Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Qualitative and quantitative assessment of smoking-related lung disease: effect of iterative reconstruction on low-dose computed tomographic examinations.

PURPOSE: The purpose of this research is to examine the role that differing levels of adaptive statistical iterative reconstruction (ASIR) have on the qualitative and quantitative assessment of smoking-related lung disease. MATERIALS AND METHODS: Institutional board review approval was obtained. A total of 52 patients undergoing clinically indicated low-dose computed tomographic (CT) examinations of the chest (100 kVp, 65 mAs, mean radiation dose 1.0±0.12 mSv), with reconstruction of data with different levels of blended ASIR (0%, 40%, and 100%), were consented. Qualitative assessment of CT data sets was performed by 2 trained thoracic radiologists blinded to clinical history, spirometry, and quantitative data for the presence of emphysema (%/lung zone) and the degree of respiratory bronchiolitis. Quantitative analysis was performed (Apollo Image analysis, VIDA Diagnostics) to assess emphysema and airway measures of chronic obstructive pulmonary disease. RESULTS: The application of ASIR results in alterations in both qualitative and quantitative assessment of smoking-related lung disease. As levels of ASIR increased, both readers scored more respiratory bronchiolitis (P<0.05). At increased levels of ASIR (ie, 100% vs. 0%), the amount of emphysema measured (% below -950 HU) decreased, the number of airways measured diminished, and the airway thickness (Pi10mm) increased (P<0.001). CONCLUSIONS: The use of ASIR alters both the qualitative and quantitative assessment of smoking-related lung disease. Although a powerful tool to allow dose reduction, caution must be exercised when iterative reconstruction techniques are utilized when evaluating CT examinations for findings of chronic obstructive pulmonary disease.

What to do when a smoker's CT scan is "normal"?: Implications for lung cancer screening.

Lung cancer is the leading cause of cancer-related mortality in the United States and around the world. There are > 90 million current and ex-smokers in the United States who are at increased risk of lung cancer. The published data from the National Lung Screening Trial (NLST) suggest that yearly screening with low-dose thoracic CT scan in heavy smokers can reduce lung cancer mortality by 20% and all-cause mortality by 7%. However, to implement this program nationwide using the NLST inclusion and exclusion criteria would be extremely expensive, with CT scan costs alone > $2 billion per annum. In this article, we offer a possible low-cost strategy to risk-stratify smokers on the basis of spirometry measurements and emphysema scoring by radiologists on CT scans.

Quantitative assessment of the airway wall using computed tomography and optical coherence tomography.

Ever since the site and nature of airflow obstruction in chronic obstructive pulmonary disease was described by Hogg, Thurlbeck, and Macklem, investigators have been looking for methods to noninvasively measure the airway wall dimensions. Recent advances in computed tomography technology and new computer algorithms have made it possible to visualize and measure the airway wall and lumen without the need for tissue. However, while there is great hope for computed tomographic assessment of airways, it is well known that the spatial resolution does not allow small airways to be visualized and there are still concerns about the sensitivity of these measurements obtained from these airways. Optical coherence tomography is a new bronchoscopic imaging technique that has generated considerable interest because the spatial resolution is much higher than computed tomography. While relatively more invasive than computed tomography, it has the advantage of not exposing the patient to ionizing radiation. This review discusses some of the data surrounding these two imaging techniques in patients with chronic obstructive pulmonary disease. These imaging techniques are extremely important in the assessment of patients with chronic obstructive pulmonary disease because therapy that is designed to modulate the inflammation in airways may be contraindicated in subjects with the emphysema phenotype and visa versa. Therefore, these new imaging techniques are very likely to play a front-line role in the study of chronic obstructive pulmonary disease and will, hopefully, allow clinicians to phenotype individuals, thereby personalizing their treatment.

Quantitative computed tomography assessment of airway wall dimensions: current status and potential applications for phenotyping chronic obstructive pulmonary disease.

Airway remodeling is extremely important in the pathophysiology of chronic obstructive pulmonary disease (COPD). Since the site and nature of airflow obstruction was described by Hogg, Thurlbeck, and Macklem, investigators have been looking for methods to noninvasively measure the airway wall dimensions in subjects with and at risk for COPD. The advent and proliferation of computed tomography (CT) initially allowed investigators to quantify changes in lung parenchymal structure in subjects with emphysema, and more recently attention has turned to the measurement of airway wall dimensions. Unfortunately, while the lung density is relatively easy to quantify, reliable airway measurements have proven to be more difficult to obtain. However, recent advances in CT technology and new computer algorithms have changed the way investigators have measured airways using CT, and it is now hoped that many of the early issues surrounding airway measurements can be resolved. The measurement of airway wall dimensions is important because it is well known that chronic airflow limitation can be caused by a combination of airway and parenchymal changes. The phenotypic expression of these different subtypes of COPD is vital because a therapy designed to modulate the inflammation in airways may be contraindicated in subjects with the emphysema phenotype and visa versa. Therefore, these new imaging techniques are very likely to play a front-line role in the study of COPD and will, hopefully, allow clinicians to phenotype individuals, thereby personalizing their treatment.

New concepts in the radiological assessment of COPD.

Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder in which environmental factors, such as tobacco smoke, interact with genetic susceptibility to cause disease. Airway obstruction in COPD is due to an exaggerated inflammatory response that ultimately destroys the lung parenchyma (emphysema) and increases airway resistance by remodeling the airway wall. Until recently, assessment of these disease processes required the examination of resected tissue. However, computed tomography (CT) now allows researchers to measure the structure of the lung parenchyma and airway wall without having to remove the tissue. This review describes some of the new CT techniques for quantitative assessment of lung structure. These techniques are extremely important to study the pathogenesis of COPD as well as differentiate patients with predominantly emphysema disease from those with airway wall remodeling, and to assess the effects of therapeutic interventions.