The quantitative assessment of interstitial lung disease with positron emission tomography scanning in systemic sclerosis patients

Daphne M Peelen, Ben G J C Zwezerijnen, Esther J Nossent, Lilian J Meijboom, Otto S Hoekstra, Conny J Van der Laken, Alexandre E Voskuyl, Daphne M Peelen, Ben G J C Zwezerijnen, Esther J Nossent, Lilian J Meijboom, Otto S Hoekstra, Conny J Van der Laken, Alexandre E Voskuyl

Abstract

Objectives: The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD.

Methods: 18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren's syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t).

Results: SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT.

Conclusion: Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.

Keywords: 18F-FDG PET/CT; Systemic sclerosis; interstitial lung disease; lung fibrosis; positron emission tomography.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Visual examination of 18F-FDG-PET and HRCT Transverse and sagittal slides of 18F-FDG-PET scans and HRCT scans of a SSc patient without ILD (A) and a SSc patient with ILD (B). Increased 18F-FDG uptake in dorsobasal lung areas is marked by red arrows. FDG: fluorodeoxyglucose; HRCT: high resolution CT; ILD: interstitial lung disease.
Fig . 2
Fig. 2
18F-FDG uptake in dorsobasal ROIs Each data point represents the mean of six dorsobasal SUVmean values of a patient. Mean values for the different groups were: SSc with ILD: 1.19; SSc without ILD: 0.60; SLE: 0.62; pSS: 0.74. SUVmean values were significantly higher in the SSc with ILD group compared with the SSc without ILD patients, SLE patients and pSS patients (P = 0.04, P = 0.003 and P = 0.03, respectively). Statistic test: Mann–Whitney U-test. FDG: fluorodeoxyglucose; ILD: interstitial lung disease; SUV: standardized uptake value; ROI: region of interest; SUVmean: mean SUV.
Fig . 3
Fig. 3
B/A-p and B/A-t ratios (A) Mean values of B/A-p ratios were: SSc with ILD: 2.63; SSc without ILD: 1.65; SLE: 1.36; pSS: 1.42. The B/A-p ratio was higher in patients with ILD compared with patients without ILD, SLE patients and pSS patients (P = 0.07, P = 0.002 and P = 0.02, respectively). (B) Mean values of B/A-t ratios were: normal lung parenchyma: 1.45; ground glass: 2.95; reticulation: 2.79; reticulation with architectural distortion: 2.45. The B/A-t ratio was significantly higher in areas of ground glass and in areas of reticulation with architectural distortion compared with normal lung parenchyma (P = 0.02 and P = 0.02, respectively), but not in areas of reticulation without architectural distortion (P = 0.13). Statistic test: Mann-Whitney U-test. B/A-p ratio: basal/apical ratio at patient level; B/A-t ratio: basal/apical ratio at tissue level; ILD: interstitial lung disease; SUVmean: mean SUV.

References

    1. Steen VD, Medsger TA.. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007;66:940–4.
    1. Morales-Cardenas A, Perez-Madrid C, Arias L. et al. Pulmonary involvement in systemic sclerosis. Autoimmun Rev 2016;15:1094–108.
    1. Goh NS, Desai SR, Veeraraghavan S. et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008;177:1248–54.
    1. Denton CP, Khanna D.. Systemic sclerosis. Lancet 2017;390:1685–99.
    1. Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM.. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J 2009;33:882–96.
    1. Kowal-Bielecka O, Fransen J, Avouac J. et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017;76:1327–39.
    1. Schoenfeld SR, Castelino FV.. Evaluation and management approaches for scleroderma lung disease. Therapeutic Adv Respir Dis 2017;11:327–40.
    1. Wells AU. High-resolution computed tomography and scleroderma lung disease. Rheumatology 2008;47(Suppl 5):v59–61.
    1. Le Gouellec N, Duhamel A, Perez T. et al. Predictors of lung function test severity and outcome in systemic sclerosis-associated interstitial lung disease. PLoS One 2017;12:e0181692.
    1. Behr J, Furst DE.. Pulmonary function tests. Rheumatology 2008;47(Suppl 5):v65–7.
    1. Chen DL, Schiebler ML, Goo JM, van Beek E.. PET imaging approaches for inflammatory lung diseases: current concepts and future directions. Eur J Radiol 2017;86:371–6.
    1. Jacquelin V, Mekinian A, Brillet PY. et al. FDG-PET/CT in the prediction of pulmonary function improvement in nonspecific interstitial pneumonia. A pilot study. Eur J Radiol 2016;85:2200–5.
    1. Justet A, Laurent-Bellue A, Thabut G. et al. [18F]FDG PET/CT predicts progression-free survival in patients with idiopathic pulmonary fibrosis. Respir Res 2017;18:74.
    1. Win T, Thomas BA, Lambrou T. et al. Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients. Eur J Nucl Med Mol Imaging 2014;41:337–42.
    1. Nobashi T, Kubo T, Nakamoto Y. et al. 18F-FDG uptake in less affected lung field provides prognostic stratification in patients with interstitial lung disease. J Nucl Med 2016;57:1899–904.
    1. Umeda Y, Demura Y, Morikawa M. et al. Prognostic value of dual-time-point 18F-FDG PET for idiopathic pulmonary fibrosis. J Nucl Med 2015;56:1869–75.
    1. El-Chemaly S, Malide D, Yao J. et al. Glucose transporter-1 distribution in fibrotic lung disease: association with [18F]-2-fluoro-2-deoxyglucose-PET scan uptake, inflammation, and neovascularization. Chest 2013;143:1685–91.
    1. Wang ZG, Yu MM, Han Y. et al. Correlation of Glut-1 and Glut-3 expression with F-18 FDG uptake in pulmonary inflammatory lesions. Medicine (Baltimore) 2016;95:e5462.
    1. Bagnato G, Harari S.. Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev 2015;24:102–14.
    1. Todd NW, Scheraga RG, Galvin JR. et al. Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis. J Inflamm Res 2013;6:63–70.
    1. Batra K, Butt Y, Gokaslan T. et al. Pathology and radiology correlation of idiopathic interstitial pneumonias. Hum Pathol 2018;72:1–17.
    1. Cohen C, Mekinian A, Uzunhan Y. et al. 18F-fluorodeoxyglucose positron emission tomography/computer tomography as an objective tool for assessing disease activity in Sjogren's syndrome. Autoimmun Rev 2013;12:1109–14.
    1. Uehara T, Takeno M, Hama M. et al. Deep-inspiration breath-hold 18F-FDG-PET/CT is useful for assessment of connective tissue disease associated interstitial pneumonia. Mod Rheumatol 2016;26:121–7.
    1. Nishiyama Y, Yamamoto Y, Dobashi H, Kameda T.. Clinical value of 18F-fluorodeoxyglucose positron emission tomography in patients with connective tissue disease. Jpn J Radiol 2010;28:405–13.
    1. Meissner HH, Soo Hoo GW, Khonsary SA. et al. Idiopathic pulmonary fibrosis: evaluation with positron emission tomography. Respiration 2006;73:197–202.
    1. Groves AM, Win T, Screaton NJ. et al. Idiopathic pulmonary fibrosis and diffuse parenchymal lung disease: implications from initial experience with 18F-FDG PET/CT. J Nucl Med 2009;50:538–45.
    1. Lee EY, Wong CS, Fung SL, Yan PK, Ho JC.. SUV as an adjunct in evaluating disease activity in idiopathic pulmonary fibrosis – a pilot study. Nucl Med Commun 2014;35:631–7.
    1. Win T, Lambrou T, Hutton BF. et al. 18F-Fluorodeoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials. Eur J Nucl Med Mol Imaging 2012;39:521–8.
    1. Bellando-Randone S, Tartarelli L, Cavigli E. et al. 18F-fluorodeoxyglucose positron-emission tomography/CT and lung involvement in systemic sclerosis. Ann Rheum Dis 2019;78:577–8.
    1. Travis WD, Costabel U, Hansell DM. et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188:733–48.
    1. Travis WD, Hunninghake G, King TE Jr. et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med 2008;177:1338–47.
    1. Holman BF, Cuplov V, Millner L. et al. Improved correction for the tissue fraction effect in lung PET/CT imaging. Phys Med Biol 2015;60:7387–402.
    1. Chen DL, Cheriyan J, Chilvers ER. et al. Quantification of lung PET images: challenges and opportunities. J Nucl Med 2017;58:201–7.
    1. Galvin I, Drummond GB, Nirmalan M.. Distribution of blood flow and ventilation in the lung: gravity is not the only factor. Br J Anaesth 2007;98:420–8.
    1. Millar AB, Denison DM.. Vertical gradients of lung density in healthy supine men. Thorax 1989;44:485–90.
    1. van den Hoogen F, Khanna D, Fransen J. et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737–47.
    1. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
    1. Shiboski CH, Shiboski SC, Seror R. et al. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjogren's Syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol (Hoboken) 2017;69:35–45.
    1. Boellaard R, Delgado-Bolton R, Oyen WJ. et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015;42:328–54.
    1. Hansell DM, Bankier AA, MacMahon H. et al. Fleischner society: glossary of terms for thoracic imaging. Radiology 2008;246:697–722.
    1. Boktor RR, Walker G, Stacey R, Gledhill S, Pitman AG.. Reference range for intrapatient variability in blood-pool and liver SUV for 18F-FDG PET. J Nucl Med 2013;54:677–82.
    1. Meignan M, Gallamini A, Meignan M, Gallamini A, Haioun C.. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma 2009;50:1257–60.
    1. Herzog EL, Mathur A, Tager AM. et al. Review: interstitial lung disease associated with systemic sclerosis and idiopathic pulmonary fibrosis: how similar and distinct? Arthritis Rheumatol (Hoboken) 2014;66:1967–78.
    1. Tanti JF, Gautier N, Cormont M. et al. Potential involvement of the carboxy-terminus of the Glut 1 transporter in glucose transport. Endocrinology 1992;131:2319–24.
    1. Frood R, McDermott G, Scarsbrook A.. Respiratory-gated PET/CT for pulmonary lesion characterisation—promises and problems. Br J Radiol 2018;91:20170640.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever