Patient recruitment
In our supraregional outpatient department for patients with AATD, we routinely perform α1-antiproteinase-inhibitor augmentation therapy in non-smoking patients with the genotype PiZZ or PiZ0 and reduced lung function following ATS/ERS statement [1, 25]. For surveillance, we periodically monitor lung volumes by lung function testing. Conventional CXR is performed when clinically indicated. To consider a lung volume reduction, a detailed evaluation by CT is obtained if the patient is an appropriate candidate.
Patient recruitment in the pulmonary outpatient clinic was part of a larger, ongoing, world´s first study at the department of radiology evaluating dark-field CXR for the early detection of emphysema in patients with chronic obstructive pulmonary disease (COPD), including patients with confirmed COPD on spirometry and patients without COPD for reference. To assess whether lung parenchymal changes could be visualised in this rare lung disease, patients with AATD were also included. Data from AATD patients were pooled from the study.
The study was approved by the institutional ethics review board and the Federal Office for Radiation Protection. All participants gave written informed consent.
Inclusion and exclusion criteria
We included adult patients with confirmed AATD and a patient without AATD with clinically indicated CXR. We excluded patients with any other additional pulmonary disease apart from AATD-associated emphysema, pregnant patients, and patients not capable of giving consent. Due to the size of the grating interferometer prototype, only a limited field of view was studied. Therefore, patients with a body height larger than 182 cm or a body mass index greater than 30 were excluded.
Study design
Patients included in this preliminary study received dark-field CXR in posteroanterior and lateral projection, in inspiration and expiration. Conventional CXR was acquired in posteroanterior and lateral projection in inspiration. Whole-body plethysmography was performed. One AATD and one healthy patient received CT imaging for clinical reasons to exclude infiltrates or malignancies. Additionally, the CT in the patient with AATD was performed to obtain information regarding distribution of emphysema planning endoscopic lung volume reduction. Results for the four AATD patients were compared to those obtained for the patient without AATD or other pulmonary diseases as a reference (see the “Patient recruitment” section).
Dark-field radiography
In grating-based dark-field imaging, a high frequency intensity modulation, typically of a few microns in size, is imposed on the x-ray wavefront. If this wave front penetrates an object with high fluctuations of the refractive index on the micron scale, the amplitude of this pattern is reduced because of multiple small-angle scattering. The magnitude of this reduction corresponds to the dark-field signal intensity [22]. Figure 1 schematically illustrates the basic working principle. The mean value of the intensity pattern encodes the conventional attenuation signal which can be reconstructed in addition to the dark-field signal, from the same dataset. Consequently, two perfectly registered images representing different physical interaction principles are obtained in one single acquisition. Detailed information regarding scanning and reading technique were described earlier by our group [26]. A clinical prototype system developed in-house was utilised to acquire dark-field and attenuation thoracic radiography images of the AATD patients and one patient without obstructive lung disease [20]. The system is based on a combination of a three grating x-ray interferometer and standard medical x-ray components such as high voltage generator (Velara, Philips Healthcare, The Netherlands), source (MRC 200 0508 ROT GS, Philips Healthcare, The Netherlands), collimator (MTR 302, Ralco, Milan, Italy), and flat-panel detector (Pixium FE 4343 F, Trixell, Moirans, France). Prior to the scan, the region to be imaged was adjusted according to the patient’s size. Similarly to conventional CXR, the patient was standing upright and was advised to hold breath for the duration of the image acquisition. The acquisition procedure relies on a scanning approach, where an active area of about 42 × 6.5 cm2 is scanned across the patient’s thorax in about 7 s.
Conventional CXR and CT imaging
Attenuation CXRs were obtained using a commercial radiography system (DigitalDiagnost, Philips Medical Systems, Hamburg, Germany) with a tube voltage of 125 kVp. Two patients received a contrast-enhanced chest CT (IQon Spectral CT, Royal Philips, Amsterdam, The Netherlands), as clinically indicated. Tube voltage was 120 kVp and automatic angular tube current modulation was utilised. Images were reconstructed with 0.9-mm slice thickness, high-resolution kernel, and noise suppression level 6 (iDose 6, Royal Philips, Amsterdam, The Netherlands).
Pulmonary function test (PFT)
All participants underwent a standardised lung function test at our centre according to the European Respiratory Society Recommendations [27, 28]. The PFT consisted of a combination of spirometry with whole-body plethysmography (MasterScreen Body, Jaeger, Wuerzburg, Germany). If applicable, a measurement of diffusing capacity of carbon monoxide (DLCO) was added (MS-PFT, Jaeger, Wuerzburg, Germany).
Image evaluation
On both dark-field and conventional radiographs, lungs were divided into six regions: right and left lung upper, middle and lower zone (RLUZ, RLMZ, RLLZ, LLUZ, LLMZ, LLLZ, respectively) [24]. On dark-field images, pulmonary signal strength, as a marker for alveolar integrity, was visually graded for each zone separately using a 6-point scale in consensus reading (G.S.Z., A.A.F): 0 (absent), 1 (very low), 2 (low), 3 (moderate), 4 (high), and 5 (very high). Lateral and posteroanterior dark-field images in expiration were included in this evaluation. Conventional radiographs were evaluated regarding the presence of signs of hyperinflation and vascular changes associated with emphysema on a 2-point scale: 0 (absent) and 1 (present). The extent of emphysema in the clinically indicated CT scan of one patient was visualised in a coronal image by thresholding lung density of -950 HU using vendor-specific software (IntelliSpace Portal, Royal Philips, Amsterdam, The Netherlands). The reading was conducted according to a standardised protocol by consensus reading. Due to the small sample size, no multiple readings were conducted.