<i>In Vivo</i> X-Ray Imaging Reveals Improved Airway Surface Hydration after a Therapy Designed for Cystic Fibrosis

Morgan, Kaye S.; Donnelley, Martin; Farrow, Nigel; Fouras, Andreas; Yagi, Naoto; Suzuki, Yoshio; Takeuchi, Akihisa; Uesugi, Kentaro; Boucher, Richard C.; Siu, Karen Kit Wan; Parsons, David

doi:10.1164/rccm.201405-0855le

Cited by 31 publications

(31 citation statements)

References 14 publications

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“…Despite the lack of pulmonary symptoms, the mechanisms described occur in CF lungs from the first months of the life, therefore it is critical to apply early treatment and establish imaging techniques that allow for non-invasive ASLiq depth assessment [66]. Currently all PCXI CF lung imaging experiments have been performed in animal models due to the high radiation dose of phase-contrast imaging sources [68][69][70].…”

Section: Phase-contrast X-ray Imaging In Cystic Fibrosismentioning

confidence: 99%

“…Recently the same technique was used for in vivo imaging of CF mice airways and after administrating hypertonic saline statistically significant differences (p ≤ 0.0001) were noted from 9, 12 and 15 min acquisitions compared to isotonic saline response [70]. Synchrotron based X-Ray Phase contrast x-ray imaging • Assessment of structural and functional changes in a microscale + very high spatial and temporal resolution of images + cimaging function and morphology in microscale -ionizing radiation method-not applicable for humans [66,[68][69][70] PXCI offers extraordinary detail for the assessment of CF lung disease progression, and while the application of the above techniques in humans is certainly challenging, it offers insight into the mechanisms in pre-clinical animal models and can be used to provide excellent spatial resolution and track the effectiveness of applied therapies.…”

Section: Phase-contrast X-ray Imaging In Cystic Fibrosismentioning

confidence: 99%

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Evaluation of high resolution computed tomography findings of cystic fibrosis

Şaşihüseyinoğlu

Altıntaş

Soyupak

et al. 2019

Korean J Intern Med

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Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

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Section: Phase-contrast X-ray Imaging In Cystic Fibrosismentioning

confidence: 99%

Section: Phase-contrast X-ray Imaging In Cystic Fibrosismentioning

confidence: 99%

Evaluation of high resolution computed tomography findings of cystic fibrosis

Şaşihüseyinoğlu

Altıntaş

Soyupak

et al. 2019

Korean J Intern Med

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“…However, the beam coherence requirements for propagation-based imaging are more strict than for grating-based imaging, so in a laboratory environment the technique typically uses a micro-focus source [30,31], and the associated long exposure times limit applications to static samples. For this reason most studies that perform dynamic x-ray lung imaging have been performed at high-flux synchrotron facilities [32,33,34,35,36,37,1,38]. However, these facilities are expensive, rarely designed for small-animal imaging, and access is very limited, which can prohibit longitudinal experiments, or time-critical imaging (i.e.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The setup for instillation of a liquid into the mouse lungs is shown in Fig. 1 (a), which was similar to that described in Donnelley et al [36,37]. The intra-tracheally intubated mice were mechanically ventilated throughout the delivery and imaging period using a flexiVent small-animal ventilator (flexiVent FX, Scireq, Montreal, QC, Canada).…”

Section: Instillationmentioning

confidence: 99%

Visualizing treatment delivery and deposition in mouse lungs using in vivo x-ray imaging

Gradl

Dierolf

Yang³

et al. 2019

Journal of Controlled Release

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The complexity of lung diseases makes pre-clinical in vivo respiratory research in mouse lungs of great importance for a better understanding of physiology and therapeutic effects. Synchrotron-based imaging has been successfully applied to lung research studies, however longitudinal studies can be difficult to perform due to limited facility access. Laboratory-based x-ray sources, such as inverse Compton x-ray sources, remove this access limitation and open up new possibilities for pre-clinical small-animal lung research at high spatial and temporal resolution. The in vivo visualization of drug deposition in mouse lungs is of interest, particularly in longitudinal research, because the therapeutic outcome is not only dependent on the delivered dose of the drug, but also on the spatial distribution of the drug. An additional advantage of this approach, when compared to other imaging techniques, is that anatomic and dynamic information is collected simultaneously. Here we report the use of dynamic x-ray phase-contrast imaging to observe pulmonary drug delivery via liquid instillation, and by inhalation of micro-droplets. Different liquid volumes (4 l  , 20 l  , 50 l ) were tested and a range of localized and global distributions were observed with a temporal resolution of up to 1.5 fps. The in vivo imaging results were confirmed by ex vivo x-ray and fluorescence imaging. This ability to visualize pulmonary substance deposition in live small animals has provided a better understanding of the two key methods of delivery; instillation and nebulization.

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“…Subsequent to this, pollutant and other marker particles were used to measure mucociliary transport mechanisms [94]. PBI has been used to measure airway surface liquid depth, specifically for assessment of therapies for cystic fibrosis lung disease [95,96]. Donnelley et al [97] measured the variability of in vivo fluid dose distribution in liquid doses delivered through the pulmonary system.…”

Section: Propagation-based Phase-contrast Imagingmentioning

confidence: 99%

Imaging regional lung function: A critical tool for developing inhaled antimicrobial therapies

Dubsky

Fouras

2015

Advanced Drug Delivery Reviews

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Alterations in regional lung function due to respiratory infection have a significant effect on the deposition of inhaled treatments. This has consequences for treatment effectiveness and hence recovery of lung function. In order to advance our understanding of respiratory infection and inhaled treatment delivery, we must develop imaging techniques that can provide regional functional measurements of the lung. In this review, we explore the role of functional imaging for the assessment of respiratory infection and development of inhaled treatments. We describe established and emerging functional lung imaging methods. The effect of infection on lung function is described, and the link between regional disease, function, and inhaled treatments is discussed. The potential for lung function imaging to provide unique insights into the functional consequences of infection, and its treatment, is also discussed.

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In Vivo X-Ray Imaging Reveals Improved Airway Surface Hydration after a Therapy Designed for Cystic Fibrosis

Cited by 31 publications

References 14 publications

Evaluation of high resolution computed tomography findings of cystic fibrosis

Evaluation of high resolution computed tomography findings of cystic fibrosis

Visualizing treatment delivery and deposition in mouse lungs using in vivo x-ray imaging

Imaging regional lung function: A critical tool for developing inhaled antimicrobial therapies

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