Introduction
Interstitial lung diseases (ILDs) include a large group of different diseases, characterised by inflammation and pulmonary fibrosis.1 Treatment consists of anti-inflammatory and/or antifibrotic medication. ILD diagnosis and identification of patients with ILD with a (progressive) fibrotic phenotype is challenging, but of key importance for treatment decisions and prognosis.2–4
For ILD diagnosis, no single diagnostic test exists. Guidelines recommend evaluating all available diagnostic information during a multidisciplinary team (MDT) discussion to establish a high confident diagnosis.5 To identify the fibrotic phenotype, pulmonary function testing and high-resolution CT (HRCT) are used as diagnostic parameters. However, changes in pulmonary function tests can be non-specific and HRCT has limitations in fibrosis detection and in differentiating fibrotic from inflammatory progression. Indeed, a weak correlation exists between fibrotic extent as detected by HRCT and prognosis.6 7 For disease pattern identification, lung biopsy is considered to be the reference standard, but is associated with morbidity and in rare case mortality. Lung tissue acquisition is, therefore, only performed in highly selected patients with ILD and is not appropriate for longitudinal measurements to evaluate fibrotic progression. Thus, there is an unmet need in fibrotic ILD diagnostics and ILD progression detection.
Conventional optical coherence tomography (OCT) is an imaging technique that uses near-infrared light to provide structural images of tissue with a resolution of ~10 µm.8 Endobronchial OCT (EB-OCT) refers to a technique in which a thin flexible OCT probe is advanced through the working channel of the bronchoscope to the periphery of the lung. The procedure is minimally invasive, can be performed under conscious sedation and can easily be combined with the standard diagnostic techniques including broncho alveolar lavage. In the last decade, EB-OCT emerged as a bronchoscopic imaging modality to generate cross-sectional images of the airways and lung parenchyma. Several studies reported EB-OCT in obstructive lung diseases,9–12 detection of malignancies13–15 and ILDs.16 17 Conventional EB-OCT provides volumetric reconstructions of lung tissue with microscopic resolution, but has limitations in fibrotic tissue-specific contrast.18 Polarisation sensitive OCT (PS-OCT) is an extension of conventional OCT that adds tissue-specific contrast by assessing presence of birefringence. Birefringence is an optical property exhibited by collagen in fibrous tissues including muscle, connective tissue and nerve fibres.19 As pulmonary fibrosis is characterised by an increase in collagen, PS-OCT can visualise pulmonary fibrosis. To date, the potential of EB-PS-OCT in pulmonary medicine has been demonstrated in vivo in a canine model20 and in asthma patients21 22 to detect airway smooth muscle reduction after bronchial thermoplasty. Recently, Nandy et al performed EB-PS-OCT in patients with ILD and manually quantified birefringence across tissue types including destructive and interstitial fibrosis.23
In this study, we use in vivo EB-PS-OCT to automatically quantify the area of birefringent tissue to assess fibrotic content in patients with ILD. For the first time, we compare the ability of EB-PS-OCT and HRCT for fibrosis detection and quantification using histopathology as reference standard. Additionally, we retrieve the orientation of birefringent tissues fibres, which provides a valuable tool to distinguish fibrous tissue from other birefringent tissues such as airway smooth muscle and perichondrium.