Quantification of the Pulmonary Vasculature in Mice under Chronic Hypoxia with Contrast Free Pulmonary Angiography In Vivo Imaging.

Innovative advancements in preclinical imaging have led to the development of cone-beam computed tomography (CBCT) combined with contrast free pulmonary angiography (CFPA), a novel lung scanning technology capable of assessing lung function and pulmonary vascular morphology. This cutting-edge approach integrates CBCT to provide detailed quantification of the pulmonary vascular tree. The application of this technique to image and quantify changes in the pulmonary vascular tree of mice exposed to chronic hypoxia has not been investigated.

Quantifying ventilation by X-ray velocimetry in healthy adults.

Rationale: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means.

Objectives: To assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation.

Methods: XV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing.

Association of x-ray velocimetry (XV) ventilation analysis compared to spirometry.

Introduction: X-ray Velocimetry (XV) ventilation analysis is a 4-dimensional imaging-based method for quantifying regional ventilation, aiding in the assessment of lung function. We examined the performance characteristics of XV ventilation analysis by examining correlation to spirometry and measurement repeatability.

Methods: XV analysis was assessed in 27 patients receiving thoracic radiotherapy for non-lung cancer malignancies.

Functional imaging for assessing regional lung ventilation in preclinical and clinical research.

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function.

Innovations in thoracic imaging: CT, radiomics, AI and x-ray velocimetry.

In recent years, pulmonary imaging has seen enormous progress, with the introduction, validation and implementation of new hardware and software. There is a general trend from mere visual evaluation of radiological images to quantification of abnormalities and biomarkers, and assessment of 'non visual' markers that contribute to establishing diagnosis or prognosis. Important catalysts to these developments in thoracic imaging include new indications (like computed tomography [CT] lung cancer screening) and the COVID-19 pandemic.

Preclinical Four-Dimensional Functional Lung Imaging and Quantification of Regional Airflow: A New Standard in Lung Function Evaluation in Murine Models.

The current standard for lung function evaluation in murine models is based on forced oscillation technology, which provides a measure of the total airway function but cannot provide information on regional heterogeneity in function. Limited detection of regional airflow may contribute to a discontinuity between airway inflammation and airflow obstruction in models of asthma. Here, we describe quantification of regional airway function using novel dynamic quantitative imaging and analysis to quantify and visualize lung motion and regional pulmonary airflow in four dimensions (4D).

The association between regional transcriptome profiles and lung volumes in response to mechanical ventilation and lung injury.

Background: Lung inhomogeneity plays a pivotal role in the development of ventilator-induced lung injury (VILI), particularly in the context of pre-existing lung injury. The mechanisms that underlie this interaction are poorly understood. We aimed to elucidate the regional transcriptomic response to mechanical ventilation (MV), with or without pre-existing lung injury, and link this to the regional lung volume response to MV.

The proteomic response is linked to regional lung volumes in ventilator-induced lung injury.

It is unclear how acid-induced lung injury alters the regional lung volume response to mechanical ventilation (MV) and how this impacts protein expression. Using a mouse model, we investigated the separate and combined effects of acid aspiration and MV on regional lung volumes and how these were associated with the proteome. Adult BALB/c mice were divided into four groups: intratracheal saline, intratracheal acid, saline/MV, or acid/MV.

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry.

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung.

Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source.

Most measures of lung health independently characterise either global lung function or regional lung structure. The ability to measure airflow and lung function regionally would provide a more specific and physiologically focused means by which to assess and track lung disease in both pre-clinical and clinical settings. One approach for achieving regional lung function measurement is via phase contrast X-ray imaging (PCXI), which has been shown to provide highly sensitive, high-resolution images of the lungs and airways in small animals.

Interaction between regional lung volumes and ventilator-induced lung injury in the normal and endotoxemic lung.

Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end-expiratory lung volume exist that minimize lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxemic lung.

The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation.

The aim of this study was to assess the association between regional tidal volume (Vt), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB/c mice ( = 8 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional Vt and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.

Application of a novel in vivo imaging approach to measure pulmonary vascular responses in mice.

Noninvasive imaging of the murine pulmonary vasculature is challenging due to the small size of the animal, limits of resolution of the imaging technology, terminal nature of the procedure, or the need for intravenous contrast. We report the application of laboratory-based high-speed, high-resolution x-ray imaging, and image analysis to detect quantitative changes in the pulmonary vascular tree over time in the same animal without the need for intravenous contrast. Using this approach, we detected an increased number of vessels in the pulmonary vascular tree of animals after 30 min of recovery from a brief exposure to inspired gas with 10% oxygen plus 5% carbon dioxide (mean ± standard deviation: 2193 ± 382 at baseline vs.

High resolution propagation-based imaging system for in vivo dynamic computed tomography of lungs in small animals.

We have developed an x-ray imaging system for in vivo four-dimensional computed tomography (4DCT) of small animals for pre-clinical lung investigations. Our customized laboratory facility is capable of high resolution in vivo imaging at high frame rates. Characterization using phantoms demonstrate a spatial resolution of slightly below 50 μm at imaging rates of 30 Hz, and the ability to quantify material density differences of at least 3%.

Cardiogenic Airflow in the Lung Revealed Using Synchrotron-Based Dynamic Lung Imaging.

The beating heart is known to produce pressure and airflow oscillations in the lungs of mammals. This phenomenon is often disregarded as detailed measurement of its effects in the lung have hitherto not been possible. Previous studies have attempted to measure the effect of these oscillations on gas mixing.

Array-source X-ray velocimetry.

X-ray velocimetry (XV) has shown promise for investigations into various dynamic biological systems, including the motion of lungs and the flow of blood. Prior research in the field of XV has highlighted the need for both high spatial resolution to resolve features for tracking, and temporal resolution for accurate velocity measurement. In X-ray imaging systems, enhancement of spatial and temporal resolution requires a small focal spot size and high power output respectively, increasing anode power density requirements.

Novel analysis of 4DCT imaging quantifies progressive increases in anatomic dead space during mechanical ventilation in mice.

Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation/perfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation.

Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion.

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH.

Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge.

Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown.

Requirements for dynamical differential phase contrast x-ray imaging with a laboratory source.

X-ray phase contrast enables weakly-attenuating structures to be imaged, with bright synchrotron sources adding the ability to capture time sequences and analyse sample dynamics. Here, we describe the translation of dynamical differential phase contrast imaging from the synchrotron to a compact x-ray source, in order to achieve this kind of time sequence imaging in the laboratory. We formulate broadly-applicable set-up guidelines for the single-grid, single-exposure imaging technique using a divergent source, exploring the experimental factors that restrict set-up size, imaging sensitivity and sample size.

Technical Note: Contrast free angiography of the pulmonary vasculature in live mice using a laboratory x-ray source.

Purpose: In vivo imaging of the pulmonary vasculature in small animals is difficult yet highly desirable in order to allow study of the effects of a host of dynamic biological processes such as hypoxic pulmonary vasoconstriction. Here the authors present an approach for the quantification of changes in the vasculature.

Methods: A contrast free angiography technique is validated in silico through the use of computer-generated images and in vivo through microcomputed tomography (μCT) of live mice conducted using a laboratory-based x-ray source.

Quantification of heterogeneity in lung disease with image-based pulmonary function testing.

Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease.

Optimizing lung aeration at birth using a sustained inflation and positive pressure ventilation in preterm rabbits.

Background: A sustained inflation (SI) facilitates lung aeration, but the most effective pressure and duration are unknown. We investigated the effect of gestational age (GA) and airway liquid volume on the required inflation pressure and SI duration.

Methods: Rabbit kittens were delivered at 27, 29, and 30 d gestation, intubated and airway liquid was aspirated.

Phase contrast x-ray velocimetry of small animal lungs: optimising imaging rates.

Chronic lung diseases affect a vast portion of the world's population. One of the key difficulties in accurately diagnosing and treating chronic lung disease is our inability to measure dynamic motion of the lungs in vivo. Phase contrast x-ray imaging (PCXI) allows us to image the lungs in high resolution by exploiting the difference in refractive indices between tissue and air.

Imaging lung tissue oscillations using high-speed X-ray velocimetry.

This work utilized synchrotron imaging to achieve a regional assessment of the lung's response to imparted oscillations. The forced oscillation technique is increasingly being used in clinical and research settings for the measurement of lung function. During the forced oscillation technique, pressure oscillations are imparted to the lungs via the subjects' airway opening and the response is measured.