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

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).

METHODS

In 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 (7 s, 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

INTERPRETATION

X-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.

FUNDING

European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests TK is an employee of Philips Innovative Technologies, Research Laboratories, which is part of Royal Philips. AY and TP are employees of Philips Medical System DMC, which is part of Royal Philips. GSZ receives payments for lectures from Boehringer Ingelheim, AstraZeneca, Novartis, GlaxoSmithKline, Bayer Healthcare, and Roche; and receives travel support from Novartis and Roche. FP received a European Research Council Advanced Grant and a hardware loan (x-ray source and detector) from Royal Philips. The authorship of patents related to technical implementation of the demonstrator system are KW has coauthored GB3687403B2 and US20200187893A1; FDM has coauthored GB3687403B2 and US20200187893A1; TU has coauthored PCT/EP2021/063949; TK has coauthored US10417761B2, US10945690B2, GB3687403B2, US10912532B2, PCT/EP2020/082799, PCT/EP2021/057524, PCT/EP2021/064497, PCT/EP2021/063949, and US20200187893A1; AY has coauthored GB3687403B2, US10912532B2, PCT/EP2020/082799, and US20200187893A1; TP has coauthored PCT/EP2020/082799; and FP has coauthored US10945690B2 and PCT/EP2021/063949. Royal Philips is the assignee for all patents listed. All other authors declare no competing interests.