Experimental and quantitative imaging techniques in interstitial lung disease

Abstract

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions, with a wide and complex variety of imaging features. Difficulty in monitoring, treating and exploring novel therapies for these conditions is in part due to the lack of robust, readily available biomarkers. Radiological studies are vital in the assessment and follow-up of ILD, but currently CT analysis in clinical practice is qualitative and therefore somewhat subjective. In this article, we report on the role of novel and quantitative imaging techniques across a range of imaging modalities in ILD and consider how they may be applied in the assessment and understanding of ILD. We critically appraised evidence found from searches of Ovid online, PubMed and the TRIP database for novel and quantitative imaging studies in ILD. Recent studies have explored the capability of texture-based lung parenchymal analysis in accurately quantifying several ILD features. Newer techniques are helping to overcome the challenges inherent to such approaches, in particular distinguishing peripheral reticulation of lung parenchyma from pleura and accurately identifying the complex density patterns that accompany honeycombing. Robust and validated texture-based analysis may remove the subjectivity that is inherent to qualitative reporting and allow greater objective measurements of change over time. In addition to lung parenchymal feature quantification, pulmonary vessel volume analysis on CT has demonstrated prognostic value in two retrospective analyses and may be a sign of vascular changes in ILD which, to date, have been difficult to quantify in the absence of overt pulmonary hypertension. Novel applications of existing imaging techniques, such as hyperpolarised gas MRI and positron emission tomography (PET), show promise in combining structural and functional information. Although structural imaging of lung tissue is inherently challenging in terms of conventional proton MRI techniques, inroads are being made with ultrashort echo time, and dynamic contrast-enhanced MRI may be used for lung perfusion assessment. In addition, inhaled hyperpolarised 129Xenon gas MRI may provide multifunctional imaging metrics, including assessment of ventilation, intra-acinar gas diffusion and alveolar-capillary diffusion. PET has demonstrated high standard uptake values (SUVs) of 18F-fluorodeoxyglucose in fibrosed lung tissue, challenging the assumption that these are ‘burned out’ and metabolically inactive regions. Regions that appear structurally normal also appear to have higher SUV, warranting further exploration with future longitudinal studies to assess if this precedes future regions of macroscopic structural change. Given the subtleties involved in diagnosing, assessing and predicting future deterioration in many forms of ILD, multimodal quantitative lung structure-function imaging may provide the means of identifying novel, sensitive and clinically applicable imaging markers of disease. Such imaging metrics may provide mechanistic and phenotypic information that can help direct appropriate personalised therapy, can be used to predict outcomes and could potentially be more sensitive and specific than global pulmonary function testing. Quantitative assessment may objectively assess subtle change in character or extent of disease that can assist in efficacy of antifibrotic therapy or detecting early changes of potentially pneumotoxic drugs involved in early intervention studies.

18F-FDG positron emission tomography scanning in systemic sclerosis-associated interstitial lung disease: a pilot study

“…However, it remains difficult to accurately predict ILD evolution [ 15 – 17 ]. Tools and biomarkers must be developed to assess ILD activity and the predictors of ILD progression and treatment response to optimize the decision-making [ 18 , 19 ] in an era where, beyond immunosuppressants, new antifibrotic treatments, for example, nintedanib, are or will be available [ 20 ].…”

Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency—Features of CT and 18F-FDG Positron Emission Tomography/CT in Clinically Progressive Disease

“…In contrast to CT and FDG PET-CT, magnetic resonance imaging (MRI) have the advantage of using non-ionizing radiation but has not been systematically evaluated for follow-up of interstitial lung disease ( 30 ).…”

Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme

“…These results suggest that changes in FVC do not necessarily reflect response to antifibrotic treatment in individual patients. Change in disease extent quantified by automated interpretation of HRCT is being evaluated as a method of assessing disease progression, but is not established in clinical practice [51,54]. A quantitative lung fibrosis (QLF) score, derived from HRCT images, has been developed in patients with systemic sclerosis-associated ILD (SSc-ILD) [55].…”