Deep Learning-based Segmentation of Computed Tomography Scans Predicts Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort.

Seven Pillars of Small Airways Disease in Asthma and COPD: Supporting Opportunities for Novel Therapies.

Identification of pathologic changes in early and mild obstructive lung disease has shown the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found prior to any overt airway obstruction being detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression.

Quantitative Assessment of Regional Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging.

Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study investigates the value of regional clearance measurements in assessing MCC in mild-to-moderate disease. Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (i) healthy nonsmoking controls (NSCs) ( = 9), (ii) smoking controls (SCs) who were current smokers with normal lung function ( = 10), and (iii) current smokers with mild-to-moderate COPD and bronchitis ( = 15).

OptiJ: Open-source optical projection tomography of large organ samples.

The three-dimensional imaging of mesoscopic samples with Optical Projection Tomography (OPT) has become a powerful tool for biomedical phenotyping studies. OPT uses visible light to visualize the 3D morphology of large transparent samples. To enable a wider application of OPT, we present OptiJ, a low-cost, fully open-source OPT system capable of imaging large transparent specimens up to 13 mm tall and 8 mm deep with 50 µm resolution.

Quantitative Assessment of Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging Using the Change in Penetration Index.

Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls ( = 9), (2) smoking controls who were current smokers with normal lung function ( = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis ( = 15).

Modeling Gadoxetate Liver Uptake and Efflux Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging Enables Preclinical Quantification of Transporter Drug-Drug Interactions.

Objectives: The aim of this study was to model the in vivo transporter-mediated uptake and efflux of the hepatobiliary contrast agent gadoxetate in the liver. The efficacy of the proposed technique was assessed for its ability to provide quantitative insights into drug-drug interactions (DDIs), using rifampicin as inhibitor.

Materials And Methods: Three groups of C57 mice were scanned twice with a dynamic gadoxetate-enhanced magnetic resonance imaging protocol, using a 3-dimensional spoiled gradient-echo sequence for approximately 72 minutes.

The use of 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) as a non-invasive pharmacodynamic biomarker to determine the minimally pharmacologically active dose of AZD8835, a novel PI3Kα inhibitor.

Background: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development.

Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.

Objective: The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers.

Materials And Methods: Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent.

The use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) as a pathway-specific biomarker with AZD8186, a PI3Kβ/δ inhibitor.

Background: The phosphatidylinositol 3 kinase (PI3K) signalling pathway is frequently altered in human cancer and a promising therapeutic target. AZD8186 (AstraZeneca) is a PI3Kβ/δ inhibitor, currently in phase 1 clinical trials. (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is often used as a biomarker for inhibitors targeting the PI3K axis because of the association of this pathway with glucose metabolism.

Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: Evidence from a seven-center multivendor study.

Purpose: To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems.

Materials And Methods: A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.

Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin.

Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10(-4) to 1.7 × 10(-2), which was enough to allow fluorescence detection and imaging of its distribution.

In vivo visualization of macrophage infiltration and activity in inflammation using magnetic resonance imaging.

Because macrophages play a key role on host defense, visualization of the migration of these cells is of high relevance for both diagnostic purposes and the evaluation of therapeutic interventions. The present article addresses the use of iron oxide and gadolinium-based particles for the noninvasive in vivo detection of macrophage infiltration into inflamed areas by magnetic resonance imaging (MRI). A general introduction on the functions and general characteristics of macrophages is followed by a discussion of some of the agents and acquisition schemes currently used to track the cells in vivo.

In vivo assessments of mucus dynamics in the rat lung using a Gd-Cy5.5-bilabeled contrast agent for magnetic resonance and optical imaging.

Dysfunctions in mucociliary clearance are associated with the accelerated loss of lung function in several respiratory diseases. Approaches enabling the in vivo visualization of mucus dynamics in rodents at high resolution and sensitivity would be beneficial for experimental lung research. We describe the synthesis and characterization of two bilabeled amino dextran-based probes binding specifically to mucin.

Allergen-induced lung inflammation in actively sensitized mice assessed with MR imaging.

Purpose: To demonstrate the feasibility of using proton magnetic resonance (MR) imaging to noninvasively detect extravascular and luminal fluid in a murine model of allergen-induced airway inflammation.

Materials And Methods: The Basel Veterinary Authority approved this experiment. Actively sensitized female Balb/c mice received ovalbumin or saline and underwent MR imaging (a) once 24 hours after the fourth administration of ovalbumin or saline (n = 25) or (b) several times between and after ovalbumin or saline administrations (n = 22) to determine the volume of fluid signal induced by an allergen.

Lung MRI for experimental drug research.

Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal.

Bleomycin-induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI.

Purpose: To apply proton magnetic resonance imaging (MRI) techniques to assess noninvasively and in spontaneously breathing rats, structural changes following a single intratracheal administration of bleomycin (BLM).

Materials And Methods: Rats were scanned by MRI prior to BLM or vehicle administration and at six hours, 24 hours, week 1, and at weeks 2, 3, 6, and 8 after treatment. Bronchoalveolar lavage (BAL) fluid and histological analyses were performed at 24 hours, and at weeks 1 and 8 (histology only).

In vivo mouse imaging and spectroscopy in drug discovery.

Imaging modalities such as micro-computed tomography (micro-CT), micro-positron emission tomography (micro-PET), high-resolution MRI, optical imaging, and high-resolution ultrasound have become invaluable tools in preclinical pharmaceutical research. They can be used to non-invasively investigate, in vivo, rodent biology and metabolism, disease models, and pharmacokinetics and pharmacodynamics of drugs. The advantages and limitations of each approach usually determine its application, and therefore a small-rodent imaging laboratory in a pharmaceutical environment should ideally provide access to several techniques.

Non-invasive methods: investigation of airways diseases by MRI in rats.

Current techniques to evaluate the efficacy of potential treatments for airways diseases in small animal models are generally invasive and terminal. In this contribution we illustrate the usefulness of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung, with the scope of developing a non-invasive approach for the routine testing of drugs in rat models of airways diseases. With MRI, the disease progression can be followed in the same animal.

Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI.

Magnetic resonance imaging (MRI) has been used previously to follow noninvasively inflammatory processes in rat acute models of lung inflammation. Here the technique was applied to a model involving repeated intratracheal administration of ovalbumin (OA). Anatomical MRI was performed at different time points with respect to a single or multiple OA challenges in Brown Norway rats actively sensitized to the allergen.

Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.