This project aims to investigate the potential of non-invasive imaging to identify and monitor the earliest signs and physiological effects of pulmonary fibrosis and resulting cardiac dysfunction in patients with fibrosing interstitial lung disease. Second, to evaluate baseline risk factors the progression and therapeutic responses to anti-fibrotic drugs.

Fibrosing interstitial lung diseases (F-ILD) represent a heterogeneous disease category involving several disease entities with different clinical, radiological, and histological characteristics. The common denominator for F-ILD patients is similarities regarding development of scarring of the lungs. Idiopathic pulmonary fibrosis (IPF) is the prototype, and all patients will eventually suffer from irreversible progression. In other type of F-ILD, a proportion of patients will also develop symptom worsening, treatment resistance towards immunomodulatory therapy, a decline in lung physiological parameters, worsening of radiologic findings and irreversible self-sustaining progression of pulmonary fibrosis i.e., a phenotype of progressive pulmonary fibrosis (PPF), defined by worsening of symptoms, lung physiology and radiology within 12 months Chest High Resolution Computed Tomography (HRCT) is considered the golden standard to diagnose and quantify the type and extent of pulmonary fibrosis. Extent of fibrosis and specific features like traction bronchiectasis and honeycombing seem in some disease to be associated with a worse outcome. However, findings do not always correspond to disease severity or disease course, and at later stages, HRCT is limited in proving the progression of the disease. Identifying progression is currently based on a decrease in forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), worsening of symptoms or progression of radiologic features (Table 1). Identification of radiologic biomarkers for progression will allow to better support treatment decisions and inform patients. Patients with F-ILD often suffer from a high burden of comorbidities, including ischemic heart disease, congestive heart failure, and pulmonary hypertension. It is currently unknown if these is solely associated to common risk factors like smoking and age, or could be due to fibrosis developing in the myocardium. Furthermore, it is not well described if the development of a restrictive lung physiology plays a role and affects cardiac physiology.

This study proposes that MR (magnetic resonance) Imaging with hyperpolarized 129Xenon will be able to detect subtle, regional dysfunction of the gas exchange of the lungs in patients with F-ILDs at a higher level of sensitivity than currently applied techniques. Utilizing the improved sensitivity of the hyperpolarized xenon MRI the study aims to improve the diagnostic distinction between the different subtypes of F-ILDs and additionally point-out MR biomarkers to be assess F-ILD severity, progression, and potential treatment response. Simultaneously with the hyperpolarized 129Xe scans, imaging of myocardial strain and ejection fraction is performed. In addition, a Gadolinium Based Contrast Agent (GBCA) is administered to evaluate the degree of myocardial fibrous tissue and lung perfusion. Thus, the impact of thoracic restrictive physiology on the heart can be detected and quantified.

Inclusion Criteria:

• Informed signed consent
• Age 18-90
• Pre-menopausal women must be confirmed non-pregnant by an onsite test.
• Patients diagnosed with IPF or fibrotic ILD who fulfills PPF criteria, and are prescribed antifibrotic treatment.
• Cognitively able to understand and participate in the study

Exclusion Criteria:

• Contraindications for MRI:

  • Pacemaker, neurostimulator or cochlear implant
  • Metal foreign bodies such as fragments and irremovable piercings
  • Unsafe medical implants (safety of heart valves, hips and the like must be confirmed)
  • Intrathoracic clips or coils
  • Cardiac pacemakers
  • Claustrophobia
  • Largest circumference including arms > 160 cm

• Contraindications to gadolinium contrast

  • eGFR < 30 mL/min/1.73m2
  • Previous adverse reactions to gadolinium

• Overlapping emphysemic disease where the emphysema-component outweighs the fibrosis

• Unable to perform breath-hold of minimum 20 seconds.

• Allergy to Xenon

• Breast feeding

• Evidence of ongoing respiratory infections at time of MR examinations

Patients who have recently recieved a diagnosis of progressive fibrosing interstial lung disease and are expected to recieve antifibrotic therapy