summary measures of the image texture data. It was found that an unsupervised clustering within predefined lung regions colocates with expected differences in anatomy along the cranial–caudal axis in upright mice. It was also found that specifically selected inflation pressures—here, a purposeful surrogate of distinct states of mechanical expansion—can be predicted from the lung image texture alone, that the prediction model itself varies from apex to base and that prediction is accurate regardless of overlap with nonpulmonary structures such as the ribs, mediastinum, and heart. Cross‐validation analysis indicated low inter‐animal variation in the image texture classifications. Together, these results suggest that the image texture observed in a single X‐ray phase‐contrast‐enhanced projection image could be used across a range of pressure states to study regional variations in regional lung function.

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Novel imaging approaches for small animal models of lung disease (2017 Grover Conference series)

Cited by 9 publications

References 75 publications

Assessment of mustard vesicant lung injury and anti‐TNF‐α efficacy in rodents using live‐animal imaging

Assessment of mustard vesicant lung injury and anti‐TNF‐α efficacy in rodents using live‐animal imaging

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging

Quantification of image texture in X‐ray phase‐contrast‐enhanced projection images of in vivo mouse lungs observed at varied inflation pressures

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