X-ray dark field imaging: a tool for early diagnosis of emphysema in chronic obstructive pulmonary disease?
Authors: Sundaresh Ram, MeiLan K Han
Journal: The Lancet Digital Health (2021)

Grating-based x-ray dark-field imaging is a novel imaging modality that has been refined during the past decade for applications in biomedical imaging.1Pfeiffer F Herzen J Willner M et al.Grating-based x-ray phase contrast for biomedical imaging applications.Z Med Phys. 2013; 23: 176-185Crossref PubMed Scopus (66) Google Scholar This technique exploits the wave-like behaviour of x-rays to detect, quantify, and visualise small-angle x-ray scattering. The strength of the dark-field signal reflects the amount of small-angle x-ray scattering that cannot be detected with conventional x-ray devices. Small-angle x-ray scattering occurs at interfaces between structures of different electron density—eg, at air and tissue interfaces in the lung, making the lung an organ of special interest for x-ray dark-field imaging. Even though x-ray dark-field imaging has been used to detect and quantify pulmonary emphysema in small animals,2Yaroshenko A Meinel FG Bech M et al.Pulmonary emphysema diagnosis with a preclinical small-animal x-ray dark-field scatter-contrast scanner.Radiology. 2013; 269: 427-433Crossref PubMed Scopus (96) Google Scholar x-ray dark-field radiography has never been used for clinical radiology in humans. In this issue of The Lancet Digital Health, Konstantin Willer and colleagues have built a novel dark-field chest x-ray system.3Willer K Fingerle AA Noichl W et al.X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.Lancet Digit Health. 2021; 3: e733-e744Scopus (25) Google Scholar Willer and colleagues describe the first live human application of x-ray dark-field imaging for early detection and quantification of emphysema among patients undergoing chest CT for medically indicated reasons. Their study involved 77 patients, in which x-ray dark-field and CT images were acquired and then visually assessed by five readers. Pulmonary function tests were also done for every patient. The authors report that compared with CT-based parameters (quantitative emphysema ρ=–0·27, p=0·089, visual emphysema ρ=–0·45, p=0·0028), the dark field signal (ρ=0·62, p<0·0001) yielded a stronger correlation with diffusion capacity (sub-cohort, n=42). The authors also noted that although the dark-field signal decreased with decreasing lung function, there was modest correlation with FEV1/FVC (ρ=0·49, p<0·0001, n=77). The relationships between dark-filed signal intensity and either visual emphysema scoring or quantitative emphysema scoring were not examined. The authors suggest that much of the value in x-ray dark-field imaging might come from its ability to detect early structural impairments associated with chronic obstructive pulmonary disease (COPD). Certainly, early detection of COPD is a worthy goal. COPD is currently the third leading cause of death worldwide.4WHOChronic obstructive pulmonary disease (COPD) fact sheet.https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)#:~:text=Chronic%20Obstructive%20Pulmonary%20Disease%20(COPD)%20is%20the%20third%20leading%20cause,%2Dincome%20countries%20(LMIC)Date: 2021Date accessed: September 1, 2021Google Scholar The majority of patients are identified relatively late in the disease course, and there is no single screening tool that has been widely adopted.5Vogelmeier CF Criner GJ Martinez FJ et al.Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary.Am J Respir Crit Care Med. 2017; 195: 557-582Crossref PubMed Scopus (1879) Google Scholar COPD screening typically involves questionnaires, peak expiratory flow meters, or microspirometers. Imaging is not currently being used to screen for COPD or as part of routine care, outside of assessment for advanced therapies and lung cancer screening. Because the dark-field metric showed only a modest correlation with FEV1/FVC ratio in a small cohort of patients, it needs to be validated on a large multi-ethnic cohort before it can be considered as a screening tool for established disease. The authors suggest that the FEV1/FVC ratio itself is insensitive to early structural changes, particularly emphysema. Multiple studies have identified a host of structural changes including small airway abnormality and emphysema that can be identified on CT in individuals with FEV1/FVC ratio greater than 0·70.6Regan EA Lynch DA Curran-Everett D et al.Clinical and radiologic disease in smokers with normal spirometry.JAMA Intern Med. 2015; 175: 1539-1549Crossref PubMed Scopus (279) Google Scholar However, correlation of the dark-field metrics with longitudinal data indicating progression to airflow obstruction will still be required to show that the abnormalities identified are clinically significant. However, stronger correlations were seen between dark-field imaging and diffusion capacity. Diffusion capacity has been linked to development of COPD among individuals without obstruction.7Harvey BG Strulovici-Barel Y Kaner RJ et al.Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.Eur Respir J. 2015; 46: 1589-1597Crossref PubMed Scopus (78) Google Scholar Diffusion capacity testing is relatively inexpensive, is easy to perform, and does not expose individuals to radiation. The associations for dark-field signals were also stronger with visual than quantitative CT scoring. Although the differences between visually assessed versus quantitatively identified emphysema are not fully understood, reports from the COPDGene study do suggest that visual emphysema metrics might have greater association with subsequent loss in lung density.8Park J Hobbs BD Crapo JD et al.Subtyping COPD by using visual and quantitative CT imaging features.Chest. 2020; 157: 47-60Summary Full Text Full Text PDF PubMed Scopus (41) Google Scholar The authors also highlight that one of the potential benefits of x-ray dark-field radiography is the very low effective radiation dose of 0·035 mSv, which is much below that of low-dose CT. A 2019 study used ultra-low-dose CT imaging with comparable mean effective radiation dosages, which has already shown potential for detecting chest pathology in a clinical setting.9Kroft LJM van der Velden L Girón IH Roelofs JJH de Roos A Geleijns J Added value of ultra-low-dose computed tomography, dose equivalent to chest x-ray radiography, for diagnosing chest pathology.J Thorac Imaging. 2019; 34: 179-186Crossref PubMed Scopus (62) Google Scholar Overall, this study presents an interesting technology for pulmonary imaging and provides a methodology to spur much needed action for assessment of pulmonary microstructural changes that remains challenging in routine clinical practice. X-ray dark-field radiography has shown to deliver complementary imaging information on the lung's microstructure beyond conventional chest x-rays in a preclinical setting.2Yaroshenko A Meinel FG Bech M et al.Pulmonary emphysema diagnosis with a preclinical small-animal x-ray dark-field scatter-contrast scanner.Radiology. 2013; 269: 427-433Crossref PubMed Scopus (96) Google Scholar In animal studies, x-ray dark-field radiography has also shown better diagnostic performance than conventional x-ray for the detection of pulmonary fibrosis and acute lung inflammation suggesting some of the greatest potential use for this technology is yet to be explored.10Fingerle AA De Marco F Andrejewski J et al.Imaging features in post-mortem x-ray dark-field chest radiographs and correlation with conventional x-ray and CT.Eur Radiol Exp. 2019; 3: 25Crossref PubMed Scopus (16) Google Scholar This study helps us to understand some of the exciting potential of this methodology, and we look forward to further studies that continue to help us understand how this technology might best be applied in the clinical setting. MKH reports consulting for AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, GlaxoSmithKline, Merck, Novartis, Pulmonx, Sanofi, Sunovion, Teva, and Verona; and research support from Nuvaira, Novartis, Sunovion, and Sanofi. SR reports no competing interests. X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy studyX-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. Full-Text PDF Open Access