X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study

Abstract

Background Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). MethodsIn this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph ( 7s, 0•035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. Findings Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0•27, p=0•089 and visual emphysema ρ=-0•45, p=0•0028), the dark-field signal (ρ=0•62, p<0•0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0•21, for forced expiratory volume in 1 s (FEV 1 )/functional vital capacity is 0•25, for FEV 1 % of predicted is 0•23, for residual volume % of predicted is 0•24, for CT emphysema index is 0•35, for dark-field signal homogeneity within lungs is 0•38, for dark-field signal texture within lungs is 0•38, and for darkfield-based emphysema severity is 0•42. Interpretation X-r...

Dark-field computed tomography reaches the human scale

“…In MRI, a similar duality of contrast mechanisms, namely T1 and T2, is already well known and successfully applied in clinical routine. After dark-field CT systems are approved and available in clinics, we expect an immediate impact in lung imaging ( 4 , 27 ), as this has already been demonstrated in previous small-animal studies on COPD, emphysema, fibrosis, and lung cancer. Potential further clinical applications include foreign body detection ( 44 ) and characterization of trabecular bone microstructure ( 45 ) and calcifications as they can occur in tissue or as plaques in blood vessels, as well as differentiation between different types of kidney stones ( 46 ).…”

“…There have been a number of important technical advances in fabrication of the required grating optics ( 14 – 18 ), and new data processing approaches were introduced ( 19 – 23 ). More recently, first clinical prototypes have been developed for two-dimensional radiographic grating–based X-ray imaging, again supporting strongly the significant benefit of diagnostic information, particularly for lung diseases ( 24 – 27 ). The implementation into a human-scale CT system for first clinical studies, however, could so far not be achieved.…”

Retrieval of 3D information in X-ray dark-field imaging with a large field of view

“…Nevertheless, both vials are still visible in these images. At the same time the effective dose applied is only two-times higher than for clinical X-ray dark-field radiography 34 .…”

“…However, translating this method to large samples is not straightforward, especially as the fabrication of large gratings is difficult. Nevertheless, methods for X-ray dark-field radiography of large objects (in the vicinity of ) were developed 29 – 34 . In this paper we present a method to obtain 3D X-ray dark-field information of large objects, which is similar to classic tomography, tomosynthesis and line trajectory X–ray tomography.…”

Dark-field chest x-ray imaging: first experience in patients with alpha1-antitrypsin deficiency

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